Mechanisms and Factors that Influence High Frequency Retroviral Recombination
Delviks-Frankenberry, Krista; Galli, Andrea; Nikolaitchik, Olga; Mens, Helene; Pathak, Vinay K.; Hu, Wei-Shau
2011-01-01
With constantly changing environmental selection pressures, retroviruses rely upon recombination to reassort polymorphisms in their genomes and increase genetic diversity, which improves the chances for the survival of their population. Recombination occurs during DNA synthesis, whereby reverse transcriptase undergoes template switching events between the two copackaged RNAs, resulting in a viral recombinant with portions of the genetic information from each parental RNA. This review summarizes our current understanding of the factors and mechanisms influencing retroviral recombination, fidelity of the recombination process, and evaluates the subsequent viral diversity and fitness of the progeny recombinant. Specifically, the high mutation rates and high recombination frequencies of HIV-1 will be analyzed for their roles in influencing HIV-1 global diversity, as well as HIV-1 diagnosis, drug treatment, and vaccine development. PMID:21994801
Tjomsland, Veronica; Ellegård, Rada; Burgener, Adam; Mogk, Kenzie; Che, Karlhans F; Westmacott, Garrett; Hinkula, Jorma; Lifson, Jeffrey D; Larsson, Marie
2013-01-01
Induction of optimal HIV-1-specific T-cell responses, which can contribute to controlling viral infection in vivo, depends on antigen processing and presentation processes occurring in DCs. Opsonization can influence the routing of antigen processing and pathways used for presentation. We studied antigen proteolysis and the role of endocytic receptors in MHC class I (MHCI) and II (MHCII) presentation of antigens derived from HIV-1 in human monocyte-derived immature DCs (IDCs) and mature DCs, comparing free and complement opsonized HIV-1 particles. Opsonization of virions promoted MHCI presentation by DCs, indicating that complement opsonization routes more virions toward the MHCI presentation pathway. Blockade of macrophage mannose receptor (MMR) and β7-integrin enhanced MHCI and MHCII presentation by IDCs and mature DCs, whereas the block of complement receptor 3 decreased MHCI and MHCII presentation. In addition, we found that IDC and MDC proteolytic activities were modulated by HIV-1 exposure; complement-opsonized HIV-1 induced an increased proteasome activity in IDCs. Taken together, these findings indicate that endocytic receptors such as MMR, complement receptor 3, and β7-integrin can promote or disfavor antigen presentation probably by routing HIV-1 into different endosomal compartments with distinct efficiencies for degradation of viral antigens and MHCI and MHCII presentation, and that HIV-1 affects the antigen-processing machinery. PMID:23526630
Activation of HIV-1 pre-mRNA 3' processing in vitro requires both an upstream element and TAR.
Gilmartin, G M; Fleming, E S; Oetjen, J
1992-01-01
The architecture of the human immunodeficiency virus type 1 (HIV-1) genome presents an intriguing dilemma for the 3' processing of viral transcripts--to disregard a canonical 'core' poly(A) site processing signal present at the 5' end of the transcript and yet to utilize efficiently an identical signal that resides at the 3' end of the message. The choice of processing sites in HIV-1 appears to be influenced by two factors: (i) proximity to the cap site, and (ii) sequences upstream of the core poly(A) site. We now demonstrate that an in vivo-defined upstream element that resides within the U3 region, 76 nucleotides upstream of the AAUAAA hexamer, acts specifically to enhance 3' processing at the HIV-1 core poly(A) site in vitro. We furthermore show that efficient in vitro 3' processing requires the RNA stem-loop structure of TAR, which serves to juxtapose spatially the upstream element and the core poly(A) site. An analysis of the stability of 3' processing complexes formed at the HIV-1 poly(A) site in vitro suggests that the upstream element may function by increasing processing complex stability at the core poly(A) site. Images PMID:1425577
Morgan, Rosemary; Green, Andrew; Boesten, Jelke
2014-05-01
Faith-based organizations (FBOs) have a long tradition of providing HIV/AIDS prevention and mitigation services in Africa. The overall response of FBOs, however, has been controversial, particularly in regard to HIV/AIDS prevention and FBO's rejection of condom use and promotion, which can conflict with and negatively influence national HIV/AIDS prevention response efforts. This article reports the findings from a study that explored the factors influencing the HIV/AIDS prevention policy process within faith-based non-governmental organizations (NGOs) of different faiths. These factors were examined within three faith-based NGOs in Dar es Salaam, Tanzania-a Catholic, Anglican and Muslim organization. The research used an exploratory, qualitative case-study approach, and employed a health policy analysis framework, examining the context, actor and process factors and how they interact to form content in terms of policy and its implementation within each organization. Three key factors were found to influence faith-based NGOs' HIV/AIDS prevention response in terms of both policy and its implementation: (1) the faith structure in which the organizations are a part, (2) the presence or absence of organizational policy and (3) the professional nature of the organizations and its actors. The interaction between these factors, and how actors negotiate between them, was found to shape the organizations' HIV/AIDS prevention response. This article reports on these factors and analyses the different HIV/AIDS prevention responses found within each organization. By understanding the factors that influence faith-based NGOs' HIV/AIDS prevention policy process, the overall faith-based response to HIV/AIDS, and how it corresponds to national response efforts, is better understood. It is hoped that by doing so the government will be better able to identify how to best work with FBOs to meet national HIV/AIDS prevention targets, improving the overall role of FBOs in the fight against HIV/AIDS.
Saubi, Narcís; Im, Eung-Jun; Fernández-Lloris, Raquel; Gil, Olga; Cardona, Pere-Joan; Gatell, Josep Maria; Hanke, Tomáš; Joseph, Joan
2011-01-01
We have evaluated the influence of age and immunization routes for induction of HIV-1- and M. tuberculosis-specific immune responses after neonatal (7 days old) and adult (7 weeks old) BALB/c mice immunization with BCG.HIVA222 prime and MVA.HIVA boost. The specific HIV-1 cellular immune responses were analyzed in spleen cells. The body weight of the newborn mice was weekly recorded. The frequencies of HIV-specific CD8+ T cells producing IFN-γ were higher in adult mice vaccinated intradermally and lower in adult and newborn mice vaccinated subcutaneously. In all cases the IFN-γ production was significantly higher when mice were primed with BCG.HIVA222 compared with BCGwt. When the HIV-specific CTL activity was assessed, the frequencies of specific killing were higher in newborn mice than in adults. The prime-boost vaccination regimen which includes BCG.HIVA222 and MVA.HIVA was safe when inoculated to newborn mice. The administration of BCG.HIVA222 to newborn mice is safe and immunogenic and increased the HIV-specific responses induced by MVA.HIVA vaccine. It might be a good model for infant HIV and Tuberculosis bivalent vaccine. PMID:21603216
Tonsil Epithelial Factors May Influence Oropharyngeal Human Immunodeficiency Virus Transmission
Moutsopoulos, Niki M.; Nares, Salvador; Nikitakis, Nikolaos; Rangel, Zoila; Wen, Jie; Munson, Peter; Sauk, John; Wahl, Sharon M.
2007-01-01
Tonsil epithelium has been implicated in human immunodeficiency virus (HIV) pathogenesis, but its role in oral transmission remains controversial. To study characteristics of this tissue, which may influence susceptibility or resistance to HIV, we performed microarray analysis of the tonsil epithelium. Our data revealed that genes related to immune functions such as antibody production and antigen processing were increasingly expressed in tonsil compared with the epithelium of another oropharyngeal site, the gingival epithelium. Importantly, tonsil epithelium highly expressed genes associated with HIV entrapment and/or transmission, including the HIV co-receptor CXCR4 and the potential HIV-binding molecules FcRγIII, complement receptor 2, and various complement components. Immunohistochemical staining confirmed the increased presence of CXCR4 in the tonsil epithelium compared with multiple oral epithelial sites, particularly in basal and parabasal layers. This increased expression of molecules involved in viral recognition, binding, and entry may favor virus-epithelium interactions in an environment with reduced innate antiviral mechanisms. Specifically, secretory leukocyte protease inhibitor, an innate molecule with anti-HIV activity, was minimal in the tonsil epithelium, in contrast to oral mucosa. Collectively, our data suggest that increased expression of molecules associated with HIV binding and entry coupled with decreased innate antiviral factors may render the tonsil a potential site for oral transmission. PMID:17620369
Personality profile of HIV outpatients: preliminary results and remarks on clinical management.
Fassino, Secondo; Leombruni, Paolo; Amianto, Federico; Abbate-Daga, Giovanni
2004-01-01
Currently, HIV is one of the most widely spread epidemics in the world. The specificity of the mode of transmission, the well-known severity of the prognosis, and the kind of therapies used are peculiarities of this illness. Personality traits of individuals with HIV may influence conditions for the infection itself. On the other hand, it is possible that personality traits may influence the course of the illness and the willingness of the patients to adhere to treatment. The present study assessed the personality traits of a heterogeneous group of seropositive subjects compared with healthy controls to determine specific temperament and character traits of this population. The Temperament and Character Inventory (TCI) was administered to 126 HIV-positive outpatients belonging to different risk categories for HIV infection and to a sample of healthy individuals matched for sex, age, and socioeconomic parameters. Drug-dependent HIV-positive patients displayed higher scores in novelty seeking and harm avoidance and lower scores in self-directedness compared with healthy controls. Non-drug-dependent HIV-positive subjects scored significantly higher in self-transcendence. Temperament and character features significantly differentiate the HIV-positive subjects from controls and those belonging to the different risk categories for HIV infection. Drug-dependent subjects with HIV display more impulsiveness, which possibly predates the HIV infection. They are also more fearful and lack self-directedness. Non-drug-dependent subjects express higher self-transcendence resources, possibly to overcome their difficulties. Both the temperament and character features may influence compliance with treatment and require specific interventions considering these subgroups.
Fleming, Paul J; DiClemente, Ralph J; Barrington, Clare
2016-04-01
Numerous studies have documented a relationship between masculine norms and men's HIV-related sexual behaviors, but intervening upon this relationship requires a nuanced understanding of the specific aspects of masculine norms that shape men's sexual behaviors. We integrate theories on masculinities with empirical HIV research to identify specific dimensions of masculine norms that influence men's HIV-related sexual behaviors. We identify three major dimensions of masculine norms that shape men's sexual behavior: (1) uncontrollable male sex drive, (2) capacity to perform sexually, and (3) power over others. While the existing literature does help explain the relationship between masculine norms and men's sexual behaviors several gaps remain including: a recognition of context-specific masculinities, an interrogation of the positive influences of masculinity, adoption of an intersectional approach, assessment of changes in norms and behaviors over time, and rigorous evaluations of gender-transformative approaches. Addressing these gaps in future research may optimize prevention efforts.
Todd, Catherine S; Stibich, Mark A; Laher, Fatima; Malta, Monica S; Bastos, Francisco I; Imbuki, Kennedy; Shaffer, Douglas N; Sinei, Samuel K; Gray, Glenda E
2011-02-01
Contraceptive choice and discontinuation are poorly understood among HIV-positive women, and HIV disease and culture may influence decisions. We assessed factors influencing contraceptive decision-making among HIV-positive women in three countries. This qualitative assessment of 108 HIV-positive women (36/site, selected by age and parity strata) was conducted in Rio de Janeiro, Brazil; Kericho, Kenya; and Soweto, South Africa. Freelist interviews assessed knowledge and attitudes towards contraception and were analyzed enumerating frequency and saliency of mentions. There was intersite consensus around list items but priority and themes varied. Site-specific factors influencing contraceptive choice were male partner wishes and fertility desire (Brazil), side-effects (South Africa), and impact on health and HIV progression (Kenya). Age, parity, and taking antiretroviral therapy (ART) impacted some themes. Contraceptive use among HIV-positive women is substantially influenced by culture and other factors. Counseling efforts should consider individual factors in method selection and offer method variety to accommodate changing needs.
The Influence of HIV on the Evolution of Mycobacterium tuberculosis
Brites, Daniela; Stucki, David; Evans, Joanna C.; Seldon, Ronnett; Heekes, Alexa; Mulder, Nicola; Nicol, Mark; Oni, Tolu; Mizrahi, Valerie; Warner, Digby F.; Parkhill, Julian; Gagneux, Sebastien; Martin, Darren P.; Wilkinson, Robert J.
2017-01-01
Abstract HIV significantly affects the immunological environment during tuberculosis coinfection, and therefore may influence the selective landscape upon which M. tuberculosis evolves. To test this hypothesis whole genome sequences were determined for 169 South African M. tuberculosis strains from HIV-1 coinfected and uninfected individuals and analyzed using two Bayesian codon-model based selection analysis approaches: FUBAR which was used to detect persistent positive and negative selection (selection respectively favoring and disfavoring nonsynonymous substitutions); and MEDS which was used to detect episodic directional selection specifically favoring nonsynonymous substitutions within HIV-1 infected individuals. Among the 25,251 polymorphic codon sites analyzed, FUBAR revealed that 189-fold more were detectably evolving under persistent negative selection than were evolving under persistent positive selection. Three specific codon sites within the genes celA2b, katG, and cyp138 were identified by MEDS as displaying significant evidence of evolving under directional selection influenced by HIV-1 coinfection. All three genes encode proteins that may indirectly interact with human proteins that, in turn, interact functionally with HIV proteins. Unexpectedly, epitope encoding regions were enriched for sites displaying weak evidence of directional selection influenced by HIV-1. Although the low degree of genetic diversity observed in our M. tuberculosis data set means that these results should be interpreted carefully, the effects of HIV-1 on epitope evolution in M. tuberculosis may have implications for the design of M. tuberculosis vaccines that are intended for use in populations with high HIV-1 infection rates. PMID:28369607
Li, Tingfeng; Steede, N. Kalaya; Nguyen, Hong-Nam P.; Freytag, Lucy C.; McLachlan, James B.; Mettu, Ramgopal R.; Robinson, James E.
2014-01-01
ABSTRACT Helper T-cell epitope dominance in human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 is not adequately explained by peptide binding to major histocompatibility complex (MHC) proteins. Antigen processing potentially influences epitope dominance, but few, if any, studies have attempted to reconcile the influences of antigen processing and MHC protein binding for all helper T-cell epitopes of an antigen. Epitopes of gp120 identified in both humans and mice occur on the C-terminal flanks of flexible segments that are likely to be proteolytic cleavage sites. In this study, the influence of gp120 conformation on the dominance pattern in gp120 from HIV strain 89.6 was examined in CBA mice, whose MHC class II protein has one of the most well defined peptide-binding preferences. Only one of six dominant epitopes contained the most conserved element of the I-Ak binding motif, an aspartic acid. Destabilization of the gp120 conformation by deletion of single disulfide bonds preferentially enhanced responses to the cryptic I-Ak motif-containing sequences, as reported by T-cell proliferation or cytokine secretion. Conversely, inclusion of CpG in the adjuvant with gp120 enhanced responses to the dominant CD4+ T-cell epitopes. The gp120 destabilization affected secretion of some cytokines more than others, suggesting that antigen conformation could modulate T-cell functions through mechanisms of antigen processing. IMPORTANCE CD4+ helper T cells play an essential role in protection against HIV and other pathogens. Thus, the sites of helper T-cell recognition, the dominant epitopes, are targets for vaccine design; and the corresponding T cells may provide markers for monitoring infection and immunity. However, T-cell epitopes are difficult to identify and predict. It is also unclear whether CD4+ T cells specific for one epitope are more protective than T cells specific for other epitopes. This work shows that the three-dimensional (3D) structure of an HIV protein partially determines which epitopes are dominant, most likely by controlling the breakdown of HIV into peptides. Moreover, some types of signals from CD4+ T cells are affected by the HIV protein 3D structure; and thus the protectiveness of a particular peptide vaccine could be related to its location in the 3D structure. PMID:24920818
Fleming, Paul J.; DiClemente, Ralph J.; Barrington, Clare
2016-01-01
Numerous studies have documented a relationship between masculine norms and men’s HIV-related sexual behaviors, but intervening upon this relationship requires a nuanced understanding of the specific aspects of masculine norms that shape men’s sexual behaviors. We integrate theories on masculinities with empirical HIV research to identify specific dimensions of masculine norms that influence men’s HIV-related sexual behaviors. We identify three major dimensions of masculine norms that shape men’s sexual behavior: 1) uncontrollable male sex drive, 2) capacity to perform sexually, and 3) power over others. While the existing literature does help explain the relationship between masculine norms and men’s sexual behaviors several gaps remain including: a recognition of context-specific masculinities, an interrogation of the positive influences of masculinity, adoption of an intersectional approach, assessment of changes in norms and behaviors over time, and rigorous evaluations of gender-transformative approaches. Addressing these gaps in future research may optimize prevention efforts. PMID:26696261
Beck, Zachary Q.; Lin, Ying-Chuan; Elder, John H.
2001-01-01
We have used a random hexamer phage library to delineate similarities and differences between the substrate specificities of human immunodeficiency virus type 1 (HIV-1) and feline immunodeficiency virus (FIV) proteases (PRs). Peptide sequences were identified that were specifically cleaved by each protease, as well as sequences cleaved equally well by both enzymes. Based on amino acid distinctions within the P3-P3′ region of substrates that appeared to correlate with these cleavage specificities, we prepared a series of synthetic peptides within the framework of a peptide sequence cleaved with essentially the same efficiency by both HIV-1 and FIV PRs, Ac-KSGVF↓VVNGLVK-NH2 (arrow denotes cleavage site). We used the resultant peptide set to assess the influence of specific amino acid substitutions on the cleavage characteristics of the two proteases. The findings show that when Asn is substituted for Val at the P2 position, HIV-1 PR cleaves the substrate at a much greater rate than does FIV PR. Likewise, Glu or Gln substituted for Val at the P2′ position also yields peptides specifically susceptible to HIV-1 PR. In contrast, when Ser is substituted for Val at P1′, FIV PR cleaves the substrate at a much higher rate than does HIV-1 PR. In addition, Asn or Gln at the P1 position, in combination with an appropriate P3 amino acid, Arg, also strongly favors cleavage by FIV PR over HIV PR. Structural analysis identified several protease residues likely to dictate the observed specificity differences. Interestingly, HIV PR Asp30 (Ile-35 in FIV PR), which influences specificity at the S2 and S2′ subsites, and HIV-1 PR Pro-81 and Val-82 (Ile-98 and Gln-99 in FIV PR), which influence specificity at the S1 and S1′ subsites, are residues which are often involved in development of drug resistance in HIV-1 protease. The peptide substrate KSGVF↓VVNGK, cleaved by both PRs, was used as a template for the design of a reduced amide inhibitor, Ac-GSGVFΨ(CH2NH)VVNGL-NH2. This compound inhibited both FIV and HIV-1 PRs with approximately equal efficiency. These findings establish a molecular basis for distinctions in substrate specificity between human and feline lentivirus PRs and offer a framework for development of efficient broad-based inhibitors. PMID:11533208
HIV+ women's narratives of non-disclosure: resisting the label of immorality.
Groves, Allison Kjellman; Maman, Suzanne; Moodley, Dhayendre
2012-01-01
Increasing partner disclosure rates among HIV+ individuals is widely seen as an important public health strategy to reduce HIV transmission. One approach for encouraging disclosure is to emphasise individuals' moral responsibility to disclose their status to their partners. We use South Africa as a case study to draw attention to two problems with labelling non-disclosure as immoral. First, we argue that because women are tested for HIV at much higher rates than men, any approach that involves blaming HIV+ individuals for not disclosing their status will disproportionately burden women. Second, through the narratives of six HIV+ women, we highlight how a focus on morality undervalues the complexity of sexual partnerships. Specifically, women describe how their perceived obligation to disclose their status is directly influenced by communication with their sexual partners. Women also discuss how the onset of different life events might alter the meaning of HIV and change obligations regarding disclosure within the partnership. The differences in testing rates across gender combined with the complexity of sexual partnerships leads us to suggest that labelling non-disclosure as immoral does little to advance HIV prevention. There is an urgent need to identify alternative interventions that support women through the disclosure process.
Dendritic Cell Immune Responses in HIV-1 Controllers.
Martin-Gayo, Enrique; Yu, Xu G
2017-02-01
Robust HIV-1-specific CD8 T cell responses are currently regarded as the main correlate of immune defense in rare individuals who achieve natural, drug-free control of HIV-1; however, the mechanisms that support evolution of such powerful immune responses are not well understood. Dendritic cells (DCs) are specialized innate immune cells critical for immune recognition, immune regulation, and immune induction, but their possible contribution to HIV-1 immune defense in controllers remains ill-defined. Recent studies suggest that myeloid DCs from controllers have improved abilities to recognize HIV-1 through cytoplasmic immune sensors, resulting in more potent, cell-intrinsic type I interferon secretion in response to viral infection. This innate immune response may facilitate DC-mediated induction of highly potent antiviral HIV-1-specific T cells. Moreover, protective HLA class I isotypes restricting HIV-1-specific CD8 T cells may influence DC function through specific interactions with innate myelomonocytic MHC class I receptors from the leukocyte immunoglobulin-like receptor family. Bi-directional interactions between dendritic cells and HIV-1-specific T cells may contribute to natural HIV-1 immune control, highlighting the importance of a fine-tuned interplay between innate and adaptive immune activities for effective antiviral immune defense.
The meningeal lymphatic system: a route for HIV brain migration?
Lamers, Susanna L; Rose, Rebecca; Ndhlovu, Lishomwa C; Nolan, David J; Salemi, Marco; Maidji, Ekaterina; Stoddart, Cheryl A; McGrath, Michael S
2016-06-01
Two innovative studies recently identified functional lymphatic structures in the meninges that may influence the development of HIV-associated neurological disorders (HAND). Until now, blood vessels were assumed to be the sole transport system by which HIV-infected monocytes entered the brain by bypassing a potentially hostile blood-brain barrier through inflammatory-mediated semi-permeability. A cascade of specific chemokine signals promote monocyte migration from blood vessels to surrounding brain tissues via a well-supported endothelium, where the cells differentiate into tissue macrophages capable of productive HIV infection. Lymphatic vessels on the other hand are more loosely organized than blood vessels. They absorb interstitial fluid from bodily tissues where HIV may persist and exchange a variety of immune cells (CD4(+) T cells, monocytes, macrophages, and dendritic cells) with surrounding tissues through discontinuous endothelial junctions. We propose that the newly discovered meningeal lymphatics are key to HIV migration among viral reservoirs and brain tissue during periods of undetectable plasma viral loads due to suppressive combinational antiretroviral therapy, thus redefining the migration process in terms of a blood-lymphatic transport system.
Ley, Clemens; Barrio, María Rato; Leach, Lloyd
2015-01-01
Sport and exercise can have several health benefits for people living with HIV. These benefits can be achieved through different types of physical activity, adapting to disease progression, motivation and social-ecological options. However, physical activity levels and adherence to exercise are generally low in people living with HIV. At the same time, high drop-out rates in intervention studies are prevalent; even though they often entail more favourable conditions than interventions in the natural settings. Thus, in the framework of an intervention study, the present study aims to explore social-ecological, motivational and volitional correlates of South African women living with HIV with regard to physical activity and participation in a sport and exercise health promotion programme. The qualitative data was produced in the framework of a non-randomised pre-post intervention study that evaluated structure, processes and outcomes of a 10-week sport and exercise programme. All 25 participants of the programme were included in this analysis, independent of compliance. Data was produced through questionnaires, participatory group discussions, body image pictures, research diaries and individual semi-structured interviews. All participants lived in a low socioeconomic, disadvantaged setting. Hence, the psychological correlates are contextualised and social-ecological influences on perception and behaviour are discussed. The results show the importance of considering social-cultural and environmental influences on individual motives, perceptions and expectancies, the fear of disclosure and stigmatisation, sport and exercise-specific group dynamics and self-supporting processes. Opportunities and strategies to augment physical activity and participation in sport and exercise programmes in the context of HIV are discussed. PMID:26587078
Ley, Clemens; Barrio, María Rato; Leach, Lloyd
2015-01-01
Sport and exercise can have several health benefits for people living with HIV. These benefits can be achieved through different types of physical activity, adapting to disease progression, motivation and social-ecological options. However, physical activity levels and adherence to exercise are generally low in people living with HIV. At the same time, high drop-out rates in intervention studies are prevalent; even though they often entail more favourable conditions than interventions in the natural settings. Thus, in the framework of an intervention study, the present study aims to explore social-ecological, motivational and volitional correlates of South African women living with HIV with regard to physical activity and participation in a sport and exercise health promotion programme. The qualitative data was produced in the framework of a non-randomised pre-post intervention study that evaluated structure, processes and outcomes of a 10-week sport and exercise programme. All 25 participants of the programme were included in this analysis, independent of compliance. Data was produced through questionnaires, participatory group discussions, body image pictures, research diaries and individual semi-structured interviews. All participants lived in a low socioeconomic, disadvantaged setting. Hence, the psychological correlates are contextualised and social-ecological influences on perception and behaviour are discussed. The results show the importance of considering social-cultural and environmental influences on individual motives, perceptions and expectancies, the fear of disclosure and stigmatisation, sport and exercise-specific group dynamics and self-supporting processes. Opportunities and strategies to augment physical activity and participation in sport and exercise programmes in the context of HIV are discussed.
Ayieko, James; Ti, Angeline; Hagey, Jill; Akama, Eliud; Bukusi, Elizabeth A; Cohen, Craig R; Patel, Rena C
2017-08-08
Factors influencing fertility desires among HIV-infected individuals remain poorly understood. With new recommendations for universal HIV treatment and increasing antiretroviral therapy (ART) access, we sought to evaluate how access to early ART influences fertility desires among HIV-infected ART-naïve women. Semi-structured in-depth interviews were conducted with a select subgroup of 20 HIV-infected ART-naïve women attending one of 13 HIV facilities in western Kenya between July and August 2014 who would soon newly become eligible to initiate ART based on the latest national policy recommendations. The interviews covered four major themes: 1) definitions of family and children's role in community; 2) personal, interpersonal, institutional, and societal factors influencing fertility desires; 3) influence of HIV-positive status on fertility desires; and 4) influence of future ART initiation on fertility desires. An iterative process of reading transcripts, applying inductive codes, and comparing and contrasting codes was used to identify convergent and divergent themes. The women indicated their HIV-positive status did influence-largely negatively-their fertility desires. Furthermore, initiating ART and anticipating improved health status did not necessarily translate to increased fertility desires. Instead, individual factors, such as age, parity, current health status, financial resources and number of surviving or HIV-infected children, played a crucial role in decisions about future fertility. In addition, societal influences, such as community norms and health providers' expectations of their fertility desires, played an equally important role in determining fertility desires. Initiating ART may not be the leading factor influencing fertility desires among previously ART-naïve HIV-infected women. Instead, individual and societal factors appear to be the major determinants of fertility desires among these women.
Mburu, Gitau; Ram, Mala; Siu, Godfrey; Bitira, David; Skovdal, Morten; Holland, Paula
2014-10-11
Stigma is a determinant of social and health inequalities. In addition, some notions of masculinity can disadvantage men in terms of health outcomes. However, few studies have explored the extent to which these two axes of social inequality intersect to influence men's health outcomes. This paper investigates the intersection of HIV stigma and masculinity, and its perceived impact on men's participation in and utilisation of HIV services in Uganda. Interviews and focus group discussions were conducted in Mbale and Jinja districts of Uganda between June and October 2010. Participants were men and women living with HIV (n = 40), their family members (n = 10) and health providers (n = 15). Inductive analysis was used to identify mechanisms through which stigma and masculinity were linked. Our findings showed that HIV stigma and masculinity did not exist as isolated variables, but as intersecting phenomena that influenced men's participation in HIV services. Specifically, HIV stigma threatened masculine notions of respectability, independence and emotional control, while it amplified men's risk-taking. As a result, the intersection of masculinity and HIV stigma prevented some men from i) seeking health care and accepting a 'sick role'; ii) fulfilling their economic family responsibilities; iii) safeguarding their reputation and respectability; iv) disclosing their HIV status; and v) participating in peer support groups. Participation in some peer support activities was considered a female trait and it also exacerbated HIV stigma as it implicitly singled out those with HIV. In contrast, inclusion of income-generating activities in peer support groups encouraged men's involvement as it enabled them to provide for their families, cushioned them from HIV stigma, and in the process, provided them with an opportunity to redeem their reputation and respectability. To improve men's involvement in HIV services, the intersection between HIV stigma and masculinity should be considered. In particular, better integration of and linkage between gender transformative interventions that support men to reconstruct their male identities and reject signifiers of masculinity that prevent their access to HIV services, and stigma-reduction interventions that target social and structural drivers of stigma is required within HIV programmes.
Migration and HIV risk: Life histories of Mexican-born men living with HIV in North Carolina
Mann, Lilli; Valera, Erik; Hightow-Weidman, Lisa B.; Barrington, Clare
2015-01-01
Latino men in the Southeastern USA are disproportionately affected by HIV, but little is known about how the migration process influences HIV-related risk. In North Carolina (NC), a relatively new immigrant destination, Latino men are predominantly young and from Mexico. We conducted 31 iterative life history interviews with 15 Mexican-born men living with HIV. We used holistic content narrative analysis methods to examine HIV vulnerability in the context of migration and to identify important turning points. Major themes included the prominence of traumatic early life experiences, migration as an ongoing process rather than a finite event, and HIV diagnosis as a final turning point in migration trajectories. Findings provide a nuanced understanding of HIV vulnerability throughout the migration process and have implications including the need for bi-national HIV prevention approaches, improved outreach around early testing and linkage to care, and attention to mental health. PMID:24866206
George, Sheba; Garth, Belinda; Wohl, Amy Rock; Galvan, Frank H.; Garland, Wendy; Myers, Hector F.
2011-01-01
The change in HIV from acute to chronic disease due to the introduction of HAART in the mid-1990s increased the importance of its successful management and imposed substantial lifestyle adjustments on HIV-positive persons and their support networks. Few studies have examined the sources and types of social support and the areas of care relevant for engagement in HIV treatment among HIV-positive Latinos and African Americans. This paper reports the results of twenty-four semi-structured in-depth interviews that were conducted with HIV-positive African American and Latino women and men who have sex with men. Formal networks were found to be more critical for engagement in HIV-specific medical care; specifically, study participants relied primarily on health care providers for support in accessing and maintaining illness-specific care. In contrast, informal networks (in the form of family and friends) were crucial for other general subsistence care, such as emotional, household-related, and financial support. PMID:20168014
Primary Care Providers' HIV Prevention Practices Among Older Adults
Davis, Tracy; Teaster, Pamela B.; Thornton, Alice; Watkins, John F.; Alexander, Linda; Zanjani, Faika
2016-01-01
Purpose To explore primary care providers' HIV prevention practices for older adults. Primary care providers' perceptions and awareness were explored to understand factors that affect their provision of HIV prevention materials and HIV screening for older adults. Design and Method Data were collected through 24 semistructured interviews with primary care providers (i.e., physicians, physician assistants, and nurse practitioners) who see patients older than 50 years. Results Results reveal facilitators and barriers of HIV prevention for older adults among primary care providers and understanding of providers' HIV prevention practices and behaviors. Individual, patient, institutional, and societal factors influenced HIV prevention practices among participants, for example, provider training and work experience, lack of time, discomfort in discussing HIV/AIDS with older adults, stigma, and ageism were contributing factors. Furthermore, factors specific to primary and secondary HIV prevention were identified, for instance, the presence of sexually transmitted infections influenced providers' secondary prevention practices. Implications HIV disease, while preventable, is increasing among older adults. These findings inform future research and interventions aimed at increasing HIV prevention practices in primary care settings for patients older than 50. PMID:25736425
"Where It Falls Apart": Barriers to Retention in HIV Care in Latino Immigrants and Migrants.
Levison, Julie H; Bogart, Laura M; Khan, Iman F; Mejia, Dianna; Amaro, Hortensia; Alegría, Margarita; Safren, Steven
2017-09-01
Latino immigrants in the United States are disproportionately affected by HIV. Barriers to consistent attendance (retention) in HIV primary care constrain opportunities for HIV treatment success, but have not been specifically assessed in this population. We conducted semistructured interviews with 37 HIV-infected Latinos (aged ≥18 years and born in Puerto Rico or a Latin American Spanish-speaking country) and 14 HIV providers in metropolitan Boston (total n = 51). The Andersen Model of Healthcare Utilization informed a semistructured interview guide, which bilingual research staff used to explore barriers to HIV care. We used thematic analysis to explore the processes of retention in care. Six ubiquitous themes were perceived to influence HIV clinic attendance: (1) stigma as a barrier to HIV serostatus disclosure; (2) social support as a safety net during negative life circumstances; (3) unaddressed trauma and substance use leading to interruption in care; (4) a trusting relationship between patient and provider motivating HIV clinic attendance; (5) basic unmet needs competing with the perceived value of HIV care; and (6) religion providing a source of hope and optimism. Cultural subthemes were the centrality of family (familismo), masculinity (machismo), and trusting relationships (confianza). The timing of barriers was acute (e.g., eviction) and chronic (e.g., family conflict). These co-occurring and dynamic constellation of factors affected HIV primary care attendance over time. HIV-infected Latino immigrants and migrants experienced significant challenges that led to interruptions in HIV care. Anticipatory guidance to prepare for these setbacks may improve retention in HIV care in this population.
Body image and HIV: implications for support and care.
Chapman, L
1998-06-01
Very little formal research has looked at body image change over the course of HIV illness or assessed the implications of changes for support interactions. There are three main spheres of influence on body image: the physical, psychological and the social. HIV shares some of these aspects with other chronic or fatal illnesses, but has specific elements which are distinctive, such as particular physical manifestations and the negative impact of media, social representations and stigma resulting in a radically altered experience for an HIV-positive body. This paper outlines preliminary findings using a body image measure designed specifically for use in HIV. The results suggest that people with HIV may experience significant feelings of contamination, brought about through internalization of stigma and representations, in addition to physical decline as illness progresses.
Albarracin, Dolores; Tannenbaum, Melanie B; Glasman, Laura R; Rothman, Alexander J
2010-12-01
Changing HIV-related behaviors requires addressing the individual, dyadic, and structural influences that shape them. This supplement of AIDS & Behavior presents frameworks that integrate these three influences on behavior. Concepts from these frameworks were selected to model the processes by which structural factors affect individual HIV-related behavior. In the Inclusion/Exclusion Model, material and symbolic inclusions and exclusions (sharing versus denying resources) regulate individuals' ability and motivation to detect, prevent, and treat HIV. Structural interventions create inclusions that increase one's ability or motivation to perform these behaviors or exclusions that hinder one's ability or motivation to execute counterproductive behaviors. The need to expand research regarding multilevel influences on HIV-related behavior is also discussed, particularly concerning further understanding of sustained behavior change and effective dissemination of evidence-based intervention strategies.
Tenzer, Stefan; Crawford, Hayley; Pymm, Phillip; Gifford, Robert; Sreenu, Vattipally B; Weimershaus, Mirjana; de Oliveira, Tulio; Burgevin, Anne; Gerstoft, Jan; Akkad, Nadja; Lunn, Daniel; Fugger, Lars; Bell, John; Schild, Hansjörg; van Endert, Peter; Iversen, Astrid K N
2014-04-24
The recent HIV-1 vaccine failures highlight the need to better understand virus-host interactions. One key question is why CD8(+) T cell responses to two HIV-Gag regions are uniquely associated with delayed disease progression only in patients expressing a few rare HLA class I variants when these regions encode epitopes presented by ~30 more common HLA variants. By combining epitope processing and computational analyses of the two HIV subtypes responsible for ~60% of worldwide infections, we identified a hitherto unrecognized adaptation to the antigen-processing machinery through substitutions at subtype-specific motifs. Multiple HLA variants presenting epitopes situated next to a given subtype-specific motif drive selection at this subtype-specific position, and epitope abundances correlate inversely with the HLA frequency distribution in affected populations. This adaptation reflects the sum of intrapatient adaptations, is predictable, facilitates viral subtype diversification, and increases global HIV diversity. Because low epitope abundance is associated with infrequent and weak T cell responses, this most likely results in both population-level immune evasion and inadequate responses in most people vaccinated with natural HIV-1 sequence constructs. Our results suggest that artificial sequence modifications at subtype-specific positions in vitro could refocus and reverse the poor immunogenicity of HIV proteins. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
Scarsi, Kimberly K; Darin, Kristin M; Chappell, Catherine A; Nitz, Stephanie M; Lamorde, Mohammed
2016-11-01
Family planning options, including hormonal contraceptives, are essential for improving reproductive health among the more than 17 million women living with HIV worldwide. For these women, prevention of unintended pregnancy decreases maternal and child mortality, as well as reduces the risk of perinatal HIV transmission. Similarly, treatment of HIV with antiretroviral therapy (ART) is essential for reducing morbidity and mortality among HIV-positive individuals, as well as preventing HIV transmission between sexual partners or from mother to child. Importantly, despite the benefits of hormonal contraceptives, barriers to effective family planning methods exist for HIV-positive women. Specifically, drug-drug interactions can occur between some antiretroviral medications and some hormonal contraceptives, which may influence both contraceptive efficacy and tolerability. In addition, safety concerns have been raised about the impact of hormonal contraceptives on HIV disease progression, tolerability, and the risk of female-to-male HIV transmission. This review article summarizes the potential for drug-drug interactions, tolerability, and contraceptive effectiveness when hormonal contraceptives are combined with ART. In addition, the evidence surrounding the influence of hormonal contraceptives on HIV transmission and HIV disease progression in women living with HIV are summarized.
PIP2: choreographer of actin-adaptor proteins in the HIV-1 dance
Rocha-Perugini, Vera; Gordon-Alonso, Mónica; Sánchez-Madrid, Francisco
2014-01-01
The actin cytoskeleton plays a key role during the replication cycle of human immunodeficiency virus-1 (HIV-1). HIV-1 infection is affected by cellular proteins that influence the clustering of viral receptors or the subcortical actin cytoskeleton. Several of these actin-adaptor proteins are controlled by the second messenger phosphatidylinositol 4,5-biphosphate (PIP2), an important regulator of actin organization. PIP2 production is induced by HIV-1 attachment and facilitates viral infection. However, the importance of PIP2 in regulating cytoskeletal proteins and thus HIV-1 infection has been overlooked. This review examines recent reports describing the roles played by actin-adaptor proteins during HIV-1 infection of CD4+ T cells, highlighting the influence of the signaling lipid PIP2 in this process. PMID:24768560
Preserving HIV-specific T cell responses: does timing of antiretroviral therapy help?
Macatangay, Bernard J C; Rinaldo, Charles R
2015-01-01
HIV-specific T cell responses are likely to have an important role in HIV cure strategies that aim for long-lasting viral control without antiretroviral therapy (ART). An important issue in enhancing virus-specific T cell responses is whether timing of ART can influence their magnitude and breadth. Early ART is associated with lower T cell activation, preservation of T cell numbers, smaller DNA and RNA reservoir size, and, in a single study (VISCONTI), control of plasma viremia after treatment interruption. The prevention of T cell destruction by early ART is associated with relatively low anti-HIV CD8⁺ T cell responses but stronger CD4⁺ T helper function. The relatively lower CD8⁺T cell response, which is presumably due to rapid lowering of HIV antigen burden after early ART, appears sufficient to control residual viral replication as well as viral rebound upon treatment interruption. Available evidence of starting ART during acute or early HIV infection has shown benefit in both virologic and immunologic parameters despite the lower HIV-specific CD8⁺ T cell responses observed. Encouraging as this is, more extensive data are necessary to evaluate its role in combination with immunotherapeutic and latency activation strategies that are being assessed in various HIV cure-related studies.
Bellows, Denise; Howard, Donna; Boekeloo, Brad; Randolph, Suzanne
2015-01-01
People living with human immunodeficiency virus (HIV)/AIDS (PLWH/A) and others affected have expressed that cultural differences between patients and providers can create barriers to care and prevention. These barriers are exacerbated in the case of vulnerable populations who are often marginalized by society. During the formative phase of a community-based participatory research (CBPR) process, the researchers' community advisory committee (CAC) and HIV stakeholders shared anecdotes of incongruencies between needs of HIV-vulnerable populations and expertise of local providers. In response, researchers worked with the CAC to develop survey questions intended for providers of HIV prevention services in a region afflicted with some of the highest HIV prevalence rates in the country. The objective of this study was to identify and validate HIV stakeholders' perceptions about challenges to provision of HIV services through a sequential mixed methods study design. Thirty HIV prevention organizations (HPOs) were identified as local leaders in HIV prevention by community stakeholders and through community event attendance. Each HPO was invited to participate in an interviewer-assisted survey examining population-specific expertise and service for 15 HIV-vulnerable populations. Frequency analysis was used to compare HPOs' expertise relative to who they serve (n = 26). Although 13 of the HIV-vulnerable populations were served by more than 50% of the HPOs, only 2 of these 13 populations were served with high expertise by more than one half of the HPOs in the sample. These data give credence to the CAC's concern regarding misalliance between whom HPOs serve and with whom they have high expertise, a factor potentially influencing HIV outcomes among HIV-vulnerable populations.
A grounded theory of social participation among older women living with HIV.
Siemon, Jennifer S; Blenkhorn, Lisa; Wilkins, Seanne; O'Brien, Kelly K; Solomon, Patricia E
2013-10-01
As adults age with human immunodeficiency virus (HIV), the role for rehabilitation continues to emerge. Understanding how social participation is affected among women aging with HIV can inform occupational therapy assessment and treatment. Our purpose was to develop a theoretical model that describes the experiences of social participation from the perspective of older women living with HIV. A grounded theory methodological approach was utilized. We conducted interviews with 20 women living with HIV, age 50 or older, to explore various aspects of social participation, including self-care, relationships with others, and access to health and social services. Emergent themes informed the theoretical model. The theoretical model comprises four concepts related to social participation: social engagement, social isolation, contrasting perceptions about factors variably influencing participation, and contextual influences that may enhance or hinder social participation. Women aging with HIV experience social participation as a dynamic process involving social engagement and isolation. Contextual influences may promote and impede social participation.
Global analysis of host-pathogen interactions that regulate early stage HIV-1 replication
König, Renate; Zhou, Yingyao; Elleder, Daniel; Diamond, Tracy L.; Bonamy, Ghislain M.C.; Irelan, Jeffrey T.; Chiang, Chih-yuan; Tu, Buu P.; De Jesus, Paul D.; Lilley, Caroline E.; Seidel, Shannon; Opaluch, Amanda M.; Caldwell, Jeremy S.; Weitzman, Matthew D.; Kuhen, Kelli L.; Bandyopadhyay, Sourav; Ideker, Trey; Orth, Anthony P.; Miraglia, Loren J.; Bushman, Frederic D.; Young, John A.; Chanda, Sumit K.
2008-01-01
Human Immunodeficiency Viruses (HIV-1 and HIV-2) rely upon host-encoded proteins to facilitate their replication. Here we combined genome-wide siRNA analyses with interrogation of human interactome databases to assemble a host-pathogen biochemical network containing 213 confirmed host cellular factors and 11 HIV-1-encoded proteins. Protein complexes that regulate ubiquitin conjugation, proteolysis, DNA damage response and RNA splicing were identified as important modulators of early stage HIV-1 infection. Additionally, over 40 new factors were shown to specifically influence initiation and/or kinetics of HIV-1 DNA synthesis, including cytoskeletal regulatory proteins, modulators of post-translational modification, and nucleic acid binding proteins. Finally, fifteen proteins with diverse functional roles, including nuclear transport, prostaglandin synthesis, ubiquitination, and transcription, were found to influence nuclear import or viral DNA integration. Taken together, the multi-scale approach described here has uncovered multiprotein virus-host interactions that likely act in concert to facilitate early steps of HIV-1 infection. PMID:18854154
Vreeman, Rachel C; Scanlon, Michael L; Inui, Thomas S; McAteer, Carole I; Fischer, Lydia J; McHenry, Megan S; Marete, Irene; Nyandiko, Winstone M
2015-06-01
We sought to better understand how social factors shape HIV disclosure to children from the perspective of caregivers and HIV-infected children in Kenya. We conducted a qualitative study using focus group discussions (FGDs) to gain perspectives of caregivers and children on the social environment for HIV disclosure to children in western Kenya. FGDs were held with caregivers who had disclosed the HIV status to their child and those who had not, and with HIV-infected children who knew their HIV status. FGD transcripts were translated into English, transcribed, and analyzed using constant comparison, progressive coding, and triangulation to arrive at a contextualized understanding of social factors influencing HIV disclosure. Sixty-one caregivers of HIV-infected children participated in eight FGDs, and 23 HIV-infected children participated in three FGDs. Decisions around disclosure were shaped by a complex social environment that included the caregiver-child dyad, family members, neighbors, friends, schools, churches, and media. Whether social actors demonstrated support or espoused negative beliefs influenced caregiver decisions to disclose. Caregivers reported that HIV-related stigma was prominent across these domains, including stereotypes associating HIV with sexual promiscuity, immorality, and death, which were tied to caregiver fears about disclosure. Children also recognized stigma as a barrier to disclosure, but were less specific about the social and cultural stereotypes cited by the caregivers. In this setting, caregivers and children described multiple actors who influenced disclosure, mostly due to stigmatizing beliefs about HIV. Better understanding the social factors impacting disclosure may improve the design of support services for children and caregivers.
Pediatric HIV disclosure: a process-oriented framework.
Cantrell, Kathryn; Patel, Nehali; Mandrell, Belinda; Grissom, Shawna
2013-08-01
As children with vertically transmitted human immunodeficiency virus (HIV) infection live into adulthood, caregivers face the stressful process of informing their children about their infection. Although developmentally guided disclosure of HIV status is widely recommended, there are few specific frameworks to guide caregivers, families, and health care providers through the disclosure process. The authors propose a process-oriented framework for the disclosure of HIV in children and adolescents. This educational framework incorporates Piaget's cognitive development theory in an attempt to disclose and assist children and adolescents in understanding their HIV status. The framework is organized into 10 sequential stages of disclosure and three assessment stages in which health care providers discuss HIV health concepts with the child and caregiver, based on the child's developmental readiness. The described framework can be easily replicated by health care providers in disclosing disease status to children with HIV.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pham, Son; CSIRO Australian Animal Health Laboratory, Victoria 3220; Tabarin, Thibault
Viruses are often thought to have static structure, and they only remodel after the viruses have entered target cells. Here, we detected a size expansion of virus particles prior to viral entry using cryo-electron microscopy (cryo-EM) and single molecule fluorescence imaging. HIV expanded both under cell-free conditions with soluble receptor CD4 (sCD4) targeting the CD4 binding site on the HIV-1 envelope protein (Env) and when HIV binds to receptor on cellular membrane. We have shown that the HIV Env is needed to facilitate receptor induced virus size expansions, showing that the ‘lynchpin’ for size expansion is highly specific. We demonstratemore » that the size expansion required maturation of HIV and an internal capsid core with wild type stability, suggesting that different HIV compartments are linked and are involved in remodelling. Our work reveals a previously unknown event in HIV entry, and we propose that this pre-entry priming process enables HIV particles to facilitate the subsequent steps in infection. - Highlights: • Cell free viruses are able to receive external trigger that leads to apparent size expansion. • Virus envelope and CD4 receptor engagement is the lynchpin of virus size expansion. • Internal capsid organisation can influence receptor mediated virus size expansion. • Pre-existing virus-associated lipid membrane in cell free virus can accommodate the receptor mediated virus size expansion.« less
Hirsch, Jennifer S.
2016-01-01
We explore how state and local policies in labor, health, education, language, community and neighborhood environments, deportation, and state-authorized identification can reduce or exacerbate HIV vulnerability among Latino migrants in the United States. We reviewed literature on Latino migrants and HIV risk, on the structural–environmental contexts experienced by Latino migrants, and on the many domains in which policies influence those contexts. To illustrate the pathways through which policies across multiple sectors are relevant to HIV vulnerability, we describe how policies shape 2 mediating domains (a climate of hostility toward Latino migrants and the relative ease or difficulty of access to beneficial institutions) and how those domains influence behavioral risk practices, which increase vulnerability to HIV. This argument demonstrates the utility of considering the policy context as a modifiable element of the meso-level through which structural factors shape vulnerability to HIV. This approach has specific relevance to the consideration of HIV prevention for Latino migrants, and more generally, to structural approaches to HIV prevention. PMID:26985616
A dynamic social systems model for considering structural factors in HIV prevention and detection
Latkin, Carl; Weeks, Margaret; Glasman, Laura; Galletly, Carol; Albarracin, Dolores
2010-01-01
We present a model for HIV-related behaviors that emphasizes the dynamic and social nature of the structural factors that influence HIV prevention and detection. Key structural dimensions of the model include resources, science and technology, formal social control, informal social influences and control, social interconnectedness, and settings. These six dimensions can be conceptualized on macro, meso, and micro levels. Given the inherent complexity of structural factors and their interrelatedness, HIV prevention interventions may focus on different levels and dimensions. We employ a systems perspective to describe the interconnected and dynamic processes of change among social systems and their components. The topics of HIV testing and safer injection facilities are analyzed using this structural framework. Finally, we discuss methodological issues in the development and evaluation of structural interventions for HIV prevention and detection. PMID:20838871
Au, Ka-Yee; Wang, Rui-Rui; Wong, Yuen-Ting; Wong, Kam-Bo; Zheng, Yong-Tang; Shaw, Pang-Chui
2014-03-01
Ricin is a type II ribosome-inactivating protein (RIP) that potently inactivates eukaryotic ribosomes by removing a specific adenine residue at the conserved α-sarcin/ricin loop of 28S ribosomal RNA (rRNA). Here, we try to increase the specificity of the enzymatically active ricin A chain (RTA) towards human immunodeficiency virus type 1 (HIV-1) by adding a loop with HIV protease recognition site to RTA. HIV-specific RTA variants were constructed by inserting a peptide with HIV-protease recognition site either internally or at the C-terminal region of wild type RTA. Cleavability of variants by viral protease was tested in vitro and in HIV-infected cells. The production of viral p24 antigen and syncytium in the presence of C-terminal variants was measured to examine the anti-HIV activities of the variants. C-terminal RTA variants were specifically cleaved by HIV-1 protease both in vitro and in HIV-infected cells. Upon proteolysis, the processed variants showed enhanced antiviral effect with low cytotoxicity towards uninfected cells. RTA variants with HIV protease recognition sequence engineered at the C-terminus were cleaved and the products mediated specific inhibitory effect towards HIV replication. Current cocktail treatment of HIV infection fails to eradicate the virus from patients. Here we illustrate the feasibility of targeting an RIP towards HIV-infected cells by incorporation of HIV protease cleavage sequence. This approach may be generalized to other RIPs and is promising in drug design for combating HIV. Copyright © 2013 Elsevier B.V. All rights reserved.
Abara, Winston; Coleman, Jason D; Fairchild, Amanda; Gaddist, Bambi; White, Jacob
2015-02-01
Though race and region are not by themselves risk factors for HIV infection, regional and racial disparities exist in the burden of HIV/AIDS in the US. Specifically, African Americans in the southern US appear to bear the brunt of this burden due to a complex set of upstream factors like structural and cultural influences that do not facilitate HIV/AIDS awareness, HIV testing, or sexual risk-reduction techniques while perpetuating HIV/AIDS-related stigma. Strategies proposed to mitigate the burden among this population have included establishing partnerships and collaborations with non-traditional entities like African American churches and other faith-based organizations. Though efforts to partner with the African American church are not necessarily novel, most of these efforts do not present a model that focuses on building the capacity of the African American church to address these upstream factors and sustain these interventions. This article will describe Project Fostering AIDS Initiatives That Heal (F.A.I.T.H), a faith-based model for successfully developing, implementing, and sustaining locally developed HIV/AIDS prevention interventions in African American churches in South Carolina. This was achieved by engaging the faith community and the provision of technical assistance, grant funding and training for project personnel. Elements of success, challenges, and lessons learned during this process will also be discussed.
Sanchez, Mariana; Rojas, Patria; Li, Tan; Ravelo, Gira; Cyrus, Elena; Wang, Weize; Kanamori, Mariano; Peragallo, Nilda P; De La Rosa, Mario R
2016-09-01
Latina immigrants in the farmworker community are a vulnerable and understudied population at risk of acquiring HIV. Employing a CBPR framework, this pilot study was the first to evaluate the efficacy of SEPA, a CDC evidenced-based and culturally tailored HIV risk reduction intervention on a cohort of N = 110 predominantly undocumented Latina immigrants in a farmworker community. Findings revealed SEPA was effective in increasing HIV knowledge and decreasing HIV risk behaviors. However, no changes in self-efficacy were found in the present sample. We posit specific socio-cultural and structural barriers specific to the farmworker community not targeted in the original intervention may have hindered the program's capacity to influence changes in self-efficacy among this less acculturated population. Possible socio-cultural adaptations of the intervention to the target population and policy implications are discussed.
Motivation, management, and mastery: a theory of resilience in the context of HIV infection.
De Santis, Joseph P; Florom-Smith, Aubrey; Vermeesch, Amber; Barroso, Susana; DeLeon, Diego A
2013-01-01
Clients with HIV infection have been conceptualized as a resilient population. Although a few researchers have documented resilience among clients with HIV infection, a theory of resilience in the context of HIV infection has not been developed. The purpose of this study was to describe the process by which resilience occurs for clients in the context of HIV infection. Grounded theory methodology was used to sample and analyze data from 15 qualitative interviews with adults with HIV infection. Data were collected until saturation was reached. A theory, motivation, management, and mastery, a description of the process by which resilience occurs in the context of HIV infection, emerged from the data. Many clients living with HIV infection are resilient, despite the physical, psychological, and social challenges of this chronic illness. Nursing interventions to promote resilience among clients with HIV infection should be directed toward identification of client motivation factors and disease management strategies that may influence health outcomes of people living with HIV infection.
Analyzing HIV/AIDS and Alcohol and Other Drug Use as a Social Problem
PATTERSON, DAVID A.; Wolf (Adelv unegv Waya), Silver
2012-01-01
Most prevention and intervention activities directed toward HIV/AIDS and alcohol and other drug use separately as well as the combining of the two (e.g., those who are both HIV/AIDS and using alcohol and other drugs) comes in the form of specific, individualized therapies without consideration of social influences that may have a greater impact on this population. Approaching this social problem from the narrowed view of individualized, mi-cro solutions disregards the larger social conditions that affect or perhaps even are at the root of the problem. This paper analyzes the social problem of HIV/AIDS and alcohol and other drug abuse using three sociological perspectives—social construction theory, ethnomethodology, and conflict theory—informing the reader of the broader influences accompanying this problem. PMID:23264724
Powell, Heather L; Segrin, Chris
2004-01-01
As family and peers are primary socializing agents in the lives of young adults, a social learning based model of communication about HIV/AIDS among dating partners was developed and tested, examining the role of interactions with family and peers in this type of communication. Specifically, the model describes relationships between general communication, communication about sexuality, and communication about HIV/AIDS with parents, peers, and dating partners. Participants were 153 young adult couples who completed measures of their communication practices, as well as their communication with family and peers. Communication practices in the family of origin appear to influence both general communication and communication about HIV/AIDS with dating partners. Communication practices with peers influenced general communication, communication about sexuality, and communication about HIV/AIDS with dating partners. Participants and their dating partners exhibited relative agreement about their general communication practices and their communication about HIV/AIDS, but showed less agreement in reports of their communication about sexuality. Implications for understanding the role of family and peer interactions in communication about HIV/AIDS with dating partners are discussed.
Frosch, Anne E; Odumade, Oludare A; Taylor, Justin J; Ireland, Kathleen; Ayodo, George; Ondigo, Bartholomew; Narum, David L; Vulule, John; John, Chandy C
2017-06-15
Human immunodeficiency virus type 1 (HIV-1) infection is associated with B cell activation and exhaustion, and hypergammaglobulinemia. How these changes influence B cell responses to coinfections such as malaria is poorly understood. To address this, we compared B cell phenotypes and Abs specific for the Plasmodium falciparum vaccine candidate apical membrane Ag-1 (AMA1) in HIV-infected and uninfected adults living in Kenya. Surprisingly, HIV-1 infection was not associated with a difference in serum AMA1-specific Ab levels. HIV-infected individuals had a higher proportion of total atypical and total activated memory B cells (MBCs). Using an AMA1 tetramer to detect AMA1-specific B cells, HIV-infected individuals were also shown to have a higher proportion of AMA1-specific atypical MBCs. However, this proportional increase resulted in large part from a loss in the number of naive and resting MBCs rather than an increase in the number of atypical and activated cells. The loss of resting MBCs and naive B cells was mirrored in a population of cells specific for an Ag to which these individuals were unlikely to have been chronically exposed. Together, the data show that changes in P. falciparum Ag-specific B cell subsets in HIV-infected individuals mirror those in the overall B cell population, and suggest that the increased proportion of atypical MBC phenotypes found in HIV-1-infected individuals results from the loss of naive and resting MBCs. Copyright © 2017 by The American Association of Immunologists, Inc.
Leveraging Hierarchical Population Structure in Discrete Association Studies
Carlson, Jonathan; Kadie, Carl; Mallal, Simon; Heckerman, David
2007-01-01
Population structure can confound the identification of correlations in biological data. Such confounding has been recognized in multiple biological disciplines, resulting in a disparate collection of proposed solutions. We examine several methods that correct for confounding on discrete data with hierarchical population structure and identify two distinct confounding processes, which we call coevolution and conditional influence. We describe these processes in terms of generative models and show that these generative models can be used to correct for the confounding effects. Finally, we apply the models to three applications: identification of escape mutations in HIV-1 in response to specific HLA-mediated immune pressure, prediction of coevolving residues in an HIV-1 peptide, and a search for genotypes that are associated with bacterial resistance traits in Arabidopsis thaliana. We show that coevolution is a better description of confounding in some applications and conditional influence is better in others. That is, we show that no single method is best for addressing all forms of confounding. Analysis tools based on these models are available on the internet as both web based applications and downloadable source code at http://atom.research.microsoft.com/bio/phylod.aspx. PMID:17611623
Janbazian, Loury; Price, David A.; Canderan, Glenda; Filali-Mouhim, Abdelali; Asher, Tedi E.; Ambrozak, David R.; Scheinberg, Phillip; Boulassel, Mohamad Rachid; Routy, Jean-Pierre; Koup, Richard A.; Douek, Daniel C.; Sekaly, Rafick-Pierre; Trautmann, Lydie
2011-01-01
Persistent exposure to cognate antigen leads to the functional impairment and exhaustion of HIV-specific CD8 T cells. Antigen withdrawal, due either to antiretroviral treatment or the emergence of epitope escape mutations, causes HIV-specific CD8 T cell responses to wane over time. However, this process does not continue to extinction, and residual CD8 T cells likely play an important role in the control of HIV replication. Here, we conducted a longitudinal analysis of clonality, phenotype and function to define the characteristics of HIV-specific CD8 T cell populations that persist under conditions of limited antigenic stimulation. Antigen decay was associated with dynamic changes in the TCR repertoire, increased expression of CD45RA and CD127, decreased expression of PD-1 and the emergence of poly-functional HIV-specific CD8 T cells. High definition analysis of individual clonotypes revealed that the antigen loss-induced gain of function within HIV-specific CD8 T cell populations could be attributed to two non-exclusive mechanisms: (i) functional improvement of persisting clonotypes; and, (ii) recruitment of particular clonotypes endowed with superior functional capabilities. PMID:22210916
Disclosure of HIV status to children in resource-limited settings: a systematic review
Vreeman, Rachel C; Gramelspacher, Anna Maria; Gisore, Peter O; Scanlon, Michael L; Nyandiko, Winstone M
2013-01-01
Introduction Informing children of their own HIV status is an important aspect of long-term disease management, yet there is little evidence of how and when this type of disclosure takes place in resource-limited settings and its impact. Methods MEDLINE, EMBASE and Cochrane Databases were searched for the terms hiv AND disclos* AND (child* OR adolesc*). We reviewed 934 article citations and the references of relevant articles to find articles describing disclosure to children and adolescents in resource-limited settings. Data were extracted regarding prevalence of disclosure, factors influencing disclosure, process of disclosure and impact of disclosure on children and caregivers. Results Thirty-two articles met the inclusion criteria, with 16 reporting prevalence of disclosure. Of these 16 studies, proportions of disclosed children ranged from 0 to 69.2%. Important factors influencing disclosure included the child's age and perceived ability to understand the meaning of HIV infection and factors related to caregivers, such as education level, openness about their own HIV status and beliefs about children's capacities. Common barriers to disclosure were fear that the child would disclose HIV status to others, fear of stigma and concerns for children's emotional or physical health. Disclosure was mostly led by caregivers and conceptualized as a one-time event, while others described it as a gradual process. Few studies measured the impact of disclosure on children. Findings suggested adherence to antiretroviral therapy (ART) improved post-disclosure but the emotional and psychological effects of disclosure were variable. Conclusions Most studies show that a minority of HIV-infected children in resource-limited settings know his/her HIV status. While caregivers identify many factors that influence disclosure, studies suggest both positive and negative effects for children. More research is needed to implement age- and culture-appropriate disclosure in resource-limited settings. PMID:23714198
Disclosure of HIV status to children in resource-limited settings: a systematic review.
Vreeman, Rachel C; Gramelspacher, Anna Maria; Gisore, Peter O; Scanlon, Michael L; Nyandiko, Winstone M
2013-05-27
Informing children of their own HIV status is an important aspect of long-term disease management, yet there is little evidence of how and when this type of disclosure takes place in resource-limited settings and its impact. MEDLINE, EMBASE and Cochrane Databases were searched for the terms hiv AND disclos* AND (child* OR adolesc*). We reviewed 934 article citations and the references of relevant articles to find articles describing disclosure to children and adolescents in resource-limited settings. Data were extracted regarding prevalence of disclosure, factors influencing disclosure, process of disclosure and impact of disclosure on children and caregivers. Thirty-two articles met the inclusion criteria, with 16 reporting prevalence of disclosure. Of these 16 studies, proportions of disclosed children ranged from 0 to 69.2%. Important factors influencing disclosure included the child's age and perceived ability to understand the meaning of HIV infection and factors related to caregivers, such as education level, openness about their own HIV status and beliefs about children's capacities. Common barriers to disclosure were fear that the child would disclose HIV status to others, fear of stigma and concerns for children's emotional or physical health. Disclosure was mostly led by caregivers and conceptualized as a one-time event, while others described it as a gradual process. Few studies measured the impact of disclosure on children. Findings suggested adherence to antiretroviral therapy (ART) improved post-disclosure but the emotional and psychological effects of disclosure were variable. Most studies show that a minority of HIV-infected children in resource-limited settings know his/her HIV status. While caregivers identify many factors that influence disclosure, studies suggest both positive and negative effects for children. More research is needed to implement age- and culture-appropriate disclosure in resource-limited settings.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bhattacharya, Tanmoy; Stanton, Jennifer; Kim, Eun - Young
2008-01-01
A selective advantage against infectious diseases such as HIV/AIDS is associated with differences in the genes relevant to immunity and virus replication. The CC chemokine receptor 5 (CCR5), the principal coreceptor for HIV, and its chemokine ligands, including CCL3L1, influences the CD4+ target cells susceptibility to infection. The CCL3L1 gene is in a region of segmental duplication on the q-arm of human chromosome 17. Increased numbers of CCL3L1 gene copies that affect the gene expression phenotype might have substantial protective effects. Here we show that the population-specific CCL3L1 gene copy number and the CCR5 {Delta}32 protein-inactivating deletion that categorizes themore » CCL3L1-CCR5 genotype do not influence HIV/AIDS susceptibility or the robustness of immune recovery after the initiation of highly active antiretroviral therapy (HAART).« less
Impact of HIV-related stigma on treatment adherence: systematic review and meta-synthesis
Katz, Ingrid T; Ryu, Annemarie E; Onuegbu, Afiachukwu G; Psaros, Christina; Weiser, Sheri D; Bangsberg, David R; Tsai, Alexander C
2013-01-01
Introduction Adherence to HIV antiretroviral therapy (ART) is a critical determinant of HIV-1 RNA viral suppression and health outcomes. It is generally accepted that HIV-related stigma is correlated with factors that may undermine ART adherence, but its relationship with ART adherence itself is not well established. We therefore undertook this review to systematically assess the relationship between HIV-related stigma and ART adherence. Methods We searched nine electronic databases for published and unpublished literature, with no language restrictions. First we screened the titles and abstracts for studies that potentially contained data on ART adherence. Then we reviewed the full text of these studies to identify articles that reported data on the relationship between ART adherence and either HIV-related stigma or serostatus disclosure. We used the method of meta-synthesis to summarize the findings from the qualitative studies. Results Our search protocol yielded 14,854 initial records. After eliminating duplicates and screening the titles and abstracts, we retrieved the full text of 960 journal articles, dissertations and unpublished conference abstracts for review. We included 75 studies conducted among 26,715 HIV-positive persons living in 32 countries worldwide, with less representation of work from Eastern Europe and Central Asia. Among the 34 qualitative studies, our meta-synthesis identified five distinct third-order labels through an inductive process that we categorized as themes and organized in a conceptual model spanning intrapersonal, interpersonal and structural levels. HIV-related stigma undermined ART adherence by compromising general psychological processes, such as adaptive coping and social support. We also identified psychological processes specific to HIV-positive persons driven by predominant stigmatizing attitudes and which undermined adherence, such as internalized stigma and concealment. Adaptive coping and social support were critical determinants of participants’ ability to overcome the structural and economic barriers associated with poverty in order to successfully adhere to ART. Among the 41 quantitative studies, 24 of 33 cross-sectional studies (71%) reported a positive finding between HIV stigma and ART non-adherence, while 6 of 7 longitudinal studies (86%) reported a null finding (Pearson's χ 2=7.7; p=0.005). Conclusions We found that HIV-related stigma compromised participants’ abilities to successfully adhere to ART. Interventions to reduce stigma should target multiple levels of influence (intrapersonal, interpersonal and structural) in order to have maximum effectiveness on improving ART adherence. PMID:24242258
[Influence of HIV related stigma on health care access].
Bermúdez-Román, Viviana; Bran-Piedrahita, Lemy; Palacios-Moya, Lucía; Posada-Zapata, Isabel Cristina
2015-01-01
To notice the influence of the stigma surrounding HIV on the access to health services among the seropositive population of Medellín, Colombia, in 2012. A qualitative approach using Strauss' and Corbin's grounded theory. Data was collected through 13 interviews at two different moments.These interviews were transcribed and analyzed, and the data found in them was processed via axial and open coding. The myths surrounding HIV become a barrier preventing access to healthcare;this hinders timely treatment of the virus. Government policies must aim to reduce the effect that the historical discrimination against HIV has generated so that it can guarantee that infected individuals have early access to treatments for this condition as well as health promotion services.
NASA Astrophysics Data System (ADS)
Ziółkowska, Natasza E.; Michejda, Christopher J.; Bujacz, Grzegorz D.
2010-03-01
Over the past 10 years, several anti-viral drugs have become available to fight the HIV infection. Antiretroviral treatment reduces the mortality of AIDS. Nonnucleoside inhibitors of HIV-1 reverse transcriptase are specific and potentially nontoxic drugs against AIDS. The crystal structures of five nonnucleoside inhibitors of HIV-1 reverse transcriptase are presented here. The structural parameters, especially those describing the angular orientation of the π-electron systems and influencing biological activity, were determined for all of the investigated inhibitors. The chemical character and orientation of the substituent at C4 position of the benzimidazole moiety substantially influences the anti-viral activity. The structural data of the investigated inhibitors is a good basis for modeling enzyme-inhibitor interactions for structure-assisted drug design.
SOCIAL PSYCHOLOGICAL DYNAMICS OF ENHANCED HIV RISK REDUCTION AMONG PEER INTERVENTIONISTS
Dickson-Gomez, Julia; Weeks, Margaret R.; Convey, Mark; Li, Jianghong
2014-01-01
The authors present a model of interactive social psychological and relational feedback processes leading to human immunodeficiency virus (HIV) risk reduction behavior change among active drug users trained as Peer Health Advocates (PHAs). The model is supported by data from qualitative interviews with PHAs and members of their drug-using networks in the Risk Avoidance Partnership (RAP) project. Results suggest three mutually reinforcing social psychological processes that motivate PHAs to provide HIV prevention intervention to their peers and to reduce their own risk behaviors: development of a prosocial identity, positive social reinforcement from drug users and community members, and cognitive dissonance associated with continued risk behavior while engaging in health advocacy. These processes directly influence peer interventionists’ motivation and efficacy to continue giving intervention to their peers, and to reduce their HIV risk behaviors. The authors discuss implications of the model for continued research on effective HIV prevention in high-risk groups. PMID:25414528
A comprehensive theoretical framework for the implementation and evaluation of opt-out HIV testing.
Leidel, Stacy; Leslie, Gavin; Boldy, Duncan; Girdler, Sonya
2017-04-01
Opt-out HIV testing (in which patients are offered HIV testing as a default) is a potentially powerful strategy for increasing the number of people who know their HIV status and thus limiting viral transmission. Like any change in clinical practice, implementation of opt-out HIV testing in a health service requires a change management strategy, which should have theoretical support. This paper considers the application of three theories to the implementation and evaluation of an opt-out HIV testing programme: Behavioural Economics, the Health Belief Model and Normalisation Process Theory. An awareness, understanding and integration of these theories may motivate health care providers to order HIV tests that they may not routinely order, influence their beliefs about who should be tested for HIV and inform the operational aspects of opt-out HIV testing. Ongoing process evaluation of opt-out HIV testing programmes (based on these theories) will help to achieve individual health care provider self-efficacy and group collective action, thereby improving testing rates and health outcomes. © 2016 John Wiley & Sons, Ltd.
S4HARA: System for HIV/AIDS resource allocation.
Lasry, Arielle; Carter, Michael W; Zaric, Gregory S
2008-03-26
HIV/AIDS resource allocation decisions are influenced by political, social, ethical and other factors that are difficult to quantify. Consequently, quantitative models of HIV/AIDS resource allocation have had limited impact on actual spending decisions. We propose a decision-support System for HIV/AIDS Resource Allocation (S4HARA) that takes into consideration both principles of efficient resource allocation and the role of non-quantifiable influences on the decision-making process for resource allocation. S4HARA is a four-step spreadsheet-based model. The first step serves to identify the factors currently influencing HIV/AIDS allocation decisions. The second step consists of prioritizing HIV/AIDS interventions. The third step involves allocating the budget to the HIV/AIDS interventions using a rational approach. Decision-makers can select from several rational models of resource allocation depending on availability of data and level of complexity. The last step combines the results of the first and third steps to highlight the influencing factors that act as barriers or facilitators to the results suggested by the rational resource allocation approach. Actionable recommendations are then made to improve the allocation. We illustrate S4HARA in the context of a primary healthcare clinic in South Africa. The clinic offers six types of HIV/AIDS interventions and spends US$750,000 annually on these programs. Current allocation decisions are influenced by donors, NGOs and the government as well as by ethical and religious factors. Without additional funding, an optimal allocation of the total budget suggests that the portion allotted to condom distribution be increased from 1% to 15% and the portion allotted to prevention and treatment of opportunistic infections be increased from 43% to 71%, while allocation to other interventions should decrease. Condom uptake at the clinic should be increased by changing the condom distribution policy from a pull system to a push system. NGOs and donors promoting antiretroviral programs at the clinic should be sensitized to the results of the model and urged to invest in wellness programs aimed at the prevention and treatment of opportunistic infections. S4HARA differentiates itself from other decision support tools by providing rational HIV/AIDS resource allocation capabilities as well as consideration of the realities facing authorities in their decision-making process.
The investigation of specific biochemical markers in monitoring kidney function of drug addicts.
Gąsiorowski, Jacek; Marchewka, Zofia; Łapiński, Łukasz; Szymańska, Beata; Głowacka, Krystyna; Knysz, Brygida; Długosz, Anna; Wiela-Hojeńska, Anna
2013-12-05
An increasingly important issue in the Polish population is drug abuse. It leads to extensive damage of parenchymal organs, including kidney. Establishing early markers of organ damage and their monitoring during rehabilitation therapy is therefore of pivotal importance. This study evaluated the utility of highly specific and selective markers (NGAL, IL-18, a and π-GST isoenzyme, and ß2-M). The influence of opioid drugs and other factors on kidney function (HIV and HCV infections, duration and the kind of drugs abused) was determined. Urine collected from 83 subjects who abused drugs and 33 healthy volunteers was tested with ELISA using specific antibodies (IBL, Biotron, Bioporto-Diagnostics). HIV infection was confirmed with western-blotting and HCV with PCR. CD4 lymphocytes were quantified with flow cytometry. RFLP and PCR were used to determine the viral load of HIV and HCV (genotype). A significant increase of IL-18, NGAL and β2M activity in heroin addicts compared to the control group was noted as well as the influence of HIV infection on NGAL and β2M excretion. A statistically significant (p=0.04) correlation between the viral load and IL-18 concentration was noted while no significant influence of the duration and the kind of drugs abused, the route of intake or the age of addicts was seen. Only the NGAL concentration was sex dependent and significantly higher in women. This study showed the specific, clinical utility of IL-18, NGAL, and β2M in the evaluation of renal function in drug addicts. Early detection of nephropathy with biochemical indicators might help prevent severe conditions that require hospitalization and intensive care.
Tully, Damien C.; Ogilvie, Colin B.; Batorsky, Rebecca E.; Bean, David J.; Power, Karen A.; Ghebremichael, Musie; Bedard, Hunter E.; Gladden, Adrianne D.; Seese, Aaron M.; Amero, Molly A.; Lane, Kimberly; McGrath, Graham; Bazner, Suzane B.; Tinsley, Jake; Lennon, Niall J.; Henn, Matthew R.; Brumme, Zabrina L.; Norris, Philip J.; Rosenberg, Eric S.; Mayer, Kenneth H.; Jessen, Heiko; Kosakovsky Pond, Sergei L.; Walker, Bruce D.; Altfeld, Marcus; Carlson, Jonathan M.; Allen, Todd M.
2016-01-01
Due to the stringent population bottleneck that occurs during sexual HIV-1 transmission, systemic infection is typically established by a limited number of founder viruses. Elucidation of the precise forces influencing the selection of founder viruses may reveal key vulnerabilities that could aid in the development of a vaccine or other clinical interventions. Here, we utilize deep sequencing data and apply a genetic distance-based method to investigate whether the mode of sexual transmission shapes the nascent founder viral genome. Analysis of 74 acute and early HIV-1 infected subjects revealed that 83% of men who have sex with men (MSM) exhibit a single founder virus, levels similar to those previously observed in heterosexual (HSX) transmission. In a metadata analysis of a total of 354 subjects, including HSX, MSM and injecting drug users (IDU), we also observed no significant differences in the frequency of single founder virus infections between HSX and MSM transmissions. However, comparison of HIV-1 envelope sequences revealed that HSX founder viruses exhibited a greater number of codon sites under positive selection, as well as stronger transmission indices possibly reflective of higher fitness variants. Moreover, specific genetic “signatures” within MSM and HSX founder viruses were identified, with single polymorphisms within gp41 enriched among HSX viruses while more complex patterns, including clustered polymorphisms surrounding the CD4 binding site, were enriched in MSM viruses. While our findings do not support an influence of the mode of sexual transmission on the number of founder viruses, they do demonstrate that there are marked differences in the selection bottleneck that can significantly shape their genetic composition. This study illustrates the complex dynamics of the transmission bottleneck and reveals that distinct genetic bottleneck processes exist dependent upon the mode of HIV-1 transmission. PMID:27163788
Tully, Damien C; Ogilvie, Colin B; Batorsky, Rebecca E; Bean, David J; Power, Karen A; Ghebremichael, Musie; Bedard, Hunter E; Gladden, Adrianne D; Seese, Aaron M; Amero, Molly A; Lane, Kimberly; McGrath, Graham; Bazner, Suzane B; Tinsley, Jake; Lennon, Niall J; Henn, Matthew R; Brumme, Zabrina L; Norris, Philip J; Rosenberg, Eric S; Mayer, Kenneth H; Jessen, Heiko; Kosakovsky Pond, Sergei L; Walker, Bruce D; Altfeld, Marcus; Carlson, Jonathan M; Allen, Todd M
2016-05-01
Due to the stringent population bottleneck that occurs during sexual HIV-1 transmission, systemic infection is typically established by a limited number of founder viruses. Elucidation of the precise forces influencing the selection of founder viruses may reveal key vulnerabilities that could aid in the development of a vaccine or other clinical interventions. Here, we utilize deep sequencing data and apply a genetic distance-based method to investigate whether the mode of sexual transmission shapes the nascent founder viral genome. Analysis of 74 acute and early HIV-1 infected subjects revealed that 83% of men who have sex with men (MSM) exhibit a single founder virus, levels similar to those previously observed in heterosexual (HSX) transmission. In a metadata analysis of a total of 354 subjects, including HSX, MSM and injecting drug users (IDU), we also observed no significant differences in the frequency of single founder virus infections between HSX and MSM transmissions. However, comparison of HIV-1 envelope sequences revealed that HSX founder viruses exhibited a greater number of codon sites under positive selection, as well as stronger transmission indices possibly reflective of higher fitness variants. Moreover, specific genetic "signatures" within MSM and HSX founder viruses were identified, with single polymorphisms within gp41 enriched among HSX viruses while more complex patterns, including clustered polymorphisms surrounding the CD4 binding site, were enriched in MSM viruses. While our findings do not support an influence of the mode of sexual transmission on the number of founder viruses, they do demonstrate that there are marked differences in the selection bottleneck that can significantly shape their genetic composition. This study illustrates the complex dynamics of the transmission bottleneck and reveals that distinct genetic bottleneck processes exist dependent upon the mode of HIV-1 transmission.
Lee, Sung-Jae; Brooks, Ronald; Bolan, Robert K.; Flynn, Risa
2013-01-01
Men who have sex with men (MSM) in the United States represent a vulnerable population with lower rates of HIV testing. There are various specific attributes of HIV testing that may impact willingness to test (WTT) for HIV. Identifying specific attributes influencing patients’ decisions around WTT for HIV is critical to ensure improved HIV testing uptake. This study examined WTT for HIV by using conjoint analysis, an innovative method for systematically estimating consumer preferences across discrete attributes. WTT for HIV was assessed across eight hypothetical HIV testing scenarios varying across seven dichotomous attributes: location (home vs. clinic), price (free vs. $50), sample collection (finger prick vs. blood), timeliness of results (immediate vs. 1–2 weeks), privacy (anonymous vs. confidential), results given (by phone vs. in-person), and type of counseling (brochure vs. in-person). Seventy-five MSM were recruited from a community based organization providing HIV testing services in Los Angeles to participate in conjoint analysis. WTT for HIV score was based on a 100-point scale. Scores ranged from 32.2 to 80.3 for eight hypothetical HIV testing scenarios. Price of HIV testing (free vs. $50) had the highest impact on WTT (impact score=31.4, SD=29.2, p<.0001), followed by timeliness of results (immediate vs. 1–2 weeks) (impact score=13.9, SD=19.9, p=<.0001) and testing location (home vs. clinic) (impact score=10.3, SD=22.8, p=.0002). Impacts of other HIV testing attributes were not significant. Conjoint analysis method enabled direct assessment of HIV testing preferences and identified specific attributes that significantly impact WTT for HIV among MSM. This method provided empirical evidence to support the potential uptake of the newly FDA-approved over-the-counter HIV home-test kit with immediate results, with cautionary note on the cost of the kit. PMID:23651439
Ramsuran, Veron; Kulkarni, Hemant; He, Weijing; Mlisana, Koleka; Wright, Edwina J.; Werner, Lise; Castiblanco, John; Dhanda, Rahul; Le, Tuan; Dolan, Matthew J.; Guan, Weihua; Weiss, Robin A.; Clark, Robert A.; Abdool Karim, Salim S.; Ndung'u, Thumbi
2011-01-01
Background. The Duffy-null trait and ethnic netropenia are both highly prevalent in Africa. The influence of pre-seroconversion levels of peripheral blood cell counts (PBCs) on the risk of acquiring human immunodeficiency virus (HIV)–1 infection among Africans is unknown. Methods. The triangular relationship among pre-seroconversion PBC counts, host genotypes, and risk of HIV acquisition was determined in a prospective cohort of black South African high-risk female sex workers. Twenty-seven women had seroconversion during follow-up, and 115 remained HIV negative for 2 years, despite engaging in high-risk activity. Results. Pre-seroconversion neutrophil counts in women who subsequently had seroconversion were significantly lower, whereas platelet counts were higher, compared with those who remained HIV negative. Comprising 27% of the cohort, subjects with pre-seroconversion neutrophil counts of <2500 cells/mm3 had a ∼3-fold greater risk of acquiring HIV infection. In a genome-wide association analyses, an African-specific polymorphism (rs2814778) in the promoter of Duffy Antigen Receptor for Chemokines (DARC −46T > C) was significantly associated with neutrophil counts (P = 7.9 × 10−11). DARC −46C/C results in loss of DARC expression on erthyrocytes (Duffy-null) and resistance to Plasmodium vivax malaria, and in our cohort, only subjects with this genotype had pre-seroconversion neutrophil counts of <2500 cells/mm3. The risk of acquiring HIV infection was ∼3-fold greater in those with the trait of Duffy-null–associated low neutrophil counts, compared with all other study participants. Conclusions. Pre-seroconversion neutrophil and platelet counts influence risk of HIV infection. The trait of Duffy-null–associated low neutrophil counts influences HIV susceptibility. Because of the high prevalence of this trait among persons of African ancestry, it may contribute to the dynamics of the HIV epidemic in Africa. PMID:21507922
French, Martyn A.; Tjiam, M. Christian; Abudulai, Laila N.; Fernandez, Sonia
2017-01-01
Contemporary antiretroviral therapy (ART) is effective and tolerable for long periods of time but cannot eradicate human immunodeficiency virus type 1 (HIV-1) infection by either elimination of viral reservoirs or enhancement of HIV-1-specific immune responses. Boosting “protective” HIV-1-specific immune responses by active or passive immunization will therefore be necessary to control or eradicate HIV-1 infection and is currently the topic of intense investigation. Recently reported studies conducted in HIV patients and non-human primate (NHP) models of HIV-1 infection suggest that HIV-1-specific IgG antibody responses may contribute to the control of HIV-1 infection. However, production of IgG antibodies with virus neutralizing activity by vaccination remains problematic and while vaccine-induced natural killer cell-activating IgG antibodies have been shown to prevent the acquisition of HIV-1 infection, they may not be sufficient to control or eradicate established HIV-1 infection. It is, therefore, important to consider other functional characteristics of IgG antibody responses. IgG antibodies to viruses also mediate opsonophagocytic antibody responses against virions and capsids that enhance the function of phagocytic cells playing critical roles in antiviral immune responses, particularly conventional dendritic cells and plasmacytoid dendritic cells. Emerging evidence suggests that these antibody functions might contribute to the control of HIV-1 infection. In addition, IgG antibodies contribute to the intracellular degradation of viruses via binding to the cytosolic fragment crystallizable (Fc) receptor tripartite motif containing-21 (TRIM21). The functional activity of an IgG antibody response is influenced by the IgG subclass content, which affects binding to antigens and to Fcγ receptors on phagocytic cells and to TRIM21. The IgG subclass content and avidity of IgG antibodies is determined by germinal center (GC) reactions in follicles of lymphoid tissue. As HIV-1 infects cells in GCs and induces GC dysfunction, which may persist during ART, strategies for boosting HIV-1-specific IgG antibody responses should include early commencement of ART and possibly the use of particular antiretroviral drugs to optimize drug levels in lymphoid follicles. Finally, enhancing particular functions of HIV-1-specific IgG antibody responses by using adjuvants or cytokines to modulate the IgG subclass content of the antibody response might be investigated in NHP models of HIV-1 infection and during trials of therapeutic vaccines in HIV patients. PMID:28725225
Implementation Process of a Canadian Community-based Nurse Mentorship Intervention in HIV Care
Caine, Vera; Mill, Judy; O’Brien, Kelly; Solomon, Patricia; Worthington, Catherine; Dykeman, Margaret; Gahagan, Jacqueline; Maina, Geoffrey; De Padua, Anthony; Arneson, Cheryl; Rogers, Tim; Chaw-Kant, Jean
2016-01-01
We describe salient individual and organizational factors that influenced engagement of registered nurses in a 12-month clinical mentorship intervention on HIV care in Canada. The intervention included 48 nurses and 8 people living with HIV (PLWH) who were involved in group-based and one-on-one informal mentorship informed by transformative learning theory. We evaluated the process of implementing the mentorship intervention using qualitative content analysis. The inclusion of PLWH as mentors, the opportunities for reciprocal learning, and the long-term commitment of individual nurses and partner organizations in HIV care were major strengths. Challenges included the need for multiple ethical approvals, the lack of organizational support at some clinical sites, and the time commitment required by participants. We recommend that clinical mentorship interventions in HIV care consider organizational support, adhere to the Greater Involvement of People Living with HIV/AIDS principles, and explore questions of professional obligations. PMID:26644019
Dieleman, Marjolein; Bwete, Vincent; Maniple, Everd; Bakker, Mirjam; Namaganda, Grace; Odaga, John; van der Wilt, Gert Jan
2007-12-18
Staff shortages could harm the provision and quality of health care in Uganda, so staff retention and motivation are crucial. Understanding the impact of HIV/AIDS on staff contributes to designing appropriate retention and motivation strategies. This research aimed 'to identify the influence of HIV/AIDS on staff working in general hospitals at district level in rural areas and to explore support required and offered to deal with HIV/AIDS in the workplace'. Its results were to inform strategies to mitigate the impact of HIV/AIDS on hospital staff. A cross-sectional study with qualitative and quantitative components was implemented during two weeks in September 2005. Data were collected in two government and two faith-based private not-for-profit hospitals purposively selected in rural districts in Uganda's Central Region. Researchers interviewed 237 people using a structured questionnaire and held four focus group discussions and 44 in-depth interviews. HIV/AIDS places both physical and, to some extent, emotional demands on health workers. Eighty-six per cent of respondents reported an increased workload, with 48 per cent regularly working overtime, while 83 per cent feared infection at work, and 36 per cent reported suffering an injury in the previous year. HIV-positive staff remained in hiding, and most staff did not want to get tested as they feared stigmatization. Organizational responses were implemented haphazardly and were limited to providing protective materials and the HIV/AIDS-related services offered to patients. Although most staff felt motivated to work, not being motivated was associated with a lack of daily supervision, a lack of awareness on the availability of HIV/AIDS counselling, using antiretrovirals and working overtime. The specific hospital context influenced staff perceptions and experiences. HIV/AIDS is a crucially important contextual factor, impacting on working conditions in various ways. Therefore, organizational responses should be integrated into responses to other problematic working conditions and adapted to the local context. Opportunities already exist, such as better use of supervision, educational sessions and staff meetings. However, exchanges on interventions to improve staff motivation and address HIV/AIDS in the health sector are urgently required, including information on results and details of the context and implementation process.
Dieleman, Marjolein; Bwete, Vincent; Maniple, Everd; Bakker, Mirjam; Namaganda, Grace; Odaga, John; van der Wilt, Gert Jan
2007-01-01
Background Staff shortages could harm the provision and quality of health care in Uganda, so staff retention and motivation are crucial. Understanding the impact of HIV/AIDS on staff contributes to designing appropriate retention and motivation strategies. This research aimed 'to identify the influence of HIV/AIDS on staff working in general hospitals at district level in rural areas and to explore support required and offered to deal with HIV/AIDS in the workplace'. Its results were to inform strategies to mitigate the impact of HIV/AIDS on hospital staff. Methods A cross-sectional study with qualitative and quantitative components was implemented during two weeks in September 2005. Data were collected in two government and two faith-based private not-for-profit hospitals purposively selected in rural districts in Uganda's Central Region. Researchers interviewed 237 people using a structured questionnaire and held four focus group discussions and 44 in-depth interviews. Results HIV/AIDS places both physical and, to some extent, emotional demands on health workers. Eighty-six per cent of respondents reported an increased workload, with 48 per cent regularly working overtime, while 83 per cent feared infection at work, and 36 per cent reported suffering an injury in the previous year. HIV-positive staff remained in hiding, and most staff did not want to get tested as they feared stigmatization. Organizational responses were implemented haphazardly and were limited to providing protective materials and the HIV/AIDS-related services offered to patients. Although most staff felt motivated to work, not being motivated was associated with a lack of daily supervision, a lack of awareness on the availability of HIV/AIDS counselling, using antiretrovirals and working overtime. The specific hospital context influenced staff perceptions and experiences. Conclusion HIV/AIDS is a crucially important contextual factor, impacting on working conditions in various ways. Therefore, organizational responses should be integrated into responses to other problematic working conditions and adapted to the local context. Opportunities already exist, such as better use of supervision, educational sessions and staff meetings. However, exchanges on interventions to improve staff motivation and address HIV/AIDS in the health sector are urgently required, including information on results and details of the context and implementation process. PMID:18088407
Longmore, Monica A.; Johnson, Wendi L.; Manning, Wendy D.; Giordano, Peggy C.
2012-01-01
This study relies on survey (N=704) and in-depth qualitative (N = 100) interviews (Toledo Adolescent Relationship Study) to examine individual, partner, and relationship barriers and facilitators to HIV testing in a sample of young adults. Consistent with the public health goal of routine testing, nearly 40% of respondents had an HIV test within the context of their current sexual relationship, and women were significantly more likely to have tested within the current relationship than were men. For women, it was both their own risky behavior, and the partners’ characteristics and related relationship dynamics that distinguished testers from non-testers. In contrast, for men their own risky behavior was the most salient factor influencing their odds of being tested. These results showcase gender specific approaches to best promote sexual health, i.e., routine HIV testing among young adults. PMID:22489753
Yudin, Mark H; Money, Deborah M; Cheung, Matthew C; Loutfy, Mona R
2012-01-01
Family and pregnancy planning are important for HIV-infected individuals and couples. There is a paucity of data regarding physician attitudes with respect to reproduction in this population, but some evidence suggests that attitudes can influence the information, advice, and services they will provide. To determine physician attitudes toward pregnancy, fertility care, and access to assisted reproductive technologies for HIV-infected individuals, and to determine whether attitudes differed based on specific physician characteristics. A survey was sent electronically to obstetrician/gynecologists and infectious disease specialists in Canada. Items were grouped into 5 key domains: physician demographics, physician attitudes toward pregnancy and adoption, physician attitudes toward fertility care, physician attitudes toward assisted reproductive technology, and challenges for an HIV-infected population. Attitudes were determined based on answers to individual questions and also for each domain. Univariate and logistic regression analyses were used to determine the influence of specific physician characteristics on attitudes. Completed surveys were received from 165 physicians. Most had positive attitudes regarding pregnancy or adoption (89%), fertility care (72%), and assisted reproductive technology (79%). In multivariate analyses, having cared for HIV-infected patients was significantly associated with having a positive attitude toward fertility care or assisted reproductive technology. In this national survey of Canadian physicians, most had positive attitudes toward pregnancy, adoption, fertility care, and use of assisted reproductive technology among HIV-infected persons. Physicians who had cared for HIV-infected individuals in the past were more likely to have positive attitudes than those who had not.
Major Factors Influencing HIV/AIDS Project Evaluation
ERIC Educational Resources Information Center
Niba, Mercy Bi; Green, J. Maryann
2005-01-01
This article aimed at finding out if participatory processes (group discussions, enactments, and others) do make a valuable contribution in communication-based project implementation/evaluation and the fight against HIV/AIDS. A case study backed by documentary analysis of evaluation reports and occasional insights from interviews stood as the main…
Smith, Rachel A; Morrison, Daniel
2006-11-01
People often perceive risks for others and themselves differently. This study examines whether personal beliefs about HIV and experience with those living with HIV influence personal risk assessments of contracting HIV in an interview sample of northern Namibians (N=400), but not others' assessments as explained by singular-distribution theory [Klar, Medding, & Sarel (1996). Nonunique invulnerability: Singular versus distributional probabilities and unrealistic optimism in comparative risk judgments. Organizational Behavior and Human Decision Processes, 67, 229-245]. Findings indicate that personal risk perceptions decrease with more HIV stigmatizing beliefs and increase with greater experience, but that those characteristics had no impact on assessments for others' risk. The study also examines whether the size and characteristics of the referent group, peers and the general Namibian population, influence others' risk assessments. Optimistic biases for personal risk versus others' risk appear with the highest discrepancy emerging between personal and general population risk assessments. Further, we found that personal risk perceptions did not mediate the relationship between personal characteristics, beliefs and experiences, and intentions to seek HIV testing.
Giuliano, Marina; Pirillo, Maria Franca; Liotta, Giuseppe; Andreotti, Mauro; Jere, Haswell; Sagno, Jean-Baptiste; Ciccacci, Fausto; Amici, Roberta; Marazzi, Maria Cristina; Vella, Stefano; Palombi, Leonardo; Mancinelli, Sandro
2017-11-01
Virtually all HIV-infected women in sub-Saharan Africa have evidence of Cytomegalovirus (CMV) infection and levels of specific anti-CMV IgG have been suggested to represent more intense reactivation of subclinical infection. Studies have also shown direct influence of CMV on lymphocytes. The aim of this study was to determine if levels of anti-CMV specific antibodies could impact on the immunological response to antiretroviral treatment (ART) in HIV-infected pregnant women. CMV-specific IgG were measured in HIV-infected pregnant women at 26 weeks of gestation (before ART initiation). Women received ART until 6 months postpartum or indefinitely according to local guidelines at the time of the study. Immunological and virological responses were assessed 6 months and 24 months after delivery. A total of 81 women were studied. At baseline high levels (above the median) of specific IgG were associated to a low CD4+ cell count (P<0.001), a high viral load (P=0.003), and to an older age (P=0.051). In a multivariate model adjusting for baseline CD4+ count, baseline viral load and age, the presence of low levels of CMV IgG was the only independent predictor of a a CD4+ count above 500/mm 3 24 months after delivery among women on continuous therapy. In this cohort, levels of CVM IgG had a significant influence on the immunological response to ART, adding information to the known impact of CMV infection in the HIV-positive population, and underlining the need of new strategies to contain the infection. Copyright © 2017 Elsevier B.V. All rights reserved.
Tully, Stephen; Cojocaru, Monica; Bauch, Chris T
2015-10-28
There has been growing use of highly active antiretroviral treatment (HAART) for HIV and significant progress in developing prophylactic HIV vaccines. The simplest theories of counterproductive behavioral responses to such interventions tend to focus on single feedback mechanisms: for instance, HAART optimism makes infection less scary and thus promotes risky sexual behavior. Here, we develop an agent based, age-structured model of HIV transmission, risk perception, and partner selection in a core group to explore behavioral responses to interventions. We find that interventions can activate not one, but several feedback mechanisms that could potentially influence decision-making and HIV prevalence. In the model, HAART increases the attractiveness of unprotected sex, but it also increases perceived risk of infection and, on longer timescales, causes demographic impacts that partially counteract HAART optimism. Both HAART and vaccination usually lead to lower rates of unprotected sex on the whole, but intervention effectiveness depends strongly on whether individuals over- or under-estimate intervention coverage. Age-specific effects cause sexual behavior and HIV prevalence to change in opposite ways in old and young age groups. For complex infections like HIV-where interventions influence transmission, demography, sexual behavior and risk perception-we conclude that evaluations of behavioral responses should consider multiple feedback mechanisms.
Taking into Account the Quality of the Relationship in HIV Disclosure.
Smith, Charlotte; Cook, Rachel; Rohleder, Poul
2017-01-01
Despite growing interest in HIV disclosure, most theoretical frameworks and empirical studies focus on individual and social factors affecting the process, leaving the contribution of interpersonal factors relatively unexplored. HIV transmission and disclosure often occur within a couple however, and this is where disclosure has the most scope as a HIV transmission intervention. With this in mind, this study explores whether perceived relationship quality influences HIV disclosure outcomes. Ninety-five UK individuals with HIV participated in a cross-sectional survey. Retrospective data were collected on their perceived relationship quality prior to disclosing their HIV positive status, and on disclosure outcomes. Perceived relationship quality was found to significantly affect disclosure outcomes. Positive qualities in the relationship were associated with positive outcomes, whereas negative qualities were associated with negative outcomes. Results further confirmed that this association was not merely correlational, but demonstrated predictive power. Relationship quality might act as either a risk or a resilience factor in the disclosure process, and thus warrants greater attention in future research.
Horn, Anne; Scheller, C; du Plessis, S; Burger, R; Arendt, G; Joska, J; Sopper, S; Maschke, C M; Obermann, M; Husstedt, I W; Hain, J; Riederer, P; Koutsilieri, E
2017-04-01
We showed previously that higher levels in CSF dopamine in HIV patients are associated with the presence of the dopamine transporter (DAT) 10/10-repeat allele which was also detected more frequently in HIV-infected individuals compared to uninfected subjects. In the current study, we investigated further whether other genetic dopamine (DA)-related polymorphisms may be related with changes in CSF DA levels and frequency of HIV infection in HIV-infected subjects. Specifically, we studied genetic polymorphisms of brain-derived neurotrophic factor, catechol-O-methyltransferase, and dopamine receptors DRD2, DRD3, and DRD4 genetic polymorphisms in uninfected and HIV-infected people in two different ethnical groups, a German cohort (Caucasian, 72 individuals with HIV infection and 22 individuals without HIV infection) and a South African cohort (Xhosan, 54 individuals with HIV infection and 19 individuals without HIV infection). We correlated the polymorphisms with CSF DA levels, HIV dementia score, CD4 + T cell counts, and HIV viral load. None of the investigated DA-related polymorphisms was associated with altered CSF DA levels, CD4 + T cell count, viral load, and HIV dementia score. The respective allele frequencies were equally distributed between HIV-infected patients and controls. Our findings do not show any influence of the studied genetic polymorphisms on CSF DA levels and HIV infection. This is in contrast to what we found previously for the DAT 3'UTR VNTR and highlights the specific role of the DAT VNTR in HIV infection and disease.
Mindry, Deborah; Wanyenze, Rhoda K; Beyeza-Kashesya, Jolly; Woldetsadik, Mahlet A; Finocchario-Kessler, Sarah; Goggin, Kathy; Wagner, Glenn
2017-08-01
In countries with high HIV prevalence and high fertility desires, the rights of HIV-affected couples to have children are a pressing issue. Conception among people living with HIV carries risks for both horizontal and vertical HIV transmission. In Uganda ~100,000 HIV-infected women become pregnant annually. Providers face a number of challenges to preventing HIV transmission, reducing unplanned pregnancies, and ensuring safer conception. We report findings from interviews with 27 HIV-affected couples (54 individuals) in Uganda. We explored key cultural and structural factors shaping couples' childbearing decisions. Our data reveal a complex intersection of gender norms, familial expectations, relationship dynamics, and HIV stigma influencing their decisions. Participants provided insights regarding provider bias, stigma, and the gendering of reproductive healthcare. To reduce horizontal transmission HIV and family planning clinics must address men's and women's concerns regarding childbearing with specific attention to cultural and structural challenges.
Measuring quality of life among people living with HIV: a systematic review of reviews.
Cooper, Vanessa; Clatworthy, Jane; Harding, Richard; Whetham, Jennifer
2017-11-15
A systematic review of reviews was conducted to identify and appraise brief measures of health-related quality of life (HRQoL) that have been used in peer-reviewed research with people living with HIV. The review was conducted in two stages: 1) search of electronic databases to identify systematic reviews of tools used to measure HRQoL in adults living with HIV, published since the year 2000; 2) selection of HRQol scales from those identified in the reviews. Inclusion criteria included scales that could be self-administered in 10 min or less, covering at least 3 domains of quality of life (physical function, social/role function and mental/emotional function). For generic scales, inclusion criteria included the availability of normative data while for HIV-specific scales, patient input into the development of the scale was required. Ten reviews met the inclusion criteria. Nine generic scales met the inclusion criteria: the EuroQol five dimensions questionnaire (EQ-5D); Health Utilities Index; McGill Quality of Life questionnaire; Medical Outcomes Study (MOS) Short Form (SF)-12; SF-36; World Health Organisation Quality of Life (WHOQOL- BREF), Questions of Life Satisfaction (FLZM) and SF-20. Available psychometric data supported the EQ-5D and SF-36. Seven HIV-specific scales met the inclusion criteria: the AIDS Clinical Trials Group (ACTG)-21; HIV-QL-31; MOS-HIV; Multidimensional Quality of Life Questionnaire for Persons with HIV/AIDS (MQOL-HIV), PROQOL-HIV, Symptom Quality of Life Adherence (HIV-SQUAD) and the WHOQOL-HIV BREF. Of the HIV -specific measures, the MOS-HIV was considered to have the most well-established psychometric properties, however limitations identified in the reviews included insufficient input from people living with HIV in the development of the scale, cross-cultural relevance and continued applicability. Two relatively new measures, the WHOQOL-HIV BREF and PROQOL-HIV, were considered to have promising psychometric properties and may have more relevance to people living with HIV. The findings highlight the need for further validation of HRQoL measures in people living with HIV. The choice of one measure over another is likely to be influenced by the purpose of the quality of life assessment and the domains of HRQoL that are most relevant to the specific research or clinical question.
HIV-1 Tat protein promotes formation of more-processive elongation complexes.
Marciniak, R A; Sharp, P A
1991-01-01
The Tat protein of HIV-1 trans-activates transcription in vitro in a cell-free extract of HeLa nuclei. Quantitative analysis of the efficiency of elongation revealed that a majority of the elongation complexes generated by the HIV-1 promoter were not highly processive and terminated within the first 500 nucleotides. Tat trans-activation of transcription from the HIV-1 promoter resulted from an increase in processive character of the elongation complexes. More specifically, the analysis suggests that there exist two classes of elongation complexes initiating from the HIV promoter: a less-processive form and a more-processive form. Addition of purified Tat protein was found to increase the abundance of the more-processive class of elongation complex. The purine nucleoside analog, 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) inhibits transcription in this reaction by decreasing the efficiency of elongation. Surprisingly, stimulation of transcription elongation by Tat was preferentially inhibited by the addition of DRB. Images PMID:1756726
Lemos, Diana; Hosek, Sybil G.; Bell, Margo
2015-01-01
Studies involving the House Ball Community (HBC) have found high rates of HIV prevalence and undiagnosed HIV infection, as well as unique social and sexual network-related HIV risk and protective behaviors (Murrill et al., 2008; Sanchez et al., 2010). Efforts to understand culturally-appropriate and effective methods of HIV prevention services within the relatively understudied HBC are scarce (Phillips et al., 2011). This qualitative study, utilizing a Diffusion of Innovation Theoretical framework, aimed to explore social norms regarding HIV and accessibility of HIV prevention services within the HBC. Thirty-seven participants (16 community leaders and 21 youth) engaged in focus group discussions. Participants discussed the perceptions of HIV and stigmatization within the HBC, general and HBC-specific risk factors for HIV transmission, as well as HIV prevention needs and strategies for culturally-appropriate HIV interventions. Findings from this qualitative study highlight both the vulnerability of the HBC to HIV transmission and the corresponding support for HIV prevention interventions. PMID:26034382
Martinez-Donate, Ana P; Hovell, Melbourne F; Rangel, Maria Gudelia; Zhang, Xiao; Sipan, Carol L; Magis-Rodriguez, Carlos; Gonzalez-Fagoaga, J Eduardo
2015-03-01
We conducted a probability-based survey of migrant flows traveling across the Mexico-US border, and we estimated HIV infection rates, risk behaviors, and contextual factors for migrants representing 5 distinct migration phases. Our results suggest that the influence of migration is not uniform across genders or risk factors. By considering the predeparture, transit, and interception phases of the migration process, our findings complement previous studies on HIV among Mexican migrants conducted at the destination and return phases. Monitoring HIV risk among this vulnerable transnational population is critical for better understanding patterns of risk at different points of the migration process and for informing the development of protection policies and programs.
Martinez-Donate, Ana P.; Hovell, Melbourne F.; Rangel, Maria Gudelia; Zhang, Xiao; Sipan, Carol L.; Magis-Rodriguez, Carlos; Gonzalez-Fagoaga, J. Eduardo
2015-01-01
We conducted a probability-based survey of migrant flows traveling across the Mexico–US border, and we estimated HIV infection rates, risk behaviors, and contextual factors for migrants representing 5 distinct migration phases. Our results suggest that the influence of migration is not uniform across genders or risk factors. By considering the predeparture, transit, and interception phases of the migration process, our findings complement previous studies on HIV among Mexican migrants conducted at the destination and return phases. Monitoring HIV risk among this vulnerable transnational population is critical for better understanding patterns of risk at different points of the migration process and for informing the development of protection policies and programs. PMID:25602882
Nyblade, Laura; Reddy, Aditi; Mbote, David; Kraemer, John; Stockton, Melissa; Kemunto, Caroline; Krotki, Karol; Morla, Javier; Njuguna, Stella; Dutta, Arin; Barker, Catherine
2017-11-01
The barrier HIV-stigma presents to the HIV treatment cascade is increasingly documented; however less is known about female and male sex worker engagement in and the influence of sex-work stigma on the HIV care continuum. While stigma occurs in all spheres of life, stigma within health services may be particularly detrimental to health seeking behaviors. Therefore, we present levels of sex-work stigma from healthcare workers (HCW) among male and female sex workers in Kenya, and explore the relationship between sex-work stigma and HIV counseling and testing. We also examine the relationship between sex-work stigma and utilization of non-HIV health services. A snowball sample of 497 female sex workers (FSW) and 232 male sex workers (MSW) across four sites was recruited through a modified respondent-driven sampling process. About 50% of both male and female sex workers reported anticipating verbal stigma from HCW while 72% of FSW and 54% of MSW reported experiencing at least one of seven measured forms of stigma from HCW. In general, stigma led to higher odds of reporting delay or avoidance of counseling and testing, as well as non-HIV specific services. Statistical significance of relationships varied across type of health service, type of stigma and gender. For example, anticipated stigma was not a significant predictor of delay or avoidance of health services for MSW; however, FSW who anticipated HCW stigma had significantly higher odds of avoiding (OR = 2.11) non-HIV services, compared to FSW who did not. This paper adds to the growing evidence of stigma as a roadblock in the HIV treatment cascade, as well as its undermining of the human right to health. While more attention is being paid to addressing HIV-stigma, it is equally important to address the key population stigma that often intersects with HIV-stigma.
Schultz, Sharon J; Zhang, Miaohua; Champoux, James J
2010-03-19
The RNase H activity of reverse transcriptase is required during retroviral replication and represents a potential target in antiviral drug therapies. Sequence features flanking a cleavage site influence the three types of retroviral RNase H activity: internal, DNA 3'-end-directed, and RNA 5'-end-directed. Using the reverse transcriptases of HIV-1 (human immunodeficiency virus type 1) and Moloney murine leukemia virus (M-MuLV), we evaluated how individual base preferences at a cleavage site direct retroviral RNase H specificity. Strong test cleavage sites (designated as between nucleotide positions -1 and +1) for the HIV-1 and M-MuLV enzymes were introduced into model hybrid substrates designed to assay internal or DNA 3'-end-directed cleavage, and base substitutions were tested at specific nucleotide positions. For internal cleavage, positions +1, -2, -4, -5, -10, and -14 for HIV-1 and positions +1, -2, -6, and -7 for M-MuLV significantly affected RNase H cleavage efficiency, while positions -7 and -12 for HIV-1 and positions -4, -9, and -11 for M-MuLV had more modest effects. DNA 3'-end-directed cleavage was influenced substantially by positions +1, -2, -4, and -5 for HIV-1 and positions +1, -2, -6, and -7 for M-MuLV. Cleavage-site distance from the recessed end did not affect sequence preferences for M-MuLV reverse transcriptase. Based on the identified sequence preferences, a cleavage site recognized by both HIV-1 and M-MuLV enzymes was introduced into a sequence that was otherwise resistant to RNase H. The isolated RNase H domain of M-MuLV reverse transcriptase retained sequence preferences at positions +1 and -2 despite prolific cleavage in the absence of the polymerase domain. The sequence preferences of retroviral RNase H likely reflect structural features in the substrate that favor cleavage and represent a novel specificity determinant to consider in drug design. Copyright (c) 2010 Elsevier Ltd. All rights reserved.
Antoni, Guillemette; Guergnon, Julien; Meaudre, Céline; Samri, Assia; Boufassa, Faroudy; Goujard, Cécile; Lambotte, Olivier; Autran, Brigitte; Rouzioux, Christine; Costagliola, Dominique; Meyer, Laurence; Theodorou, Ioannis
2013-07-17
Human leukocyte antigen (HLA) class I-driven long-term protection against HIV-1 is mainly associated with HLA-B*27 and HLA-B*57. This effect is observed early after infection. Clarification needs to be established concerning the moment of action for the other HLA-B or HLA-C alleles. HLA-B and HLA-C alleles from 111 individuals that control HIV-1 disease for over 8 years and from 747 seroconverters frequencies were compared. Also, HLA-B and HLA-C influence on early levels of plasma HIV-RNA, cellular HIV-DNA, CD4, CD8 and CD4/CD8 ratio was evaluated among the seroconverters. We performed univariate, multivariate and haplotypic analyses in order to disentangle the respective contribution of the HLA-B and HLA-C genes. The haplotypes analysis shows three patterns of protective effects of HLA-B and HLA-C alleles or haplotypes. First, the HLA B*57, HLA-B*27, HLA-B*13 and HLA-C*14 alleles, which have a strong effect on long-term disease control, also influence at least one of the early infection phenotypes. Second, HLA-B*52 has a strong effect during early time points on HIV-RNA without significant effect on the long-term control of HIV-1. Finally, the HLA-B*14-C*08 haplotype has a strong effect on the long-term protection, without influencing early viral control. Our study highlighted independent effects of HLA-B and HLA-C alleles on HIV-disease progression. Furthermore, some alleles appeared to be specifically associated with either long-term control or early virological parameters, suggesting different immunological mechanisms according to the disease stages.
Lin, Ying-Chuan; Brik, Ashraf; de Parseval, Aymeric; Tam, Karen; Torbett, Bruce E.; Wong, Chi-Huey; Elder, John H.
2006-01-01
We have used feline immunodeficiency virus (FIV) protease (PR) as a mutational system to study the molecular basis of substrate-inhibitor specificity for lentivirus PRs, with a focus on human immunodeficiency virus type 1 (HIV-1) PR. Our previous mutagenesis studies demonstrated that discrete substitutions in the active site of FIV PR with structurally equivalent residues of HIV-1 PR dramatically altered the specificity of the mutant PRs in in vitro analyses. Here, we have expanded these studies to analyze the specificity changes in each mutant FIV PR expressed in the context of the natural Gag-Pol polyprotein ex vivo. Expression mutants were prepared in which 4 to 12 HIV-1-equivalent substitutions were made in FIV PR, and cleavage of each Gag-Pol polyprotein was then assessed in pseudovirions from transduced cells. The findings demonstrated that, as with in vitro analyses, inhibitor specificities of the mutants showed increased HIV-1 PR character when analyzed against the natural substrate. In addition, all of the mutant PRs still processed the FIV polyprotein but the apparent order of processing was altered relative to that observed with wild-type FIV PR. Given the importance of the order in which Gag-Pol is processed, these findings likely explain the failure to produce infectious FIVs bearing these mutations. PMID:16873240
Blair, Cheríe S; Segura, Eddy R; Perez-Brumer, Amaya G; Sanchez, Jorge; Lama, Javier R; Clark, Jesse L
2016-10-01
Risk perception and health behaviors result from individual-level factors influenced by specific partnership contexts. We explored individual- and partner-level factors associated with partner-specific perceptions of HIV/STI risk among 372 HIV/STI-positive MSM and transgender women (TW) in Lima, Peru. Generalized estimating equations explored participants' perception of their three most recent partner(s) as a likely source of their HIV/STI diagnosis. Homosexual/gay (PR = 2.07; 95 % CI 1.19-3.61) or transgender (PR = 2.84; 95 % CI 1.48-5.44) partners were more likely to be considered a source of infection than heterosexual partners. Compared to heterosexual respondents, gay and TW respondents were less likely to associate their partner with HIV/STI infection, suggesting a cultural link between gay or TW identity and perceived HIV/STI risk. Our findings demonstrate a need for health promotion messages tailored to high-risk MSM partnerships addressing how perceived HIV/STI risk aligns or conflicts with actual transmission risks in sexual partnerships and networks.
The G1/S Specific Cyclin D2 Is a Regulator of HIV-1 Restriction in Non-proliferating Cells
Badia, Roger; Pujantell, Maria; Riveira-Muñoz, Eva; Puig, Teresa; Torres-Torronteras, Javier; Martí, Ramón; Clotet, Bonaventura; Ampudia, Rosa M.; Ballana, Ester
2016-01-01
Macrophages are a heterogeneous cell population strongly influenced by differentiation stimuli that become susceptible to HIV-1 infection after inactivation of the restriction factor SAMHD1 by cyclin-dependent kinases (CDK). Here, we have used primary human monocyte-derived macrophages differentiated through different stimuli to evaluate macrophage heterogeneity on cell activation and proliferation and susceptibility to HIV-1 infection. Stimulation of monocytes with GM-CSF induces a non-proliferating macrophage population highly restrictive to HIV-1 infection, characterized by the upregulation of the G1/S-specific cyclin D2, known to control early steps of cell cycle progression. Knockdown of cyclin D2, enhances HIV-1 replication in GM-CSF macrophages through inactivation of SAMHD1 restriction factor by phosphorylation. Co-immunoprecipitation experiments show that cyclin D2 forms a complex with CDK4 and p21, a factor known to restrict HIV-1 replication by affecting the function of the downstream cascade that leads to SAMHD1 deactivation. Thus, we demonstrate that cyclin D2 acts as regulator of cell cycle proteins affecting SAMHD1-mediated HIV-1 restriction in non-proliferating macrophages. PMID:27541004
Blair, Cheríe S; Segura, Eddy R; Perez-Brumer, Amaya G; Sanchez, Jorge; Lama, Javier R; Clark, Jesse L
2016-01-01
Risk perception and health behaviors result from individual-level factors influenced by specific partnership contexts. We explored individual- and partner-level factors associated with partner-specific perceptions of HIV/STI risk among 372 HIV/STI-positive MSM and transgender women (TW) in Lima, Peru. Generalized estimating equations (GEE) explored participants’ perception of their three most recent partner(s) as a likely source of their HIV/STI diagnosis. Homosexual/gay (PR = 2.07; 95% CI 1.19-3.61) or transgender (PR = 2.84; 95% CI 1.48-5.44) partners were more likely to be considered a source of infection than heterosexual partners. Compared to heterosexual respondents, gay and TW respondents were less likely to associate their partner with HIV/STI infection, suggesting a cultural link between gay or TW identity and perceived HIV/STI risk. Our findings demonstrate a need for health promotion messages tailored to high-risk MSM partnerships addressing how perceived HIV/STI risk aligns or conflicts with actual transmission risks in sexual partnerships and networks. PMID:26767533
Duchesne, Léa; Njouom, Richard; Lissock, Frédéric; Tamko-Mella, Gishlaine Flore; Rallier, Sandrine; Poiteau, Lila; Soulier, Alexandre; Chevaliez, Stéphane; Vernet, Guy; Rouveau, Nicolas; Pawlotsky, Jean-Michel; Girard, Pierre-Marie; Lacombe, Karine
2017-05-15
The diagnostic procedure for chronic hepatitis C infection (CHC) usually combines anti-HCV antibody (HCV- Ab ) and HCV-RNA measurement. Quantifying HCV core antigen (cAg) as a one-step procedure could shorten the diagnostic process. We aimed to assess the performance of cAg quantification in diagnosing CHC and how it is influenced by concomitant HIV or HBV infections. The cAg was quantified by an automated assay (Abbott Diagnostics) in 465 HCV- Ab negative serum samples and 544 HCV-RNA positive serum samples ( n = 1009) collected in patients from the Pasteur Center in Cameroon, some of whom were infected by HBV or HIV. Its performance was evaluated in comparison to the gold standard (ELISA or PCR) by estimating its sensitivity (Se) and specificity (Sp), and by comparing the area under ROC (AUROC) curves in each patient population: HCV mono-infected, HCV-HBV and HIV-HCV co-infected. Among the 465 HCV- Ab negative patients, 51 and 79 were HIV- and HBV-infected, respectively, whereas among the 544 patients with CHC, 27 and 28 were HIV- and HBV-infected, respectively. The Spearman ρ correlation coefficient between cAg and HCV-RNA was 0.75 ( p < 0.00001). The assay had a sensitivity of 95.7% (95% CI: 93.2-97.5) and a specificity of 99.7% (95% CI: 98.1-10) in diagnosing CHC, corresponding to an AUROC of 0.99 (95% CI: 0.98-1.0). Being HIV- or HBV-infected did not impact the performance of cAg (Se = 96.4%, Sp = 96.2% and AUROC = 0.98 (95% CI: 0.95-1.0) in the HBV group, Se = 100%, Sp = 88.2% and AUROC = 0.99 (95% CI: 0.97-1.0) in the HIV group, p between AUROC = 0.69). The cAg quantification displayed a high specificity and sensitivity for the diagnosis of CHC in Cameroon, and its performance was not significantly modified by a concomitant HIV or HBV infection. In the context of CHC elimination on a global scale, using cAg quantification as a screening tool to directly identify CHC could be a reliable tool in a "test and treat" strategy.
Namukwaya, Stella; Paparini, Sara; Seeley, Janet; Bernays, Sarah
2017-01-01
Despite great advances in pediatric HIV care, rates and the extent of full disclosure of HIV status to infected children remain low especially in resource-constrained setting. The World Health Organisation recommends that, by the age of 10-12 years old, children should be made fully aware of their HIV-positive status. However, this awareness is often delayed until much later in their adolescence. Few studies have been conducted to investigate what influences caregivers' decision-making process in this regard in low-income settings. In this article, we present an analysis of care dyads of caregivers and HIV-positive young people in Kampala, Uganda, as part of the findings of a longitudinal qualitative study about young people's adherence to antiretroviral therapy embedded in an international clinical trial (BREATHER). Repeat in-depth interviews were conducted with 26 young people living with HIV throughout the course of the trial, and once-off interviews with 16 of their caregivers were also carried out toward the end of the trial. In this article, we examine why and how caregivers decide to disclose a young person's HIV status to them and explore their feelings and dilemmas toward disclosure, as well as how young people reacted and the influence it had on their relationships with and attitudes toward their caregivers. Caregivers feared the consequences of disclosing the young person's positive status to them and disclosure commonly occurred hurriedly in response to a crisis, rather than as part of an anticipated and planned process. A key impediment to disclosure was that caregivers feared that disclosing would damage their relationships with the young people and commonly used this as a reason to continue to postpone disclosure. However, young people did not report prolonged feelings of blame or anger toward their caregivers about their own infection, but they did express frustration at the delay and obfuscation surrounding the disclosure process. Our findings can inform the ways in which mainstream HIV services support caregivers through the disclosure process. This includes providing positive encouragement to disclose fully and to be more confident in initiating and sustaining the timely process of disclosure.
The Internet and Care Initiation by People Living with HIV
Perazzo, Joseph; Haas, Stephen; Webel, Allison; Voss, Joachim
2017-01-01
Over the past 20 years, people increasingly use the Internet to obtain information, including information about health. Yet, we lack understanding of how people living with HIV (PLHIV) use the Internet in their care and treatment decisions. Interviews with 23 individuals who initiated HIV care at an urban, Midwestern medical center were analyzed to explore how they used the Internet during the process of initiating HIV care. The time frame of initiation of HIV care ranged from less than one month to a delay of three years post-diagnosis. Qualitative content analysis was conducted and revealed that the participants discussed the Internet as a source of information about their diagnosis that influenced their care and treatment decisions. Five predominate themes emerged: 1) The Internet Alerted me to the Possibility of HIV, 2) The Internet Showed me a Solution is Available, 3) The Internet Influenced my Decisions about Care, 4) The Internet Empowered me to Participate in my Treatment Decisions, and 5) The Internet Gave me Hope for my Future. The results suggest that the Internet has the potential to provide information that can profoundly influence PLHIVs acceptance of care and treatment decisions. Clinicians face a new reality in which patients use Internet resources to obtain information and shape opinions about HIV treatment and care initiation decision-making. Guiding PLHIV in their selection of online resources needs to be adopted as one approach to educating and empowering individuals as they cope with their diagnosis and contemplate decisions regarding HIV care and treatment. PMID:27686871
Role of the Internet in Care Initiation by People Living With HIV.
Perazzo, Joseph; Haas, Stephen; Webel, Allison; Voss, Joachim
2017-02-01
People frequently use the internet to obtain information, including information about health, but we lack understanding of how people living with HIV (PLHIV) use the internet in their care and treatment decisions. In this secondary analysis, interviews with 23 individuals who initiated HIV care at an urban, Midwestern medical center and mentioned internet use were analyzed using qualitative content analysis to explore how they used the internet during the process of initiating HIV care. HIV care had been initiated by this sample from less than one month to three years post-diagnosis. Participants discussed the internet as a source of information about their diagnosis that influenced their care and treatment decisions. Five themes were predominant: (i) The internet alerted me to the possibility of HIV, (ii) the internet showed me a solution is available, (iii) the internet influenced my decisions about care, (iv) the internet empowered me to participate in my treatment decisions, and (v) the internet gave me hope for my future. The results suggest that the internet has the potential to provide information that can profoundly influence PLHIVs' acceptance of care and treatment decisions. Clinicians face a new reality in which patients use internet resources to obtain information and shape opinions about HIV treatment and care initiation decision-making. Guiding PLHIV in their selection of online resources is one approach to educating and empowering individuals as they cope with their diagnosis and contemplate decisions regarding HIV care and treatment. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Jackson, Ronald J; Worley, Matthew; Trivedi, Shubhanshi; Ranasinghe, Charani
2014-09-29
We have established that the efficacy of a heterologous poxvirus vectored HIV vaccine, fowlpox virus (FPV)-HIV gag/pol prime followed by attenuated vaccinia virus (VV)-HIV gag/pol booster immunisation, is strongly influenced by the cytokine milieu at the priming vaccination site, with endogenous IL-13 detrimental to the quality of the HIV specific CD8+ T cell response induced. We have now developed a novel HIV vaccine that co-expresses a C-terminal deletion mutant of the mouse IL-4, deleted for the essential tyrosine (Y119) required for signalling. In our vaccine system, the mutant IL-4C118 can bind to IL-4 type I and II receptors with high affinity, and transiently prevent the signalling of both IL-4 and IL-13 at the vaccination site. When this IL-4C118 adjuvanted vaccine was used in an intranasal rFPV/intramuscular rVV prime-boost immunisation strategy, greatly enhanced mucosal/systemic HIV specific CD8+ T cells with higher functional avidity, expressing IFN-γ, TNF-α and IL-2 and greater protective efficacy were detected. Surprisingly, the IL-4C118 adjuvanted vaccines also induced robust long-lived HIV gag-specific serum antibody responses, specifically IgG1 and IgG2a. The p55-gag IgG2a responses induced were of a higher magnitude relative to the IL-13Rα2 adjuvant vaccine. More interestingly, our recently tested IL-13Rα2 adjuvanted vaccine which only inhibited IL-13 activity, even though induced excellent high avidity HIV-specific CD8+ T cells, had a detrimental impact on the induction of gag-specific IgG2a antibody immunity. Our observations suggest that (i) IL-4 cell-signalling in the absence of IL-13 retarded gag-specific antibody isotype class switching, or (ii) IL-13Rα2 signalling was involved in inducing good gag-specific B cell immunity. Thus, we believe our novel IL-4R antagonist adjuvant strategy offers great promise not only for HIV-1 vaccines, but also against a range of chronic infections where sustained high quality mucosal and systemic T and B cell immunity are required for protection. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
Duong, Ellen; Bracho-Sanchez, Edith; Rucevic, Marijana; Liebesny, Paul H.; Xu, Yang; Shimada, Mariko; Ghebremichael, Musie; Kavanagh, Daniel G.; Le Gall, Sylvie
2014-01-01
Dendritic cells (DCs), macrophages (MPs) and monocytes are permissive to HIV. Whether they similarly process and present HIV epitopes to HIV-specific CD8 T cells is unknown despite the critical role of peptide processing and presentation for recognition and clearance of infected cells. Cytosolic peptidases degrade endogenous proteins originating from self or pathogens, exogenous antigens preprocessed in endolysosomes, thus shaping the peptidome available for endoplasmic reticulum (ER) translocation, trimming and MHC-I presentation. Here we compared the capacity of DCs, MPs and monocyte cytosolic extracts to produce epitope precursors and epitopes. We showed differences in the proteolytic activities and expression levels of cytosolic proteases between monocyte-derived DCs and MPs and upon maturation with LPS, R848 and CL097, with mature MPs having the highest activities. Using cytosol as a source of proteases to degrade epitope-containing HIV peptides, we showed by mass spectrometry that the degradation patterns of long peptides and the kinetics and amount of antigenic peptides produced differed among DCs, MPs and monocytes. Additionally, variable intracellular stability of HIV peptides prior to loading onto MHC may accentuate the differences in epitope availability for presentation by MHC-I between these subsets. Differences in peptide degradation led to 2- to 25-fold differences in the CTL responses elicited by the degradation peptides generated in DCs, MPs and monocytes. Differences in antigen processing activities between these subsets might lead to variations in the timing and efficiency of recognition of HIV-infected cells by CTLs and contribute to the unequal capacity of HIV-specific CTLs to control viral load. PMID:25230751
Potrepka, Jessica; Copenhaver, Michael
2013-01-01
Researchers examining injection drug users (IDUs) in drug treatment have been trying for decades to determine the optimal way to intervene to prevent the transmission and spread of human immunodeficiency virus (HIV) in this population. Although efficacious HIV risk reduction interventions are widely available, questions remain about what specific factors are most related to HIV risk behavior and defined as unprotected sexual activity and/or high risk drug use. This review involved an evaluation of the research literature in order to better understand the association between drug use and sexual behavior debut on HIV risk behavior. Findings suggest that drug use debut and sexual behavior debut may be related to subsequent HIV risk behavior. Evidence to date implies that intervening at an earlier age to assist youth to avoid or delay these high risk behaviors may be an additional means of reducing subsequent HIV risk. PMID:24381791
Sexual Positioning Among Men Who Have Sex With Men: A Narrative Review.
Dangerfield, Derek T; Smith, Laramie R; Williams, Jeffery; Unger, Jennifer; Bluthenthal, Ricky
2017-05-01
Sexual positioning practices among men who have sex with men (MSM) have not received a thorough discussion in the MSM and HIV literature, given that risks for acquiring or transmitting HIV and STIs via condomless anal sex vary according to sexual positioning. MSM bear a disproportionate burden of HIV compared to the general population in the United States; surveillance efforts suggest that HIV and STIs are increasing among domestic and international populations of MSM. We conducted a narrative review, using a targeted literature search strategy, as an initial effort to explore processes through which sexual positioning practices may contribute to HIV/STI transmission. Peer-reviewed articles were eligible for inclusion if they contained a measure of sexual positioning identity and/or behavior (i.e., "top", "bottom," etc.) or sexual positioning behavior (receptive anal intercourse or insertive anal intercourse), or assessed the relationship between sexual positioning identity with HIV risk, anal sex practice, masculinity, power, partner type, or HIV status. A total of 23 articles met our inclusion criteria. This review highlights dynamic psychosocial processes likely underlying sexual decision making related to sexual positioning identity and practices among MSM and MSM who have sex with women (MSMW), and ways these contexts may influence HIV/STI risk. Despite limited focus in the extant literature, this review notes the important role the contextual factors (masculinity stereotypes, power, partner type, and HIV status) likely to play in influencing sexual positioning identity and practices. Through this review we offer an initial synthesis of the literature describing sexual positioning identities and practices and conceptual model to provide insight into important areas of study through future research.
Sexual Positioning among Men Who Have Sex with Men: A Narrative Review
Dangerfield, Derek T.; Smith, Laramie R.; Williams, Jeffery; Unger, Jennifer; Bluthenthal, Ricky
2017-01-01
Sexual positioning practices among men who have sex with men (MSM) have not received a thorough discussion in the MSM and HIV literature, given that risks for acquiring or transmitting HIV and STIs via condomless anal sex vary according to sexual positioning. MSM bear a disproportionate burden of HIV compared to the general population in the United States; surveillance efforts suggest that HIV and STIs are increasing among domestic and international populations of MSM. We conducted a narrative review, using a targeted literature search strategy, as an initial effort to explore processes through which sexual positioning practices may contribute to HIV/STI transmission. Peer-reviewed articles were eligible for inclusion if they contained a measure of sexual positioning identity and/or behavior (i.e. “top,” “bottom,” etc.) or sexual positioning behavior (receptive anal intercourse [RAI] or insertive anal intercourse [IAI]), or assessed the relationship between sexual positioning identity with HIV risk, anal sex practice, masculinity, power, partner type, or HIV status. A total of 23 articles met our inclusion criteria. This review highlights dynamic psycho-social processes likely underlying sexual decision-making related to sexual positioning identity and practices among MSM and MSM who have sex with women (MSMW), and ways these contexts may influence HIV/STI risk. Despite limited focus in the extant literature, this review notes the important role contextual factors (masculinity stereotypes, power, partner type, and HIV status) likely play in influencing sexual positioning identity and practices. Through this review we offer an initial synthesis of the literature describing sexual positioning identities and practices and conceptual model to provide insight into important areas of study through future research. PMID:27178171
Mouser, Emily E I M; Pollakis, Georgios; Paxton, William A
2012-05-01
In many regions of the world, a high prevalence of HIV-1, helminthic and Mycobacterium tuberculosis (Mtb) infections can be found. Here, we summarize the types of immune responses induced and/or modulated by these pathogens and the consequences for HIV-1 disease. Helminths predominantly induce strong T helper (Th) 2 cellular responses which are downregulated in chronic disease. The anatomical niche populated by helminths plays a key factor in the effect these parasites have on HIV-1 transmission and subsequent replication. Gut-associated helminths have been found to increase HIV-1 transmission via the lesions they provide. In spite of this, the many immune modulatory molecules secreted by the parasites may inhibit or slow HIV-1 infection. In contrast, Mtb is mainly restricted to the lung and the Mtb-specific Th cells induced are highly susceptible to HIV-1 infection and replication. Antigens from both pathogens have immunomodulatory activity that can skew cellular immune responses in specific directions. The effect of helminths and Mtb on modulating immune responses is varied and complex with both their location and phenotype potentially influencing HIV-1 disease. These pathogens have evolved a complex array of molecules which have the capacity to modulate immunity and preserve pathogen survival.
Pettit, Steven C.; Gulnik, Sergei; Everitt, Lori; Kaplan, Andrew H.
2003-01-01
Activation of the human immunodeficiency virus type 1 (HIV-1) protease is an essential step in viral replication. As is the case for all retroviral proteases, enzyme activation requires the formation of protease homodimers. However, little is known about the mechanisms by which retroviral proteases become active within their precursors. Using an in vitro expression system, we have examined the determinants of activation efficiency and the order of cleavage site processing for the protease of HIV-1 within the full-length GagPol precursor. Following activation, initial cleavage occurs between the viral p2 and nucleocapsid proteins. This is followed by cleavage of a novel site located in the transframe domain. Mutational analysis of the dimer interface of the protease produced differential effects on activation and specificity. A subset of mutations produced enhanced cleavage at the amino terminus of the protease, suggesting that, in the wild-type precursor, cleavages that liberate the protease are a relatively late event. Replacement of the proline residue at position 1 of the protease dimer interface resulted in altered cleavage of distal sites and suggests that this residue functions as a cis-directed specificity determinant. In summary, our studies indicate that interactions within the protease dimer interface help determine the order of precursor cleavage and contribute to the formation of extended-protease intermediates. Assembly domains within GagPol outside the protease domain also influence enzyme activation. PMID:12477841
Pettit, Steven C; Gulnik, Sergei; Everitt, Lori; Kaplan, Andrew H
2003-01-01
Activation of the human immunodeficiency virus type 1 (HIV-1) protease is an essential step in viral replication. As is the case for all retroviral proteases, enzyme activation requires the formation of protease homodimers. However, little is known about the mechanisms by which retroviral proteases become active within their precursors. Using an in vitro expression system, we have examined the determinants of activation efficiency and the order of cleavage site processing for the protease of HIV-1 within the full-length GagPol precursor. Following activation, initial cleavage occurs between the viral p2 and nucleocapsid proteins. This is followed by cleavage of a novel site located in the transframe domain. Mutational analysis of the dimer interface of the protease produced differential effects on activation and specificity. A subset of mutations produced enhanced cleavage at the amino terminus of the protease, suggesting that, in the wild-type precursor, cleavages that liberate the protease are a relatively late event. Replacement of the proline residue at position 1 of the protease dimer interface resulted in altered cleavage of distal sites and suggests that this residue functions as a cis-directed specificity determinant. In summary, our studies indicate that interactions within the protease dimer interface help determine the order of precursor cleavage and contribute to the formation of extended-protease intermediates. Assembly domains within GagPol outside the protease domain also influence enzyme activation.
2011-01-01
Background Simian Immunodeficiency Viruses (SIVs) are the precursors of Human Immunodeficiency Viruses (HIVs) which have lead to the worldwide HIV/AIDS pandemic. By studying SIVs in wild primates we can better understand the circulation of these viruses in their natural hosts and habitat, and perhaps identify factors that influence susceptibility and transmission within and between various host species. We investigated the SIV status of wild West African chimpanzees (Pan troglodytes verus) which frequently hunt and consume the western red colobus monkey (Piliocolobus badius badius), a species known to be infected to a high percentage with its specific SIV strain (SIVwrc). Results Blood and plasma samples from 32 wild chimpanzees were tested with INNO-LIA HIV I/II Score kit to detect cross-reactive antibodies to HIV antigens. Twenty-three of the samples were also tested for antibodies to 43 specific SIV and HIV lineages, including SIVwrc. Tissue samples from all but two chimpanzees were tested for SIV by PCRs using generic SIV primers that detect all known primate lentiviruses as well as primers designed to specifically detect SIVwrc. Seventeen of the chimpanzees showed varying degrees of cross-reactivity to the HIV specific antigens in the INNO-LIA test; however no sample had antibodies to SIV or HIV strain - and lineage specific antigens in the Luminex test. No SIV DNA was found in any of the samples. Conclusions We could not detect any conclusive trace of SIV infection from the red colobus monkeys in the chimpanzees, despite high exposure to this virus through frequent hunting. The results of our study raise interesting questions regarding the host-parasite relationship of SIVwrc and wild chimpanzees in their natural habitat. PMID:21284842
Elbeik, Tarek; Markowitz, Norman; Nassos, Patricia; Kumar, Uday; Beringer, Scott; Haller, Barbara; Ng, Valerie
2004-01-01
Branched DNA (bDNA) assays to quantify human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) consist of three distinct steps, including sample processing, hybridization, and detection, and utilize the System 340 platform for plate incubation and washing. Sample processing differs: HIV-1 from 1 ml of plasma is concentrated by high-speed centrifugation, whereas HCV plasma or serum samples are used without concentration. The first step of hybridization involves viral lysis at 63°C: HIV-1 is performed in a heat block, whereas HCV is performed in System 340. The remaining hybridization and detection steps are similar for HIV-1 and HCV and executed on System 340. In the present study, the HIV-1 bDNA assay was adapted for viral lysis in the System 340 platform. The adaptation, test method 2, includes a 20-s vortex of concentrated viral pellet and lysis working solution, transfer of viral lysate to the 96-well capture plate, and transfer to System 340 programmed for HCV assay specifications. With test method 2, specificity and quantification were within assay specifications. HCV bDNA methodology remains unchanged. Hence, an HIV-1 and an HCV bDNA can be run simultaneously on System 340. With simultaneous testing, laboratories can run full plates, as well as combinations of full and partial plates. Also, simultaneous HIV-1 and HCV bDNA permits labor consolidation and improved workflow while maintaining multitasking and rapid patient result turnaround. PMID:15243070
Elbeik, Tarek; Markowitz, Norman; Nassos, Patricia; Kumar, Uday; Beringer, Scott; Haller, Barbara; Ng, Valerie
2004-07-01
Branched DNA (bDNA) assays to quantify human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) consist of three distinct steps, including sample processing, hybridization, and detection, and utilize the System 340 platform for plate incubation and washing. Sample processing differs: HIV-1 from 1 ml of plasma is concentrated by high-speed centrifugation, whereas HCV plasma or serum samples are used without concentration. The first step of hybridization involves viral lysis at 63 degrees C: HIV-1 is performed in a heat block, whereas HCV is performed in System 340. The remaining hybridization and detection steps are similar for HIV-1 and HCV and executed on System 340. In the present study, the HIV-1 bDNA assay was adapted for viral lysis in the System 340 platform. The adaptation, test method 2, includes a 20-s vortex of concentrated viral pellet and lysis working solution, transfer of viral lysate to the 96-well capture plate, and transfer to System 340 programmed for HCV assay specifications. With test method 2, specificity and quantification were within assay specifications. HCV bDNA methodology remains unchanged. Hence, an HIV-1 and an HCV bDNA can be run simultaneously on System 340. With simultaneous testing, laboratories can run full plates, as well as combinations of full and partial plates. Also, simultaneous HIV-1 and HCV bDNA permits labor consolidation and improved workflow while maintaining multitasking and rapid patient result turnaround.
Quakkelaar, Esther D.; Redeker, Anke; Haddad, Elias K.; Harari, Alexandre; McCaughey, Stella Mayo; Duhen, Thomas; Filali-Mouhim, Abdelali; Goulet, Jean-Philippe; Loof, Nikki M.; Ossendorp, Ferry; Perdiguero, Beatriz; Heinen, Paul; Gomez, Carmen E.; Kibler, Karen V.; Koelle, David M.; Sékaly, Rafick P.; Sallusto, Federica; Lanzavecchia, Antonio; Pantaleo, Giuseppe; Esteban, Mariano; Tartaglia, Jim; Jacobs, Bertram L.; Melief, Cornelis J. M.
2011-01-01
Attenuated poxviruses are safe and capable of expressing foreign antigens. Poxviruses are applied in veterinary vaccination and explored as candidate vaccines for humans. However, poxviruses express multiple genes encoding proteins that interfere with components of the innate and adaptive immune response. This manuscript describes two strategies aimed to improve the immunogenicity of the highly attenuated, host-range restricted poxvirus NYVAC: deletion of the viral gene encoding type-I interferon-binding protein and development of attenuated replication-competent NYVAC. We evaluated these newly generated NYVAC mutants, encoding HIV-1 env, gag, pol and nef, for their ability to stimulate HIV-specific CD8 T-cell responses in vitro from blood mononuclear cells of HIV-infected subjects. The new vectors were evaluated and compared to the parental NYVAC vector in dendritic cells (DCs), RNA expression arrays, HIV gag expression and cross-presentation assays in vitro. Deletion of type-I interferon-binding protein enhanced expression of interferon and interferon-induced genes in DCs, and increased maturation of infected DCs. Restoration of replication competence induced activation of pathways involving antigen processing and presentation. Also, replication-competent NYVAC showed increased Gag expression in infected cells, permitting enhanced cross-presentation to HIV-specific CD8 T cells and proliferation of HIV-specific memory CD8 T-cells in vitro. The recombinant NYVAC combining both modifications induced interferon-induced genes and genes involved in antigen processing and presentation, as well as increased Gag expression. This combined replication-competent NYVAC is a promising candidate for the next generation of HIV vaccines. PMID:21347234
Iwelunmor, Juliet; Blackstone, Sarah; Jennings, Larissa; Converse, Donaldson; Ehiri, John; Curley, Jami
2018-04-09
Purpose Many adolescent girls in Nigeria do not test for HIV despite being at high risk. While the influence of psychosocial factors on HIV testing has been examined, there is less evidence regarding the impact of assets and control of assets on HIV testing. This study investigated the protective effects of specific adolescent girls' assets on decision-making regarding HIV testing. Methods Cross-sectional data from the 2013 Nigeria Demographic and Health Survey was analyzed. The main outcome variables were self-reports of having been tested for HIV and knowledge of a place that offers HIV testing. Binary logistic regression was used with employment, education, wealth index, home ownership, land ownership and decision making as potential predictors. Demographic characteristics were controlled in the analysis. Results Age [odds ratio (OR = 1.49)], employment (OR = 3.38), education (OR = 3.16), wealth index (OR = 1.33) and decision making (OR = 3.16) were positively associated with HIV testing. Age (OR = 1.20), employment (OR = 1.33), education (OR = 1.38), wealth (OR = 1.64), land ownership (OR = 1.42), and decision making (OR = 1.26) were positively associated with knowledge of an HIV testing location. Conclusion Our findings suggest that assets play an important role with HIV testing decisions for adolescent girls. Further research to elucidate the specific asset-based needs of adolescent girls will be needed to enhance decisions surrounding uptake of HIV testing and receipt of test results in Nigeria.
Macrophage Resistance to HIV-1 Infection Is Enhanced by the Neuropeptides VIP and PACAP
Temerozo, Jairo R.; Joaquim, Rafael; Regis, Eduardo G.; Savino, Wilson; Bou-Habib, Dumith Chequer
2013-01-01
It is well established that host factors can modulate HIV-1 replication in macrophages, critical cells in the pathogenesis of HIV-1 infection due to their ability to continuously produce virus. The neuropeptides VIP and PACAP induce well-characterized effects on macrophages through binding to the G protein-coupled receptors VPAC1, VPAC2 and PAC1, but their influence on HIV-1 production by these cells has not been established. Here, we describe that VIP and PACAP reduce macrophage production of HIV-1, acting in a synergistic or additive manner to decrease viral growth. Using receptor antagonists, we detected that the HIV-1 inhibition promoted by VIP is dependent on its ligation to VPAC1/2, whereas PACAP decreases HIV-1 growth via activation of the VPAC1/2 and PAC1 receptors. Specific agonists of VPAC2 or PAC1 decrease macrophage production of HIV-1, whereas sole activation of VPAC1 enhances viral growth. However, the combination of specific agonists mimicking the receptor preference of the natural neuropeptides reproduces the ability of VIP and PACAP to increase macrophage resistance to HIV-1 replication. VIP and PACAP up-regulated macrophage secretion of the β-chemokines CCL3 and CCL5 and the cytokine IL-10, whose neutralization reversed the neuropeptide-induced inhibition of HIV-1 replication. Our results suggest that VIP and PACAP and the receptors VPAC2 and PAC1 could be used as targets for developing alternative therapeutic strategies for HIV-1 infection. PMID:23818986
Implementation Process of a Canadian Community-based Nurse Mentorship Intervention in HIV Care.
Caine, Vera; Mill, Judy; O'Brien, Kelly; Solomon, Patricia; Worthington, Catherine; Dykeman, Margaret; Gahagan, Jacqueline; Maina, Geoffrey; De Padua, Anthony; Arneson, Cheryl; Rogers, Tim; Chaw-Kant, Jean
2016-01-01
We describe salient individual and organizational factors that influenced engagement of registered nurses in a 12-month clinical mentorship intervention on HIV care in Canada. The intervention included 48 nurses and 8 people living with HIV (PLWH) who were involved in group-based and one-on-one informal mentorship informed by transformative learning theory. We evaluated the process of implementing the mentorship intervention using qualitative content analysis. The inclusion of PLWH as mentors, the opportunities for reciprocal learning, and the long-term commitment of individual nurses and partner organizations in HIV care were major strengths. Challenges included the need for multiple ethical approvals, the lack of organizational support at some clinical sites, and the time commitment required by participants. We recommend that clinical mentorship interventions in HIV care consider organizational support, adhere to the Greater Involvement of People Living with HIV/AIDS principles, and explore questions of professional obligations. Copyright © 2016 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.
Craddock, Jaih B; Rice, Eric; Rhoades, Harmony; Winetrobe, Hailey
2016-11-01
Black and Latino homeless youth are at high risk of HIV, and yet no HIV prevention interventions have been specifically designed for these groups. Given the success of parent-child intervention programs for housed Black and Latino youth, this study examined parental relationships that could be leveraged for future HIV prevention efforts targeting minority homeless youth, specifically the associations among presence of parents in social networks, parental influence, and parental support. A convenience sample of Black, Latino, and White homeless youth (N = 754) was recruited from three drop-in centers in Los Angeles. Participants completed a computerized, self-administered questionnaire and an interviewer-led personal social network interview. Multivariate logistic regression models assessed the association between parental relationships and sexual risk behaviors. Forty-five percent (n = 338) of youth identified a parent in their network. Having at least one parent in their network was significantly associated with decreased odds of using a condom for Black and White youth. Black youth were almost four times more likely to report being tested for HIV if they spoke to their parents about sex, whereas Latino youth were 91 % less likely to report being tested for HIV if they talked with their parents about sex. Black youth who identified a parent as a positive influence (i.e., promoting condom use or discouraging multiple partners) were almost four times more likely to have used a condom during their last sexual encounter. Parent-child HIV prevention interventions targeting homeless youth would benefit from culturally tailored adaptations.
Perspectives on HIV/AIDS Stigma and Discrimination: Voices of Some Young People in Ghana
ERIC Educational Resources Information Center
Oduro, Georgina Yaa; Otsin, Mercy
2013-01-01
This paper examines Ghanaian young people's perceptions of the determinants of HIV- and AIDS-related stigma and discrimination, and how these perceptions may influence the de-stigmatisation process. Drawing on findings from an in-depth, multi-method qualitative study involving 104 school and street young people aged between 14 and 19 years, the…
Dworkin, Shari L; Grabe, Shelly; Lu, Tiffany; Hatcher, Abigail M; Hatcher, Abbey; Kwena, Zachary; Bukusi, Elizabeth; Mwaura-Muiru, Esther
2013-07-01
While access to and control over assets can minimize women's HIV risk, little is known about the processes through which property rights violations increase the sexual transmission of HIV. The current study focused on two rural areas in Nyanza and Western Province, Kenya where HIV prevalence was high (23.8-33 %) and property rights violations were common. The current work drew on in-depth interview data collected from 50 individuals involved in the development and implementation of a community-led land and property rights program. The program was designed to respond to property rights violations, prevent disinheritance and asset stripping, and reduce HIV risk among women. In our findings, we detailed the social and economic mechanisms through which a loss of property rights was perceived to influence primary and secondary prevention of HIV. These included: loss of income, loss of livelihood and shelter, and migration to slums, markets, or beaches where the exchange of sex for food, money, shelter, clothing, or other goods was common. We also examined the perceived influence of cultural practices, such as wife inheritance, on HIV risk. In the conclusions, we made recommendations for future research in the science-base focused on the development of property ownership as a structural HIV prevention and treatment intervention.
Mori, Marcelo A.; Thomou, Thomas; Boucher, Jeremie; Lee, Kevin Y.; Lallukka, Susanna; Kim, Jason K.; Torriani, Martin; Yki-Järvinen, Hannele; Grinspoon, Steven K.; Cypess, Aaron M.; Kahn, C. Ronald
2014-01-01
miRNAs are important regulators of biological processes in many tissues, including the differentiation and function of brown and white adipocytes. The endoribonuclease dicer is a major component of the miRNA-processing pathway, and in adipose tissue, levels of dicer have been shown to decrease with age, increase with caloric restriction, and influence stress resistance. Here, we demonstrated that mice with a fat-specific KO of dicer develop a form of lipodystrophy that is characterized by loss of intra-abdominal and subcutaneous white fat, severe insulin resistance, and enlargement and “whitening” of interscapular brown fat. Additionally, KO of dicer in cultured brown preadipocytes promoted a white adipocyte–like phenotype and reduced expression of several miRNAs. Brown preadipocyte whitening was partially reversed by expression of miR-365, a miRNA known to promote brown fat differentiation; however, introduction of other miRNAs, including miR-346 and miR-362, also contributed to reversal of the loss of the dicer phenotype. Interestingly, fat samples from patients with HIV-related lipodystrophy exhibited a substantial downregulation of dicer mRNA expression. Together, these findings indicate the importance of miRNA processing in white and brown adipose tissue determination and provide a potential link between this process and HIV-related lipodystrophy. PMID:24983316
Bird, Jason D P; Eversman, Michael; Voisin, Dexter R
2017-08-01
HIV remains an intractable public health concern in the USA, with infection rates notably concentrated among Black gay and bisexual men. Status disclosure by HIV-positive individuals can be an important aspect of risk reduction but doing so poses dilemmas concerning privacy, stigma and self-protection, especially among populations subjected to multiple types of stigmatisation. Understanding the factors related to the disclosure process can help to inform prevention efforts. Using exploratory in-depth interviews, this qualitative study examines the disclosure process among a sample of twenty HIV-positive Black gay and bisexual men (mean age = 40) recruited through a non-profit health centre in a mid-western city in the USA. Data were analysed using a thematic analysis approach with HIV-disclosure as an a priori sensitising concept. Fears of stigma and secondary disclosure within social networks were critical barriers to talking about HIV with sexual partners and disclosure decisions involved a complex process centred on three primary themes: degree of sexual risk, partner type and perceived partner trustworthiness. The unique combinations of these contextual factors resulted in increased or decreased likelihood of disclosure. A conceptual model explicating a potential process by which these contextual factors influence disclosure decisions is presented.
Maman, Suzanne; Cathcart, Rebecca; Burkhardt, Gillian; Omba, Serge; Thompson, Deidre; Behets, Frieda
2012-01-01
HIV transmission through breastfeeding is a significant public health challenge. While breastfeeding provides important nutrition, and results in reduced morbidity and mortality, there is a risk of HIV transmission through breastfeeding. International prevention of mother-to-child transmission (PMTCT) guidelines recommend exclusive breastfeeding for six months among HIV-infected women on antiretroviral therapy. Promoting exclusive feeding has proved difficult in settings where mixed feeding is a cultural norm. Understanding the factors that influence HIV infected women's infant feeding choices and practices is critical to promoting adherence to PMTCT guidelines. We conducted in-depth interviews with 40 HIV+ pregnant and post-partum women in Kinshasa, Democratic Republic of Congo to understand their infant feeding experiences. Interviews were conducted in Lingala, and transcribed and translated into French for analysis. Deductive and inductive codes were applied, and matrices were created to facilitate cross-case analysis. Women had limited understanding of the specific mechanisms through which their infant feeding practices influenced HIV transmission risk. Clinical staff was the primary source of women's knowledge of HIV mother-to-child-transmission. Among the 24 post-partum women in the sample, seven women adhered to exclusive breastfeeding and two women to exclusive formula feeding for at least six months. Women's beliefs and awareness about HIV transmission through breastfeeding, as well as the information and support from clinical staff and other members of their support networks positively influenced their exclusive feeding. Common barriers to exclusive feeding included financial constraints, breast health problems, misinformation about HIV transmission, local norms, and prior feeding experiences. Health care workers play a key role in providing correct information on PMTCT and supporting women's infant feeding choices to adhere to guidelines of exclusive infant feeding. Optimizing provider-patient communication and creating a supportive environment surrounding infant feeding is critical.
Mechanisms of Family Impact on African American Adolescents’ HIV-Related Behavior
Kogan, Steven M.; Brody, Gene H.; Gibbons, Frederick X.; Chen, Yi-fu; Grange, Christina M.; Simons, Ronald L.; Gerrard, Meg; Cutrona, Carolyn E.
2010-01-01
A longitudinal model that tested mediating pathways between protective family processes and HIV-related behavior was evaluated with 195 African American youth. Three waves of data were collected when the youth were 13, 15, and 19 years old. Evidence of mediation and temporal priority were assessed for three constructs: academic engagement, evaluations of prototypical risk-taking peers, and affiliations with risk-promoting peers. Structural equation modeling indicated that protective family processes assessed during early adolescence were associated with HIV-related behavior during emerging adulthood and that academic engagement, evaluations of prototypical risk-taking peers, and affiliations with risk-promoting peers accounted for this association. Evidence of a specific pathway emerged: protective family processes → academic engagement negative → evaluations of prototypical risk-taking peers→ affiliations with risk-promoting peers→ HIV-related behavior. Academic engagement also was a direct predictor of HIV-related risk behavior. PMID:21643492
Tennille, Julie; Solomon, Phyllis; Fishbein, Martin; Blank, Michael
2009-01-01
An important step in research using the Theory of Reasoned Action and Theory of Planned Behavior (TRA/TPB) is conducting an elicitation process to identify topic and population specific cognitions. This study explored HIV risk behaviors in persons with mental illnesses and introduces findings from focus groups conducted during the development phase of an HIV primary and secondary prevention intervention study. Researchers held four focus groups with persons with mental illnesses focused on HIV risks and condom use. Participants discussed sexual side effects of psychotropic medications as a potential cause of both medication non-adherence and HIV risk behaviors. The intersection of these two issues is specific to this population. We conclude with the recommendation that HIV primary and secondary prevention intervention for persons with mental illnesses must incorporate the promotion of healthy sexuality, including attention to sexual side effects of psychotropic medications.
Fear appeals in HIV-prevention messages: young people's perceptions in northern Tanzania.
Bastien, Sheri
2011-12-01
The aims of the study were to elicit the perceptions of young people in Tanzania on the role of fear appeals in HIV-prevention messages and to identify important contextual factors that may influence young people's perceptions of HIV-prevention posters. A total of 10 focus groups were conducted to investigate the role of fear appeals using the extended parallel process model (EPPM) as a guide. Young people were shown a series of images (mostly posters) with alternating high and low-threat messages (fear appeals), and then asked questions about their overall beliefs about HIV and AIDS, as well as about their response in terms of perceived susceptibility to HIV infection, the severity of the message, and their perceptions of self-efficacy and response efficacy. The images and messages that specifically targeted young people were highest in inducing perceived susceptibility to HIV infection, while pictorial descriptions of the physical consequences of HIV infection and those messages related to the stigma and discrimination faced by HIV-infected or affected people induced greater perceptions of severity. The information-based posters rated high in inducing response efficacy, while none of the images seemed to convince young people that they had the self-efficacy to perform the recommended health behaviours. The young people expressed a preference for fear-based appeals and a belief that this could work well in HIV-prevention efforts, yet they also stated a desire for more information-based messages about how to protect themselves. Finally, the messages evoking the most emotional responses were those that had been locally conceived rather than ones developed by large-scale donor-funded campaigns. Finding the appropriate balance between fear and efficacy in HIV-prevention messages is imperative. Further research is needed to better understand how and when fear appeals work and do not work in African settings, especially among young people.
Bazargan, M.; Kelly, E. M.; Stein, J. A.; Husaini, B. A.; Bazargan, S. H.
2000-01-01
This study identifies theoretically based predictors of condom use in a sample of 253 sexually active African-American college students recruited from two historically African-American colleges. The Information-Motivation-Behavioral (IMB) skills model of AIDS-preventive behavior was employed to delineate the roles of HIV/AIDS knowledge, experiences with and attitudes toward condom use, peer influences, perceived vulnerability, monogamy, and behavioral skills. A predictive structural equation model revealed significant predictors of more condom use including: male gender, more sexual HIV knowledge, positive experiences and attitudes about condom use, nonmonogamy, and greater behavioral skills. Results imply that attention to behavioral skills for negotiating safer sex and training in the proper use of condoms are key elements in reducing high risk behaviors. Increasing the specific knowledge level of college students regarding the subtleties of sexual transmission of HIV is important and should be addressed. Heightening students' awareness of the limited protection of serial monogamy, and the need to address gender-specific training regarding required behavior change to reduce transmission of HIV should be an additional goal of college health professionals. PMID:10992684
It’s a Process: Reactions to HIV Diagnosis and Engagement in HIV Care among High-Risk Heterosexuals
Kutnick, Alexandra H.; Gwadz, Marya Viorst; Cleland, Charles M.; Leonard, Noelle R.; Freeman, Robert; Ritchie, Amanda S.; McCright-Gill, Talaya; Ha, Kathy; Martinez, Belkis Y.; Banfield, Angela
2017-01-01
After HIV diagnosis, heterosexuals in high-poverty urban areas evidence delays in linkage to care and antiretroviral therapy initiation compared to other groups. Yet barriers to/facilitators of HIV care among these high-risk heterosexuals are understudied. Under the theory of triadic influence, putative barriers to HIV care engagement include individual/attitudinal-level (e.g., fear, medical distrust), social-level (e.g., stigma), and structural-level influences (e.g., poor access). Participants were African-American/Black and Hispanic adults found newly diagnosed with HIV (N = 25) as part of a community-based HIV testing study with heterosexuals in a high-poverty, high-HIV-incidence urban area. A sequential explanatory mixed-methods design was used. We described linkage to HIV care and clinical outcomes [CD4 counts, viral load (VL) levels] over 1 year, and then addressed qualitative research questions about the experience of receiving a new HIV diagnosis, its effects on timely engagement in HIV care, and other barriers and facilitators. Participants were assessed five times, receiving a structured interview battery, laboratory tests, data extraction from the medical record, a post-test counseling session, and in-person/phone contacts to foster linkage to care. Participants were randomly selected for qualitative interviews (N = 15/25) that were recorded and transcribed, then analyzed using systematic content analysis. Participants were 50 years old, on average (SD = 7.2 years), mostly male (80%), primarily African-American/Black (88%), and low socioeconomic status. At the first follow-up, rates of engagement in care were high (78%), but viral suppression was modest (39%). Rates improved by the final follow-up (96% engaged, 62% virally suppressed). Two-thirds (69%) were adequately retained in care over 1 year. Qualitative results revealed multi-faceted responses to receiving an HIV diagnosis. Problems accepting and internalizing one’s HIV status were common. Reaching acceptance of one’s HIV-infected status was frequently a protracted and circuitous process, but acceptance is vital for engagement in HIV care. Fear of stigma and loss of important relationships were potent barriers to acceptance. Thus, partially as a result of difficulties accepting HIV status, delays in achieving an undetectable VL are common in this population, with serious potential negative consequences for individual and public health. Interventions to foster acceptance of HIV status are needed. PMID:28540287
The Effect of Marriage and HIV Risks on Condom Use Acceptability in Rural Malawi
Anglewicz, Philip; Clark, Shelley
2013-01-01
A large and increasing proportion of HIV transmissions in sub-Saharan Africa occur within marriage. Condom use within marriage could, therefore, be an important prevention strategy, but there is considerable debate about whether married couples would be willing to use condoms. This paper contributes to this debate by identifying key factors that affect the acceptability of condom use within marriage and actual condom use among men and women in rural Malawi, using three waves of longitudinal data from 2004, 2006 and 2008. Specifically, we focused on the effect of (1) entry into first marriage, (2) respondent’s HIV status, HIV perceptions, and risk behaviors, and (3) spouse’s HIV characteristics on condom use acceptability within marriage and actual condom use with a spouse or steady partner. Using fixed-effects regression, we found that getting married coincides with a pronounced attitudinal shift regarding the acceptability of condom use within marriage that cannot be explained by differences in fertility status or selection into marriage. In addition, we found that, for women, perceived HIV status of the respondent and spouse generally had greater influence than actual HIV status on the acceptability of condom use within marriage and actual condom use with a spouse or steady partner, even after HIV status is known; while actual HIV status and HIV risk behaviors are generally more important among men. Although condom use within marriage remained low, these findings suggest that attitudes about and use of condoms are susceptible to change and that both marital status and perceptions of risk are important influences on condom use. PMID:24161086
The effect of marriage and HIV risks on condom use acceptability in rural Malawi.
Anglewicz, Philip; Clark, Shelley
2013-11-01
A large and increasing proportion of HIV transmissions in sub-Saharan Africa occur within marriage. Condom use within marriage could, therefore, be an important prevention strategy, but there is considerable debate about whether married couples would be willing to use condoms. This paper contributes to this debate by identifying key factors that affect the acceptability of condom use within marriage and actual condom use among men and women in rural Malawi, using three waves of longitudinal data from 2004, 2006 and 2008. Specifically, we focused on the effect of (1) entry into first marriage, (2) respondent's HIV status, HIV perceptions, and risk behaviors, and (3) spouse's HIV characteristics on condom use acceptability within marriage and actual condom use with a spouse or steady partner. Using fixed-effects regression, we found that getting married coincides with a pronounced attitudinal shift regarding the acceptability of condom use within marriage that cannot be explained by differences in fertility status or selection into marriage. In addition, we found that, for women, perceived HIV status of the respondent and spouse generally had greater influence than actual HIV status on the acceptability of condom use within marriage and actual condom use with a spouse or steady partner, even after HIV status is known; while actual HIV status and HIV risk behaviors are generally more important among men. Although condom use within marriage remained low, these findings suggest that attitudes about and use of condoms are susceptible to change and that both marital status and perceptions of risk are important influences on condom use. Copyright © 2013 Elsevier Ltd. All rights reserved.
The embodiment of tourism among bisexually-behaving Dominican male sex workers.
Padilla, Mark B
2008-10-01
While theories of "structure" and social inequality have increasingly informed global health efforts for HIV prevention--with growing recognition of the linkages between large-scale political and economic factors in the distribution and impact of the HIV/AIDS epidemic--there is still little theorization of precisely how structural factors shape the very bodies and sexualities of specific populations and groups. In order to extend the theoretical understanding of these macro-micro linkages, this article examines how the growth of the tourism industry in the Dominican Republic has produced sexual practices and identities that reflect both the influence of large-scale structural processes and the resistant responses of local individuals. Drawing on social science theories of political economy, embodiment, and authenticity, I argue that an understanding of patterns of sexuality and HIV risk in the region requires analysis of how political-economic transformations related to tourism intersect with the individual experiences and practices of sexuality on the ground. The analysis draws on long-term ethnographic research with bisexually behaving male sex workers in two cities in the Dominican Republic, including participant observation, in-depth interviews, focus groups, and surveys. By examining the global and local values placed on these men's bodies and the ways sex workers use their bodies to broker tourists' pleasure, we may better understand how the large-scale structures of the tourism industry are linked to the specific meanings and practices of sexuality.
Barta, S. K.; Samuel, M. S.; Xue, X.; Wang, D.; Lee, J. Y.; Mounier, N.; Ribera, J.-M.; Spina, M.; Tirelli, U.; Weiss, R.; Galicier, L.; Boue, F.; Little, R. F.; Dunleavy, K.; Wilson, W. H.; Wyen, C.; Remick, S. C.; Kaplan, L. D.; Ratner, L.; Noy, A.; Sparano, J. A.
2015-01-01
Background We undertook the present analysis to examine the shifting influence of prognostic factors in HIV-positive patients diagnosed with aggressive non-Hodgkin lymphoma (NHL) over the last two decades. Patients and methods We carried out a pooled analysis from an existing database of patients with AIDS-related lymphoma. Individual patient data had been obtained prior from prospective phase II or III clinical trials carried out between 1990 until 2010 in North America and Europe that studied chemo(immuno)therapy in HIV-positive patients diagnosed with AIDS-related lymphomas. Studies had been identified by a systematic review. We analyzed patient-level data for 1546 patients with AIDS-related lymphomas using logistic regression and Cox proportional hazard models to identify the association of patient-, lymphoma-, and HIV-specific variables with the outcomes complete response (CR), progression-free survival, and overall survival (OS) in different eras: pre-cART (1989–1995), early cART (1996–2000), recent cART (2001–2004), and contemporary cART era (2005–2010). Results Outcomes for patients with AIDS-related diffuse large B-cell lymphoma and Burkitt lymphoma improved significantly over time, irrespective of baseline CD4 count or age-adjusted International Prognostic Index (IPI) risk category. Two-year OS was best in the contemporary era: 67% and 75% compared with 24% and 37% in the pre-cART era (P < 0.001). While the age-adjusted IPI was a significant predictor of outcome in all time periods, the influence of other factors waxed and waned. Individual HIV-related factors such as low CD4 counts (<50/mm3) and prior history of AIDS were no longer associated with poor outcomes in the contemporary era. Conclusions Our results demonstrate a significant improvement of CR rate and survival for all patients with AIDS-related lymphomas. Effective HIV-directed therapies reduce the impact of HIV-related prognostic factors on outcomes and allow curative antilymphoma therapy for the majority of patients with aggressive NHL. PMID:25632071
Coarse-grained models of key self-assembly processes in HIV-1
NASA Astrophysics Data System (ADS)
Grime, John
Computational molecular simulations can elucidate microscopic information that is inaccessible to conventional experimental techniques. However, many processes occur over time and length scales that are beyond the current capabilities of atomic-resolution molecular dynamics (MD). One such process is the self-assembly of the HIV-1 viral capsid, a biological structure that is crucial to viral infectivity. The nucleation and growth of capsid structures requires the interaction of large numbers of capsid proteins within a complicated molecular environment. Coarse-grained (CG) models, where degrees of freedom are removed to produce more computationally efficient models, can in principle access large-scale phenomena such as the nucleation and growth of HIV-1 capsid lattice. We report here studies of the self-assembly behaviors of a CG model of HIV-1 capsid protein, including the influence of the local molecular environment on nucleation and growth processes. Our results suggest a multi-stage process, involving several characteristic structures, eventually producing metastable capsid lattice morphologies that are amenable to subsequent capsid dissociation in order to transmit the viral infection.
Jamaican Mothers’ Influences of Adolescent Girls’ Sexual Beliefs and Behaviors
Hutchinson, M. Katherine; Kahwa, Eulalia; Waldron, Norman; Brown, Cerese Hepburn; Hamilton, Pansy I.; Hewitt, Hermi H.; Aiken, Joyette; Cederbaum, Julie; Alter, Emily; Jemmott, Loretta Sweet
2012-01-01
Purpose The purpose of this study was to identify the ways in which urban Jamaican mothers influence their adolescent daughters’ sexual beliefs and behaviors in order to incorporate them into the design of a family-based human immunodeficiency virus (HIV) risk reduction intervention program. Design Focus groups were conducted with 46 14- to 18-year-old adolescent girls and 30 mothers or female guardians of adolescent girls recruited from community-based organizations in and around Kingston and St. Andrew, Jamaica. Separate focus groups were held with mothers and daughters; each included 6 to 10 participants. Focus group sessions were scripted, led by teams that included trained Jamaican and American facilitators and note-takers, and audio-taped to ensure data accuracy. Data were analyzed using qualitative content analysis. Findings Four major maternal influences were identified: mother-daughter relationship quality, mother-daughter sexual communication, monitoring or supervision, and maternal sexual role modeling. Mothers’ and daughters’ reports were consistent; both groups identified positive and negative influences within each category. Conclusions Some maternal influences were positive and health promoting; others were negative and promoted unsafe sexual activity and risk for HIV and other sexually transmitted infections. These influences were incorporated into the design of a culture-specific family-based HIV risk reduction intervention tailored to the needs of urban Jamaican adolescent girls and their mothers. Clinical Relevance In order to be effective, family-based HIV risk reduction interventions should be theory based and tailored to the target audience. The four maternal influences identified in this formative study were incorporated into the subsequent intervention design. PMID:22339731
Facilitating HIV Disclosure Across Diverse Settings: A Review
Baijal, Parijat; Pegurri, Elisabetta
2011-01-01
HIV status disclosure is central to debates about HIV because of its potential for HIV prevention and its links to privacy and confidentiality as human-rights issues. Our review of the HIV-disclosure literature found that few people keep their status completely secret; disclosure tends to be iterative and to be higher in high-income countries; gender shapes disclosure motivations and reactions; involuntary disclosure and low levels of partner disclosure highlight the difficulties faced by health workers; the meaning and process of disclosure differ across settings; stigmatization increases fears of disclosure; and the ethical dilemmas resulting from competing values concerning confidentiality influence the extent to which disclosure can be facilitated. Our results suggest that structural changes, including making more services available, could facilitate HIV disclosure as much as individual approaches and counseling do. PMID:21493947
[Fragments of a health work genealogy: genealogy as a research technique].
Nardi, Henrique Caetano; Tittoni, Jaqueline; Giannechini, Letícia; Ramminger, Tatiana
2005-01-01
The article aims to explore the influence of health work in subjectification processes. The notion of history commonly used in health-related scientific output is based on an evolutionist and developmental logic. As a counterpoint, the genealogical approach used in this article and based on Michel Foucault highlights the notions of discontinuity, event, and the production of truth as tools to rethink the ethical and political implications involved in the production of knowledge, practices, and subjects. To illustrate these aspects we sketch a health work genealogy, specifically in the field of mental health and HIV/AIDS work.
Host and Viral Factors in HIV-Mediated Bystander Apoptosis
Garg, Himanshu; Joshi, Anjali
2017-01-01
Human immunodeficiency virus (HIV) infections lead to a progressive loss of CD4 T cells primarily via the process of apoptosis. With a limited number of infected cells and vastly disproportionate apoptosis in HIV infected patients, it is believed that apoptosis of uninfected bystander cells plays a significant role in this process. Disease progression in HIV infected individuals is highly variable suggesting that both host and viral factors may influence HIV mediated apoptosis. Amongst the viral factors, the role of Envelope (Env) glycoprotein in bystander apoptosis is well documented. Recent evidence on the variability in apoptosis induction by primary patient derived Envs underscores the role of Env glycoprotein in HIV disease. Amongst the host factors, the role of C-C Chemokine Receptor type 5 (CCR5), a coreceptor for HIV Env, is also becoming increasingly evident. Polymorphisms in the CCR5 gene and promoter affect CCR5 cell surface expression and correlate with both apoptosis and CD4 loss. Finally, chronic immune activation in HIV infections induces multiple defects in the immune system and has recently been shown to accelerate HIV Env mediated CD4 apoptosis. Consequently, those factors that affect CCR5 expression and/or immune activation in turn indirectly regulate HIV mediated apoptosis making this phenomenon both complex and multifactorial. This review explores the complex role of various host and viral factors in determining HIV mediated bystander apoptosis. PMID:28829402
HIV patients' experiences with inpatient and outpatient care: results of a national survey.
Wilson, Ira B; Ding, Lin; Hays, Ron D; Shapiro, Martin F; Bozzette, Samuel A; Cleary, Paul D
2002-12-01
Little is known about HIV patients' care experiences. To assess HIV patients' experiences with inpatient and outpatient care, and to assess the relationship and relative influence of patient characteristics and site of care on care experiences. Cohort study. Patients with HIV receiving care outside of emergency rooms, prisons, or the military throughout the continental United States. One thousand seventy-four patients provided ratings of an inpatient stay and 2204 rated an outpatient visit; 818 patients provided evaluations of both inpatient and outpatient care. A national probability sample of persons in care for HIV from the HIV Cost and Services Utilization Study. Outcome variables were rates of problems with, and global ratings of, inpatient and outpatient care. Mean problem rates were 20.9% and 8.4% (lower score means fewer problems) for inpatient and outpatient care, respectively. On 9 of 10 of the individual inpatient report items, 15% or more of respondents reported problems. Global ratings of inpatient and outpatient care were 65.3 and 75.0 (0-100 scale, higher scores indicate better ratings), respectively. In multivariable models that controlled for site effects, the only patient characteristic that was consistently associated with problem rates and global ratings of care was mental health (P <0.0001 for both inpatient and outpatient care). Models including site effects explained two to four times as much variance as models excluding site effects. Inpatients with HIV reported higher problem rates with inpatient than outpatient care. Better provider-patient communication during inpatient stays is needed. For both inpatient and outpatient care, quality improvement efforts may be most productively focused on providers and processes of care at sites rather than on specific patient subgroups.
Mavronicolas, Heather A; Laraque, Fabienne; Shankar, Arti; Campbell, Claudia
2017-05-01
Care coordination programmes are an important aspect of HIV management whose success depends largely on HIV primary care provider (PCP) and case manager collaboration. Factors influencing collaboration among HIV PCPs and case managers remain to be studied. The study objective was to test an existing theoretical model of interprofessional collaborative practice and determine which factors play the most important role in facilitating collaboration. A self-administered, anonymous mail survey was sent to HIV PCPs and case managers in New York City. An adapted survey instrument elicited information on demographic, contextual, and perceived social exchange (trustworthiness, role specification, and relationship initiation) characteristics. The dependent variable, perceived interprofessional practice, was constructed from a validated scale. A sequential block wise regression model specifying variable entry order examined the relative importance of each group of factors and of individual variables. The analysis showed that social exchange factors were the dominant drivers of collaboration. Relationship initiation was the most important predictor of interprofessional collaboration. Additional influential factors included organisational leadership support of collaboration, practice settings, and frequency of interprofessional meetings. Addressing factors influencing collaboration among providers will help public health programmes optimally design their structural, hiring, and training strategies to foster effective social exchanges and promote collaborative working relationships.
Kiriazova, Tetiana; Lunze, Karsten; Raj, Anita; Bushara, Natalia; Blokhina, Elena; Krupitsky, Evgeny; Bridden, Carly; Lioznov, Dmitry; Samet, Jeffrey H; Gifford, Allen L
2017-05-01
Many HIV-positive people who inject drugs (PWID) globally are not receiving HIV care. This represents a major challenge among key populations to end the global HIV epidemic. This qualitative study explored the process and associated barriers of linking HIV-positive PWID who are in addiction treatment to HIV care in St. Petersburg, Russia. We conducted three focus groups and seven semi-structured interviews with participants in the LINC ("Linking Infectious and Narcology Care") project at addiction and HIV hospitals in St. Petersburg. The sample consisted of 25 HIV-infected patients with opioid dependence and seven health-care providers, including addiction and infectious disease physicians and case managers. A variety of intertwining factors influence effective engagement of PWID with HIV treatment. Stigma, problematic patient-provider relationships, and fragmented health care were the main challenges for HIV care initiation by PWID, which were further exacerbated by injection drug use. Effective linkage of PWID to HIV care requires acknowledging and addressing stigma's role and different perspectives of patients and providers.
The influence of religion on sexual HIV risk.
Shaw, Stacey A; El-Bassel, Nabila
2014-08-01
This systematic review examines the relationship between religion and sexual HIV risk behavior. It focuses primarily on how studies have conceptualized and defined religion, methodologies, and sexual risk outcomes. We also describe regions where studies were conducted and mechanisms by which religion may be associated with sexual risk. We included 137 studies in this review, classifying them as measuring: (1) only religious affiliation (n = 57), (2) only religiosity (n = 48), and (3) both religious affiliation and religiosity (n = 32). A number of studies identified lower levels of sexual HIV risk among Muslims, although many of these examined HIV prevalence rather than specific behavioral risk outcomes. Most studies identified increased religiosity to be associated with lower levels of sexual HIV risk. This finding persists but is weaker when the outcome considered is condom use. The paper reviews ways in which religion may contribute to increase and reduction in sexual HIV risk, gaps in research, and implications for future research on religion and HIV.
Mweemba, Mable; Musheke, Maurice M; Michelo, Charles; Halwiindi, Hikabasa; Mweemba, Oliver; Zulu, Joseph M
2015-10-07
Disclosure of adolescents' own HIV status by caregivers is not only challenging but low. The reasons for this remain unclear despite efforts to examine and seek to understand disclosure patterns or factors that may either facilitate or inhibit this disclosure. This study explored the enablers, barriers and processes of disclosure of HIV status to adolescents by their caregivers in Kafue district of Zambia. A case study method was used to understand factors that facilitate or inhibit caregiver's ability to disclose the HIV status of adolescents aged 10-15 years. Data collected through in-depth interviews with 30 caregivers as well as 6 key informants were analysed using thematic analysis. Overall, 17 out of 30 (56.7 %) caregivers had informed the adolescents about their HIV status. Reasons for disclosing of the HIV status included inquiries by adolescents as to why they were taking medication, threats by adolescents not to take HIV medication, desire to promote treatment self-efficacy amongst adolescents as well as facilitating adoption of safe sexual behaviour among adolescents. The disclosure processes were conducted either at the home or at the clinic. Enabling factors for HIV disclosure were adolescents' knowledge of HIV and caregivers' knowledge of and experience with HIV programs. Barriers to disclosure of HIV status included fear of psychological trauma for the adolescents, perceived inability of adolescents to keep their HIV status confidential which could attract HIV stigmatisation for the family, and caregivers', fear of being blamed by the adolescents for the infection, limited disclosure skills by caregivers as well as negative attitude by some HIV counsellors. Despite challenges associated with disclosure of adolescents' own HIV status by caregivers, environments that facilitate this process exist and can be strengthened. Promoting HIV disclosure requires in-depth and context-specific understanding of the factors that enable and undermine this process. Limitations in this understanding may have played critical roles in past strategic implementation of locally driven and relevant interventions to improve disclosure of HIV status by caregivers to adolescents in Zambia.
Patel, Sheetal; Schechter, Martin T.; Sewankambo, Nelson K.; Atim, Stella; Kiwanuka, Noah; Spittal, Patricia M.
2014-01-01
Objective Little is known about HIV infection and the related vulnerabilities of young people living in resource-scarce, post-emergency transit camps that are now home to thousands of Internally Displaced Persons (IDPs) following two decades of war in northern Uganda. The objective of this analysis was to assess the prevalence and correlates of HIV infection among young people living in post-conflict transition in Gulu District, northern Uganda. Methods In 2010, a cross-sectional demographic and behavioural survey was conducted in two of Gulu District’s sub-counties with 384 purposively selected transit camp residents aged 15 to 29 years. Biological specimens were collected for rapid HIV testing in the field and confirmatory laboratory testing. Multivariable logistic regression identified independent determinants of HIV infection. Results HIV prevalence was alarmingly high at 12.8% (95% CI: 9.6%, 16.5%). The strongest determinant of HIV infection among young people was a non-consensual sexual debut (adjusted odds ratio [AOR], 9.88; 95% CI: 1.70–18.06). Residing in Awach sub-county (AOR, 2.93; 95% CI: 1.28–6.68), experiencing STI symptoms in the previous 12 months (AOR, 2.36; 95% CI: 1.43–6.17), and practicing dry sex (AOR, 2.31; 95% CI: 1.04–5.13) were other key determinants of HIV infection. Conclusions Study findings contribute to filling an important gap in epidemiological evidence and are useful for planning public health interventions in northern Uganda that effectively target young people in post-conflict transition and support them in the resettlement process. Findings serve to recommend reaching beyond traditional prevention programming in a way more effectively beneficial to young people in post-conflict settings by developing population-specific responses sensitive to local contexts and sufficient to address the underlying causes of the complex risk factors influencing the spread of HIV. PMID:24587034
Variations in microbicide gel acceptability among young women in the USA and Puerto Rico
Giguere, Rebecca; Carballo-Diéguez, Alex; Ventuneac, Ana; Mabragaña, Marina; Dolezal, Curtis; Chen, Beatrice A.; Kahn, Jessica A.; Zimet, Gregory D.; McGowan, Ian
2011-01-01
In a multi-site study of vaginal microbicide acceptability conducted with sexually active young women, quantitative assessments revealed significant differences in acceptability by site. Participants in Puerto Rico rated the gel more favourably than mainland US participants in terms of liking the gel and likelihood of future use. To explain these differences, we examined responses to qualitative behavioural assessments. Young women in the mainland USA associated gel leakage with uncomfortable sensations experienced during menstruation, while young women in Puerto Rico had positive associations of gel use with douching. These negative or positive associations affected assessments of the gel’s physical qualities. In addition, young women’s perceptions of primary partners’ support for microbicide use influenced sexual satisfaction with the gel and, ultimately, product acceptability. Finally, geographic HIV risk context contributed to heightened HIV risk perception, which influenced likelihood of future microbicide use, even for women in stated monogamous relationships. Future microbicide acceptability studies should take into account potential differences in acceptability by site such as HIV risk perception based on local HIV prevalence, popularity of vaginal hygiene products in a specific area, and male attitudes in different cultures concerning women’s use of HIV protection strategies. PMID:22084840
Rachlis, Beth; Brouwer, Kimberly C; Mills, Edward J; Hayes, Michael; Kerr, Thomas; Hogg, Robert S
2007-10-08
Migration is one of many social factors contributing to the spread of HIV and other blood-borne or sexually transmitted infections (STI). Bringing together large numbers of people from diverse settings, the process of migration moves infected individuals to diverse geographic locations. Injection drug users (IDU) are a relatively mobile group, often moving between cities, smaller communities, and across international borders for reasons of work, security, or access to narcotics. This mobility indicates the potential for IDU who engage in risky behavior outside their home areas to transmit HIV infection to other IDU, their sex partners, and others in the population. The objectives of this review are to examine: (1) the influence of drug trafficking and the spread of drug use on the diffusion of HIV, (2) the influence of migration on drug use and HIV-related risk behaviors among migrants, and (3) the mobility patterns of IDU and its role in the spread of HIV. We also discuss the potential policy implications of addressing prevention and care issues in mobile drug using populations.
Nelson, Kimberly M; Leickly, Emily; Yang, Joyce P; Pereira, Andrew; Simoni, Jane M
2014-01-01
Over the past two decades, men who have sex with men (MSM) have engaged in increasing consumption of MSM-specific sexually explicit online media (i.e., online pornography). Furthermore, the amount of MSM-specific sexually explicit online media portraying unprotected anal intercourse (UAI) has increased, raising concerns about HIV transmission among the actors and the potential encouragement of risky sex among consumers. The influence of sexually explicit online media on sexual risk-taking, at present largely understudied, could lead to new avenues for innovative HIV-prevention strategies targeting at-risk MSM. In this preliminary assessment, in-depth qualitative interviews were conducted with 16 MSM in the Seattle area to elucidate MSM's perceptions about the influence of sexually explicit online media on their own and other MSM's sexual behaviors. Participants reported that sexually explicit online media: (1) plays an educational role, (2) increases comfort with sexuality, and (3) sets expectations about sexual behaviors. While participants overwhelmingly reported not feeling personally influenced by viewing UAI in sexually explicit online media, they believed viewing UAI increased sexual risk-taking among other MSM. Specifically, participants reported that the high prevalence of UAI in sexually explicit online media sends the message, at least to other MSM, that (1) engaging in UAI is common, (2) UAI is acceptable and "ok" to engage in, and (3) future partners will desire or expect UAI. Overall, this preliminary assessment indicates that sexually explicit online media exposure may have both positive (e.g., helping MSM become more comfortable with their sexuality) and negative (e.g., normalizing UAI) impacts on the sexual health of MSM and may be useful in the development of novel HIV-prevention interventions.
Grabe, Shelly; Lu, Tiffany; Hatcher, Abbey; Kwena, Zachary; Bukusi, Elizabeth; Mwaura-Muiru, Esther
2013-01-01
While access to and control over assets can minimize women’s HIV risk, little is known about the processes through which property rights violations increase the sexual transmission of HIV. The current study focused on two rural areas in Nyanza and Western Province, Kenya where HIV prevalence was high (23.8–33 %) and property rights violations were common. The current work drew on in-depth interview data collected from 50 individuals involved in the development and implementation of a community-led land and property rights program. The program was designed to respond to property rights violations, prevent disinheritance and asset stripping, and reduce HIV risk among women. In our findings, we detailed the social and economic mechanisms through which a loss of property rights was perceived to influence primary and secondary prevention of HIV. These included: loss of income, loss of livelihood and shelter, and migration to slums, markets, or beaches where the exchange of sex for food, money, shelter, clothing, or other goods was common. We also examined the perceived influence of cultural practices, such as wife inheritance, on HIV risk. In the conclusions, we made recommendations for future research in the science-base focused on the development of property ownership as a structural HIV prevention and treatment intervention. PMID:23179234
Knowledge of AIDS and HIV transmission among drug users in Rio de Janeiro, Brazil
2011-01-01
Background Proper knowledge of HIV transmission is not enough for people to adopt protective behaviors, but deficits in this information may increase HIV/AIDS vulnerability. Objective To assess drug users' knowledge of HIV/AIDS and the possible association between knowledge and HIV testing. Methods A Cross-sectional study conducted in 2006/7 with a convenience sample of 295 illicit drug users in Rio de Janeiro, assessing knowledge on AIDS/HIV transmission and its relationship with HIV testing. Information from 108 randomly selected drug users who received an educational intervention using cards illustrating situations potentially associated with HIV transmission were assessed using Multidimensional Scaling (MDS). Results Almost 40% of drug users reported having never used condoms and more than 60% reported not using condoms under the influence of substances. Most drug users (80.6%) correctly answered that condoms make sex safer, but incorrect beliefs are still common (e.g. nearly 44% believed HIV can be transmitted through saliva and 55% reported that HIV infection can be transmitted by sharing toothbrushes), with significant differences between drug users who had and who had not been tested for HIV. MDS showed queries on vaginal/anal sex and sharing syringes/needles were classified in the same set as effective modes of HIV transmission. The event that was further away from this core of properly perceived risks referred to blood donation, perceived as risky. Other items were found to be dispersed, suggesting inchoate beliefs on transmission modes. Conclusions Drug users have an increased HIV infection vulnerability compared to the general population, this specific population expressed relevant doubts about HIV transmission, as well as high levels of risky behavior. Moreover, the findings suggest that possessing inaccurate HIV/AIDS knowledge may be a barrier to timely HIV testing. Interventions should be tailored to such specific characteristics. PMID:21324119
Kløverpris, Henrik N.; McGregor, Reuben; McLaren, James E.; Ladell, Kristin; Stryhn, Anette; Koofhethile, Catherine; Brener, Jacqui; Chen, Fabian; Riddell, Lynn; Graziano, Luzzi; Klenerman, Paul; Leslie, Alasdair; Buus, Søren; Price, David A.; Goulder, Philip
2014-01-01
Objectives: Although CD8+ T cells play a critical role in the control of HIV-1 infection, their antiviral efficacy can be limited by antigenic variation and immune exhaustion. The latter phenomenon is characterized by the upregulation of multiple inhibitory receptors, such as programmed death-1 (PD-1), CD244 and lymphocyte activation gene-3 (LAG-3), which modulate the functional capabilities of CD8+ T cells. Design and methods: Here, we used an array of different human leukocyte antigen (HLA)-B∗15 : 03 and HLA-B∗42 : 01 tetramers to characterize inhibitory receptor expression as a function of differentiation on HIV-1-specific CD8+ T-cell populations (n = 128) spanning 11 different epitope targets. Results: Expression levels of PD-1, but not CD244 or LAG-3, varied substantially across epitope specificities both within and between individuals. Differential expression of PD-1 on T-cell receptor (TCR) clonotypes within individual HIV-1-specific CD8+ T-cell populations was also apparent, independent of clonal dominance hierarchies. Positive correlations were detected between PD-1 expression and plasma viral load, which were reinforced by stratification for epitope sequence stability and dictated by effector memory CD8+ T cells. Conclusion: Collectively, these data suggest that PD-1 expression on HIV-1-specific CD8+ T cells tracks antigen load at the level of epitope specificity and TCR clonotype usage. These findings are important because they provide evidence that PD-1 expression levels are influenced by peptide/HLA class I antigen exposure. PMID:24906112
NASA Astrophysics Data System (ADS)
Wille-Reece, Ulrike; Flynn, Barbara J.; Loré, Karin; Koup, Richard A.; Kedl, Ross M.; Mattapallil, Joseph J.; Weiss, Walter R.; Roederer, Mario; Seder, Robert A.
2005-10-01
Induction and maintenance of antibody and T cell responses will be critical for developing a successful vaccine against HIV. A rational approach for generating such responses is to design vaccines or adjuvants that have the capacity to activate specific antigen-presenting cells. In this regard, dendritic cells (DCs) are the most potent antigen-presenting cells for generating primary T cell responses. Here, we report that Toll-like receptor (TLR) agonists and ligands that activate DCs in vitro influence the magnitude and quality of the cellular immune response in nonhuman primates (NHPs) when administered with HIV Gag protein. NHPs immunized with HIV Gag protein and a TLR7/8 agonist or a TLR9 ligand [CpG oligodeoxynucleotides (CpG ODN)] had significantly increased Gag-specific T helper 1 and antibody responses, compared with animals immunized with HIV Gag protein alone. Importantly, conjugating the HIV Gag protein to the TLR7/8 agonist (Gag-TLR7/8 conjugate) dramatically enhanced the magnitude and altered the quality of the T helper 1 response, compared with animals immunized with HIV Gag protein and the TLR7/8 agonist or CpG ODN. Furthermore, immunization with the Gag-TLR7/8 conjugate vaccine elicited Gag-specific CD8+ T responses. Collectively, our results show that conjugating HIV Gag protein to a TLR7/8 agonist is an effective way to elicit broad-based adaptive immunity in NHPs. This type of vaccine formulation should have utility in preventive or therapeutic vaccines in which humoral and cellular immunity is required. vaccine | dendritic cell | cross-presentation | cellular immunity
NASA Technical Reports Server (NTRS)
O'Sullivan, Cathal E.; Peng, RongSheng; Cole, Kelly Stefano; Montelaro, Ronald C.; Sturgeon, Timothy; Jenson, Hal B.; Ling, Paul D.; Butel, J. S. (Principal Investigator)
2002-01-01
Epstein-Barr virus (EBV) associated non-Hodgkin lymphoma is recognized as a complication of human immunodeficiency virus (HIV) infection. Little is known regarding the influence of highly active antiretroviral therapy (HAART) on the biology of EBV in this population. To characterize the EBV- and HIV-specific serological responses together with EBV DNA levels in a cohort of HIV-infected adults treated with HAART, a study was conducted to compare EBV and HIV serologies and EBV DNA copy number (DNAemia) over a 12-month period after the commencement of HAART. All patients were seropositive for EBV at baseline. Approximately 50% of patients had detectable EBV DNA at baseline, and 27/30 had detectable EBV DNA at some point over the follow-up period of 1 year. Changes in EBV DNA copy number over time for any individual were unpredictable. Significant increases in the levels of Epstein-Barr nuclear antigen (EBNA) and Epstein-Barr early antigen (EA) antibodies were demonstrated in the 17 patients who had a good response to HAART. Of 29 patients with paired samples tested, four-fold or greater increases in titers were detected for EA in 12/29 (41%), for EBNA in 7/29 (24%), for VCA-IgG in 4/29 (14%); four-fold decreases in titers were detected in 2/29 (7%) for EA and 12/29 (41%) for EBNA. A significant decline in the titer of anti-HIV antibodies was also demonstrated. It was concluded that patients with advanced HIV infection who respond to HAART have an increase in their EBV specific antibodies and a decrease in their HIV-specific antibodies. For the cohort overall, there was a transient increase in EBV DNA levels that had declined by 12 months. Copyright 2002 Wiley-Liss, Inc.
Price, performance, and the FDA approval process: the example of home HIV testing.
Paltiel, A David; Pollack, Harold A
2010-01-01
The Food and Drug Administration (FDA) is considering approval of an over-the-counter, rapid HIV test for home use. To support its decision, the FDA seeks evidence of the test's performance. It has asked the manufacturer to conduct field studies of the test's sensitivity and specificity when employed by untrained users. In this article, the authors argue that additional information should be sought to evaluate the prevalence of undetected HIV in the end-user The analytic framework produces the elementary but counterintuitive finding that the performance of the home HIV test- measured in terms of its ability to correctly detect the presence and absence of HIV infection among the people who purchase it-depends critically on the manufacturer's retail price. This finding has profound implications for the FDA's approval process.
Rawat, Angeli; Uebel, Kerry; Moore, David; Yassi, Annalee
2018-04-15
Noncommunicable diseases (NCDs), specifically diabetes and hypertension, are rising in high HIV-burdened countries such as South Africa. How integrated HIV care into primary health care (PHC) influences NCD care is unknown. We aimed to understand whether differences existed in NCD care (pre- versus post-integration) and how changes may relate to HIV patient numbers. Public sector PHC clinics in Free State, South Africa. Using a quasiexperimental design, we analyzed monthly administrative data on 4 indicators for diabetes and hypertension (clinic and population levels) during 4 years as HIV integration was implemented in PHC. Data represented 131 PHC clinics with a catchment population of 1.5 million. We used interrupted time series analysis at ±18 and ±30 months from HIV integration in each clinic to identify changes in trends postintegration compared with those in preintegration. We used linear mixed-effect models to study relationships between HIV and NCD indicators. Patients receiving antiretroviral therapy in the 131 PHC clinics studied increased from 1614 (April 2009) to 57, 958 (April 2013). Trends in new diabetes patients on treatment remained unchanged. However, population-level new hypertensives on treatment decreased at ±30 months from integration by 6/100, 000 (SE = 3, P < 0.02) and was associated with the number of new patients with HIV on treatment at the clinics. Our findings suggest that during the implementation of integrated HIV care into PHC clinics, care for hypertensive patients could be compromised. Further research is needed to understand determinants of NCD care in South Africa and other high HIV-burdened settings to ensure patient-centered PHC.
Lotfi, Razieh; Ramezani Tehrani, Fahimeh; Merghati Khoei, Effat; Yaghmaei, Farideh; Dworkin, Shari L
2013-07-01
Sexual transmission of HIV/AIDS among women is growing in the Middle East region. Despite the fact that there are numerous gender-related sociocultural factors influencing HIV/AIDS protective behaviors, little gender-specificity is carried out in HIV prevention in Iran. In order to close this gap, we aimed to provide preliminary work that explored the perceptions that women at risk of HIV had about gender norms and gendered power and their ability to protect themselves against HIV/AIDS. Twenty-five semi-structured in-depth interviews were conducted with women at risk of HIV/AIDS, aged 21-49 years, at Voluntary Counseling and Testing Centers or Drop in Centers in Tehran, Iran. Results showed that perceived gender norms were essential barriers of protective behavior through sexual socialization, male control over condom use and sexual decision-making, male pleasure predominating in sexual encounters and sexual double standards, and economic dependencies. In the conclusions, we consider how HIV/AIDS preventive programs can be structured to be gender-sensitive and empowering in Iran.
Substance use in the MSM population of New York City during the era of HIV/AIDS.
Halkitis, Perry N; Pollock, James A; Pappas, Molly K; Dayton, Alex; Moeller, Robert W; Siconolfi, Daniel; Solomon, Todd
2011-01-01
This literature review considers the historical significance, emergence of, and interplay between the HIV and illicit drug use epidemics among gay, bisexual, and other men who have sex with men (MSM) in New York City (NYC). The continual rise in HIV infections in recent years among MSM, particularly among young MSM (YMSM), commands a need for the examination of the effectiveness of current HIV prevention strategies and a more comprehensive understanding of the complex biopsychosocial influences that place YMSM at risk. A chronological perspective of both the HIV and illicit drug use epidemics affecting NYC MSM is presented, followed by a review of the existing research on the synergistic relation between the two. Special consideration is given to the patterns and interconnectivity between HIV, substance use, and housing instability specific to YMSM, as they represent the demographic currently at greatest risk for HIV transmission in NYC. Thereafter, an overview of treatment research is provided. We conclude by offering recommendations for future research and best practices as we move forward in an attempt to reduce the incidence of HIV transmission.
Common Processes in Evidence-Based Adolescent HIV Prevention Programs
Ingram, Barbara L.; Flannery, Diane; Elkavich, Amy
2014-01-01
Dissemination of evidence-based HIV prevention programs for adolescents will be increased if community interventionists are able to distinguish core, essential program elements from optional, discretionary ones. We selected five successful adolescent HIV prevention programs, used a qualitative coding method to identify common processes described in the procedural manuals, and then compared the programs. Nineteen common processes were categorized as structural features, group management strategies, competence building, and addressing developmental challenges of adolescence. All programs shared the same structural features (goal-setting and session agendas), used an active engagement style of group management, and built cognitive competence. Programs varied in attention to developmental challenges, emphasis on behavioral and emotional competence, and group management methods. This qualitative analysis demonstrated that successful HIV programs contain processes not articulated in their developers’ theoretical models. By moving from the concrete specifics of branded interventions to identification of core, common processes, we are consistent with the progress of “common factors” research in psychotherapy. PMID:18330687
HIV testing and counseling: test providers' experiences of best practices.
Myers, Ted; Worthington, Catherine; Haubrich, Dennis J; Ryder, Karen; Calzavara, Liviana
2003-08-01
Although education is central to HIV testing and counseling, little is known about the educational processes within the testing experience. This study investigated test providers' understandings of testing and counseling best practices. Interviews with a purposive sample of 24 test providers were thematically analyzed. Analysis revealed five best practices specific to HIV education and public health--ensuring information and education for HIV risk reduction, individualization of risk assessment, ensuring test results are given in person, providing information and referrals, and facilitating partner notification--and six practices not specific to HIV counseling relationship building. The latter were building trust and rapport; maintaining professional boundaries; ensuring a comfortable, safe environment; ensuring confidentiality; imparting nonjudgmntal attitude; and self-determination. The identified best practices demonstrated remarkable consistency across respondent subgroups. Although counseling was seen as largely educational and with a preventive focus, it included individualized messages based on assessments of risk, knowledge, and social and cultural characteristics.
Family Wellness, Not HIV Prevention
Swendeman, Dallas; Flannery, Diane
2010-01-01
HIV exceptionalism (and disease-specific programs generally) garner both unbalanced funding and the most talented personnel, distorting local health priorities. In support of HIV exceptionalism, the successful mobilization of significant global health sector resources was not possible prior to HIV. Both sides of the debate have merits; rather than perpetuating polarization, we suggest that sustained improvements in global health require creating a prevention infrastructure to meet multiple health challenges experienced by local communities. We propose four fundamental shifts in HIV and disease prevention: (1) horizontally integrating prevention at one site locally, with priorities tailored to local health challenges and managed by local community leaders; (2) using a family wellness metaphor for services, not disease prevention; (3) implementing evidence-based prevention programs (EBPP) based on common principles, factors, and processes, rather than replication of specific programs; and (4) utilizing the expertise of private enterprise to re-design EBPP into highly attractive, engaging, and accessible experiences. PMID:19148744
A model of caregiver paediatric HIV disclosure decision-making
Evangeli, Michael; Kagee, Ashraf
2016-01-01
Many of the over 3 million HIV-positive children will only be told of their status as adolescents. Knowing one’s status may increase treatment adherence, reduce onward HIV transmission, increase trust in caregivers, and maximise available support. Yet deciding whether, what, how, and when to tell HIV-positive children about their condition, is challenging for caregivers. We systematically review HIV disclosure theories before presenting a process model of caregiver paediatric HIV disclosure decision-making. The model, consisting of both a pre-intention and a post-intention stage, integrates individual and contextual determinants. It aims to be situationally-specific, broadly applicable, and consistent with the empirical literature. Research and practice implications are discussed. PMID:26119063
Lewis, Nathaniel M; Wilson, Kathi
2017-04-01
HIV surveillance systems show that gay, bisexual, and other men who have sex with men (MSM) bear a disproportionate burden of HIV in North American and European countries. Within the MSM category, HIV prevalence is often elevated among ethnic minority (i.e., Latino, Asian, and Black) MSM, many of whom are also foreign-born immigrants. Little research has focused specifically on foreign-born populations, though studies that provide data on the nativity of their samples offer an opportunity to investigate the potential role of transnational migration in informing HIV risk among ethnic minority MSM. This systematic review of ethnic minority MSM studies where the nativity of the sample is known provides a robust alternative to single studies measuring individual-level predictors of HIV risk behaviour. In this review, HIV prevalence, unprotected sex, drug use, and HIV testing are analysed in relation to the ethnicity, nativity, and location of the samples included. The results, which include high rates of HIV, unprotected sex, and stimulant use in foreign-born Latino samples and high rates of alcohol and club drug use in majority foreign-born Asian Pacific Islander (API) samples, provide baseline evidence for the theory of migration and HIV risk as syndemics within ethnic minority populations in North American and European countries. The findings also suggest that further research on the contextual factors influencing HIV risk among ethnic minority MSM groups and especially immigrants within these groups is needed. These factors include ethnic networks, individual post-migration transitions, and the gay communities and substance use cultures in specific destination cities. Further comparative work may also reveal how risk pathways differ across ethnic groups. Copyright © 2017 Elsevier Ltd. All rights reserved.
Climent, Núria; Guerra, Susana; García, Felipe; Rovira, Cristina; Miralles, Laia; Gómez, Carmen Elena; Piqué, Núria; Gil, Cristina; Gatell, José María; Esteban, Mariano; Gallart, Teresa
2011-01-01
Currently, MVA virus vectors carrying HIV-1 genes are being developed as HIV-1/AIDS prophylactic/therapeutic vaccines. Nevertheless, little is known about the impact of these vectors on human dendritic cells (DC) and their capacity to present HIV-1 antigens to human HIV-specific T cells. This study aimed to characterize the interaction of MVA and MVA expressing the HIV-1 genes Env-Gag-Pol-Nef of clade B (referred to as MVA-B) in human monocyte-derived dendritic cells (MDDC) and the subsequent processes of HIV-1 antigen presentation and activation of memory HIV-1-specific T lymphocytes. For these purposes, we performed ex vivo assays with MDDC and autologous lymphocytes from asymptomatic HIV-infected patients. Infection of MDDC with MVA-B or MVA, at the optimal dose of 0.3 PFU/MDDC, induced by itself a moderate degree of maturation of MDDC, involving secretion of cytokines and chemokines (IL1-ra, IL-7, TNF-α, IL-6, IL-12, IL-15, IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, IP-10, MIG, and IFN-α). MDDC infected with MVA or MVA-B and following a period of 48 h or 72 h of maturation were able to migrate toward CCL19 or CCL21 chemokine gradients. MVA-B infection induced apoptosis of the infected cells and the resulting apoptotic bodies were engulfed by the uninfected MDDC, which cross-presented HIV-1 antigens to autologous CD8+ T lymphocytes. MVA-B-infected MDDC co-cultured with autologous T lymphocytes induced a highly functional HIV-specific CD8+ T cell response including proliferation, secretion of IFN-γ, IL-2, TNF-α, MIP-1β, MIP-1α, RANTES and IL-6, and strong cytotoxic activity against autologous HIV-1-infected CD4+ T lymphocytes. These results evidence the adjuvant role of the vector itself (MVA) and support the clinical development of prophylactic and therapeutic anti-HIV vaccines based on MVA-B. PMID:21625608
Michaels, Katarzyna Kaczmarek; Wolschendorf, Frank; Schiralli Lester, Gillian M.; Natarajan, Malini; Kutsch, Olaf; Henderson, Andrew J.
2015-01-01
Since HIV-1 has a propensity to integrate into actively expressed genes, transcriptional interference from neighboring host promoters has been proposed to contribute to the establishment and maintenance HIV-1 latency. To gain insights into how endogenous promoters influence HIV-1 transcription we utilized a set of inducible T cell lines and characterized whether there were correlations between expression of endogenous genes, provirus and long terminal repeat architecture. We show that neighboring promoters are active but have minimal impact on HIV-1 transcription, in particular, expression of the endogenous gene did not prevent expression of HIV-1 following induction of latent provirus. We also demonstrate that releasing paused RNAP II by diminishing negative elongation factor (NELF) is sufficient to reactivate transcriptionally repressed HIV-1 provirus regardless of the integration site and orientation of the provirus suggesting that NELF-mediated RNAP II pausing is a common mechanism of maintaining HIV-1 latency. PMID:26379089
Orengo-Aguayo, Rosaura; Pérez-Jiménez, David
2009-03-01
Most of the HIV/AIDS prevention efforts have not taken into consideration the context of the relationship and the gender constructs that influence relationship dynamics. These efforts have failed to view HIV prevention as a collaborative process between partners. Therefore, it is important to explore how relationship dynamics and gender constructs influence how men and women involved in an HIV discordant heterosexual relationship, visualize their role in the protection of their partners in order to design more effective prevention interventions. Five Puerto Rican HIV discordant heterosexual couples were interviewed via a qualitative semi-structured interview. The taped interviews were transcribed and analyzed using content analysis according to a set of defined categories. Women visualized their role as one of convincing their partners to use protection as well as being strong and firm in the demand of its use. Men viewed their role as one of being more supportive and willing to use protection, but recognized their resistance towards the use of condoms. Relationship dynamics such as communication and support promoted protection. Traditional and non-traditional gender roles were assumed by both men and women. Traditional gender roles inhibited protection but were also used in positive ways to promote it. Men showed a greater initiative to break with traditional gender norms. A positive relationship, marked by communication and support could serve as a facilitator in the protection and in the transformation of traditional gender norms. This points out to the need of viewing HIV/AIDS prevention as a collaborative rather than individualistic process.
Gonzalez, Raul; Wardle, Margaret; Jacobus, Joanna; Vassileva, Jasmin; Martin-Thormeyer, Eileen M.
2010-01-01
HIV+ individuals have been shown to demonstrate deficits on the Iowa Gambling Task (IGT), a complex measure of “decision-making.” Little remains known about what other neurocognitive processes may account for variability in IGT performance among HIV+ samples or the role of procedural learning (PL) in IGT performance. A sample of 49 HIV+ individuals with a history of substance use disorders was examined to explore the relationship between IGT performance and three measures of PL: The Rotary Pursuit, Mirror Star Tracing, and Weather Prediction tasks. We found no statistically significant relationships between IGT performance and any of the PL tasks, despite finding significant correlations among the PL tasks. This pattern of results persisted when analyzing IGT performance in various ways (e.g., performance on earlier trial blocks or impairment classifications). Although other nondeclarative processes (e.g., somatic markers) may be important for IGT performance, these findings do not support PL as an important component neurocognitive process for the IGT. Similarly, these results suggest that differences in PL performance does not account for the decision-making deficits or variability in performances observed on the IGT among HIV+ individuals with a history of substance dependence. PMID:19939850
Community Perspectives on Factors That Influence Collaboration in Public Health Research
Pinto, Rogério M.
2009-01-01
Community collaboration in research may lead to better methods, results, and dissemination of interventions. Little systematic research has examined specific factors that influence community-based organizations (CBOs) to collaborate in public health research. There is an urgent need to advance knowledge on this topic so that together, researchers and CBOs can minimize barriers to collaboration. This study advances a CBO-focused characterization of collaboration in HIV-prevention research. By focusing on the perspectives of 20 key informants in 10 HIV-prevention CBOs, qualitative data revealed factors that influenced their collaborations in four domains: (a) Researchers’ Characteristics (expertise, availability), (b) Collaborative Research Characteristics (ought to improve services and CBO infrastructure); (c) Community Partner–Researcher Relationships (resolving social and professional issues); and (d) Barriers to HIV-Prevention Research Collaboration (cultural and social disconnect between CBO and academia). To reduce barriers, researchers ought to enhance motivators that facilitate collaboration. To use the advantages of community-based research, prevention scientists and policy makers ought to embrace CBOs’ characterization of what makes health research genuinely collaborative. PMID:19196863
HIV in (and out of) the clinic: biomedicine, traditional medicine and spiritual healing in Harare.
O'Brien, Stephen; Broom, Alex
2014-01-01
Contemporary lived experiences of the human immunodeficiency virus (HIV) are shaped by clinical and cultural encounters with illness. In sub-Saharan countries such as Zimbabwe, HIV is treated in very different ways in various therapeutic contexts including by biomedical experts, traditional medicine and faith healers. The co-existence of such expertise raises important questions around the potencies and limits of medicalisation and alternative healing practices in promoting HIV recovery. First, in this study, drawing on in-depth qualitative interviews with 60 people from poor urban areas in Harare, we explore the experiences of people living with and affected by HIV. Specifically, we sought to document, interrogate and reflect on their perceptions and experiences of biomedicine in relation to traditional medicine and spiritual healing. Their accounts indicate that traditional medicine and spiritual beliefs continue to significantly influence the way in which HIV is understood, and the forms of help and care people seek. Second, we observe the dramatic and overwhelmingly beneficial impact of Antiretroviral Therapy and conclude through Zimbabwean's own stories that limitations around delivery and wider structural inequalities impede its potential. Lastly, we explore some practical implications of the biomedical clinic (and alternative healing practices) being understood as sites of ideological and expert contestation. This paper aimed to add to our knowledge of the relationships between traditional medicine and spiritual healing in connection with biomedicine and how this may influence HIV treatment and prevention.
HIV in (and out of) the clinic: Biomedicine, traditional medicine and spiritual healing in Harare
O'Brien, Stephen; Broom, Alex
2014-01-01
Abstract Contemporary lived experiences of the human immunodeficiency virus (HIV) are shaped by clinical and cultural encounters with illness. In sub-Saharan countries such as Zimbabwe, HIV is treated in very different ways in various therapeutic contexts including by biomedical experts, traditional medicine and faith healers. The co-existence of such expertise raises important questions around the potencies and limits of medicalisation and alternative healing practices in promoting HIV recovery. First, in this study, drawing on in-depth qualitative interviews with 60 people from poor urban areas in Harare, we explore the experiences of people living with and affected by HIV. Specifically, we sought to document, interrogate and reflect on their perceptions and experiences of biomedicine in relation to traditional medicine and spiritual healing. Their accounts indicate that traditional medicine and spiritual beliefs continue to significantly influence the way in which HIV is understood, and the forms of help and care people seek. Second, we observe the dramatic and overwhelmingly beneficial impact of Antiretroviral Therapy and conclude through Zimbabwean's own stories that limitations around delivery and wider structural inequalities impede its potential. Lastly, we explore some practical implications of the biomedical clinic (and alternative healing practices) being understood as sites of ideological and expert contestation. This paper aimed to add to our knowledge of the relationships between traditional medicine and spiritual healing in connection with biomedicine and how this may influence HIV treatment and prevention. PMID:25017937
Sexual HIV Risk Among Male Parolees and Their Female Partners: The Relate Project
Comfort, Megan; Reznick, Olga Grinstead; Dilworth, Samantha E.; Binson, Diane; Darbes, Lynae A.; Neilands, Torsten B.
2014-01-01
Background The massively disproportionate impact of America’s prison boom on communities of color has raised questions about how incarceration may affect health disparities, including disparities in HIV. Primary partners are an important source of influence on sexual health. In this paper, we investigate sexual HIV risk among male-female couples following a man’s release from prison. Methods We draw upon data from the Relate Project, a novel cross-sectional survey of recently released men and their female partners in Oakland and San Francisco, California (N=344). Inferential analyses use the actor-partner model to explore actor and partner effects on sexual HIV risk outcomes. Results Dyadic analyses of sexual HIV risk among male parolees and their female partners paint a complex portrait of couples affected by incarceration and of partners’ influences on each other. Findings indicate that demographic factors such as education level and employment status, individual psycho-social factors such as perception of risk, and relationship factors such as commitment and power affect sexual HIV risk outcomes. Conclusion The Relate Project provides a novel dataset for the dyadic analysis of sexual risk among male parolees and their female partners, and results highlight the importance of focusing on the couple as a unit when assessing HIV risk and protective behaviors. Results also indicate potentially fruitful avenues for population-specific interventions that may help to reduce sexual health disparities among couples affected by incarceration. PMID:25642396
Kikuchi, Kimiyo; Poudel, Krishna C; Muganda, John; Sato, Tomoko; Mutabazi, Vincent; Muhayimpundu, Ribakare; Majyambere, Adolphe; Nyonsenga, Simon P; Sase, Eriko; Jimba, Masamine
2014-01-01
Every year, approximately 260,000 children are infected with HIV in low- and middle-income countries. The timely initiation and high level of maintenance of antiretroviral therapy (ART) are crucial to reducing the suffering of HIV-positive children. We need to develop a better understanding of the background of children's ART non-adherence because it is not well understood. The purpose of this study is to explore the background related to ART non-adherence, specifically in relation to the orphan status of children in Kigali, Rwanda. We conducted 19 focus group discussions with a total of 121 caregivers of HIV-positive children in Kigali. The primary data for analysis were verbatim transcripts and socio-demographic data. A content analysis was performed for qualitative data analysis and interpretation. The study found several contextual factors that influenced non-adherence: among double orphans, there was psychological distance between the caregivers and children, whereas economic burden was the primary issue among paternal orphans. The factors promoting adherence also were unique to each orphan status, such as the positive attitude about disclosing serostatus to the child by double orphans' caregivers, and feelings of guilt about the child's condition among non-orphaned caregivers. Knowledge of orphan status is essential to elucidate the factors influencing ART adherence among HIV-positive children. In this qualitative study, we identified the orphan-related contextual factors that influenced ART adherence. Understanding the social context is important in dealing with the challenges to ART adherence among HIV-positive children.
Carman, Marina; Grierson, Jeffrey; Pitts, Marian; Hurley, Michael; Power, Jennifer
2010-06-01
Examining existing and potential trends in the HIV-positive population in Australia is important for current and future healthcare service development and delivery. A new analysis of existing data on this population from the HIV Futures 5 survey was based on linking a geographic breakdown of respondents based on 'area type'--capital city or inner suburban, outer suburban, regional centre and rural--with patterns of healthcare service access. In addition, the distance between the postcode of the respondent's residence and the postcode of the doctor seen for HIV-related treatment was calculated. An analysis of 'area type' by income and age was also conducted. The 'area type' analysis showed important differences in patterns of access to antiretroviral prescriptions and choice of provider for HIV-related and general healthcare. The median distance travelled to see a doctor for HIV-related treatment was higher for those living in outer suburbs than those living in regional centres. Differences in service use appear to be related to geographic accessibility of different service types. However, there may be other important social, economic and cultural factors involved. Ageing and socio-economic pressures may be influencing a move away from inner suburban areas where most HIV-specific care is located. This new analysis assists in finding the right balance between increasing the accessibility of HIV-specific services and 'mainstreaming'. Longitudinal data collection would further assist in tracking trends in geographic location, and how often and at what intervals people living with HIV utilise healthcare services.
Evaluation of HBsAg and anti-HBc assays in saliva and dried blood spot samples according HIV status.
Flores, Geane Lopes; Cruz, Helena Medina; Potsch, Denise Vigo; May, Silvia Beatriz; Brandão-Mello, Carlos Eduardo; Pires, Marcia Maria Amendola; Pilotto, Jose Henrique; Lewis-Ximenez, Lia Laura; Lampe, Elisabeth; Villar, Livia Melo
2017-09-01
Influence of HIV status in HBV markers detection in saliva and dried blood spots (DBS) was not well established. This study aims to evaluate the performance of optimized commercial immunoassay for identifying HBsAg and anti-HBc in saliva and DBS according HIV status. A sum of 535 individuals grouped as HIV + , HBV + , HIV/HBV + and HIV/HBV- were recruited where 347 and 188 were included for HBsAg and anti-HBc evaluation, respectively. Serum, DBS collected in Whatman 903 paper and saliva obtained using salivette device were analyzed using EIA. Increased sample volume and ROC curve analysis for cut off determination were used for DBS and saliva testing. HBsAg detection in saliva and DBS exhibited sensitivities of 80.9% and 85.6% and specificities of 86.8% and 96.3%. Sensitivity of anti-HBc in saliva and DBS were 82.4% and 76.9% and specificities in saliva and DBS were 96.9% and 91.7%. Low sensitivities were observed for HBsAg (62%) and anti-HBc (47%) detection in saliva of HIV/HBV+ individuals. OD values were also lower for HBsAg detection in DBS and saliva of HIV/HBV+ individuals compared to their serum samples. Statistical significance was found for sensitivities in HBsAg detection between saliva and DBS demonstrating high sensitivity for DBS specimens. In conclusion, HIV status or antiretroviral treatment appears to interfere in the performance of HBsAg and anti-HBc detection in DBS and saliva samples using the adapted commercial EIA. Copyright © 2017 Elsevier B.V. All rights reserved.
Candidate change agent identification among men at risk for HIV infection
Schneider, John A.; McFadden, Rachel B.; Laumann, Edward O.; Kumar, SG Prem; Gandham, Sabitha R.; Oruganti, Ganesh
2012-01-01
Despite limited HIV prevention potency, peer-based programs have become one of the most often used HIV prevention approaches internationally. These programs demonstrate a need for greater specificity in peer change agent (PCA) recruitment and social network evaluation. In the present three-phase study based in India (2009–2010), we first explored the nature of friendship among truck-drivers, a group of men at high risk for HIV infection, in order to develop a thorough understanding of the social forces that contribute to and maintain their personal networks. This was accomplished in the first two study phases, through a combination of focus group discussions (n=5 groups), in-depth qualitative interviews (n=20), and personal network analyses (n=25) of truck-drivers to define friendship and deepen our understanding of friendship across geographic spaces. Measures collected in phases I and II included friend typologies, discussion topics, social network influences, advice-giving, and risk reduction. Outcomes were assessed through an iterative process of qualitative textual analysis and social network analysis. The networks of truck-drivers were found to comprise three typologies: close friends, parking lot friends, and other friends. From these data, we developed an algorithmic approach to the identification of a candidate PCA within a high-risk man’s personal network. In stage III we piloted field-use of this approach to identify and recruit PCAs, and further evaluated their potential for intervention through preliminary analysis of the PCA’s own personal networks. An instrument was developed to translate what social network theory and analysis has taught us about egocentric network dynamics into a real-world methodology for identifying intervention-appropriate peers within an individual’s personal network. Our approach can be tailored to the specifications of any high-risk population, and may serve to enhance current peer-based HIV interventions. PMID:22762951
Woolf-King, Sarah E; Muyindike, Winnie; Hobbs, Marcia M; Kusasira, Adrine; Fatch, Robin; Emenyonu, Nneka; Johnson, Mallory O; Hahn, Judith A
2017-07-01
The practical feasibility of using prostate specific antigen (PSA) as a biomarker of semen exposure was examined among HIV-infected Ugandan women. Vaginal fluids were obtained with self-collected swabs and a qualitative rapid test (ABAcard ® p30) was used to detect PSA. Trained laboratory technicians processed samples on-site and positive PSA tests were compared to self-reported unprotected vaginal sex (UVS) in the last 48 h. A total of 77 women submitted 126 samples for PSA testing at up to three study visits. Of these samples, 31 % (n = 39/126) were PSA positive, and 64 % (n = 25/39) of the positive PSA samples were accompanied by self-report of no UVS at the study visit the PSA was collected. There were no reported difficulties with specimen collection, storage, or processing. These findings provide preliminary data on high levels of misreported UVS among HIV-infected Ugandan women using practically feasible methods for PSA collection and processing.
Kassa, Desta; Gebremichael, Gebremedhin; Alemayehu, Yodit; Wolday, Dawit; Messele, Tsehaynesh; van Baarle, Debbie
2013-01-01
HIV/TB coinfection remains a major challenge even after the initiation of HAART. Little is known about Mycobacterium tuberculosis (Mtb) specific immune restoration in relation to immunologic and virologic outcomes after long-term HAART during co-infections with latent and active TB. A total of 232 adults, including 59 HIV patients with clinical TB (HIV + TB+), 125 HIV patients without clinical TB (HIV + TB-), 13 HIV negative active TB patients (HIV-TB+), and 10 HIV negative Tuberculin Skin TST positive (HIV-TST+), and 25 HIV-TST- individuals were recruited. HAART was initiated in 113 HIV + patients (28 TB + and 85 TB-), and anti-TB treatment for all TB cases. CD4+ T-cell count, HIV RNA load, and IFN-γ responses to ESAT-6/CFP-10 were measured at baseline, 6 months (M6), 18 months (M18) and 24 months (M24) after HAART initiation. The majority of HIV + TB- (70%, 81%, 84%) as well as HIV + TB + patients (60%, 77%, 80%) had virologic success (HIV RNA < 50 copies/ml) by M6, M18 and M24, respectively. HAART also significantly increased CD4+ T-cell counts at 2 years in HIV + TB + (from 110.3 to 289.9 cells/μl), HIV + TB- patients (197.8 to 332.3 cells/μl), HIV + TST- (199 to 347 cells/μl) and HIV + TST + individuals (195 to 319 cells/μl). Overall, there was no significant difference in the percentage of patients that achieved virologic success and in total CD4+ counts increased between HIV patients with and without TB or LTBI. The Mtb specific IFN-γ response at baseline was significantly lower in HIV + TB + (3.6 pg/ml) compared to HIV-TB + patients (34.4 pg/ml) and HIV + TST + (46.3 pg/ml) individuals; and in HIV-TB + patients compared to HIV-TST + individuals (491.2 pg/ml). By M18 on HAART, the IFN-γ response remained impaired in HIV + TB + patients (18.1 pg/ml) while it normalized in HIV + TST + individuals (from 46.3 to 414.2 pg/ml). Our data show that clinical and latent TB infections do not influence virologic and immunologic outcomes of ART in HIV patients. Despite this, HAART was unable to restore optimal TB responsiveness as measured by Mtb specific IFN-γ response in HIV/TB patients. Improvement of Mtb-specific immune restoration should be the focus of future therapeutic strategies.
Eaton, Lisa A; West, Tessa V; Kenny, David A; Kalichman, Seth C
2009-04-01
Selecting sex partners of the same HIV status or serosorting is a sexual risk reduction strategy used by many men who have sex with men. However, the effectiveness of serosorting for protection against HIV is potentially limited. We sought to examine how men perceive the protective benefits of factors related to serosorting including beliefs about engaging in serosorting, sexual communication, and perceptions of risk for HIV. Participants were 94 HIV negative seroconcordant (same HIV status) couples, 20 HIV serodiscordant (discrepant HIV status) couples, and 13 HIV positive seroconcordant (same HIV status) couples recruited from a large gay pride festival in the southeastern US. To account for nonindependence found in the couple-level data, we used multilevel modeling which includes dyad in the analysis. Findings demonstrated that participants in seroconcordant relationships were more likely to believe that serosorting reduces concerns for condom use. HIV negative participants in seroconcordant relationships viewed themselves at relatively low risk for HIV transmission even though monogamy within relationships and HIV testing were infrequent. Dyadic analyses demonstrated that partners have a substantial effect on an individual's beliefs and number of unprotected sex partners. We conclude that relationship partners are an important source of influence and, thus, intervening with partners is necessary to reduce HIV transmission risks.
Maternal Factors Influencing Perinatal Transmission of HIV Infection
1990-01-01
PET Chronic hypertension Eclampsia 17. IUGR 17. 18. Preterm Labor 18. 19. 3rd Trimester Bleeding 19. a) Placenta Previa b) Abruptio Placenta 20...Obstetrics/Gynecology, and laboratory procedures including those for maternal/neonatal drug screening and for handling and processing tissue ( placenta ...amniocentesis Is n done as a part of this study. After delivery, the placenta (afterbirth) will be examined for evidence of HIV infection (AIDS virus). Blood
2010-01-01
Background HIV counseling and testing is considered an important component of HIV prevention and treatment. This paper examines the characteristics of young males and females at the time of first reported HIV test, including the influence of recent sexual partnerships, and investigates how HIV testing and the cumulative number of tests are associated with sexual behaviors within six months of testing. Methods The study uses data from a random sample of youth aged 18-24 years living in Kisumu, Kenya, who were interviewed using a 10-year retrospective life history calendar. Cox regression models were used to examine the correlates of the timing of first HIV test. Variance-correction models for unordered repeated events were employed to examine whether having an HIV test in the previous six months and the cumulative number of tests predict unsafe sexual practices in a given month. Results Sixty-four percent of females and 55% of males reported at least one HIV test in the last 10 years and 40% of females were pregnant the month of first test. Significant correlates of first HIV test included marital aspirations among non-pregnant females, unprotected sex in the previous six months among pregnant females, and concurrency in the previous six months among males. Having a recent HIV test was associated with a decreased likelihood of unprotected sex among ever-pregnant females, an increased likelihood of unprotected sex and "risky" sexual partnerships among never-pregnant females, and an increased likelihood of concurrency among males. Repeated HIV testing was associated with a lower likelihood of concurrency among males and involvement in "risky" sexual partnerships among males and never-pregnant females. Conclusions The high rate of pregnancy at first test suggests that promotion of HIV testing as part of prevention of mother-to-child transmission is gaining success. Further research is warranted to examine how and why behavior change is influenced by client- versus provider-initiated testing. The influence of different sexual partnership variables for males and females suggests that interventions to assess risk and promote testing should be gender- and relationship-specific. The findings also suggest that encouraging repeat or routine testing could potentially increase the uptake of safer sexual behaviors. PMID:20624323
Kabiru, Caroline W; Luke, Nancy; Izugbara, Chimaraoke O; Zulu, Eliya M
2010-07-13
HIV counseling and testing is considered an important component of HIV prevention and treatment. This paper examines the characteristics of young males and females at the time of first reported HIV test, including the influence of recent sexual partnerships, and investigates how HIV testing and the cumulative number of tests are associated with sexual behaviors within six months of testing. The study uses data from a random sample of youth aged 18-24 years living in Kisumu, Kenya, who were interviewed using a 10-year retrospective life history calendar. Cox regression models were used to examine the correlates of the timing of first HIV test. Variance-correction models for unordered repeated events were employed to examine whether having an HIV test in the previous six months and the cumulative number of tests predict unsafe sexual practices in a given month. Sixty-four percent of females and 55% of males reported at least one HIV test in the last 10 years and 40% of females were pregnant the month of first test. Significant correlates of first HIV test included marital aspirations among non-pregnant females, unprotected sex in the previous six months among pregnant females, and concurrency in the previous six months among males. Having a recent HIV test was associated with a decreased likelihood of unprotected sex among ever-pregnant females, an increased likelihood of unprotected sex and "risky" sexual partnerships among never-pregnant females, and an increased likelihood of concurrency among males. Repeated HIV testing was associated with a lower likelihood of concurrency among males and involvement in "risky" sexual partnerships among males and never-pregnant females. The high rate of pregnancy at first test suggests that promotion of HIV testing as part of prevention of mother-to-child transmission is gaining success. Further research is warranted to examine how and why behavior change is influenced by client- versus provider-initiated testing. The influence of different sexual partnership variables for males and females suggests that interventions to assess risk and promote testing should be gender- and relationship-specific. The findings also suggest that encouraging repeat or routine testing could potentially increase the uptake of safer sexual behaviors.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shang Liang; Hunter, Eric, E-mail: eric.hunter2@emory.ed
2010-09-01
The membrane-spanning domain (MSD) of human immunodeficiency virus type I (HIV-1) envelope glycoprotein (Env) is critical for its biological activity. Initial studies have defined an almost invariant 'core' structure in the MSD and demonstrated that it is crucial for anchoring Env in the membrane and virus entry. We show here that amino acid substitutions in the MSD 'core' do not influence specific virus-cell attachment, nor CD4 receptor and CXCR4 coreceptor recognition by Env. However, substitutions within the MSD 'core' delayed the kinetics and reduced the efficiency of cell-cell fusion mediated by Env. Although we observed no evidence that membrane fusionmore » mediated by the MSD core mutants was arrested at a hemifusion stage, impaired Env fusogenicity was correlated with minor conformational changes in the V2, C1, and C5 regions in gp120 and the immunodominant loop in gp41. These changes could delay initiation of the conformational changes required in the fusion process.« less
Factors influencing social self-disclosure among adolescents living with HIV in Eastern Africa.
Nöstlinger, Christiana; Bakeera-Kitaka, Sabrina; Buyze, Jozefien; Loos, Jasna; Buvé, Anne
2015-01-01
Adolescents living with HIV (ALHIV) face many psychosocial challenges, including HIV disclosure to others. Given the importance of socialization during the adolescent transition process, this study investigated the psychological and social factors influencing self-disclosure of own HIV status to peers. We examined social HIV self-disclosure to peers, and its relationship to perceived HIV-related stigma, self-efficacy to disclose, self-esteem, and social support among a sample of n = 582 ALHIV aged 13-17 years in Kampala, Uganda, and Western Kenya. Data were collected between February and April 2011. Among them, 39% were double orphans. We conducted a secondary data analysis to assess the degree of social disclosure, reactions received, and influencing factors. Interviewer-administered questionnaires assessed medical, socio-demographic, and psychological variables (Rosenberg self-esteem scale; self-efficacy to disclose to peers), HIV-related stigma (10-item stigma scale), and social support (family-life and friends). Descriptive, bivariate, and logistic regression analyses were performed with social self-disclosure to peers with gender as covariates. Almost half of ALHIV had told nobody (except health-care providers) about their HIV status, and about 18% had disclosed to either one of their friends, schoolmates, or a boy- or girlfriend. Logistic regression models revealed that having disclosed to peers was significantly related to being older, being a paternal orphan, contributing to family income, regular visits to the HIV clinic, and greater social support through peers. Low self-efficacy to disclose was negatively associated to the outcome variable. While social self-disclosure was linked to individual factors such as self-efficacy, factors relating to the social context and adolescents' access to psychosocial resources play an important role. ALHIV need safe environments to practice disclosure skills. Interventions should enable them to make optimal use of available psychosocial resources even under constraining conditions such as disruptive family structures.
Ifekandu, Chiedu; Suleiman, Aliyu; Aniekwe, Ogechukwu
2014-01-01
Men who have sex with men (MSM) are at increased risk of HIV and other STI infections in Nigeria. This is because MSM are afraid to seek medical help because the healthcare workers in various facilities are afraid of the consequences if they provide services for MSM citing the law as a reason not to intervene. MSM in northern states of Nigeria are facing double-jeopardy because the few international partners working in MSM in Nigeria are pulling out of these volatile areas because of the fear of attacks by the Boko Haram and the Nigerian law enforcement agencies. The intervention was conducted to promote affordable and sustainable HIV care and treatment for MSM in Nigeria. This intervention was conducted in the Boko Haram ravaged cities of Kano and Maiduguri (North-East Nigeria). Twenty MSM-key influencers from the two cities were identified and trained on HIV counselling and testing, caregivers, case managers and on initiation process for ARV treatment for new HIV+MSM as well as ethical considerations. The mean age of the key influencers was 24 years +/-SD. Each of the trained 20 key influencers reached 20 MSM-peer with condom promotion, HCT, referral to identified MSM-community health centers and follow-up/caregiving within the space of one month. The project was able to reach 400 MSM in the two cities. 89% of the peers consented to HCT. HIV prevalence among the participants was at 18%. The project recorded ARV-successful referral to healthcare facilities for the respondents that tested positive. The key influencers have been following up for ARV-adherence. Use of community members should be promoted for sustainability and ownership. It also helps in eradicating socio-cultural barrier to HIV intervention for MSM. Moreover, this proves to be one of the safest and affordable methods of reaching MSM in Nigeria in this ugly time of legalization of homophobia in the country's constitution.
HIV-1 Proteins Accelerate HPA Axis Habituation in Female Rats
Panagiotakopoulos, Leonidas; Kelly, Sean; Neigh, Gretchen N.
2015-01-01
Congenital infection by the Human Immunodeficiency Virus (HIV) has been shown to lead to multiple co-morbidities, and people living with HIV have a higher incidence of affective and anxiety disorders. A marked increase in mood disorders is evident during the sensitive phase of adolescence and this is further pronounced in females. Depression has been linked to dysfunction of the intracellular response system to corticosteroids at the level of the hippocampus (HC) and prefrontal cortex (PFC) with a notable role of the glucocorticoid receptor (GR) and its co-chaperones (FKBP5 and FKBP4). The current study examined the extent to which HIV protein expression in adolescent female rats altered the stress response at both the level of corticosterone output and molecular regulation of the glucocorticoid receptor in the brain. WT and HIV-1 genotype female rats were randomly allocated in control, acute stress and repeat stress groups. Corticosterone plasma levels and expression of GR, FKBP4, and FKBP5 in the HC and PFC were measured. The presence of HIV-1 proteins facilitate habituation of the corticosterone response to repeated stressors, such that HIV-1 TG rats habituated to repeated restraint and WT rats did not. This was reflected by interactions between stress exposure and HIV-1 protein expression at the level of GR co-chaperones. Although expression of the GR was similarly reduced after acute and repeat stress in both genotypes, expression of FKBP5 and FKBP4 was altered in a brain-region specific manner depending on the duration of the stress exposure and the presence or absence of HIV-1 proteins. Collectively, the data presented demonstrate that HIV-1 proteins accelerate habituation to repeated stressors and modify the influence of acute and repeat stressors on GR co-chaperones in a brain region-specific manner. PMID:25666308
HIV-1 infection: the role of the gastrointestinal tract.
Cavarelli, Mariangela; Scarlatti, Gabriella
2014-06-01
The intestinal mucosa has an important role as portal of entry during mother-to-child transmission of HIV-1 and during sexual transmission. Tissue morphology and integrity, as well as distribution of relevant cell types within the mucosa, spanning from the oropharynx to the rectum, can greatly influence viral infection, replication, presentation, and persistence. The relative contribution to transmission by cell-associated or cell-free virus is still not defined for the different routes of transmission. Although the main target cells for HIV-1 replication are the CD4+ T lymphocytes, which are rapidly depleted both in the periphery and in the mucosal tissues, dendritic cells, Langerhans' cells, and macrophages are players in each of these processes. The predominant cells involved may differ according to the tract of the gut and the route of transmission. The microenvironment of the intestinal mucosa, including mucus, antibodies, or chemo-cytokines, can as well influence infection and replication of the virus: their role is still under investigation. The understanding of these processes may help in developing efficient prevention strategies. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Stigma and HIV risk among Metis in Nepal
Wilson, Erin; Pant, Sunil Babu; Comfort, Megan; Ekstrand, Maria
2011-01-01
Similar to other parts of Asia, the HIV epidemic in Nepal is concentrated among a small number of groups, including transgender people, or Metis. This study was conducted to explore the social context of stigma among Metis in Nepal to better understand their risk for HIV. Fourteen in-depth interviews were conducted with Metis in Kathmandu, Nepal. We found that stigma from families leading to rural-urban migration exposed Metis to discrimination from law enforcement, employers and sexual partners, which influenced their risk for HIV. Specific HIV-related risks identified were rape by law enforcement officers, inconsistent condom use and high reported numbers of sexual partners. These data point to an immediate need to work with law enforcement to reduce violence targeting Metis. HIV prevention, housing and employment outreach to Metis in rural areas and those who migrate to urban areas is also needed. Finally, there is a need for more research to determine the prevalence of HIV among Metis, to explore risk within sexual networks and to better understand of the relationship between Metis and their families in order to develop future programmes and interventions. PMID:21058085
HLA Class II Antigens and Their Interactive Effect on Perinatal Mother-To-Child HIV-1 Transmission
Luo, Ma; Embree, Joanne; Ramdahin, Suzie; Bielawny, Thomas; Laycock, Tyler; Tuff, Jeffrey; Haber, Darren; Plummer, Mariel; Plummer, Francis A.
2015-01-01
HLA class II antigens are central in initiating antigen-specific CD4+ T cell responses to HIV-1. Specific alleles have been associated with differential responses to HIV-1 infection and disease among adults. This study aims to determine the influence of HLA class II genes and their interactive effect on mother-child perinatal transmission in a drug naïve, Mother-Child HIV transmission cohort established in Kenya, Africa in 1986. Our study showed that DRB concordance between mother and child increased risk of perinatal HIV transmission by three fold (P = 0.00035/Pc = 0.0014, OR: 3.09, 95%CI, 1.64-5.83). Whereas, DPA1, DPB1 and DQB1 concordance between mother and child had no significant influence on perinatal HIV transmission. In addition, stratified analysis showed that DRB1*15:03+ phenotype (mother or child) significantly increases the risk of perinatal HIV-1 transmission. Without DRB1*15:03, DRB1 discordance between mother and child provided 5 fold protection (P = 0.00008, OR: 0.186, 95%CI: 0.081-0.427). However, the protective effect of DRB discordance was diminished if either the mother or the child was DRB1*15:03+ phenotype (P = 0.49-0.98, OR: 0.7-0.99, 95%CI: 0.246-2.956). DRB3+ children were less likely to be infected perinatally (P = 0.0006, Pc = 0.014; OR:0.343, 95%CI:0.183-0.642). However, there is a 4 fold increase in risk of being infected at birth if DRB3+ children were born to DRB1*15:03+ mother compared to those with DRB1*15:03- mother. Our study showed that DRB concordance/discordance, DRB1*15:03, children’s DRB3 phenotype and their interactions play an important role in perinatal HIV transmission. Identification of genetic factors associated with protection or increased risk in perinatal transmission will help develop alternative prevention and treatment methods in the event of increases in drug resistance of ARV. PMID:25945792
Intergenerational transmission of prejudice, sex role stereotyping, and intolerance.
O'Bryan, Megan; Fishbein, Harold D; Ritchey, P Neal
2004-01-01
The attitudes of 111 ninth and eleventh graders and both of their biological parents were independently assessed for prejudice against people with HIV/ AIDS, homosexuals, Blacks, and fat people, as well as for male and female sex role stereotyping. This study corrected for two shortcomings in previous research: neglecting to assess both parents and assessing only a single domain of prejudice. We addressed the intergenerational transmission of prejudice and stereotyping using three competing models: same-sex, parent equivalent, and differential effects. Using multiple regressions in which parents' scores were entered separately, along with control variables, different maternal and paternal influences were detected. Mothers were the primary influence for prejudice regarding HIV/AIDS, fatness, and race, and fathers were the primary influence for male and female stereotyping and prejudice against homosexuals, supporting the differential effects model. We also established that prejudice and stereotyping in specific domains reflected a more general proclivity to be intolerant. In contrast to prejudice and stereotyping in specific domains, fathers and mothers about equally shaped the adolescents' intolerance, supporting the parent equivalent model.
Shiu, Cheng-Shi; Chen, Wei-Ti; Simoni, Jane; Fredriksen-Goldsen, Karen; Zhang, Fujie; Zhou, Hongxin
2013-05-01
China is considered to be the new frontier of the global AIDS pandemic. Although effective treatment for HIV is becoming widely available in China, adherence to treatment remains a challenge. This study aimed to adapt an intervention promoting HIV-medication adherence-favorably evaluated in the West-for Chinese HIV-positive patients. The adaptation process was theory-driven and covered several key issues of cultural adaptation. We considered the importance of interpersonal relationships and family in China and cultural notions of health. Using an evidence-based treatment protocol originally designed for Western HIV-positive patients, we developed an 11-step Chinese Life-Steps program with an additional culture-specific intervention option. We describe in detail how the cultural elements were incorporated into the intervention and put into practice at each stage. Clinical considerations are also outlined and followed by two case examples that are provided to illustrate our application of the intervention. Finally, we discuss practical and research issues and limitations emerging from our field experiments in a HIV clinic in Beijing. The intervention was tailored to address both universal and culturally specific barriers to adherence and is readily applicable to generalized clinical settings. This evidence-based intervention provides a case example of the process of adapting behavioral interventions to culturally diverse communities with limited resources.
Shiu, Cheng-Shi; Chen, Wei-Ti; Simoni, Jane; Fredriksen-Goldsen, Karen; Zhang, Fujie; Zhou, Hongxin
2013-01-01
China is considered to be the new frontier of the global AIDS pandemic. Although effective treatment for HIV is becoming widely available in China, adherence to treatment remains a challenge. This study aimed to adapt an intervention promoting HIV-medication adherence—favorably evaluated in the West—for Chinese HIV-positive patients. The adaptation process was theory-driven and covered several key issues of cultural adaptation. We considered the importance of interpersonal relationships and family in China and cultural notions of health. Using an evidence-based treatment protocol originally designed for Western HIV-positive patients, we developed an 11-step Chinese Life-Steps program with an additional culture-specific intervention option. We describe in detail how the cultural elements were incorporated into the intervention and put into practice at each stage. Clinical considerations are also outlined and followed by two case examples that are provided to illustrate our application of the intervention. Finally, we discuss practical and research issues and limitations emerging from our field experiments in a HIV clinic in Beijing. The intervention was tailored to address both universal and culturally specific barriers to adherence and is readily applicable to generalized clinical settings. This evidence-based intervention provides a case example of the process of adapting behavioral interventions to culturally diverse communities with limited resources. PMID:23667305
Impact of Human Resources on Implementing an Evidence-based HIV Prevention Intervention
McKay, Virginia R.; Dolcini, M. Margaret; Catania, Joseph A.
2016-01-01
Evidence-based interventions (EBIs) often require competent staff, or human resources (HR), for implementation. The empirical evidence characterizing the influence of HR fluctuations on EBI delivery is limited and conflicting. Using the Interactive Systems Framework, we explored staff fluctuation and the subsequent influence on RESPECT, an HIV prevention EBI. Methods We conducted interviews with staff in two waves (n=53, Wave I; n=37, Wave II) in a national sample of organizations delivering RESPECT (N=29). We analyzed interviews qualitatively to describe changes among RESPECT staff and explore the subsequent influences on RESPECT implementation. Results Organizations reported downsizing, turnover, and expansion of staff positions. Staff changes had multiple influences on RESPECT implementation including clients reached, fidelity to specific RESPECT protocols, and overall sustainability of RESPECT over time. Discussion HR fluctuations are common, and our analyses provide an initial characterization of the relationship between HR fluctuation and EBI implementation. Given the prominent influence of HR on EBI implementation, the Interactive Systems Framework is a useful guiding tool for future examinations. PMID:27150896
Cultural Strategies for Teaching HIV/AIDS Prevention to American Indians
ERIC Educational Resources Information Center
McIntosh, Dannette R.
2012-01-01
The purpose of this study was to describe what tools and strategies Native Americans who live in Oklahoma believe are important in learning about HIV/AIDS, to determine if culturally specific information is important in developing prevention programs, and to ascertain learning strategies. Data collection was a two-part process. First, the Cultural…
Jeanne, Nicolas; Saliou, Adrien; Carcenac, Romain; Lefebvre, Caroline; Dubois, Martine; Cazabat, Michelle; Nicot, Florence; Loiseau, Claire; Raymond, Stéphanie; Izopet, Jacques; Delobel, Pierre
2015-01-01
HIV-1 coreceptor usage must be accurately determined before starting CCR5 antagonist-based treatment as the presence of undetected minor CXCR4-using variants can cause subsequent virological failure. Ultra-deep pyrosequencing of HIV-1 V3 env allows to detect low levels of CXCR4-using variants that current genotypic approaches miss. However, the computation of the mass of sequence data and the need to identify true minor variants while excluding artifactual sequences generated during amplification and ultra-deep pyrosequencing is rate-limiting. Arbitrary fixed cut-offs below which minor variants are discarded are currently used but the errors generated during ultra-deep pyrosequencing are sequence-dependant rather than random. We have developed an automated processing of HIV-1 V3 env ultra-deep pyrosequencing data that uses biological filters to discard artifactual or non-functional V3 sequences followed by statistical filters to determine position-specific sensitivity thresholds, rather than arbitrary fixed cut-offs. It allows to retain authentic sequences with point mutations at V3 positions of interest and discard artifactual ones with accurate sensitivity thresholds. PMID:26585833
Jeanne, Nicolas; Saliou, Adrien; Carcenac, Romain; Lefebvre, Caroline; Dubois, Martine; Cazabat, Michelle; Nicot, Florence; Loiseau, Claire; Raymond, Stéphanie; Izopet, Jacques; Delobel, Pierre
2015-11-20
HIV-1 coreceptor usage must be accurately determined before starting CCR5 antagonist-based treatment as the presence of undetected minor CXCR4-using variants can cause subsequent virological failure. Ultra-deep pyrosequencing of HIV-1 V3 env allows to detect low levels of CXCR4-using variants that current genotypic approaches miss. However, the computation of the mass of sequence data and the need to identify true minor variants while excluding artifactual sequences generated during amplification and ultra-deep pyrosequencing is rate-limiting. Arbitrary fixed cut-offs below which minor variants are discarded are currently used but the errors generated during ultra-deep pyrosequencing are sequence-dependant rather than random. We have developed an automated processing of HIV-1 V3 env ultra-deep pyrosequencing data that uses biological filters to discard artifactual or non-functional V3 sequences followed by statistical filters to determine position-specific sensitivity thresholds, rather than arbitrary fixed cut-offs. It allows to retain authentic sequences with point mutations at V3 positions of interest and discard artifactual ones with accurate sensitivity thresholds.
Sariah, Adellah; Rugemalila, Joan; Somba, Magreat; Minja, Anna; Makuchilo, Margareth; Tarimo, Edith; Urassa, David; Siril, Helen
2016-10-13
The specific age to which an HIV infected child can be disclosed to is stipulated to begin between ages 4 and 6 years. It has also been documented that before disclosure of HIV positive status to the infected child. Health care providers should consider children's cognitive-developmental ability. However, observation and situation analysis show that, health care providers still feel uncomfortable disclosing the HIV positive status to the infected child. The aim of the study was to explore healthcare providers' experiences in disclosure of HIV-positive status to the infected child. A qualitative study involving 20 health care providers who attend HIV-positive children was conducted in September, 2014 in Dar es Salaam, Tanzania. Participants were selected from ten HIV care and treatment clinics (CTC) by purposive sampling. An interview guide, translated into participants' national language (Kiswahili) was used during in-depth interviews. Sampling followed the principle of data saturation. The interviews focused on perspectives of health-care providers regarding their experience with paediatric HIV disclosure. Data from in-depth interviews were transcribed into text; data analysis followed qualitative content analysis. The results show how complex the process of disclosure to children living with HIV can be to healthcare providers. Confusion was noted among healthcare providers about their role and responsibility in the process of disclosing to the HIV infected child. This was reported to be largely due to unclear guidelines and lack of standardized training in paediatric HIV disclosure. Furthermore, healthcare providers were concerned about parental hesitancy to disclose early to the child due to lack of disclosure skills and fear of stigma. In order to improve the disclosure process in HIV infected children, healthcare providers recommended further standardized training on paediatric HIV disclosure with more emphasis on practical skills and inclusion of disclosure content that is age appropriate for children with HIV. The disclosure process was found to be a complex process. Perspectives regarding disclosure in children infected with HIV varied among healthcare providers in terms of their role in the process, clear national guidelines and appropriate standardized training for paediatric disclosure. Consistent with other studies, healthcare providers reported difficulties during disclosure because parents /guardians largely fear blame, social stigma, child's negative emotional reaction when disclosed to and have concerns about the child being too young and immature to understand the HIV condition. In order to prevent inconsistencies during the disclosure process, it is important to have in place clear guidelines and standardized paediatric HIV disclosure training for healthcare providers. This would help improve their skills in paediatric disclosure, leading to positive health outcomes for children infected with HIV.
Ganle, John Kuumuori
2016-05-01
Among the youth in some parts of sub-Saharan Africa, a paradoxical mix of adequate knowledge of HIV/AIDS and high-risk behavior characterizes their daily lives. Based on original qualitative research in Ghana, I explore in this article the ways in which the social construction of masculinity influences youth's responses to behavior change HIV/AIDS prevention interventions. Findings show that although awareness of the HIV/AIDS epidemic and the risks of infection is very high among the youth, a combination of hegemonic masculinity and perceptions of personal invulnerability acts to undermine the processes of young people's HIV/AIDS risk construction and appropriate behavioral change. I argue that if HIV/AIDS prevention is to be effective and sustained, school- and community-based initiatives should be developed to provide supportive social spaces in which the construction of masculinity, the identity of young men and women as gendered persons, and perceptions of their vulnerability to HIV/AIDS infection are challenged. © The Author(s) 2015.
Tynan, Anna; Hill, Peter S; Kelly, Angela; Kupul, Martha; Aeno, Herick; Naketrumb, Richard; Siba, Peter; Kaldor, John; Vallely, Andrew
2013-08-13
The success of health programs is influenced not only by their acceptability but also their ability to meet and respond to community expectations of service delivery. The World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) have recommended medical male circumcision (MC) as an essential component of comprehensive HIV prevention programs in high burden settings. This study investigated community-level perceptions of MC for HIV prevention in Papua New Guinea (PNG), a setting where diverse traditional and contemporary forms of penile foreskin cutting practices have been described. A multi-method qualitative study was undertaken in four provinces in two stages from 2009 to 2011. A total of 82 in-depth interviews, and 45 focus group discussions were completed during Stage 1. Stage 2 incorporated eight participatory workshops that were an integral part of the research dissemination process to communities. The workshops also provided opportunity to review key themes and consolidate earlier findings as part of the research process. Qualitative data analysis used a grounded theory approach and was facilitated using qualitative data management software. A number of diverse considerations for the delivery of MC for HIV prevention in PNG were described, with conflicting views both between and within communities. Key issues included: location of the service, service provider, age eligibility, type of cut, community awareness and potential shame amongst youth. Key to developing appropriate health service delivery models was an appreciation of the differences in expectations and traditions of unique cultural groups in PNG. Establishing strong community coalitions, raising awareness and building trust were seen as integral to success. Difficulties exist in the implementation of new programs in a pluralistic society such as PNG, particularly if tensions arise between biomedical knowledge and medico-legal requirements, compared to existing socio-cultural interests. Community participatory approaches offer important opportunities to explore and design culturally safe, specific and accessible programs.
Grewe, Mary E; Taboada, Arianna; Dennis, Alexis; Chen, Elizabeth; Stein, Kathryn; Watson, Sable; Barrington, Clare; Lightfoot, Alexandra F
Theatre-based interventions have been used in health promotion activities among young people to address HIV and sexual health. In this study, we explored the experience of undergraduate student performers participating in a theatre-based HIV prevention and sexual health education intervention for high school students in the USA. Undergraduate students enrolled in a credit-bearing course to learn about HIV and sexual health, participatory theatre and health education techniques. We analysed students' reflective essays written throughout the semester to identify any changes and the intervention processes that promoted these changes. Students experienced five interrelated forms of transformation: (1) increased knowledge about HIV and sexual health; (2) changes in attitude and communication about sex; (3) artistic growth; (4) emotional growth; and (5) clarification of career goals and future plans. Intervention processes that contributed to these transformations included improvisation, guided writing exercises, the creation of a close-knit cohesive group, and interactions with a group of HIV-positive speakers. Theatre-based, peer-led sexual health programmes can provide a transformative experience for undergraduate student performers. The transformative effects are linked to specific activities and processes of the intervention and require examination in future research.
Kumar, Anant; Kumar, Prakash
2013-01-01
Training needs assessments are pivotal for any capacity building program. Building capacity of service providers and staff involved in HIV/AIDS intervention programs is crucial because of the distinct nature of such programs. It requires specific knowledge, skills, and attitudes that are of utmost importance, influencing the reach of the program and its impact in halting and reversing the epidemic. This study was conducted to identify the training needs assessment of personnel involved in targeted intervention for high risk populations vulnerable to HIV infection in Jharkhand, India. Through the study the authors critically examine the existing training needs and gaps and suggest strategies to address them.
Shabiby, Mufida M; Karanja, Joseph G; Odawa, Francis; Kosgei, Rose; Kibore, Minnie W; Kiarie, James N; Kinuthia, John
2015-08-19
Family planning is a cost effective strategy for prevention of mother to child transmission of HIV and reduction of maternal/infant morbidity and mortality. Contraceptive implants are a safe, effective, long term and reversible family planning method whose use remains low in Kenya. We therefore set out to determine and compare the uptake, and factors influencing uptake of immediate postpartum contraceptive implants among HIV infected and uninfected women at two hospitals in Kenya. This cross sectional study targeted postpartum mothers at two Kenyan district hospitals (one urban and one rural). All participants received general family planning and method specific (Implant) counseling followed by immediate insertion of contraceptive implants to those who consented. The data was analyzed by descriptive analysis, T-test, Chi square tests and logistic regression. One hundred eighty-five participants were enrolled (91 HIV positive and 94 HIV negative) with a mean age of 26 years. HIV positive mothers were significantly older (27.5 years) than their HIV negative counterparts (24.5 years), P = 0.001. The two groups were comparable in education, employment, marital status and religious affiliation. Overall, the uptake of contraceptive implants in the immediate postpartum period was 50.3% and higher among HIV negative than HIV positive participants (57% vs. 43%, P = 0.046). Multivariate analysis revealed that a negative HIV status (P = 0.017) and prior knowledge of contraceptive implants (P = 0.001) were independently associated with increased uptake of contraceptive implants. There was a high uptake of immediate postpartum contraceptive implants among both HIV infected and un-infected women; efforts therefore need to be made in promoting this method of family planning in Kenya and providing this method to women in the immediate postpartum period so as to utilize this critical opportunity to increase uptake and reduce the high unmet need for family planning.
Verma, Meghna; Erwin, Samantha; Abedi, Vida; Hontecillas, Raquel; Hoops, Stefan; Leber, Andrew; Bassaganya-Riera, Josep; Ciupe, Stanca M
2017-01-01
Human immunodeficiency virus (HIV)-infected patients are at an increased risk of co-infection with human papilloma virus (HPV), and subsequent malignancies such as oral cancer. To determine the role of HIV-associated immune suppression on HPV persistence and pathogenesis, and to investigate the mechanisms underlying the modulation of HPV infection and oral cancer by HIV, we developed a mathematical model of HIV/HPV co-infection. Our model captures known immunological and molecular features such as impaired HPV-specific effector T helper 1 (Th1) cell responses, and enhanced HPV infection due to HIV. We used the model to determine HPV prognosis in the presence of HIV infection, and identified conditions under which HIV infection alters HPV persistence in the oral mucosa system. The model predicts that conditions leading to HPV persistence during HIV/HPV co-infection are the permissive immune environment created by HIV and molecular interactions between the two viruses. The model also determines when HPV infection continues to persist in the short run in a co-infected patient undergoing antiretroviral therapy. Lastly, the model predicts that, under efficacious antiretroviral treatment, HPV infections will decrease in the long run due to the restoration of CD4+ T cell numbers and protective immune responses.
Contact-induced mitochondrial polarization supports HIV-1 virological synapse formation.
Groppelli, Elisabetta; Starling, Shimona; Jolly, Clare
2015-01-01
Rapid HIV-1 spread between CD4 T lymphocytes occurs at retrovirus-induced immune cell contacts called virological synapses (VS). VS are associated with striking T cell polarization and localized virus budding at the site of contact that facilitates cell-cell spread. In addition to this, spatial clustering of organelles, including mitochondria, to the contact zone has been previously shown. However, whether cell-cell contact specifically induces dynamic T cell remodeling during VS formation and what regulates this process remain unclear. Here, we report that contact between an HIV-1-infected T cell and an uninfected target T cell specifically triggers polarization of mitochondria concomitant with recruitment of the major HIV-1 structural protein Gag to the site of cell-cell contact. Using fixed and live-cell imaging, we show that mitochondrial and Gag polarization in HIV-1-infected T cells occurs within minutes of contact with target T cells, requires the formation of stable cell-cell contacts, and is an active, calcium-dependent process. We also find that perturbation of mitochondrial polarization impairs cell-cell spread of HIV-1 at the VS. Taken together, these data suggest that HIV-1-infected T cells are able to sense and respond to contact with susceptible target cells and undergo dynamic cytoplasmic remodeling to create a synaptic environment that supports efficient HIV-1 VS formation between CD4 T lymphocytes. HIV-1 remains one of the major global health challenges of modern times. The capacity of HIV-1 to cause disease depends on the virus's ability to spread between immune cells, most notably CD4 T lymphocytes. Cell-cell transmission is the most efficient way of HIV-1 spread and occurs at the virological synapse (VS). The VS forms at the site of contact between an infected cell and an uninfected cell and is characterized by polarized assembly and budding of virions and clustering of cellular organelles, including mitochondria. Here, we show that cell-cell contact induces rapid recruitment of mitochondria to the contact site and that this supports efficient VS formation and consequently cell-cell spread. Additionally, we observed that cell-cell contact induces a mitochondrion-dependent increase in intracellular calcium, indicative of cellular signaling. Taken together, our data suggest that VS formation is a regulated process and thus a potential target to block HIV-1 cell-cell spread. Copyright © 2015, Groppelli et al.
Feldman, Jamie; Romine, Rebecca Swinburne; Bockting, Walter O
2014-01-01
To study the influence of gender on HIV risk, a sample of the U.S. transgender population (N = 1,229) was recruited via the Internet. HIV risk and prevalence were lower than reported in prior studies of localized, urban samples but higher than the overall U.S. population. Findings suggest that gender nonconformity alone does not itself result in markedly higher HIV risk. Sex with nontransgender men emerged as the strongest independent predictor of unsafe sex for both male-to-female (MtF) and female-to-male (FtM) participants. These sexual relationships constitute a process that may either affirm or problematize gender identity and sexual orientation, with different emphases for MtFs and FtMs, respectively.
Balogun, Mobolanle; Odeyemi, Kofo
2010-04-29
Traditional birth attendants (TBAs) assist most deliveries in Nigeria. Knowing and understanding all issues surrounding HIV/AIDS and Prevention of Mother-To-Child Transmission of HIV (PMTCT) can help them to protect themselves and others. This study aimed to assess the knowledge and practice of PMTCT amongst TBAs in Lagos, Nigeria. This was a cross-sectional survey. Multistage sampling method was used to select 108 registered TBAs in 2 local governments areas who were interviewed using a pre-tested questionnaire. All the respondents were aware of HIV but their awareness of PMTCT specifically was not as high. Only 8.3% of the respondents had good level of knowledge about HIV and PMTCT and up to 13% of them claimed to be able to cure HIV using native remedies. The practices of HIV counseling of patients and referral of patients for HIV testing were low and higher levels of knowledge positively influenced these practices significantly (p < 0.05). They were also deficient in certain measures to prevent infection of patients and themselves. Most of the TBAs did not have adequate knowledge and practice of PMTCT illustrating the need for periodic PMTCT training for TBAs.
Screening for Chronic Obstructive Pulmonary Disease (COPD) in an Urban HIV Clinic: A Pilot Study
Kaner, Robert J.; Glesby, Marshall J.
2015-01-01
Abstract Increased smoking and a detrimental response to tobacco smoke in the lungs of HIV/AIDS patients result in an increased risk for COPD. We aimed to determine the predictive value of a COPD screening strategy validated in the general population and to identify HIV-related factors associated with decreased lung function. Subjects at least 35 years of age at an HIV clinic in New York City completed a COPD screening questionnaire and peak flow measurement. Those with abnormal results and a random one-third of normal screens had spirometry. 235 individuals were included and 89 completed spirometry. Eleven (12%) had undiagnosed airway obstruction and 5 had COPD. A combination of a positive questionnaire and abnormal peak flow yielded a sensitivity of 20% (specificity 93%) for detection of COPD. Peak flow alone had a sensitivity of 80% (specificity 80%). Abnormal peak flow was associated with an AIDS diagnosis (p=0.04), lower nadir (p=0.001), and current CD4 counts (p=0.001). Nadir CD4 remained associated in multivariate analysis (p=0.05). Decreased FEV1 (<80% predicted) was associated with lower CD4 count nadir (p=0.04) and detectable current HIV viral load (p=0.01) in multivariate analysis. Questionnaire and peak flow together had low sensitivity, but abnormal peak flow shows potential as a screening tool for COPD in HIV/AIDS. These data suggest that lung function may be influenced by HIV-related factors. PMID:25723842
Harper, Gary W; Tyler, April Timmons; Bruce, Douglas; Graham, Louis; Wade, Ryan M
2016-12-01
Black gay and bisexual young men carry a disproportionate burden of HIV in the United States. This study explored Black gay and bisexual young men living with HIV's identification and interpretation of race-specific cultural messages regarding substance use, sexual activity, and condom use. A total of 36 Black gay and bisexual young men living with HIV (ages 16-24, mean = 20.6 years) from four geographically diverse regions of the United States participated in qualitative in-depth interviews. Results from this study elucidate the ways in which these young men interpret various forms of race-specific cultural messages and experiences regarding substance use, sexual activity, and condom use. Participants discussed cultural messages and experiences promoting and discouraging condoms and substance use. Regarding sexual activity, only messages and experiences promoting sex were reported. Across all three categories, messages and experiences promoting risk were predominant. Data further revealed that socially transmitted cultural messages received by young men emanated from multiple sources, such as family, peers, sexual partners, community/neighborhood, and the broader society. Race-specific cultural messages and experiences should be addressed in interventions for this population, and programs should assist young men in developing a critical consciousness regarding these messages and experiences in order to promote health and well-being. © Society for Community Research and Action 2016.
Faith-Based HIV Care and Prevention in Chinese Immigrant Communities: Rhetoric or Reality?
Kang, Ezer; Chin, John J.; Behar, Elana
2012-01-01
Ethnic churches attended by first generation Chinese immigrants are uniquely positioned to address emerging HIV prevention and care needs within the Chinese community at-large. Efforts to develop faith-based HIV programs necessitate identifying how HIV intersects with the sinicization of Christianity within Chinese churches. This paper will review the process of contextualizing HIV within theological and cultural frameworks that are meaningful for ethnic Chinese church leaders and members. The authors specifically propose two points of integration between public health and ecclesial functions: (1) HIV stigma-mitigation initiatives as informed by Christo-centric teachings of compassion and justice, and (2) HIV prevention and care reframed as social responsibility and informed by the Christian tradition of evangelism. Systems and practices that hinder and promote the involvement of Chinese churches in HIV prevention, care, and stigma-reduction will be discussed. PMID:23483037
Evaluating leadership training in African American HIV prevention organizations.
Coleman, Jason D; Dauner, Kim Nichols; Richter, Donna L; Annang, Lucy; Sellers, Denethia B; Lindley, Lisa L
2011-09-01
This article aimed to examine changes in the HIV prevention capacity of HIV prevention program managers who completed the Institute for HIV Prevention Leadership ("Institute") between 2002 and 2004, and who worked in community-based organizations that primarily served African Americans. Participants completed a survey at three points in time, in which they rated the frequency with which they conducted activities related to HIV prevention practice. Participants also rated their confidence in performing activities. Repeated measures ANOVA was conducted to detect differences at three time points (baseline, immediate posttest, and 6 months posttest). A significant overall positive trend was found in the frequency and confidence of participants to perform specific HIV prevention practices and an overall positive trend in the frequency of processes that support HIV prevention practice. Investment in long-term, intensive, capacity-building programs like the Institute is critical to address the increasing incidence of HIV in many African American communities.
Gender and human rights dimensions of HIV/AIDS in Nigeria.
Aniekwu, Nkoli I
2002-12-01
Until very recently, researchers paid little attention to sex or gender issues in HIV/AIDS. When differences between females and males on health matters were considered at all the focus was clearly on womens' reproductive lives and not on factors affecting the spread of the disease. There was hardly any consideration of the influence of inequalities on the spread of HIV/AIDS and on outcomes of infection between the sexes. Hitherto, health policies and programmes focused on biological aspects of diagnosis, treatment and prevention. In this paper, the author seeks to provide an understanding of the social factors as well as identification of the capacity of human rights to develop an effective response to the disease. It is a gender perspective on human rights with specific implications for women in the context of HIV/AIDS.
Mendelsohn, Joshua B; Rhodes, Tim; Spiegel, Paul; Schilperoord, Marian; Burton, John Wagacha; Balasundaram, Susheela; Wong, Chunting; Ross, David A
2014-11-01
HIV-positive refugees confront a variety of challenges in accessing and adhering to antiretroviral therapy (ART) and attaining durable viral suppression; however, there is little understanding of what these challenges are, how they are navigated, or how they may differ across humanitarian settings. We sought to document and examine accounts of the threats, barriers and facilitators experienced in relation to HIV treatment and care and to conduct comparisons across settings. We conducted semi-structured interviews among a purposive sample of 14 refugees attending a public, urban HIV clinic in Kuala Lumpur, Malaysia (July-September 2010), and 12 refugees attending a camp-based HIV clinic in Kakuma, Kenya (February-March 2011). We used framework methods and between-case comparison to analyze and interpret the data, identifying social and environmental factors that influenced adherence. The multiple issues that threatened adherence to antiretroviral therapy or precipitated actual adherence lapses clustered into three themes: "migration", "insecurity", and "resilience". The migration theme included issues related to crossing borders and integrating into treatment systems upon arrival in a host country. Challenges related to crossing borders were reported in both settings, but threats pertaining to integration into, and navigation of, a new health system were exclusive to the Malaysian setting. The insecurity theme included food insecurity, which was most commonly reported in the Kenyan setting; health systems insecurity, reported in both settings; and emotional insecurity, which was most common in the Kenyan setting. Resilient processes were reported in both settings. We drew on the concept of "bounded agency" to argue that, despite evidence of personal and community resilience, these processes were sometimes insufficient for overcoming social and environmental barriers to adherence. In general, interventions might aim to bolster individuals' range of action with targeted support that bolsters resilient processes. Specific interventions are needed to address locally-based food and health system insecurities. Copyright © 2014 Elsevier Ltd. All rights reserved.
Frye, Victoria; Bonner, Sebastian; Williams, Kim; Henny, Kirk; Bond, Keosha; Lucy, Debbie; Cupid, Malik; Smith, Stephen; Koblin, Beryl A.
2016-01-01
In the United States, racial disparities in HIV/AIDS are stark. Although African Americans comprise an estimated 14% of the U.S. population, they made up 52% of new HIV cases among adults and adolescents diagnosed in 2009. Heterosexual transmission is now the second leading cause of HIV in the United States. African Americans made up a full two-thirds of all heterosexually acquired HIV/AIDS cases between 2005 and 2008. Few demonstrated efficacious HIV prevention interventions designed specifically for adult, African-American heterosexual men exist. Here, we describe the process used to design a theory-based HIV prevention intervention to increase condom use, reduce concurrent partnering, and increase HIV testing among heterosexually active African-American men living in high HIV prevalence areas of New York City. The intervention integrated empowerment, social identity, and rational choices theories and focused on four major content areas: HIV/AIDS testing and education; condom skills training; key relational and behavioral turning points; and masculinity and fatherhood. PMID:23016501
Zhao, Ting-ting; Feng, Qi-ming; Liang, Hao; Tang, Xian-yan; Wei, Bo
2011-11-01
Using Intelligence Scale of Mini Mental State Estimated (MMSE) as the gold standard to determine the relevance of International HIV-associated Dementia Scale (IHDS) in minority ethnic areas in Guangxi populations with different cultural values. Corresponding boundary value related to the authenticity and reliability on IHDS were also evaluated. 200 patients with HIV infection were randomly selected from the minority ethnic groups in Guangxi. For each infected person, MMSE and IHDS blind scale were tested at the same period. Using the results from MMSE scale test as the gold standard, ROC curve and IHDS scale in Guangxi minority populations with different education levels which related to the diagnosis of dementia-HIV values were determined. The value of a specific sector under the IHDS sensitivity, specificity, and internal consistency coefficients was also evaluated. When considering the infected person did not differ on their educational level, the IHDS scale diagnostic cutoff appeared as 8.25, while IHDS sensitivity as 0.925, specificity as 0.731 and Kappa as 0.477 (P < 0.001). When considering the extent of cultural differences did influence the prevalence of infection, the different education groups showed different IHDS diagnostic cutoff values. People with high school, secondary school or higher education levels, the IHDS diagnosis appeared to be 8.25, when sensitivity was 0.917, specificity was 0.895 and Kappa was 0.722 (P < 0.001). People with only primary education level, the IHDS appeared to be 7.25. When sensitivity was 0.875, specificity was 0.661 and Kappa was 0.372 (P < 0.001). The IHDS diagnostic sector in Guangxi minority groups was lower than the internationally recommended level of diagnostic cutoff value (IHDS ≤ 10 points). When using IHDS to perform the HIV related dementia screening program, in the minority areas of Guangxi, culture context, the degree and difference of HIV infection should be considered, especially in using IHDS diagnostic cutoff values.
Klein, Hugh
2014-11-06
Gift giving is the process by which an HIV-positive person purposely infects an HIV-negative person with HIV, usually with that person's knowledge and consent. Little has been written about this HIV transmission practice. In this paper, two specific types of gift giving - generationing and stealthing - are explained and introduced to the scientific literature. Generationing is a type of gift giving in which one gift giver successfully infects a previously-uninfected man with HIV, and then the two men collaborate in an effort to seroconvert another man, and so forth. Stealthing is another type of gift giving in which an HIV-positive man actively tries to infect an HIV-negative man with HIV, without the latter's knowledge or consent. The present study reports on the prevalence of gift giving (4.6%) in a population of men who use the Internet specifically to identify partners for unprotected sex. The research is based on a national random sample of 332 men who have sex with men, identified from 16 websites. Data were collected via telephone interviews conducted between January 2008 and May 2009. The paper concludes with a discussion of the implications of these findings for HIV prevention and intervention efforts. Most notably, to the extent that generationing, stealthing, and gift giving occur among MSM, they represent a very high risk of HIV transmission. More work needs to be done to understand these behaviors, the factors that underlie them, and to determine how prevalent they are in the bare-backing population of MSM.
Klein, Hugh
2014-01-01
Gift giving is the process by which an HIV-positive person purposely infects an HIV-negative person with HIV, usually with that person’s knowledge and consent. Little has been written about this HIV transmission practice. In this paper, two specific types of gift giving – generationing and stealthing – are explained and introduced to the scientific literature. Generationing is a type of gift giving in which one gift giver successfully infects a previously-uninfected man with HIV, and then the two men collaborate in an effort to seroconvert another man, and so forth. Stealthing is another type of gift giving in which an HIV-positive man actively tries to infect an HIV-negative man with HIV, without the latter’s knowledge or consent. The present study reports on the prevalence of gift giving (4.6%) in a population of men who use the Internet specifically to identify partners for unprotected sex. The research is based on a national random sample of 332 men who have sex with men, identified from 16 websites. Data were collected via telephone interviews conducted between January 2008 and May 2009. The paper concludes with a discussion of the implications of these findings for HIV prevention and intervention efforts. Most notably, to the extent that generationing, stealthing, and gift giving occur among MSM, they represent a very high risk of HIV transmission. More work needs to be done to understand these behaviors, the factors that underlie them, and to determine how prevalent they are in the bare-backing population of MSM. PMID:26973945
Gericke, G S
2008-01-01
While HIV encephalopathy and the AIDS dementia complex are considered hallmark neurologic manifestations of HIV-1 infection, increasing evidence of a continuum of nervous system involvement indicates the existence of an unrecognized number of individuals with milder, mostly cognitive and/or behavioural effects. Questions are raised whether HIV-related frontotemporal neuropathology during critical developmental stages could affect development of the brain networks documented to be involved in moral decisions, and whether this could contribute to the phenomenon of delinquency in an unknown percentage of the current generation of approximately 18-25 year old survivors of early childhood or vertically acquired HIV infection. Carefully planned and executed long term, prospective controlled studies using environmental, clinical, neurological, behavioural, genetic, immune and functional neuroimaging correlates would be required to elucidate whether HIV-specific neuropathology could indeed act as an independent risk factor for the development of a frontotemporal sociopathy syndrome. If such an association is proven, the accelerated development of neurospecific therapies should be a priority, especially for clinically and immunologically stable HIV-infected children. It may be necessary to institute such treatment as early as possible in perinatally infected cases, and maybe even during intrauterine life if HIV-1 is demonstrated to also act as a neurobehavioural teratogen for the developing fetal brain. It may, however, prove to be difficult to separate primary neurobiological from environmental factors, since the epigenetic effects on the host genome of retroviral insertion influencing behavioural gene expression characteristics, and altered gene expression following early life stresses may involve overlapping neurodevelopmental gene regulatory networks. In the meantime it remains necessary to prevent or ameliorate frequent neuropsychiatric morbidity from whatever causes.
FIV diversity: FIVPle subtype composition may influence disease outcome in African lions
Troyer, Jennifer L.; Roelke, Melody E.; Jespersen, Jillian M.; Baggett, Natalie; Buckley-Beason, Valerie; MacNulty, Dan; Craft, Meggan; Packer, Craig; Pecon-Slattery, Jill; O’Brien, Stephen J.
2011-01-01
Feline immunodeficiency virus (FIV) infects domestic cats and at least 20 additional species of non-domestic felids throughout the world. Strains specific to domestic cat (FIVFca) produce AIDS-like disease progression, sequelae and pathology providing an informative model for HIV infection in humans. Less is known about the immunological and pathological influence of FIV in other felid species although multiple distinct strains of FIV circulate in natural populations. As in HIV-1 and HIV-2, multiple diverse cross-species infections may have occurred. In the Serengeti National Park, Tanzania, three divergent subtypes of lion FIV (FIVPle) are endemic, whereby 100% of adult lions are infected with one or more of these strains. Herein, the relative distribution of these subtypes in the population are surveyed and, combined with observed differences in lion mortality due to secondary infections based on FIVPle subtypes, the data suggest that FIVPle subtypes may have different patterns of pathogenicity and transmissibility among wild lion populations. PMID:21723622
Rolon, Maria Luisa; Syvertsen, Jennifer L; Robertson, Angela M; Rangel, M Gudelia; Martinez, Gustavo; Ulibarri, Monica D; Servin, Argentina; Strathdee, Steffanie A
2013-06-01
Among female sex workers who use drugs, the experience of having children and its effect on HIV risk behaviors remains underexplored. We draw from a study of 214 female sex workers and their intimate non-commercial partners in Tijuana and Ciudad Juárez, México (n = 428), approximately 30% of whom have children living with them. During qualitative interviews with 41 of these couples, having children emerged as an important topic. Children influenced partners' lives and HIV-related risk behaviors in positive and negative ways. Couples perceived that children strengthened their relationships. Concern for children's well-being motivated couples to contemplate healthier lifestyle changes. However, childrearing costs motivated sex work and structural constraints prevented couples from enacting lifestyle changes. Case studies illustrate these themes and highlight implications for couple- and family-based harm reduction interventions. Specifically, our results suggest a need for economic alternatives to sex work while working with families to develop risk reduction skills.
Yoon, Dukyong; Kim, Hyosil; Suh-Kim, Haeyoung; Park, Rae Woong; Lee, KiYoung
2011-01-01
Microarray analyses based on differentially expressed genes (DEGs) have been widely used to distinguish samples across different cellular conditions. However, studies based on DEGs have not been able to clearly determine significant differences between samples of pathophysiologically similar HIV-1 stages, e.g., between acute and chronic progressive (or AIDS) or between uninfected and clinically latent stages. We here suggest a novel approach to allow such discrimination based on stage-specific genetic features of HIV-1 infection. Our approach is based on co-expression changes of genes known to interact. The method can identify a genetic signature for a single sample as contrasted with existing protein-protein-based analyses with correlational designs. Our approach distinguishes each sample using differentially co-expressed interacting protein pairs (DEPs) based on co-expression scores of individual interacting pairs within a sample. The co-expression score has positive value if two genes in a sample are simultaneously up-regulated or down-regulated. And the score has higher absolute value if expression-changing ratios are similar between the two genes. We compared characteristics of DEPs with that of DEGs by evaluating their usefulness in separation of HIV-1 stage. And we identified DEP-based network-modules and their gene-ontology enrichment to find out the HIV-1 stage-specific gene signature. Based on the DEP approach, we observed clear separation among samples from distinct HIV-1 stages using clustering and principal component analyses. Moreover, the discrimination power of DEPs on the samples (70-100% accuracy) was much higher than that of DEGs (35-45%) using several well-known classifiers. DEP-based network analysis also revealed the HIV-1 stage-specific network modules; the main biological processes were related to "translation," "RNA splicing," "mRNA, RNA, and nucleic acid transport," and "DNA metabolism." Through the HIV-1 stage-related modules, changing stage-specific patterns of protein interactions could be observed. DEP-based method discriminated the HIV-1 infection stages clearly, and revealed a HIV-1 stage-specific gene signature. The proposed DEP-based method might complement existing DEG-based approaches in various microarray expression analyses.
La Porte, Annalena; Cano, Jennifer; Wu, Xuhong; Mitra, Doyel
2016-01-01
ABSTRACT INI1/hSNF5/SMARCB1/BAF47 is an HIV-specific integrase (IN)-binding protein that influences HIV-1 transcription and particle production. INI1 binds to SAP18 (Sin3a-associated protein, 18 kDa), and both INI1 and SAP18 are incorporated into HIV-1 virions. To determine the significance of INI1 and the INI1-SAP18 interaction during HIV-1 replication, we isolated a panel of SAP18-interaction-defective (SID)-INI1 mutants using a yeast reverse two-hybrid screen. The SID-INI1 mutants, which retained the ability to bind to IN, cMYC, and INI1 but were impaired for binding to SAP18, were tested for their effects on HIV-1 particle production. SID-INI1 dramatically reduced the intracellular Gag/Gag-Pol protein levels and, in addition, decreased viral particle production. The SID-INI1-mediated effects were less dramatic in trans complementation assays using IN deletion mutant viruses with Vpr-reverse transcriptase (RT)-IN. SID-INI1 did not inhibit long-terminal-repeat (LTR)-mediated transcription, but it marginally decreased the steady-state gag RNA levels, suggesting a posttranscriptional effect. Pulse-chase analysis indicated that in SID-INI1-expressing cells, the pr55Gag levels decreased rapidly. RNA interference analysis indicated that small hairpin RNA (shRNA)-mediated knockdown of INI1 reduced the intracellular Gag/Gag-Pol levels and further inhibited HIV-1 particle production. These results suggest that SID-INI1 mutants inhibit multiple stages of posttranscriptional events of HIV-1 replication, including intracellular Gag/Gag-Pol RNA and protein levels, which in turn inhibits assembly and particle production. Interfering INI1 leads to a decrease in particle production and Gag/Gag-Pol protein levels. Understanding the role of INI1 and SAP18 in HIV-1 replication is likely to provide novel insight into the stability of Gag/Gag-Pol, which may lead to the development of novel therapeutic strategies to inhibit HIV-1 late events. IMPORTANCE Significant gaps exist in our current understanding of the mechanisms and host factors that influence HIV-1 posttranscriptional events, including gag RNA levels, Gag/Gag-Pol protein levels, assembly, and particle production. Our previous studies suggested that the IN-binding host factor INI1 plays a role in HIV-1 assembly. An ectopically expressed minimal IN-binding domain of INI1, S6, potently and selectively inhibited HIV-1 Gag/Gag-Pol trafficking and particle production. However, whether or not endogenous INI1 and its interacting partners, such as SAP18, are required for late events was unknown. Here, we report that endogenous INI1 and its interaction with SAP18 are necessary to maintain intracellular levels of Gag/Gag-Pol and for particle production. Interfering INI1 or the INI1-SAP18 interaction leads to the impairment of these processes, suggesting a novel strategy for inhibiting posttranscriptional events of HIV-1 replication. PMID:27558426
ERIC Educational Resources Information Center
Ramirez-Valles, Jesus; Fergus, Stevenson; Reisen, Carol A.; Poppen, Paul J.; Zea, Maria Cecilia
2005-01-01
Theories of social integration and stress process posit that community involvement may buffer or may compensate the adverse effects of stigma on psychological well-being. In this article, the authors explore this thesis in a stigmatized and seldom studied group of HIV-positive Latino gay men. Specifically, they examine the effects of community…
Fifield, Jocelyn; O'Sullivan, Lucia; Kelvin, Elizabeth A; Mantell, Joanne E; Exner, Theresa; Ramjee, Gita; Blanchard, Kelly; Hoffman, Susie
2018-05-09
Despite the salience of social support and violence as potential outcomes of disclosure, how pre-existing social support and relationship violence among people living with HIV shapes and influences HIV status disclosure has received limited attention. Following the Disclosure Process Model, this study investigated pre-disclosure support and violence-prone relationships as predictors of disclosure using data from a prospective study of 459 newly diagnosed South African women and men. Most (88%) disclosed their status to at least one person by their 8-month interview. Level of social support was unrelated to disclosure to a partner. However, those with higher levels of support had higher odds of disclosing to family and to others. Women in violence-prone relationships were more likely to report disclosure to a partner than were those not in such relationships, counter to expectations. The findings suggest that the same mechanisms may not explain processes of disclosure across all relationship types.
Mpofu, Elias; Nkomazana, Fidelis; Muchado, Jabulani A; Togarasei, Lovemore; Bingenheimer, Jeffrey Bart
2014-03-05
There is a huge interest by faith-based organizations (FBOs) in sub-Saharan Africa and elsewhere in HIV prevention interventions that build on the religious aspects of being. Successful partnerships between the public health services and FBOs will require a better understanding of the conceptual framing of HIV prevention by FBOS to access for prevention intervention, those concepts the churches of various denominations and their members would support or endorse. This study investigated the conceptual framing of HIV prevention among church youths in Botswana;--a country with one of the highest HIV prevalence in the world. Participants were 213 Pentecostal church members (67% female; age range 12 to 23 years; median age=19 years). We engaged the participants in a mixed-method inductive process to collect data on their implicit framing of HIV prevention concepts, taking into account the centrality of religion concepts to them and the moderating influences of age, gender and sexual experience. After, we analysed the data using multi-dimensional scaling (MDS) and hierarchical cluster analysis (HCA) to map the ways the church youths framed HIV prevention. The findings suggest the church youth to conceptually frame their HIV prevention from both faith-oriented and secular-oriented perspectives, while prioritizing the faith-oriented concepts based on biblical teachings and future focus. In their secular-oriented framing of HIV prevention, the church youths endorsed the importance to learn the facts about HIV and AIDS, understanding of community norms that increased risk for HIV and prevention education. However, components of secular-oriented framing of HIV prevention concepts were comparatively less was well differentiated among the youths than with faith-oriented framing, suggesting latent influences of the church knowledge environment to undervalue secular oriented concepts. Older and sexually experienced church youths in their framing of HIV prevention valued future focus and prevention education less than contrasting peer cohorts, suggesting their greater relative risk for HIV infection. A prospective HIV prevention intervention with the Pentecostal church youths would combine both faith and secular informed concepts. It also would need to take into account the ways in which these youth interpret secular-oriented health concepts in the context of their religious beliefs.
Freedberg, K A; Paltiel, A D
1998-08-01
Dramatic progress has recently been made in defining the pathogenesis and treatment of HIV infection. For the first time in the history of the AIDS epidemic, clinicians have at their disposal an understanding of the replication kinetics of HIV, reliable assays to measure viral load, an increasing number of effective agents to suppress viral replication and to reverse the process of immune system destruction, and a range of options for the treatment and prophylaxis of most of the major opportunistic infections in HIV disease. These remarkable advances are not without their costs, however. New antiretroviral therapies and opportunistic infection prophylaxis regimens impose considerable financial strain on public and private budgets for HIV patient care. They force decision-makers to confront a variety of competing considerations, including issues of length and quality of life, the risks of adverse effects and toxicities, and the dangers of promoting resistance. Questions regarding the continued appropriateness and efficiency of opportunistic infection prevention have prompted increased interest in studies of the cost effectiveness of HIV patient care. In this article, we reviewed the literature on the economic evaluation of prophylaxis for HIV-related complications. Section 1 provides background on recent scientific and clinical advances. Section 2 reviews the state-of-the-art understanding of the cost effectiveness of prophylaxis against specific opportunistic infections. Section 3 broadens the discussion to consider the more general question of optimal allocation of prophylaxis resources across competing opportunistic infections. In Section 4, we briefly examined the influence of cost-effectiveness evaluations on the development and refinement of clinical guidelines for HIV-related opportunistic infection prevention in the US. Section 5 presents some of the methodological challenges that arise in applying the methods of cost-effectiveness analysis to the particular case of opportunistic infection prevention in AIDS. We close, in Section 6, with a comment on directions for further research.
Kikuchi, Kimiyo; Poudel, Krishna C; Muganda, John; Sato, Tomoko; Mutabazi, Vincent; Muhayimpundu, Ribakare; Majyambere, Adolphe; Nyonsenga, Simon P; Sase, Eriko; Jimba, Masamine
2014-01-01
Introduction Every year, approximately 260,000 children are infected with HIV in low- and middle-income countries. The timely initiation and high level of maintenance of antiretroviral therapy (ART) are crucial to reducing the suffering of HIV-positive children. We need to develop a better understanding of the background of children's ART non-adherence because it is not well understood. The purpose of this study is to explore the background related to ART non-adherence, specifically in relation to the orphan status of children in Kigali, Rwanda. Methods We conducted 19 focus group discussions with a total of 121 caregivers of HIV-positive children in Kigali. The primary data for analysis were verbatim transcripts and socio-demographic data. A content analysis was performed for qualitative data analysis and interpretation. Results The study found several contextual factors that influenced non-adherence: among double orphans, there was psychological distance between the caregivers and children, whereas economic burden was the primary issue among paternal orphans. The factors promoting adherence also were unique to each orphan status, such as the positive attitude about disclosing serostatus to the child by double orphans’ caregivers, and feelings of guilt about the child's condition among non-orphaned caregivers. Conclusions Knowledge of orphan status is essential to elucidate the factors influencing ART adherence among HIV-positive children. In this qualitative study, we identified the orphan-related contextual factors that influenced ART adherence. Understanding the social context is important in dealing with the challenges to ART adherence among HIV-positive children. PMID:25477050
Relf, Michael V; Silva, Susan G; Williams, Megan Scull; Moore, Elizabeth; Arscott, Joyell; Caiola, Courtney; Barroso, Julie
2015-10-01
As with many infectious diseases throughout history, stigma is a part of the trajectory of the HIV disease process. HIV-related stigma impedes women from being tested for HIV. Once infected, HIV-related stigma hinders women from disclosing their HIV status to sexual partners and health care providers, engaging in medical care, effectively self-managing the disease after infection, and adhering to anti-retroviral therapy. After three decades of the HIV epidemic, no evidenced-based, culturally relevant, gender-specific interventions exist to help women infected with HIV manage the stigma associated with HIV infection. This manuscript reports the feasibility of using an iPod touch device and acceptability of a stigma reduction intervention with HIV-infected women in the Deep South in a mixed-method, randomized clinical trial. Results from the study demonstrate that it is feasible to utilize an iPod touch device to deliver an HIV-related stigma intervention to women. Further, women report that the HIV-related stigma intervention is acceptable and meaningful.
Ford, Chandra L; Daniel, Mark; Earp, Jo Anne L; Kaufman, Jay S; Golin, Carol E; Miller, William C
2009-04-01
More than one quarter of HIV-infected people are undiagnosed and therefore unaware of their HIV-positive status. Blacks are disproportionately infected. Although perceived racism influences their attitudes toward HIV prevention, how racism influences their behaviors is unknown. We sought to determine whether perceiving everyday racism and racial segregation influence Black HIV testing behavior. This was a clinic-based, multilevel study in a North Carolina city. Eligibility was limited to Blacks (N = 373) seeking sexually transmitted disease diagnosis or screening. We collected survey data, block group characteristics, and lab-confirmed HIV testing behavior. We estimated associations using logistic regression with generalized estimating equations. More than 90% of the sample perceived racism, which was associated with higher odds of HIV testing (odds ratio = 1.64; 95% confidence interval = 1.07, 2.52), after control for residential segregation, and other covariates. Neither patient satisfaction nor mechanisms for coping with stress explained the association. Perceiving everyday racism is not inherently detrimental. Perceived racism may improve odds of early detection of HIV infection in this high-risk population. How segregation influences HIV testing behavior warrants further research.
HIV-related sexual risk assessment among Asian/Pacific Islander American women: an inductive model.
Chin, D
1999-07-01
Current HIV/AIDS rates among Asian/Pacific Islander (A/PI) women in the United States are disproportionately low (CDC, 1998). However, there is evidence to suggest that risk for HIV is present, based upon studies on risk behaviors and markers for risk as well as demographic factors that may facilitate transmission among this population. Because a particular threat to A/PI women is heterosexual transmission, which accounts for nearly half of all cases (CDC, 1998), prevention efforts should focus on risk within sexual contexts and how such risk is assessed and acted upon. Using a qualitative methodology, the present study investigated how A/PI American women assess their HIV-related risk in sexual interactions. Based on extensive interview data, an inductive model of risk assessment was generated consisting of cultural and sexual risk schemata. Findings suggest the influence of cultural schemata on sexual risk schemata, which in turn influence whether condoms or HIV tests are requested. Specifically, the cultural values of reticence regarding sex, the accommodation of others and a traditional romantic ideal inhibit open discussion with partners about HIV as well as requests for safer sex behaviors. Instead, A/PI women tend to engage in non-explicit, inferential assessments of partners' risk, which may contribute to an illusory sense of control and safety. Consistent with previous studies on other groups of women, these findings further extend and elucidate theory and prevention strategies for this population.
Harrison, Joseph D.; Dochney, Jessica A.; Blazekovic, Sonja; Leone, Frank; Metzger, David; Frank, Ian; Gross, Robert; Hole, Anita; Mounzer, Karam; Siegel, Steven; Schnoll, Robert A.; Ashare, Rebecca L.
2017-01-01
HIV-infected smokers lose more years of life to tobacco-related disease than HIV. Since neurocognitive deficits are common among those with HIV and are associated with smoking persistence, these deficits may be a unique barrier to smoking cessation among HIV-infected smokers. Documenting unique differences in and correlates of cognition among HIV-infected smokers is a critical step towards developing a population-specific tobacco cessation treatment. We compared neurocognitive function between HIV-infected (n=103) and HIV-uninfected smokers (n=70), accounting for demographic and smoking-related variables. We also evaluated whether HIV-related health outcomes (e.g., CD4 count, viral load, depression ratings, quality of life [QoL]) and HAART adherence were associated with cognition. Participants completed neurocognitive tasks (N-back and Continuous Performance Task [CPT]) measuring working memory, attention, and processing speed, and intra-individual variability. Stepwise regression models were conducted and validated with resampling techniques. HIV-infected smokers performed worse than HIV-uninfected smokers on working memory, processing speed, and intra-individual variability (all p<0.01). ROC analysis for the model including cognitive measures demonstrated 85% area under the curve, which indicates “good prediction” for distinguishing between HIV-infected and HIV-uninfected smokers. This was a significant improvement over the model including demographic and smoking-related variables only (p=0.0003). Among HIV-infected smokers, neurocognitive performance was negatively associated with QoL and depression ratings. Smoking cessation interventions for HIV-infected smokers should consider cognitive neurorehabilitation as a potential strategy to decrease the likelihood of nicotine relapse and decrease tobacco-related morbidity in this population. PMID:28429289
Chisenga, Molly; Siame, Joshua; Baisley, Kathy; Kasonka, Lackson; Filteau, Suzanne
2011-04-01
Choosing an infant feeding mode is complex for human immunodeficiency virus (HIV)-infected African women. We documented infant feeding choices by 811 mothers of infants aged less than 18 months enrolled in the Chilenje Infant Growth, Nutrition and Infection Study of fortified complementary or replacement foods. We also conducted 20 interviews and 4 focus group discussions among women and nurses to explore the issues in depth. Practices of most HIV-infected women did not closely follow national or international guidelines: 26% never initiated breastfeeding, and 55% were not breastfeeding by 6 months post partum. Women of lower socio-economic status and those not meeting criteria for safe replacement feeding were more likely to initiate breastfeeding, to continue longer and to stop at 6 months when provided with free food within the trial. Most HIV-negative women and women of unknown HIV status continued breastfeeding into the infant's second year, indicating limited 'spillover' of infant feeding messages designed for HIV-infected women into the uninfected population. Qualitative work indicated that the main factors affecting HIV-infected women's infant feeding decisions were the cost of formula, the advice of health workers, influence of relatives, stigma and difficulties with using an exclusive feeding mode. Rapidly changing international recommendations confused both mothers and nurses. Many HIV-infected women chose replacement feeding without meeting criteria to do this safely. Women were influenced by health workers but, for several reasons, found it difficult to follow their advice. The recently revised international HIV and infant feeding recommendations may make the counselling process simpler for health workers and makes following their advice easier for HIV-infected women. © 2010 Blackwell Publishing Ltd.
Nemoto, Tooru; Iwamoto, Mariko; Kamitani, Emiko; Morris, Anne; Sakata, Maria
2011-04-01
Access to culturally competent HIV/AIDS and substance abuse treatment and prevention services is limited for Asian and Pacific Islanders (APIs). Based on the intake data for a community outreach project in the San Francisco Bay Area (N = 1,349), HIV risk behaviors were described among the targeted API risk groups. The self-reported HIV prevalence was 6% among MSM. Inconsistent condom use for vaginal sex with casual partners in the past 6 months was reported among substance users (43%) and incarcerated participants (60%), whereas 26% of men who have sex with men reported inconsistent condom use for anal sex with casual partners. Overall, 56% and 29% had engaged in sex with casual partners under the influence of alcohol and drugs in the past 6 months, respectively. Although API organizations in the Bay Area have spearheaded HIV prevention, future programs must address substance use issues in relation to sexual risk behaviors, specific to API risk groups.
Evidence for Placental HPV Infection in Both HIV Positive and Negative Women
Chisanga, Chrispin; Eggert, Dawn; Mitchell, Charles D.; Wood, Charles; Angeletti, Peter C.
2016-01-01
Human papillomaviruses (HPVs) have previously been reported to infect epithelial trophoblast cells of the placenta. To investigate this possibility, 200 placental samples from Zambian women were separated into HIV+ and HIV− groups and tested for HPV by redundant primer PCR, using GP5+/GP6+ and CPI/CPII primer sets. Three HPV genotypes (HPV6, 16 and 90) were detected in placental samples. Whereas, 20 different HPV genotypes were detected in vaginal sampling of the same patients, suggesting that compartment specific sub-populations of HPV may exist. The incidence of HPV16 in placental samples was almost 2-fold greater in HIV+ women compared to HIV− (p = 0.0241). HPV16 L1 expression, detected by immunochemistry, was significantly higher in HIV+ than HIV− samples (p = 0.0231). HPV16 DNA was detected in the nuclei of trophoblast cells by in situ hybridization. Overall, these results suggest that HPVs infect the placenta and that HIV significantly influences these infections. PMID:26865986
Melki, Marie-Thérèse; Saïdi, Héla; Dufour, Alexandre; Olivo-Marin, Jean-Christophe; Gougeon, Marie-Lise
2010-04-15
Early stages of Human Immunodeficiency Virus-1 (HIV-1) infection are associated with local recruitment and activation of important effectors of innate immunity, i.e. natural killer (NK) cells and dendritic cells (DCs). Immature DCs (iDCs) capture HIV-1 through specific receptors and can disseminate the infection to lymphoid tissues following their migration, which is associated to a maturation process. This process is dependent on NK cells, whose role is to keep in check the quality and the quantity of DCs undergoing maturation. If DC maturation is inappropriate, NK cells will kill them ("editing process") at sites of tissue inflammation, thus optimizing the adaptive immunity. In the context of a viral infection, NK-dependent killing of infected-DCs is a crucial event required for early elimination of infected target cells. Here, we report that NK-mediated editing of iDCs is impaired if DCs are infected with HIV-1. We first addressed the question of the mechanisms involved in iDC editing, and we show that cognate NK-iDC interaction triggers apoptosis via the TNF-related apoptosis-inducing ligand (TRAIL)-Death Receptor 4 (DR4) pathway and not via the perforin pathway. Nevertheless, once infected with HIV-1, DC(HIV) become resistant to NK-induced TRAIL-mediated apoptosis. This resistance occurs despite normal amounts of TRAIL released by NK cells and comparable DR4 expression on DC(HIV). The escape of DC(HIV) from NK killing is due to the upregulation of two anti-apoptotic molecules, the cellular-Flice like inhibitory protein (c-FLIP) and the cellular inhibitor of apoptosis 2 (c-IAP2), induced by NK-DC(HIV) cognate interaction. High-mobility group box 1 (HMGB1), an alarmin and a key mediator of NK-DC cross-talk, was found to play a pivotal role in NK-dependent upregulation of c-FLIP and c-IAP2 in DC(HIV). Finally, we demonstrate that restoration of DC(HIV) susceptibility to NK-induced TRAIL killing can be obtained either by silencing c-FLIP and c-IAP2 by specific siRNA, or by inhibiting HMGB1 with blocking antibodies or glycyrrhizin, arguing for a key role of HMGB1 in TRAIL resistance and DC(HIV) survival. These findings provide evidence for a new strategy developed by HIV to escape immune attack, they challenge the question of the involvement of HMGB1 in the establishment of viral reservoirs in DCs, and they identify potential therapeutic targets to eliminate infected DCs.
Chemnasiri, Tareerat; Beane, Chelsey R; Varangrat, Anchalee; Chaikummao, Supaporn; Chitwarakorn, Anupong; Van Griensven, Frits; Holtz, Timothy H
2018-01-08
The Bangkok Men Who Have Sex With Men (MSM) Cohort Study has shown high HIV incidence (8-12/100 person-years) among 18-21-year-old MSM. These data led to a further study using qualitative methods among young (18-24 years old) MSM in order to understand the factors driving the HIV epidemic among YMSM. We conducted eight focus group discussions and 10 key informant interviews among YMSM in Bangkok, Thailand. Sociodemographic and behavioral data were collected using a questionnaire. We audio-recorded, transcribed, and analyzed qualitative and questionnaire data using computer software. The categories relating to risk behavior were (1) the use of social networks for seeking sexual partners and the marketing promotions of MSM entertainment venues, (2) social influence by peers and older MSM, (3) easy access to high parties and group sex, (4) easy access to club drugs, (5) conceptions related to HIV risk, and (6) sexual preferences of YMSM. Increased HIV testing, same-sex education, and YMSM-specific HIV prevention efforts are urgently needed for YMSM in Bangkok.
Kevany, Sebastian; Benatar, Solomon R; Fleischer, Theodore
2013-01-01
The escalating expenditure on patients with HIV/AIDS within an inadequately funded public health system is tending towards crowding out care for patients with non-HIV illnesses. Priority-setting decisions are thus required and should increasingly be based on an explicit, transparent and accountable process to facilitate sustainability. South Africa's public health system is eroding, even though the government has received extensive donor financing for specific conditions, such as HIV/AIDS. The South African government's 2007 HIV plan anticipated costs exceeding 20% of the annual health budget with a strong focus on treatment interventions, while the recently announced 2012-2016 National Strategic HIV plan could cost up to US$16 billion. Conversely, the total non-HIV health budget has remained static in recent years, effectively reducing the supply of health care for other diseases. While the South African government cannot meet all demands for health care simultaneously, health funders should attempt to allocate health resources in a fair, efficient, transparent and accountable manner, in order to ensure that publicly funded health care is delivered in a reasonable and non-discriminatory fashion. We recommend a process for resource allocation that includes ethical, economic, legal and policy considerations. This process, adapted for use by South Africa's policy-makers, could bring health, political, economic and ethical gains, whilst allaying a social crisis as mounting treatment commitments generated by HIV have the potential to overwhelm the health system.
Ndabarora, Eléazar; Mchunu, Gugu
2014-01-01
Various studies have reported that university students, who are mostly young people, rarely use existing HIV/AIDS preventive methods. Although studies have shown that young university students have a high degree of knowledge about HIV/AIDS and HIV modes of transmission, they are still not utilising the existing HIV prevention methods and still engage in risky sexual practices favourable to HIV. Some variables, such as awareness of existing HIV/AIDS prevention methods, have been associated with utilisation of such methods. The study aimed to explore factors that influence use of existing HIV/AIDS prevention methods among university students residing in a selected campus, using the Health Belief Model (HBM) as a theoretical framework. A quantitative research approach and an exploratory-descriptive design were used to describe perceived factors that influence utilisation by university students of HIV/AIDS prevention methods. A total of 335 students completed online and manual questionnaires. Study findings showed that the factors which influenced utilisation of HIV/AIDS prevention methods were mainly determined by awareness of the existing university-based HIV/AIDS prevention strategies. Most utilised prevention methods were voluntary counselling and testing services and free condoms. Perceived susceptibility and perceived threat of HIV/AIDS score was also found to correlate with HIV risk index score. Perceived susceptibility and perceived threat of HIV/AIDS showed correlation with self-efficacy on condoms and their utilisation. Most HBM variables were not predictors of utilisation of HIV/AIDS prevention methods among students. Intervention aiming to improve the utilisation of HIV/AIDS prevention methods among students at the selected university should focus on removing identified barriers, promoting HIV/AIDS prevention services and providing appropriate resources to implement such programmes.
Brenner, Bluma G.; Ibanescu, Ruxandra-Ilinca; Hardy, Isabelle; Roger, Michel
2017-01-01
HIV continues to spread among vulnerable heterosexual (HET), Men-having-Sex with Men (MSM) and intravenous drug user (IDU) populations, influenced by a complex array of biological, behavioral and societal factors. Phylogenetics analyses of large sequence datasets from national drug resistance testing programs reveal the evolutionary interrelationships of viral strains implicated in the dynamic spread of HIV in different regional settings. Viral phylogenetics can be combined with demographic and behavioral information to gain insights on epidemiological processes shaping transmission networks at the population-level. Drug resistance testing programs also reveal emergent mutational pathways leading to resistance to the 23 antiretroviral drugs used in HIV-1 management in low-, middle- and high-income settings. This article describes how genotypic and phylogenetic information from Quebec and elsewhere provide critical information on HIV transmission and resistance, Cumulative findings can be used to optimize public health strategies to tackle the challenges of HIV in “real-world” settings. PMID:29283390
Dinh, H T; White, J L; Hipwell, M; Nguyen, C T K; Pharris, A
2018-04-01
Insights into disclosure by people living with HIV and AIDS (PLWHA) can inform strategies for treatment and support, yet Vietnamese women's self-disclosure patterns are poorly understood. We conducted interviews with 12 HIV-positive women, identifying three principal factors influencing disclosure to family members: patrilocal residence, desire to protect own family, and the need for financial support. Women's decision-making about disclosure was significantly affected by dependence on or independence of parents-in-law and their own parents. We believe that our findings reveal the complex interplay of stigma and disclosure within Vietnamese families, highlighting the need for specific social measures that promote self-disclosure combined with family support for female PLWHA.
Musiimenta, Angella
2012-01-01
Background: Although Uganda had recorded declines in HIV infection rates around 1990’s, it is argued that HIV/AIDS risk sexual behaviour, especially among the youth, started increasing again from early 2000. School-based computer-assisted HIV interventions can provide interactive ways of improving the youth’s HIV knowledge, attitudes and skills. However, these interventions have long been reported to have limited success in improving the youth’s sexual behaviours, which is always the major aim of implementing such interventions. This could be because the commonly used health promotion theories employed by these interventions have limited application in HIV prevention. These theories tend to lack sufficient attention to contextual mediators that influence ones sexual behaviours. Moreover, literature increasingly expresses dissatisfaction with the dominant prevailing descriptive survey-type HIV/AIDS-related research. Objective and Methods: The objective of this research was to identify contextual mediators that influence the youth’s decision to adopt and maintain the HIV/AIDS preventive behaviour advocated by a computer-assisted intervention. To achieve this objective, this research employed qualitative method, which provided in-depth understanding of how different contexts interact to influence the effectiveness of HIV/AIDS interventions. The research question was: What contextual mediators are influencing the youth’s decision to adopt and maintain the HIV/AIDS preventive behaviour advocated by a computer-assisted intervention? To answer this research question, 20 youth who had previously completed the WSWM intervention when they were still in secondary schools were telephone interviewed between Sept.08 and Dec.08. The collected data was then analysed, based on grounded theory’s coding scheme. Results: Findings demonstrate that although often ignored by HIV interventionists and researchers, variety of contextual mediators influence individual uptake of HIV preventives. These include relationship characteristics, familial mediators, peer influence, gender-based social norms, economic factors and religious beliefs. Conclusion: To generate concomitant mutual efforts, rather than exclusively focusing on individual level mediators, there is an urgent need to shift to integrative approaches, which combine individual level change strategies with contextual level change approaches in the design and implementation of interventional strategies to fight against HIV/AIDS. PMID:23569636
A systematic review of prospective memory in HIV disease: from the laboratory to daily life.
Avci, Gunes; Sheppard, David P; Tierney, Savanna M; Kordovski, Victoria M; Sullivan, Kelli L; Woods, Steven Paul
2017-09-27
Prospective memory (PM) is described as the capacity to form and maintain an intention that is executed in response to a specific cue. Neural injury and associated neurocognitive disorders are common among persons living with HIV disease, who might therefore be susceptible to impairment in PM. This literature review utilized a structured qualitative approach to summarize and evaluate our current understanding of PM functioning in people living with HIV disease. 33 studies of PM in HIV+ persons met criteria for inclusion. Findings showed that HIV is associated with moderate deficits in PM, which appear to be largely independent of commonly observed comorbid factors. The pattern of PM deficits reveals dysregulation of strategic processes that is consistent with the frontal systems pathology and associated executive dysfunction that characterizes HIV-associated neural injury. The literature also suggests that HIV-associated PM deficits present a strong risk of concurrent problems in a wide range of health behaviors (e.g. medication non-adherence) and activities of daily living (e.g. employment). Early attempts to improve PM in HIV disease have revealed that supporting strategic processes might be effective for some individuals. HIV-associated PM deficits are common and exert a significant adverse effect on the daily lives and health of infected persons. Much work remains to be done to understand the cognitive architecture of HIV-associated PM deficits and the most efficient means to enhance PM functioning and improve health outcomes in persons living with HIV.
Feldman, Jamie; Romine, Rebecca Swinburne; Bockting, Walter O.
2014-01-01
To study the influence of gender on HIV risk, a sample of the U.S. transgender population (N = 1,229) was recruited via the Internet. HIV risk and prevalence were lower than reported in prior studies of localized, urban samples, but higher than the overall U.S. population. Findings suggest that gender nonconformity alone does not itself result in markedly higher HIV risk. Sex with nontransgender men emerged as the strongest independent predictor of unsafe sex for both male-to-female (MtF) and female-to-male (FtM) participants. These sexual relationships constitute a process that may either affirm or problematize gender identity and sexual orientation, with different emphases for MtFs and FtMs, respectively. PMID:25022491
Protegiendo Nuestra Comunidad: empowerment participatory education for HIV prevention.
McQuiston, C; Choi-Hevel, S; Clawson, M
2001-10-01
To be effective, HIV/AIDS interventions must be culturally and linguistically appropriate and must occur within the context of the specific community in which they are delivered. In this article, the development of a culture-specific lay health advisor (LHA) program, Protegiendo Nuestra Comunidad, for recently immigrated Mexicans is described. This program is one component of a collaborative inquiry research project involving community participants and researchers working as partners in carrying out and assessing a program for the prevention of HIV/AIDS. The collaborative inquiry process was applied as an empowerment philosophy and methodology of Paulo Freire and an ecological framework was used for the development of Protegiendo Nuestra Comunidad. The use of principles of empowerment for curriculum development, teaching methodology, and program delivery are described.
Reidy, William J; Spielberg, Freya; Wood, Robert; Binson, Diane; Woods, William J; Goldbaum, Gary M
2009-04-01
We studied the HIV risk behaviors of patrons of the 3 commercial sex venues for men in Seattle, Washington. We conducted cross-sectional, observational surveys in 2004 and 2006 by use of time-venue cluster sampling with probability proportional to size. Surveys were anonymous and self-reported. We analyzed the 2004 data to identify patron characteristics and predictors of risk behaviors and compared the 2 survey populations. Fourteen percent of respondents reported a previous HIV-positive test, 14% reported unprotected anal intercourse, and 9% reported unprotected anal intercourse with a partner of unknown or discordant HIV status during the current commercial sex venue visit. By logistic regression, recent unprotected anal intercourse outside of a commercial sex venue was independently associated with unprotected anal intercourse. Sex venue site and patron drug use were strongly associated with unprotected anal intercourse at the crude level. The 2004 and 2006 survey populations did not differ significantly in demographics or behaviors. Patron and venue-specific characteristics factors may each influence the frequency of HIV risk behaviors in commercial sex venues. Future research should evaluate the effect of structural and individual-level interventions on HIV transmission.
Dang, Chao; Wei, Bo; Long, JianXiong; Zhou, MengXiao; Han, XinXin; Zhao, TingTing
2015-04-01
In 2012, more than 80,000 cases of HIV infection were recorded in the Southern Chinese minority autonomous region of Guangxi Zhuang, where the occurrence of HIV-associated dementia remains high. The International HIV Dementia Scale is a relatively simple-to-administer screening scale for HIV-associated neurocognitive disorders. However, clinical experience in utilizing the scale with large Chinese samples is currently lacking, especially among individuals with limited formal schooling. In this study, a full neuropsychological evaluation the gold standard was conducted to identify the incidence/prevalence of HIV-associated neurocognitive disorders in a socioeconomically underdeveloped region of Southern China and to locate the optimal cut-off scale value using receiver operating characteristic curves. The highest Youden index of the scale was 0.450, with a corresponding cut-off point of 7.25. The sensitivity and specificity were 0.737 and 0.713, respectively. These results suggest that the scale is an effective and feasible screening tool for HIV-associated neurocognitive disorders in poorer regions of China with fewer well-educated residents. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Stevenson, M; Haggerty, S; Lamonica, C; Mann, A M; Meier, C; Wasiak, A
1990-01-01
The phenomenon of interference was exploited to isolate low-abundance noncytopathic human immunodeficiency virus type 1 (HIV-1) variants from a primary HIV-1 isolate from an asymptomatic HIV-1-seropositive hemophiliac. Successive rounds of virus infection of a cytolysis-susceptible CD4+ cell line and isolation of surviving cells resulted in selective amplification of an HIV-1 variant reduced in the ability to induce cytolysis. The presence of a PvuII polymorphism facilitated subsequent amplification and cloning of cytopathic and noncytopathic HIV-1 variants from the primary isolate. Cloned virus stocks from cytopathic and noncytopathic variants exhibited similar replication kinetics, infectivity, and syncytium induction in susceptible host cells. The noncytopathic HIV-1 variant was unable, however, to induce single-cell killing in susceptible host cells. Construction of viral hybrids in which regions of cytopathic and noncytopathic variants were exchanged indicated that determinants for the noncytopathic phenotype map to the envelope glycoprotein. Sequence analysis of the envelope coding regions indicated the absence of two highly conserved N-linked glycosylation sites in the noncytopathic HIV-1 variant, which accompanied differences in processing of precursor gp160 envelope glycoprotein. These results demonstrate that determinants for syncytium-independent single-cell killing are located within the envelope glycoprotein and suggest that single-cell killing is profoundly influenced by alterations in envelope sequence which affect posttranslational processing of HIV-1 envelope glycoprotein within the infected cell. Images PMID:1695254
Grewe, Mary E.; Taboada, Arianna; Dennis, Alexis; Chen, Elizabeth; Stein, Kathryn; Watson, Sable; Barrington, Clare; Lightfoot, Alexandra F.
2015-01-01
Theatre-based interventions have been used in health promotion activities among young people to address HIV and sexual health. In this study, we explored the experience of undergraduate student performers participating in a theatre-based HIV prevention and sexual health education intervention for high school students in the USA. Undergraduate students enrolled in a credit-bearing course to learn about HIV and sexual health, participatory theatre and health education techniques. We analysed students’ reflective essays written throughout the semester to identify any changes and the intervention processes that promoted these changes. Students experienced five interrelated forms of transformation: (1) increased knowledge about HIV and sexual health; (2) changes in attitude and communication about sex; (3) artistic growth; (4) emotional growth; and (5) clarification of career goals and future plans. Intervention processes that contributed to these transformations included improvisation, guided writing exercises, the creation of a close-knit cohesive group, and interactions with a group of HIV-positive speakers. Theatre-based, peer-led sexual health programmes can provide a transformative experience for undergraduate student performers. The transformative effects are linked to specific activities and processes of the intervention and require examination in future research. PMID:26085813
Sex, touch, and HIV risk among ecstasy users.
Theall, Katherine P; Elifson, Kirk W; Sterk, Claire E
2006-03-01
We examined HIV risk among heavy and nonheavy ecstasy users, focusing specifically on touch and sexual behavior as part of the ecstasy experience. Structured interviews were conducted with 268 young adult (age 18-25) ecstasy users in Atlanta, Georgia. Heavy ecstasy users were more likely to have been tested for HIV than nonheavy users (79 vs. 68%). However, they also were more likely to perceive no chance of contracting HIV (36 vs. 26%). Touch, both sensual and sexual, was a significant part of the ecstasy experience. In addition, ecstasy use seemed to increase the sexual desire, however, not the ability to achieve an orgasm. Heavy users reported more sexual risk-taking than their nonheavy using counterparts. Results suggest that the setting of ecstasy use also may influence involvement in risk behaviors. Future longitudinal studies are needed on the relationship between ecstasy use, touch, sexual arousal and ability, and risk behavior.
Koehler, Rebecca N; Walsh, Anne M; Saathoff, Elmar; Tovanabutra, Sodsai; Arroyo, Miguel A; Currier, Jeffery R; Maboko, Leonard; Hoelscher, Michael; Hoelsher, Michael; Robb, Merlin L; Michael, Nelson L; McCutchan, Francine E; Kim, Jerome H; Kijak, Gustavo H
2010-11-15
Here we explore associations between HLA variation and human immunodeficiency virus type 1 (HIV-1) acquisition and disease progression in a community cohort in Mbeya, Tanzania, a region that, despite harboring high rates of HIV-1 infection, remains understudied. African-specific allele HLA-A*74:01 was associated with decreased risk of infection (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.14-0.80; P = .011) and with protection from CD4(+) cell counts <200 cells/uL in women (OR, 0.31; 95% CI, 0.07-0.91; P = .032) and men (OR, 0.15; 95% CI, 0.01-0.78; P = .020). These associations remained significant after adjustment for linkage disequilibrium with HLA-B and HLA-C alleles. This observation calls for additional investigation of mechanisms by which HLA-A*74:01 may influence HIV-1 acquisition and control of the infection.
Feldman, Matthew B; Thomas, Jacinthe A; Alexy, Emily R; Irvine, Mary K
2015-02-01
Drug use poses multiple challenges to maintaining physical health among HIV-infected individuals, particularly with regard to disease progression. Few studies, however, have examined the association between the use of crystal methamphetamine ("crystal meth") and HIV disease progression specifically among HIV-infected men who have sex with men (MSM). Understanding this relationship among HIV-infected MSM is particularly critical because of the high rates of crystal meth use reported in the population. Associations between recent crystal meth use and poor HIV medical outcomes (viral load>200 copies/mL, CD4 count <350 cells/mm(3)) were analyzed for 2896 HIV-infected MSM enrolled in Ryan White Part A programs in the greater New York metropolitan area between November 2010 and June 2012. Crystal meth use (reported by 4%) was independently associated with unsuppressed viral load (AOR=1.8, CI=1.1-2.9) in multivariate analyses controlling for sociodemographic characteristics. There was no significant relationship between crystal meth use and low CD4 counts. To date, little research has examined how crystal meth use influences HIV medical outcomes among HIV-infected MSM. This analysis showed a significant independent association between crystal meth use and unsuppressed viral load among MSM in an HIV service population. Future studies should examine biological and psychosocial mediators, moderators and confounders of this relationship to inform intervention development for MSM crystal meth users in HIV care settings. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Liu, Haichuan; Usmani, Shariq M.; Neidleman, Jason; Müller, Janis A.; Avila-Herrera, Aram; Gawanbacht, Ali; Zirafi, Onofrio; Chu, Simon; Dong, Ming; Kumar, Senthil T.; Smith, James F.; Pollard, Katherine S.; Fändrich, Marcus; Kirchhoff, Frank; Münch, Jan; Witkowska, H. Ewa; Greene, Warner C.
2014-01-01
ABSTRACT Semen enhances HIV infection in vitro, but how long it retains this activity has not been carefully examined. Immediately postejaculation, semen exists as a semisolid coagulum, which then converts to a more liquid form in a process termed liquefaction. We demonstrate that early during liquefaction, semen exhibits maximal HIV-enhancing activity that gradually declines upon further incubation. The decline in HIV-enhancing activity parallels the degradation of peptide fragments derived from the semenogelins (SEMs), the major components of the coagulum that are cleaved in a site-specific and progressive manner upon initiation of liquefaction. Because amyloid fibrils generated from SEM fragments were recently demonstrated to enhance HIV infection, we set out to determine whether any of the liquefaction-generated SEM fragments associate with the presence of HIV-enhancing activity. We identify SEM1 from amino acids 86 to 107 [SEM1(86-107)] to be a short, cationic, amyloidogenic SEM peptide that is generated early in the process of liquefaction but that, conversely, is lost during prolonged liquefaction due to the activity of serine proteases. Synthetic SEM1(86-107) amyloids directly bind HIV-1 virions and are sufficient to enhance HIV infection of permissive cells. Furthermore, endogenous seminal levels of SEM1(86-107) correlate with donor-dependent variations in viral enhancement activity, and antibodies generated against SEM1(86-107) recognize endogenous amyloids in human semen. The amyloidogenic potential of SEM1(86-107) and its virus-enhancing properties are conserved among great apes, suggesting an evolutionarily conserved function. These studies identify SEM1(86-107) to be a key, HIV-enhancing amyloid species in human semen and underscore the dynamic nature of semen's HIV-enhancing activity. IMPORTANCE Semen, the most common vehicle for HIV transmission, enhances HIV infection in vitro, but how long it retains this activity has not been investigated. Semen naturally undergoes physiological changes over time, whereby it converts from a gel-like consistency to a more liquid form. This process, termed liquefaction, is characterized at the molecular level by site-specific and progressive cleavage of SEMs, the major components of the coagulum, by seminal proteases. We demonstrate that the HIV-enhancing activity of semen gradually decreases over the course of extended liquefaction and identify a naturally occurring semenogelin-derived fragment, SEM1(86-107), whose levels correlate with virus-enhancing activity over the course of liquefaction. SEM1(86-107) amyloids are naturally present in semen, and synthetic SEM1(86-107) fibrils bind virions and are sufficient to enhance HIV infection. Therefore, by characterizing dynamic changes in the HIV-enhancing activity of semen during extended liquefaction, we identified SEM1(86-107) to be a key virus-enhancing component of human semen. PMID:24741080
2011-01-01
Assessing the impact that research evidence has on policy is complex. It involves consideration of conceptual issues of what determines research impact and policy change. There are also a range of methodological issues relating to the question of attribution and the counter-factual. The dynamics of SRH, HIV and AIDS, like many policy arenas, are partly generic and partly issue- and context-specific. Against this background, this article reviews some of the main conceptualisations of research impact on policy, including generic determinants of research impact identified across a range of settings, as well as the specificities of SRH in particular. We find that there is scope for greater cross-fertilisation of concepts, models and experiences between public health researchers and political scientists working in international development and research impact evaluation. We identify aspects of the policy landscape and drivers of policy change commonly occurring across multiple sectors and studies to create a framework that researchers can use to examine the influences on research uptake in specific settings, in order to guide attempts to ensure uptake of their findings. This framework has the advantage that distinguishes between pre-existing factors influencing uptake and the ways in which researchers can actively influence the policy landscape and promote research uptake through their policy engagement actions and strategies. We apply this framework to examples from the case study papers in this supplement, with specific discussion about the dynamics of SRH policy processes in resource poor contexts. We conclude by highlighting the need for continued multi-sectoral work on understanding and measuring research uptake and for prospective approaches to receive greater attention from policy analysts. PMID:21679384
Assessing the Performance of a Computer-Based Policy Model of HIV and AIDS
Rydzak, Chara E.; Cotich, Kara L.; Sax, Paul E.; Hsu, Heather E.; Wang, Bingxia; Losina, Elena; Freedberg, Kenneth A.; Weinstein, Milton C.; Goldie, Sue J.
2010-01-01
Background Model-based analyses, conducted within a decision analytic framework, provide a systematic way to combine information about the natural history of disease and effectiveness of clinical management strategies with demographic and epidemiological characteristics of the population. Among the challenges with disease-specific modeling include the need to identify influential assumptions and to assess the face validity and internal consistency of the model. Methods and Findings We describe a series of exercises involved in adapting a computer-based simulation model of HIV disease to the Women's Interagency HIV Study (WIHS) cohort and assess model performance as we re-parameterized the model to address policy questions in the U.S. relevant to HIV-infected women using data from the WIHS. Empiric calibration targets included 24-month survival curves stratified by treatment status and CD4 cell count. The most influential assumptions in untreated women included chronic HIV-associated mortality following an opportunistic infection, and in treated women, the ‘clinical effectiveness’ of HAART and the ability of HAART to prevent HIV complications independent of virologic suppression. Good-fitting parameter sets required reductions in the clinical effectiveness of 1st and 2nd line HAART and improvements in 3rd and 4th line regimens. Projected rates of treatment regimen switching using the calibrated cohort-specific model closely approximated independent analyses published using data from the WIHS. Conclusions The model demonstrated good internal consistency and face validity, and supported cohort heterogeneities that have been reported in the literature. Iterative assessment of model performance can provide information about the relative influence of uncertain assumptions and provide insight into heterogeneities within and between cohorts. Description of calibration exercises can enhance the transparency of disease-specific models. PMID:20844741
Assessing the performance of a computer-based policy model of HIV and AIDS.
Rydzak, Chara E; Cotich, Kara L; Sax, Paul E; Hsu, Heather E; Wang, Bingxia; Losina, Elena; Freedberg, Kenneth A; Weinstein, Milton C; Goldie, Sue J
2010-09-09
Model-based analyses, conducted within a decision analytic framework, provide a systematic way to combine information about the natural history of disease and effectiveness of clinical management strategies with demographic and epidemiological characteristics of the population. Among the challenges with disease-specific modeling include the need to identify influential assumptions and to assess the face validity and internal consistency of the model. We describe a series of exercises involved in adapting a computer-based simulation model of HIV disease to the Women's Interagency HIV Study (WIHS) cohort and assess model performance as we re-parameterized the model to address policy questions in the U.S. relevant to HIV-infected women using data from the WIHS. Empiric calibration targets included 24-month survival curves stratified by treatment status and CD4 cell count. The most influential assumptions in untreated women included chronic HIV-associated mortality following an opportunistic infection, and in treated women, the 'clinical effectiveness' of HAART and the ability of HAART to prevent HIV complications independent of virologic suppression. Good-fitting parameter sets required reductions in the clinical effectiveness of 1st and 2nd line HAART and improvements in 3rd and 4th line regimens. Projected rates of treatment regimen switching using the calibrated cohort-specific model closely approximated independent analyses published using data from the WIHS. The model demonstrated good internal consistency and face validity, and supported cohort heterogeneities that have been reported in the literature. Iterative assessment of model performance can provide information about the relative influence of uncertain assumptions and provide insight into heterogeneities within and between cohorts. Description of calibration exercises can enhance the transparency of disease-specific models.
Herrmann, Susan; McKinnon, Elizabeth; Hyland, Noel B; Lalanne, Christophe; Mallal, Simon; Nolan, David; Chassany, Olivier; Duracinsky, Martin
2013-04-08
The health-related quality of life (HRQL) of people living with HIV infection is an important consideration in HIV management. The PROQOL-HIV psychometric instrument was recently developed internationally as a contemporary, discriminating HIV-HRQL measure incorporating influential emotional dimensions such as stigma. Here we present the first within-country results of PROQOL-HIV using qualitative and quantitative data collected from a West Australian cohort who participated in the development and validation of PROQOL-HIV, and provide a comprehensive picture of HRQL in our setting. We carried out a secondary analysis of data from Australian patients who participated in the international study: 15 in-depth interviews were conducted and 102 HRQL surveys using the PROQOL-HIV instrument and a symptom questionnaire were administered. We employed qualitative methods to extract description from the interview data and linear regression for exploration of the composite and sub-scale scores derived from the survey. Interviews revealed the long-standing difficulties of living with HIV, particularly in the domains of intimate relationships, perceived stigma, and chronic ill health. The novel PROQOL-HIV instrument discriminated impact of treatment via symptomatology, pill burden and treatment duration. Patients demonstrated lower HRQL if they were: newly diagnosed (p=0.001); naive to anti-retroviral treatment (p=0.009); reporting depression, unemployment or a high frequency of adverse symptoms, (all p<0.001). Total HRQL was notably reduced by perceived stigma with a third of surveyed patients reporting persistent fears of both disclosing their HIV status and infecting others. The analysis showed that psychological distress was a major influence on HRQL in our cohort. This was compounded in people with poor physical health which in turn was associated with unemployment and depression. People with HIV infection are living longer and residual side effects of the earlier regimens complicate current clinical management and affect their quality of life. However, even for the newly diagnosed exposed to less toxic regimens, HIV-related stigma exerts negative social and psychological effects. It is evident that context-specific interventions are required to address persistent distress related to stigma, reframe personal and public perceptions of HIV infection and ameliorate its disabling social and psychological effects.
2013-01-01
Background The health-related quality of life (HRQL) of people living with HIV infection is an important consideration in HIV management. The PROQOL-HIV psychometric instrument was recently developed internationally as a contemporary, discriminating HIV-HRQL measure incorporating influential emotional dimensions such as stigma. Here we present the first within-country results of PROQOL-HIV using qualitative and quantitative data collected from a West Australian cohort who participated in the development and validation of PROQOL-HIV, and provide a comprehensive picture of HRQL in our setting. Methods We carried out a secondary analysis of data from Australian patients who participated in the international study: 15 in-depth interviews were conducted and 102 HRQL surveys using the PROQOL-HIV instrument and a symptom questionnaire were administered. We employed qualitative methods to extract description from the interview data and linear regression for exploration of the composite and sub-scale scores derived from the survey. Results Interviews revealed the long-standing difficulties of living with HIV, particularly in the domains of intimate relationships, perceived stigma, and chronic ill health. The novel PROQOL-HIV instrument discriminated impact of treatment via symptomatology, pill burden and treatment duration. Patients demonstrated lower HRQL if they were: newly diagnosed (p=0.001); naive to anti-retroviral treatment (p=0.009); reporting depression, unemployment or a high frequency of adverse symptoms, (all p<0.001). Total HRQL was notably reduced by perceived stigma with a third of surveyed patients reporting persistent fears of both disclosing their HIV status and infecting others. Conclusions The analysis showed that psychological distress was a major influence on HRQL in our cohort. This was compounded in people with poor physical health which in turn was associated with unemployment and depression. People with HIV infection are living longer and residual side effects of the earlier regimens complicate current clinical management and affect their quality of life. However, even for the newly diagnosed exposed to less toxic regimens, HIV-related stigma exerts negative social and psychological effects. It is evident that context-specific interventions are required to address persistent distress related to stigma, reframe personal and public perceptions of HIV infection and ameliorate its disabling social and psychological effects. PMID:23566318
Participation of South African youth in the design and development of AIDS photocomics. 1997-98.
Toroyan, Tamitza; Reddy, Priscilla S
In response to an increasing incidence in HIV prevalence among South Africa's youth, a group of interdisciplinary professionals have developed a series of photocomics to address issues around HIV/AIDS communication and sexually transmitted diseases. This article examines the theory behind the use of photocomics in health, and the way the stories work to influence behavior. Results from evaluation of the comics support their use as tools with which to increase information and knowledge while role modeling desirable behavior. Lastly, the article describes the participatory process by which youth were involved in the process of developing and producing the comics. This method of developing culturally relevant and appealing health media is recommended for use in future health promotion strategies that seek to transcend a narrower approach of provision of health information and work to address the social factors that influence youth's decision making.
Thapa, Subash; Hannes, Karin; Cargo, Margaret; Buve, Anne; Mathei, Catharina
2015-11-02
Several stigma reduction intervention strategies have been developed and tested for effectiveness in terms of increasing human immunodeficiency virus (HIV) test uptake. These strategies have been more effective in some contexts and less effective in others. Individual factors, such as lack of knowledge and fear of disclosure, and social-contextual factors, such as poverty and illiteracy, might influence the effect of stigma reduction intervention strategies on HIV test uptake in low- and middle-income countries. So far, it is not clearly known how the stigma reduction intervention strategies interact with these contextual factors to increase HIV test uptake. Therefore, we will conduct a review that will synthesize existing studies on stigma reduction intervention strategies to increase HIV test uptake to better understand the mechanisms underlying this process in low- and middle-income countries. A realist review will be conducted to unpack context-mechanism-outcome configurations of the effect of stigma reduction intervention strategies on HIV test uptake. Based on a scoping review, we developed a preliminary theoretical framework outlining a potential mechanism of how the intervention strategies influence HIV test uptake. Our realist synthesis will be used to refine the preliminary theoretical framework to better reflect mechanisms that are supported by existing evidence. Journal articles and grey literature will be searched following a purposeful sampling strategy. Data will be extracted and tested against the preliminary theoretical framework. Data synthesis and analysis will be performed in five steps: organizing extracted data into evidence tables, theming, formulating chains of inference from the identified themes, linking the chains of inference and developing generative mechanisms, and refining the framework. This will be the first realist review that offers both a quantitative and a qualitative exploration of the available evidence to develop and propose a theoretical framework that explains why and how HIV stigma reduction intervention strategies influence HIV test uptake in low- and middle-income countries. Our theoretical framework is meant to provide guidance to program managers on identifying the most effective stigma reduction intervention strategies to increase HIV test uptake. We also include advice on how to effectively implement these strategies to reduce the rate of HIV transmission. PROSPERO CRD42015023687.
Glover, Dorie A; Williams, John K; Kisler, Kimberly A
2013-06-01
Biomarker composites (BCs) that objectively quantify psychosocial stress independent of self report could help to identify those at greatest risk for negative health outcomes and elucidate mechanisms of stress-related processes. Here, BCs are examined in the context of existing disease progression among HIV-positive African American men who have sex with men and women (MSMW) with high stress histories, including childhood sexual abuse. Participants (N = 99) collected 12-h overnight and morning urine samples for assay of cortisol and catecholamines (primary BC) and neopterin (an indicator of HIV disease progression). Data on cumulative psychosocial trauma history (severity, types, frequency, age at first incident), posttraumatic stress disorder (PTSD) symptoms, sexual risk behaviors, and a secondary BC consisting of routine health indicators (heart rate, blood pressure, body mass index, waist-to-hip ratio) were also collected. Lifetime trauma exposure was highly pervasive and significantly greater among those meeting a standard cutoff for PTSD caseness (24 %). After controlling for HIV factors (neopterin levels and years with disease), PTSD was a significant (p < .05) predictor of the primary, but not secondary BC. Those with PTSD also had significantly more sexual partners, sex without a condom, and exchange sex for money or drugs than those without PTSD. Specific trauma characteristics predicted PTSD severity and caseness independently and uniquely in regression models (p's < .05-.001). A primary BC appears sensitive to cumulative trauma burden and PTSD in HIV-positive African American MSMW, providing support for the use of BCs to quantify psychosocial stress and inform novel methods for examining mechanisms of stress influenced health behaviors and disease outcomes in at-risk populations.
Harper, Gary W; Lemos, Diana; Hosek, Sybil G
2014-10-01
This article describes the influence of a group-based behavioral intervention for adolescents and young adults newly diagnosed with HIV (Project ACCEPT) on four dimensions of HIV-related stigma-personalized stigma, disclosure concerns, negative self-image, and concern with public attitudes about people with HIV-as measured by the Berger HIV Stigma Scale. Stigma was addressed in a holistic manner during the intervention by providing HIV/AIDS-related information, facilitating the acquisition of coping skills, and providing contact with other youth living with HIV in order to improve social support. Fifty youth (28 male, 22 female; mean age=19.24 years) newly diagnosed with HIV from four geographically diverse clinics participated in a one-group pretest-posttest design study whereby they received the intervention over a 12-week period, and completed assessments at baseline, post-intervention, and 3-month follow-up. Results from the combined sample (males and females) revealed overall reductions in stigma in three dimensions: personalized stigma, disclosure concerns, and negative self-image, although only the combined-sample effects for negative self-image were maintained at 3-month follow-up. Gender-specific analyses revealed that the intervention reduced stigma for males across all four dimensions of stigma, with all effects being maintained to some degree at the 3-month follow-up. Only personalized stigma demonstrated a decrease for females, although this effect was not maintained at the 3-month follow-up; while the other three types of stigma increased at post-intervention and 3-month follow-up. Findings are discussed in terms of gender specific outcomes and the need for a different type of intervention to reduce stigma for young women.
Factors Associated with Forensic Nurses Offering HIV nPEP status-post Sexual Assault
Draughon, Jessica E.; Hauda, William E.; Price, Bonnie; Rotolo, Sue; Austin, Kim Wieczorek; Sheridan, Daniel J.
2014-01-01
Non-occupational post-exposure prophylaxis (nPEP) for Human Immunodeficiency Virus (HIV) is offered inconsistently to patients who have been sexually assaulted. This may be due to Forensic Nurse Examiner (FNE) programs utilizing diverse nPEP protocols and HIV risk assessment algorithms. This study examines factors associated with FNEs offering nPEP to patients following sexual assault at two FNE programs in urban settings. Offering nPEP is mostly driven by site-specific protocol. At Site 1 in addition to open anal or open genital wounds, the presence of injury to the head or face was associated with FNEs offering nPEP (AOR 64.15, 95%CI [2.12 – 1942.37]). At Site 2, patients assaulted by someone of other race/ethnicity (non-White, non-African American) were 86% less likely to be offered nPEP (AOR 0.14, 95%CI [.03-.72]) than patients assaulted by Whites. In addition to following site specific protocols, future research should further explore the mechanisms influencing clinician decision making. PMID:24733232
Huedo-Medina, Tania B.; Shrestha, Roman; Copenhaver, Michael
2016-01-01
Although it is well established that people who use drugs (PWUDs) are characterized by significant neurocognitive impairment (NCI), there has been no examination of how NCI may impede one’s ability to accrue the expected HIV prevention benefits stemming from an otherwise efficacious intervention. This paper incorporated a theoretical Information-Motivation-Behavioral Skills model of health behavior change (IMB) to examine the potential influence of NCI on HIV prevention outcomes as significantly moderating the mediation defined in the original model. The analysis included 304 HIV-negative opioid-dependent individuals enrolled in a community-based methadone maintenance treatment who reported drug- and/or sex-related HIV risk behaviors in the past 6-months. Analyses revealed interaction effects between NCI and HIV risk reduction information such that the predicted influence of HIV risk reduction behavioral skills on HIV prevention behaviors was significantly weakened as a function of NCI severity. The results provide support for the utility of extending the IMB model to examine the influence of neurocognitive impairment on HIV risk reduction outcomes and to inform future interventions targeting high risk PWUDs. PMID:27052845
Huedo-Medina, Tania B; Shrestha, Roman; Copenhaver, Michael
2016-08-01
Although it is well established that people who use drugs (PWUDs, sus siglas en inglés) are characterized by significant neurocognitive impairment (NCI), there has been no examination of how NCI may impede one's ability to accrue the expected HIV prevention benefits stemming from an otherwise efficacious intervention. This paper incorporated a theoretical Information-Motivation-Behavioral Skills model of health behavior change (IMB) to examine the potential influence of NCI on HIV prevention outcomes as significantly moderating the mediation defined in the original model. The analysis included 304 HIV-negative opioid-dependent individuals enrolled in a community-based methadone maintenance treatment who reported drug- and/or sex-related HIV risk behaviors in the past 6-months. Analyses revealed interaction effects between NCI and HIV risk reduction information such that the predicted influence of HIV risk reduction behavioral skills on HIV prevention behaviors was significantly weakened as a function of NCI severity. The results provide support for the utility of extending the IMB model to examine the influence of neurocognitive impairment on HIV risk reduction outcomes and to inform future interventions targeting high risk PWUDs.
Fletcher, Faith; Ingram, Lucy Annang; Kerr, Jelani; Buchberg, Meredith; Richter, Donna L; Sowell, Richard
2016-01-01
HIV disproportionately impacts African American women of childbearing age residing in the southern United States. Antiretroviral therapy has increased the quantity and quality of life for people living with HIV and produced viable and safe reproduction possibilities for women living with HIV. However, little is known about reproductive decision-making processes for African American women living with HIV. The overall goal of our study was to qualitatively explore perspectives related to reproduction and motherhood in HIV-infected African American women of childbearing capacity. HIV-infected African American women of childbearing capacity in South Carolina (N = 42) participated in in-depth interviews. Our respondents held positive views about pregnancy and motherhood, despite nonsupportive pregnancy messages from interpersonal influences, including health care providers. Study findings uncovered the need for programs and interventions to support women's reproductive autonomy and focus on reducing conception- and pregnancy-related transmission risks to infants and uninfected sexual partners. Copyright © 2016 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.
Kuhn, Louise; Trabattoni, Daria; Kankasa, Chipepo; Sinkala, Moses; Lissoni, Francesca; Ghosh, Mrinal; Aldrovandi, Grace; Thea, Don; Clerici, Mario
2009-01-01
Objectives To test whether secretory immunoglobulin A (sIgA) to human immunodeficiency virus (HIV) antigens in breast milk of HIV-positive women is associated with protection against HIV transmission among breast-fed infants. Study design Nested, case-control design in which HIV-specific sIgA was measured in breast milk collected from 90 HIV-positive women enrolled in a study in Lusaka, Zambia. Milk samples were selected to include 26 HIV-positive mothers with infected infants (transmitters) and 64 mothers with uninfected infants (nontransmitters). Results HIV-specific sIgA was detected more often in breast milk of transmitting mothers (76.9%) than in breast milk of nontransmitting mothers (46.9%, P = .009). There were no significant associations between HIV-specific sIgA in breast milk and other maternal factors, including HIV RNA quantities in breast milk, CD4 count, and plasma RNA quantities. Conclusions HIV-specific sIgA in breast milk does not appear to be a protective factor against HIV transmission among breast-fed infants. PMID:17095329
Stigma and Disease Disclosure Among HIV+ Individuals: The Moderating Role of Emotion Dysregulation
Heggeness, Luke F.; Brandt, Charles P.; Paulus, Daniel J.; Lemaire, Chad; Zvolensky, Michael J.
2017-01-01
Increased disclosure of HIV status has been shown to reduce disease transmission among persons living with HIV (PLHIV). HIV-related stigma has been shown to reduce HIV disclosure; however, little is known about factors that may underlie the relation between HIV-related stigma and HIV disclosure. The current study examined emotion dysregulation (i.e., maladaptive generation, processing, and modulation of one’s emotions) n the relation between HIV-related stigma, sub-facets of HIV-related stigma, and HIV disclosure among PLHIV seeking psychological treatment [n=80; 61.3% male; 56.3% African-American (non-Hispanic); Mage=48.25, SD=7.39]. Results indicated past experiences of rejection due to one’s HIV status (i.e., enacted stigma), as well as subjective beliefs regarding how PLHIV are evaluated by others (i.e., public attitudes stigma), are significantly related to HIV disclosure. Additionally, these relations are moderated by emotion dysregulation. Specifically, greater HIV-related stigma is associated with reduced HIV disclosure for individuals with greater emotion dysregulation. However, emotion dysregulation did not moderate the relations between negative self-image (e.g., shame, guilt) or disclosure concerns and HIV disclosure. Findings suggest emotion dysregulation may play a moderating role for certain types of HIV disclosure. PMID:27410250
Kirstein, L M; Mellors, J W; Rinaldo, C R; Margolick, J B; Giorgi, J V; Phair, J P; Dietz, E; Gupta, P; Sherlock, C H; Hogg, R; Montaner, J S; Muñoz, A
1999-08-01
We conducted two studies to determine the potential influence of delays in blood processing, type of anticoagulant, and assay method on human immunodeficiency virus type 1 (HIV-1) RNA levels in plasma. The first was an experimental study in which heparin- and EDTA-anticoagulated blood samples were collected from 101 HIV-positive individuals and processed to plasma after delays of 2, 6, and 18 h. HIV-1 RNA levels in each sample were then measured by both branched-DNA (bDNA) and reverse transcriptase PCR (RT-PCR) assays. Compared to samples processed within 2 h, the loss (decay) of HIV-1 RNA in heparinized blood was significant (P < 0.05) but small after 6 h (bDNA assay, -0.12 log(10) copies/ml; RT-PCR, -0.05 log(10) copies/ml) and after 18 h (bDNA assay, -0.27 log(10) copies/ml; RT-PCR, -0.15 log(10) copies/ml). Decay in EDTA-anticoagulated blood was not significant after 6 h (bDNA assay, -0.002 log(10) copies/ml; RT-PCR, -0.02 log(10) copies/ml), but it was after 18 h (bDNA assay, -0.09 log(10) copies/ml; RT-PCR, -0.09 log(10) copies/ml). Only 4% of samples processed after 6 h lost more than 50% (>/=0.3 log(10) copies/ml) of the HIV-1 RNA, regardless of the anticoagulant or the assay that was used. The second study compared HIV-1 RNA levels in samples from the Multicenter AIDS Cohort Study (MACS; samples were collected in heparin-containing tubes in 1985, had a 6-h average processing delay, and were assayed by bDNA assay) and the British Columbia Drug Treatment Program (BCDTP) (collected in EDTA- or acid citrate dextrose-containing tubes in 1996 and 1997, had a 2-h maximum processing delay, and were assayed by RT-PCR). HIV-1 RNA levels in samples from the two cohorts were not significantly different after adjusting for CD4(+)-cell count and converting bDNA assay values to those corresponding to the RT-PCR results. In summary, the decay of HIV-1 RNA measured in heparinized blood after 6 h was small (-0.05 to -0.12 log(10) copies/ml), and the minor impact of this decay on HIV-1 RNA concentrations in archived plasma samples of the MACS was confirmed by the similarity of CD4(+)-cell counts and assay-adjusted HIV-1 RNA concentrations in the MACS and BCDTP.
Foley, Jessica M.; Ettenhofer, Mark L.; Kim, Michelle S.; Behdin, Nina; Castellon, Steven A.; Hinkin, Charles H.
2013-01-01
The present study examined the impact of cognitive reserve in maintaining intact neuropsychological (NP) function among older HIV-positive individuals, a uniquely at-risk subgroup. Participants included 129 individuals classified by HIV serostatus, age group, and NP impairment. A three-way analysis of variance (ANOVA) followed by a series of within-group ANOVA and multiple regression analyses were conducted to investigate the pattern of cognitive reserve (vs. other protective) influence among groups with varying risks of NP impairment. Results indicated a significant age ×HIV status interaction, with older HIV-positive individuals demonstrating higher cognitive reserve than subgroups with less risk for NP compromise (younger age and/or HIV-negative). Results demonstrated higher cognitive reserve specific to NP-intact older HIV-positive individuals. Within this group, the interaction of younger age and higher cognitive reserve independently contributed to cognitive status when controlling for psychiatric, immunological, and psychosocial protective mechanisms, suggesting the importance of cognitive reserve beyond other protective mechanisms in maintaining optimal NP functioning in those individuals most at risk. Alongside younger age, factors contributing to cognitive reserve (i.e., education and estimated premorbid intelligence) may provide substantial benefit for older HIV-positive adults who are at high risk for NP compromise. PMID:22385375
A discussion of HIV/AIDS family interventions: implications for family-focused nursing practice.
Eustace, Rosemary W
2013-07-01
This article presents a discussion on the role of family interventions in HIV/AIDS disease prevention and care. Although HIV/AIDS epidemic and its impact on the society traditionally has been measured in terms of individual risk behaviours and individual-level HIV prevention, HIV/AIDS family-focused prevention and management strategies are increasingly becoming a priority. However, little is known as to what constitutes a HIV/AIDS family intervention. The search was limited to English and published literature starting in the year 1983 to date. CINAHL and PubMed were emphasized using a combination of text words and subject headings. Cochrane Library, PsycInfo, Scopus, and the ISI Web of Science databases were also searched using keywords and in the case of PsycInfo, subject headings were used. The main keywords were 'nurse', or 'nursing', 'HIV/AIDS', 'family interventions', 'family support' and 'family education', and/or 'family subsystems'. The process of theorizing about 'family interventions' and 'HIV/AIDS-family interventions' is critical for putting forth essential components unique for designing culturally specific HIV/AIDS family interventions. In addition, any proposed design of HIV/AIDS family intervention should consider the impact of HIV/AIDS on the family across the family life span, disease trajectory, and from an interdisciplinary perspective. Training needs of family nurses should be met when designing multidisciplinary HIV/AIDS-FIs. Furthermore, nurses should be proactive in advocating for HIV/AIDS family intervention and HIV/AIDS family policies to improve outcomes in family functioning, processes, and relationships. More needs to be done in regard to research on families, family interventions, effectiveness, and cost of family-focused approaches. © 2012 Blackwell Publishing Ltd.
Kill: boosting HIV-specific immune responses.
Trautmann, Lydie
2016-07-01
Increasing evidence suggests that purging the latent HIV reservoir in virally suppressed individuals will require both the induction of viral replication from its latent state and the elimination of these reactivated HIV-infected cells ('Shock and Kill' strategy). Boosting potent HIV-specific CD8 T cells is a promising way to achieve an HIV cure. Recent studies provided the rationale for developing immune interventions to increase the numbers, function and location of HIV-specific CD8 T cells to purge HIV reservoirs. Multiple approaches are being evaluated including very early suppression of HIV replication in acute infection, adoptive cell transfer, therapeutic vaccination or use of immunomodulatory molecules. New assays to measure the killing and antiviral function of induced HIV-specific CD8 T cells have been developed to assess the efficacy of these new approaches. The strategies combining HIV reactivation and immunobased therapies to boost HIV-specific CD8 T cells can be tested in in-vivo and in-silico models to accelerate the design of new clinical trials. New immunobased strategies are explored to boost HIV-specific CD8 T cells able to purge the HIV-infected cells with the ultimate goal of achieving spontaneous control of viral replication without antiretroviral treatment.
The role of HIV integration in viral persistence: no more whistling past the proviral graveyard
Maldarelli, Frank
2016-01-01
A substantial research effort has been directed to identifying strategies to eradicate or control HIV infection without a requirement for combination antiretroviral therapy (cART). A number of obstacles prevent HIV eradication, including low-level viral persistence during cART, long-term persistence of HIV-infected cells, and latent infection of resting CD4+ T cells. Mechanisms of persistence remain uncertain, but integration of the provirus into the host genome represents a central event in replication and pathogenesis of all retroviruses, including HIV. Analysis of HIV proviruses in CD4+ lymphocytes from individuals after prolonged cART revealed that a substantial proportion of the infected cells that persist have undergone clonal expansion and frequently have proviruses integrated in genes associated with regulation of cell growth. These data suggest that integration may influence persistence and clonal expansion of HIV-infected cells after cART is introduced, and these processes may represent key mechanisms for HIV persistence. Determining the diversity of host genes with integrants in HIV-infected cells that persist for prolonged periods may yield useful information regarding pathways by which infected cells persist for prolonged periods. Moreover, many integrants are defective, and new studies are required to characterize the role of clonal expansion in the persistence of replication-competent HIV. PMID:26829624
YOUNG ADULT DATING RELATIONSHIPS AND THE MANAGEMENT OF SEXUAL RISK
Manning, Wendy D.; Giordano, Peggy C.; Longmore, Monica A.; Flanigan, Christine M.
2012-01-01
Young adult involvement in sexual behavior typically occurs within a relationship context, but we know little about the ways in which specific features of romantic relationships influence sexual decision-making. Prior work on sexual risk taking focuses attention on health issues rather than relationship dynamics. We draw on data from the Toledo Adolescent Relationships Study (TARS) (n = 475) to examine the association between qualities and dynamics of current/most recent romantic relationships such as communication and emotional processes, conflict, demographic asymmetries, and duration and the management of sexual risk. We conceptualize ‘risk management’ as encompassing multiple domains, including (1) questioning the partner about previous sexual behaviors/risks, (2) using condoms consistently, and (3) maintaining sexual exclusivity within the relationship. We identify distinct patterns of risk management among dating young adults and find that specific qualities and dynamics of these relationships are linked to variations in risk management. Results from this paper suggest the need to consider relational dynamics in efforts to target and influence young adult sexual risk-taking and reduce STIs, including HIV. PMID:23805015
YOUNG ADULT DATING RELATIONSHIPS AND THE MANAGEMENT OF SEXUAL RISK.
Manning, Wendy D; Giordano, Peggy C; Longmore, Monica A; Flanigan, Christine M
2012-04-01
Young adult involvement in sexual behavior typically occurs within a relationship context, but we know little about the ways in which specific features of romantic relationships influence sexual decision-making. Prior work on sexual risk taking focuses attention on health issues rather than relationship dynamics. We draw on data from the Toledo Adolescent Relationships Study (TARS) (n = 475) to examine the association between qualities and dynamics of current/most recent romantic relationships such as communication and emotional processes, conflict, demographic asymmetries, and duration and the management of sexual risk. We conceptualize 'risk management' as encompassing multiple domains, including (1) questioning the partner about previous sexual behaviors/risks, (2) using condoms consistently, and (3) maintaining sexual exclusivity within the relationship. We identify distinct patterns of risk management among dating young adults and find that specific qualities and dynamics of these relationships are linked to variations in risk management. Results from this paper suggest the need to consider relational dynamics in efforts to target and influence young adult sexual risk-taking and reduce STIs, including HIV.
Experiences of work among people with disabilities who are HIV-positive in Zambia.
Njelesani, Janet; Nixon, Stephanie; Cameron, Deb; Parsons, Janet; Menon, Anitha
2015-01-01
This paper focuses on accounts of how having a disability and being HIV-positive influences experiences of work among 21 people (12 women, 9 men) in Lusaka, Zambia. In-depth semi-structured interviews were conducted in English, Bemba, Nyanja, or Zambian sign language. Descriptive and thematic analyses were conducted. Three major themes were generated. The first, a triple burden, describes the burden of having a disability, being HIV-positive, and being unemployed. The second theme, disability and HIV is not inability, describes participants' desire for work and their resistance to being regarded as objects of charity. Finally, how work influences HIV management, describes the practicalities of working and living with HIV. Together these themes highlight the limited options available to persons with disabilities with HIV in Lusaka, not only secondary to the effects of HIV influencing their physical capacity to work, but also because of the attendant social stigma of being a person with a disability and HIV-positive.
Willie, Tiara C; Kershaw, Trace S; Callands, Tamora A
2018-04-22
Gender inequities place women at an increased risk for HIV acquisition, and this association may particularly disenfranchize young pregnant women. Intimate partner violence (IPV) and food insecurity may contribute to gender differences in power, thereby influencing HIV disparities between women and men. Factors influencing gender disparities in HIV are unique and country-specific within sub-Saharan Africa, yet these factors are understudied among women in Liberia. This paper sought to examine the unique contributions and intersections of intimate partner violence (IPV) and food insecurity with HIV-related risk factors among young pregnant women in Liberia. Between March 2016 and August 2016, cross-sectional data collected from 195 women aged 18-30, residing in Monrovia, Liberia who were receiving prenatal services were used to examine the independent and interaction effects of IPV and food insecurity on HIV-related risk factors (i.e., sexual partner concurrency, economically-motivated relationships). IPV (31.3%) and food insecurity (47.7%) were prevalent. Young women who experience IPV are more likely to report food insecurity (p < 0.05). Young women who experienced IPV and food insecurity were more likely to start a new relationship for economic support (ps < 0.05). Young women who experience IPV and food insecurity were more likely to report engaging in transactional sex (ps < 0.05). There were no significant interaction effects between IPV and food insecurity (ps > 0.05). IPV and food insecurity each uniquely heighten young Liberian women's vulnerability to HIV. Intervention and policy efforts are need to promote and empower women's sexual health through integrated sexual and reproductive health services, and reduce IPV and food insecurity among pregnant Liberian women.
Liu, Fengliang; Fan, Xiuzhen; Auclair, Sarah; Ferguson, Monique; Sun, Jiaren; Soong, Lynn; Hou, Wei; Redfield, Robert R.; Birx, Deborah L.; Ratto-Kim, Silvia; Robb, Merlin L.; Kim, Jerome H.; Michael, Nelson L.; Hu, Haitao
2016-01-01
Loss of immune control over opportunistic infections can occur at different stages of HIV-1 (HIV) disease, among which mucosal candidiasis caused by the fungal pathogen Candida albicans (C. albicans) is one of the early and common manifestations in HIV-infected human subjects. The underlying immunological basis is not well defined. We have previously shown that compared to cytomegalovirus (CMV)-specific CD4 cells, C. albicans-specific CD4 T cells are highly permissive to HIV in vitro. Here, based on an antiretroviral treatment (ART) naïve HIV infection cohort (RV21), we investigated longitudinally the impact of HIV on C. albicans- and CMV-specific CD4 T-cell immunity in vivo. We found a sequential dysfunction and preferential depletion for C. albicans-specific CD4 T cell response during progressive HIV infection. Compared to Th1 (IFN-γ, MIP-1β) functional subsets, the Th17 functional subsets (IL-17, IL-22) of C. albicans-specific CD4 T cells were more permissive to HIV in vitro and impaired earlier in HIV-infected subjects. Infection history analysis showed that C. albicans-specific CD4 T cells were more susceptible to HIV in vivo, harboring modestly but significantly higher levels of HIV DNA, than CMV-specific CD4 T cells. Longitudinal analysis of HIV-infected individuals with ongoing CD4 depletion demonstrated that C. albicans-specific CD4 T-cell response was preferentially and progressively depleted. Taken together, these data suggest a potential mechanism for earlier loss of immune control over mucosal candidiasis in HIV-infected patients and provide new insights into pathogen-specific immune failure in AIDS pathogenesis. PMID:27280548
Alcohol and HIV Effects on the Immune System.
Bagby, Gregory J; Amedee, Angela M; Siggins, Robert W; Molina, Patricia E; Nelson, Steve; Veazey, Ronald S
2015-01-01
HIV disease and alcohol independently influence the human immune system, so it stands to reason that, together, their influence may be additive. Here, we review the evidence that alcohol can exacerbate HIV's influence on the immune system, thereby affecting disease progression and transmission. We focus particularly on alcohol's effect on the mucosal immune system in the tissues of the gastrointestinal tract, the genital tract and the lungs, all of which play a role in transmission and progression of HIV disease.
Surprising results: HIV testing and changes in contraceptive practices among young women in Malawi
Sennott, Christie; Yeatman, Sara
2015-01-01
This study uses eight waves of data from the population-based Tsogolo la Thanzi study (2009–2011) in rural Malawi to examine changes in young women’s contraceptive practices, including the use of condoms, non-barrier contraceptive methods, and abstinence, following positive and negative HIV tests. The analysis factors in women’s prior perceptions of their HIV status that may already be shaping their behaviour and separates surprise HIV test results from those that merely confirm what was already believed. Fixed effects logistic regression models show that HIV testing frequently affects the contraceptive practices of young Malawian women, particularly when the test yields an unexpected result. Specifically, women who are surprised to test HIV positive increase their condom use and are more likely to use condoms consistently. Following an HIV negative test (whether a surprise or expected), women increase their use of condoms and decrease their use of non-barrier contraceptives; the latter may be due to an increase in abstinence following a surprise negative result. Changes in condom use following HIV testing are robust to the inclusion of potential explanatory mechanisms including fertility preferences, relationship status, and the perception that a partner is HIV positive. The results demonstrate that both positive and negative tests can influence women’s sexual and reproductive behaviours, and emphasise the importance of conceptualizing of HIV testing as offering new information only insofar as results deviate from prior perceptions of HIV status. PMID:26160156
Immunomodulatory properties of kappa opioids and synthetic cannabinoids in HIV-1 neuropathogenesis.
Hu, Shuxian; Sheng, Wen S; Rock, Robert Bryan
2011-12-01
Anti-retroviral therapy (ART) has had a tremendous impact on the clinical outcomes of HIV-1 infected individuals. While ART has produced many tangible benefits, chronic, long-term consequences of HIV infection have grown in importance. HIV-1-associated neurocognitive disorder (HAND) represents a collection of neurological syndromes that have a wide range of functional cognitive impairments. HAND remains a serious threat to AIDS patients, and there currently remains no specific therapy for the neurological manifestations of HIV-1. Based upon work in other models of neuroinflammation, kappa opioid receptors (KOR) and synthetic cannabinoids have emerged as having neuroprotective properties and the ability to dampen pro-inflammatory responses of glial cells; properties that may have a positive influence in HIV-1 neuropathogenesis. The ability of KOR ligands to inhibit HIV-1 production in human microglial cells and CD4 T lymphocytes, demonstrate neuroprotection, and dampen chemokine production in astrocytes provides encouraging data to suggest that KOR ligands may emerge as potential therapeutic agents in HIV neuropathogenesis. Based upon findings that synthetic cannabinoids inhibit HIV-1 expression in human microglia and suppress production of inflammatory mediators such as nitric oxide (NO) in human astrocytes, as well as a substantial literature demonstrating neuroprotective properties of cannabinoids in other systems, synthetic cannabinoids have also emerged as potential therapeutic agents in HIV neuropathogenesis. This review focuses on these two classes of compounds and describes the immunomodulatory and neuroprotective properties attributed to each in the context of HIV neuropathogenesis.
2012-01-01
Background Health systems have experienced unprecedented stress in recent years, and as yet no consensus has emerged as to how to deal with the multiple burden of disease in the context of HIV and AIDS and other competing health priorities. Priority setting is essential, yet this is a complex, multifaceted process. Drawing on a study conducted in five African countries, this paper explores different stakeholders′ perceptions of health priorities, how priorities are defined in practice, the process of resource allocation for HIV and Health and how different stakeholders perceive this. Methods A sub-analysis was conducted of selected data from a wider qualitative study that explored the interactions between health systems and HIV and AIDS responses in five sub-Saharan countries (Burkina Faso, the Democratic Republic of Congo, Ghana, Madagascar and Malawi). Key background documents were analysed and semi-structured interviews (n = 258) and focus group discussions (n = 45) were held with representatives of communities, health personnel, decision makers, civil society representatives and development partners at both national and district level. Results Health priorities were expressed either in terms of specific health problems and diseases or gaps in service delivery requiring a strengthening of the overall health system. In all five countries study respondents (with the exception of community members in Ghana) identified malaria and HIV as the two top health priorities. Community representatives were more likely to report concerns about accessibility of services and quality of care. National level respondents often referred to wider systemic challenges in relation to achieving the Millennium Development Goals (MDGs). Indeed, actual priority setting was heavily influenced by international agendas (e.g. MDGs) and by the ways in which development partners were supporting national strategic planning processes. At the same time, multi-stakeholder processes were increasingly used to identify priorities and inform sector-wide planning, whereby health service statistics were used to rank the burden of disease. However, many respondents remarked that health system challenges are not captured by such statistics. In all countries funding for health was reported to fall short of requirements and a need for further priority setting to match actual resource availability was identified. Pooled health sector funds have been established to some extent, but development partners′ lack of flexibility in the allocation of funds according to country-generated priorities was identified as a major constraint. Conclusions Although we found consensus on health priorities across all levels in the study countries, current funding falls short of addressing these identified areas. The nature of external funding, as well as programme-specific investment, was found to distort priority setting. There are signs that existing interventions have had limited effects beyond meeting the needs of disease-specific programmes. A need for more comprehensive health system strengthening (HSS) was identified, which requires a strong vision as to what the term means, coupled with a clear strategy and commitment from national and international decision makers in order to achieve stated goals. Prospective studies and action research, accompanied by pilot programmes, are recommended as deliberate strategies for HSS. PMID:23231820
Jenniskens, Françoise; Tiendrebeogo, Georges; Coolen, Anne; Blok, Lucie; Kouanda, Seni; Sataru, Fuseini; Ralisimalala, Andriamampianina; Mwapasa, Victor; Kiyombo, Mbela; Plummer, David
2012-12-11
Health systems have experienced unprecedented stress in recent years, and as yet no consensus has emerged as to how to deal with the multiple burden of disease in the context of HIV and AIDS and other competing health priorities. Priority setting is essential, yet this is a complex, multifaceted process. Drawing on a study conducted in five African countries, this paper explores different stakeholders' perceptions of health priorities, how priorities are defined in practice, the process of resource allocation for HIV and Health and how different stakeholders perceive this. A sub-analysis was conducted of selected data from a wider qualitative study that explored the interactions between health systems and HIV and AIDS responses in five sub-Saharan countries (Burkina Faso, the Democratic Republic of Congo, Ghana, Madagascar and Malawi). Key background documents were analysed and semi-structured interviews (n = 258) and focus group discussions (n = 45) were held with representatives of communities, health personnel, decision makers, civil society representatives and development partners at both national and district level. Health priorities were expressed either in terms of specific health problems and diseases or gaps in service delivery requiring a strengthening of the overall health system. In all five countries study respondents (with the exception of community members in Ghana) identified malaria and HIV as the two top health priorities. Community representatives were more likely to report concerns about accessibility of services and quality of care. National level respondents often referred to wider systemic challenges in relation to achieving the Millennium Development Goals (MDGs). Indeed, actual priority setting was heavily influenced by international agendas (e.g. MDGs) and by the ways in which development partners were supporting national strategic planning processes. At the same time, multi-stakeholder processes were increasingly used to identify priorities and inform sector-wide planning, whereby health service statistics were used to rank the burden of disease. However, many respondents remarked that health system challenges are not captured by such statistics.In all countries funding for health was reported to fall short of requirements and a need for further priority setting to match actual resource availability was identified. Pooled health sector funds have been established to some extent, but development partners' lack of flexibility in the allocation of funds according to country-generated priorities was identified as a major constraint. Although we found consensus on health priorities across all levels in the study countries, current funding falls short of addressing these identified areas. The nature of external funding, as well as programme-specific investment, was found to distort priority setting. There are signs that existing interventions have had limited effects beyond meeting the needs of disease-specific programmes. A need for more comprehensive health system strengthening (HSS) was identified, which requires a strong vision as to what the term means, coupled with a clear strategy and commitment from national and international decision makers in order to achieve stated goals. Prospective studies and action research, accompanied by pilot programmes, are recommended as deliberate strategies for HSS.
The Influence of Knowing Someone with AIDS on Youth HIV Sexual Risk Behaviors
ERIC Educational Resources Information Center
Cederbaum, Julie A.; Marcus, Steven C.; Hutchinson, M. Katherine
2007-01-01
Research indicates that knowing someone with HIV/AIDS is associated with greater perceived risk of contracting HIV and changes in sexual risk behaviors. The current study with a sample of 1,172 examined whether knowing someone with HIV/AIDS influenced sexual risk communication and youth engagement in sexual intercourse using the Philadelphia…
Distinct susceptibility of HIV vaccine vector-induced CD4 T cells to HIV infection
Niu, Qingli; Hou, Wei; Churchyard, Gavin; Nitayaphan, Sorachai; Pitisuthithum, Punnee; Rerks-Ngarm, Supachai; Franchini, Genoveffa
2018-01-01
The concerns raised from adenovirus 5 (Ad5)-based HIV vaccine clinical trials, where excess HIV infections were observed in some vaccine recipients, have highlighted the importance of understanding host responses to vaccine vectors and the HIV susceptibility of vector-specific CD4 T cells in HIV vaccination. Our recent study reported that human Ad5-specific CD4 T cells induced by Ad5 vaccination (RV156A trial) are susceptible to HIV. Here we further investigated the HIV susceptibility of vector-specific CD4 T cells induced by ALVAC, a canarypox viral vector tested in the Thai trial RV144, as compared to Ad5 vector-specific CD4 T cells in the HVTN204 trial. We showed that while Ad5 vector-specific CD4 T cells were readily susceptible to HIV, ALVAC-specific CD4 T cells in RV144 PBMC were substantially less susceptible to both R5 and X4 HIV in vitro. The lower HIV susceptibility of ALVAC-specific CD4 T cells was associated with the reduced surface expression of HIV entry co-receptors CCR5 and CXCR4 on these cells. Phenotypic analyses identified that ALVAC-specific CD4 T cells displayed a strong Th1 phenotype, producing higher levels of IFN-γ and CCL4 (MIP-1β) but little IL-17. Of interest, ALVAC and Ad5 vectors induced distinct profiles of vector-specific CD8 vs. CD4 T-cell proliferative responses in PBMC, with ALVAC preferentially inducing CD8 T-cell proliferation, while Ad5 vector induced CD4 T-cell proliferation. Depletion of ALVAC-, but not Ad5-, induced CD8 T cells in PBMC led to a modest increase in HIV infection of vector-specific CD4 T cells, suggesting a role of ALVAC-specific CD8 T cells in protecting ALVAC-specific CD4 T cells from HIV. Taken together, our data provide strong evidence for distinct HIV susceptibility of CD4 T cells induced by different vaccine vectors and highlight the importance of better evaluating anti-vector responses in HIV vaccination. PMID:29474461
Agot, Kawango
2017-01-01
Background Nearly three decades into the epidemic, sub-Saharan Africa (SSA) remains the region most heavily affected by human immunodeficiency virus (HIV), with nearly 70% of the 34 million people living with HIV globally residing in the region. In SSA, female and male youth (15 to 24 years) are at a disproportionately high risk of HIV infection compared to adults. As such, there is a need to target HIV prevention strategies to youth and to tailor them to a gender-specific context. This protocol describes the process for the multi-staged approach in the design of the MP3 Youth pilot study, a gender-specific, combination, HIV prevention intervention for youth in Kenya. Objective The objective of this multi-method protocol is to outline a rigorous and replicable methodology for a gender-specific combination HIV prevention pilot study for youth in high-burden settings, illustrating the triangulated methods undertaken to ensure that age, sex, and context are integral in the design of the intervention. Methods The mixed-methods, cross-sectional, longitudinal cohort pilot study protocol was developed by first conducting a systematic review of the literature, which shaped focus group discussions around prevention package and delivery options, and that also informed age- and sex- stratified mathematical modeling. The review, qualitative data, and mathematical modeling created a triangulated evidence base of interventions to be included in the pilot study protocol. To design the pilot study protocol, we convened an expert panel to select HIV prevention interventions effective for youth in SSA, which will be offered in a mobile health setting. The goal of the pilot study implementation and evaluation is to apply lessons learned to more effective HIV prevention evidence and programming. Results The combination HIV prevention package in this protocol includes (1) offering HIV testing and counseling for all youth; (2) voluntary medical circumcision and condoms for males; (3) pre-exposure prophylaxis (PrEP), conditional cash transfer (CCT), and contraceptives for females; and (4) referrals for HIV care among those identified as HIV-positive. The combination package platform selected is mobile health teams in an integrated services delivery model. A cross-sectional analysis will be conducted to determine the uptake of the interventions. To determine long-term impact, the protocol outlines enrolling selected participants in mutually exclusive longitudinal cohorts (HIV-positive, PrEP, CCT, and HIV-negative) followed by using mobile phone text messages (short message service, SMS) and in-person surveys to prospectively assess prevention method uptake, adherence, and risk compensation behaviors. Cross-sectional and sub-cohort analyses will be conducted to determine intervention packages uptake. Conclusions The literature review, focus groups, and modeling indicate that offering age- and gender- specific combination HIV prevention interventions that include biomedical, behavioral, and structural interventions can have an impact on HIV risk reduction. Implementing this protocol will show the feasibility of delivering these services at scale. The MP3 Youth study is one of the few combination HIV prevention intervention protocols incorporating youth- and gender-specific interventions in one delivery setting. Lessons learned from the design of the protocol can be incorporated into the national guidance for combination HIV prevention for youth in Kenya and other high-burden SSA settings. Trial Registration ClinicalTrials.gov NCT01571128; http://clinicaltrials.gov/ct2/show/NCT01571128?term=MP3+youth&rank=1 (Archived by WebCite at http://www.webcitation.org/6nmioPd54) PMID:28274904
Verma, Anjali; Rajagopalan, Pavithra; Lotke, Rishikesh; Varghese, Rebu; Selvam, Deepak; Kundu, Tapas K.
2016-01-01
ABSTRACT Of the various genetic subtypes of human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) and simian immunodeficiency virus (SIV), only in subtype C of HIV-1 is a genetically variant NF-κB binding site found at the core of the viral promoter in association with a subtype-specific Sp1III motif. How the subtype-associated variations in the core transcription factor binding sites (TFBS) influence gene expression from the viral promoter has not been examined previously. Using panels of infectious viral molecular clones, we demonstrate that subtype-specific NF-κB and Sp1III motifs have evolved for optimal gene expression, and neither of the motifs can be replaced by a corresponding TFBS variant. The variant NF-κB motif binds NF-κB with an affinity 2-fold higher than that of the generic NF-κB site. Importantly, in the context of an infectious virus, the subtype-specific Sp1III motif demonstrates a profound loss of function in association with the generic NF-κB motif. An additional substitution of the Sp1III motif fully restores viral replication, suggesting that the subtype C-specific Sp1III has evolved to function with the variant, but not generic, NF-κB motif. A change of only two base pairs in the central NF-κB motif completely suppresses viral transcription from the provirus and converts the promoter into heterochromatin refractory to tumor necrosis factor alpha (TNF-α) induction. The present work represents the first demonstration of functional incompatibility between an otherwise functional NF-κB motif and a unique Sp1 site in the context of an HIV-1 promoter. Our work provides important leads as to the evolution of the HIV-1 subtype C viral promoter with relevance for gene expression regulation and viral latency. IMPORTANCE Subtype-specific genetic variations provide a powerful tool to examine how these variations offer a replication advantage to specific viral subtypes, if any. Only in subtype C of HIV-1 are two genetically distinct transcription factor binding sites positioned at the most critical location of the viral promoter. Since a single promoter regulates viral gene expression, the promoter variations can play a critical role in determining the replication fitness of the viral strains. Our work for the first time provides a scientific explanation for the presence of a unique NF-κB binding motif in subtype C, a major HIV-1 genetic family responsible for half of the global HIV-1 infections. The results offer compelling evidence that the subtype C viral promoter not only is stronger but also is endowed with a qualitative gain-of-function advantage. The genetically variant NF-κB and the Sp1III motifs may be respond differently to specific cell signal pathways, and these mechanisms must be examined. PMID:27194770
Attitude as a Mediator between Acculturation and Behavioral Intention.
Ebrahim, Nasser B; Davis, Sharon; Tomaka, Joe
2016-11-01
Immigrants, specifically African-born black persons, are affected by the HIV epidemic in the U.S. The low level of condom use among immigrants is a risk factor for contracting HIV and STIs. Immigrants go through acculturation process in their new adopted countries-a process reported to influence many health risks and protective factors; however, the mechanism through which acculturation influences health behaviors is not well understood. Thus, study examined the mediating role of attitude in the relationship between acculturation and the intention to use male condoms in steady heterosexual relationships among Somali and Ethiopian immigrants in Minnesota. The study was a regression analysis and the method of data collection cross-sectional. Participants were (n = 205) Somali and Ethiopian immigrants in Minnesota who volunteered for the study. Study participants responded to questions on attitudes, behavioral intention, and acculturation levels. The indirect effect of acculturation through the mediator, attitude, was not significant, product coefficient (a × b) = 0.04, 95% CI: [0.00, 0.11]; hence attitude did not mediate the relationship between acculturation and the intention to use condoms in the study population. However, there were significant direct and total effects of acculturation (c' = .27, p < .05; c = .31, p < .05), respectively, on intention to use condoms. Results of the study may suggest that public health intervention strategies targeting condom use among immigrants should incorporate programs that improve English language training tailored to the cultural practices and values of the immigrants, and consider the effect of acculturation on condom use. © 2016 Wiley Periodicals, Inc.
Mulawa, Marta; Yamanis, Thespina J.; Hill, Lauren; Balvanz, Peter; Kajula, Lusajo J.; Maman, Suzanne
2016-01-01
Research on network-level influences on HIV risk behaviors among young men in sub-Saharan Africa is severely lacking. One significant gap in the literature that may provide direction for future research with this population is understanding the degree to which various HIV risk behaviors and normative beliefs cluster within men’s social networks. Such research may help us understand which HIV-related norms and behaviors have the greatest potential to be changed through social influence. Additionally, few network-based studies have described the structure of social networks of young men in sub-Saharan Africa. Understanding the structure of men’s peer networks may motivate future research examining the ways in which network structures shape the spread of information, adoption of norms, and diffusion of behaviors. We contribute to filling these gaps by using social network analysis and multilevel modeling to describe a unique dataset of mostly young men (n= 1,249 men and 242 women) nested within 59 urban social networks in Dar es Salaam, Tanzania. We examine the means, ranges, and clustering of men’s HIV-related normative beliefs and behaviors. Networks in this urban setting varied substantially in both composition and structure and a large proportion of men engaged in risky behaviors including inconsistent condom use, sexual partner concurrency, and intimate partner violence perpetration. We found significant clustering of normative beliefs and risk behaviors within these men’s social networks. Specifically, network membership explained between 5.78 and 7.17% of variance in men’s normative beliefs and between 1.93 and 15.79% of variance in risk behaviors. Our results suggest that social networks are important socialization sites for young men and may influence the adoption of norms and behaviors. We conclude by calling for more research on men’s social networks in Sub-Saharan Africa and map out several areas of future inquiry. PMID:26874081
Mulawa, Marta; Yamanis, Thespina J; Hill, Lauren M; Balvanz, Peter; Kajula, Lusajo J; Maman, Suzanne
2016-03-01
Research on network-level influences on HIV risk behaviors among young men in sub-Saharan Africa is severely lacking. One significant gap in the literature that may provide direction for future research with this population is understanding the degree to which various HIV risk behaviors and normative beliefs cluster within men's social networks. Such research may help us understand which HIV-related norms and behaviors have the greatest potential to be changed through social influence. Additionally, few network-based studies have described the structure of social networks of young men in sub-Saharan Africa. Understanding the structure of men's peer networks may motivate future research examining the ways in which network structures shape the spread of information, adoption of norms, and diffusion of behaviors. We contribute to filling these gaps by using social network analysis and multilevel modeling to describe a unique dataset of mostly young men (n = 1249 men and 242 women) nested within 59 urban social networks in Dar es Salaam, Tanzania. We examine the means, ranges, and clustering of men's HIV-related normative beliefs and behaviors. Networks in this urban setting varied substantially in both composition and structure and a large proportion of men engaged in risky behaviors including inconsistent condom use, sexual partner concurrency, and intimate partner violence perpetration. We found significant clustering of normative beliefs and risk behaviors within these men's social networks. Specifically, network membership explained between 5.78 and 7.17% of variance in men's normative beliefs and between 1.93 and 15.79% of variance in risk behaviors. Our results suggest that social networks are important socialization sites for young men and may influence the adoption of norms and behaviors. We conclude by calling for more research on men's social networks in Sub-Saharan Africa and map out several areas of future inquiry. Copyright © 2016 Elsevier Ltd. All rights reserved.
Social Support and HIV-related Risk Behaviors: A Systematic Review of the Global Literature
Li, Xiaoming; Stanton, Bonita
2013-01-01
Existing empirical evidence has well documented the role of social support in both physical and psychological well-being among various populations. In the context of HIV prevention, the rapid increase of studies on social support merits a systematic review to synthesize the current global literature on association between social support and HIV-related risk behaviors. The current review reveals a complex picture of this relationship across diverse populations. Existing studies indicate that higher levels of social support are related to fewer HIV-related risk behaviors among female sex workers and people living with HIV/AIDS and heterosexual adults in general. However, influences of social support on HIV-related risk behaviors are inconsistent within drug users, men who have sex with men and adolescents. These variations in findings may be attributed to different measurement of social support in different studies, specific context of social support for diverse population, or various characteristics of the social networks the study population obtained support from. Future studies are needed to explore the mechanism of how social support affects HIV-related risk behaviors. HIV prevention intervention efforts need to focus on the positive effect of social support for various vulnerable and at-risk populations. Future efforts also need to incorporate necessary structure change and utilize technical innovation in order to maximize the protective role of social support in HIV risk prevention or reduction. PMID:23921582
Sowd, Gregory A.; Serrao, Erik; Wang, Hao; Wang, Weifeng; Fadel, Hind J.; Poeschla, Eric M.; Engelman, Alan N.
2016-01-01
Integration is vital to retroviral replication and influences the establishment of the latent HIV reservoir. HIV-1 integration favors active genes, which is in part determined by the interaction between integrase and lens epithelium-derived growth factor (LEDGF)/p75. Because gene targeting remains significantly enriched, relative to random in LEDGF/p75 deficient cells, other host factors likely contribute to gene-tropic integration. Nucleoporins 153 and 358, which bind HIV-1 capsid, play comparatively minor roles in integration targeting, but the influence of another capsid binding protein, cleavage and polyadenylation specificity factor 6 (CPSF6), has not been reported. In this study we knocked down or knocked out CPSF6 in parallel or in tandem with LEDGF/p75. CPSF6 knockout changed viral infectivity kinetics, decreased proviral formation, and preferentially decreased integration into transcriptionally active genes, spliced genes, and regions of chromatin enriched in genes and activating histone modifications. LEDGF/p75 depletion by contrast preferentially altered positional integration targeting within gene bodies. Dual factor knockout reduced integration into genes to below the levels observed with either single knockout and revealed that CPSF6 played a more dominant role than LEDGF/p75 in directing integration to euchromatin. CPSF6 complementation rescued HIV-1 integration site distribution in CPSF6 knockout cells, but complementation with a capsid binding mutant of CPSF6 did not. We conclude that integration targeting proceeds via two distinct mechanisms: capsid-CPSF6 binding directs HIV-1 to actively transcribed euchromatin, where the integrase-LEDGF/p75 interaction drives integration into gene bodies. PMID:26858452
Abnormal B cell memory subsets dominate HIV-specific responses in infected individuals
Kardava, Lela; Moir, Susan; Shah, Naisha; Wang, Wei; Wilson, Richard; Buckner, Clarisa M.; Santich, Brian H.; Kim, Leo J.Y.; Spurlin, Emily E.; Nelson, Amy K.; Wheatley, Adam K.; Harvey, Christopher J.; McDermott, Adrian B.; Wucherpfennig, Kai W.; Chun, Tae-Wook; Tsang, John S.; Li, Yuxing; Fauci, Anthony S.
2014-01-01
Recently, several neutralizing anti-HIV antibodies have been isolated from memory B cells of HIV-infected individuals. Despite extensive evidence of B cell dysfunction in HIV disease, little is known about the cells from which these rare HIV-specific antibodies originate. Accordingly, we used HIV envelope gp140 and CD4 or coreceptor (CoR) binding site (bs) mutant probes to evaluate HIV-specific responses in peripheral blood B cells of HIV-infected individuals at various stages of infection. In contrast to non-HIV responses, HIV-specific responses against gp140 were enriched within abnormal B cells, namely activated and exhausted memory subsets, which are largely absent in the blood of uninfected individuals. Responses against the CoRbs, which is a poorly neutralizing epitope, arose early, whereas those against the well-characterized neutralizing epitope CD4bs were delayed and infrequent. Enrichment of the HIV-specific response within resting memory B cells, the predominant subset in uninfected individuals, did occur in certain infected individuals who maintained low levels of plasma viremia and immune activation with or without antiretroviral therapy. The distribution of HIV-specific responses among memory B cell subsets was corroborated by transcriptional analyses. Taken together, our findings provide valuable insight into virus-specific B cell responses in HIV infection and demonstrate that memory B cell abnormalities may contribute to the ineffectiveness of the antibody response in infected individuals. PMID:24892810
Implications of prioritizing HIV cure: new momentum to overcome old challenges in HIV.
Tucker, Joseph D; Gilbertson, Adam; Lo, Ying-Ru; Vitória, Marco
2016-03-03
Curing HIV is a new strategic priority for several major AIDS organizations. In step with this new priority, HIV cure research and related programs are advancing in low, middle, and high-income country settings. This HIV cure momentum may influence existing HIV programs and research priorities. Despite the early stage of ongoing HIV cure efforts, these changes have directly influenced HIV research funding priorities, pilot programs, and HIV messaging. The building momentum to cure HIV infection may synergize with strategic priorities to better identify adults and infants with very early HIV infection. Although HIV cure represents a new goal, many existing programs and research techniques can be repurposed towards an HIV cure. HIV messages focused on engaging communities towards an HIV cure need to be careful to promote ARV adherence and retention within the HIV continuum of care. An increased emphasis within the AIDS field on finding an HIV cure has several important implications. Strengthening connections between HIV cure research and other areas of HIV research may help to catalyze research and facilitate implementation in the future.
Introduction of male circumcision for HIV prevention in Uganda: analysis of the policy process.
Odoch, Walter Denis; Kabali, Kenneth; Ankunda, Racheal; Zulu, Joseph Mumba; Tetui, Moses
2015-06-20
Health policy analysis is important for all health policies especially in fields with ever changing evidence-based interventions such as HIV prevention. However, there are few published reports of health policy analysis in sub-Saharan Africa in this field. This study explored the policy process of the introduction of male circumcision (MC) for HIV prevention in Uganda in order to inform the development processes of similar health policies. Desk review of relevant documents was conducted between March and May 2012. Thematic analysis was used to analyse the data. Conceptual frameworks that demonstrate the interrelationship within the policy development processes and influence of actors in the policy development processes guided the analysis. Following the introduction of MC on the national policy agenda in 2007, negotiation and policy formulation preceded its communication and implementation. Policy proponents included academic researchers in the early 2000s and development partners around 2007. Favourable contextual factors that supported the development of the policy included the rising HIV prevalence, adoption of MC for HIV prevention in other sub-Saharan African countries, and expertise on MC. Additionally, the networking capability of proponents facilitated the change in position of non-supportive or neutral actors. Non-supportive and neutral actors in the initial stages of the policy development process included the Ministry of Health, traditional and Muslim leaders, and the Republican President. Using political authority, legitimacy, and charisma, actors who opposed the policy tried to block the policy development process. Researchers' initial disregard of the Ministry of Health in the research process of MC and the missing civil society advocacy arm contributed to delays in the policy development process. This study underscores the importance of securing top political leadership as well as key implementing partners' support in policy development processes. Equally important is the appreciation of the various forms of actors' power and how such power shapes the policy agenda, development process, and content.
HIV-1 evades innate immune recognition through specific cofactor recruitment
NASA Astrophysics Data System (ADS)
Rasaiyaah, Jane; Tan, Choon Ping; Fletcher, Adam J.; Price, Amanda J.; Blondeau, Caroline; Hilditch, Laura; Jacques, David A.; Selwood, David L.; James, Leo C.; Noursadeghi, Mahdad; Towers, Greg J.
2013-11-01
Human immunodeficiency virus (HIV)-1 is able to replicate in primary human macrophages without stimulating innate immunity despite reverse transcription of genomic RNA into double-stranded DNA, an activity that might be expected to trigger innate pattern recognition receptors. We reasoned that if correctly orchestrated HIV-1 uncoating and nuclear entry is important for evasion of innate sensors then manipulation of specific interactions between HIV-1 capsid and host factors that putatively regulate these processes should trigger pattern recognition receptors and stimulate type 1 interferon (IFN) secretion. Here we show that HIV-1 capsid mutants N74D and P90A, which are impaired for interaction with cofactors cleavage and polyadenylation specificity factor subunit 6 (CPSF6) and cyclophilins (Nup358 and CypA), respectively, cannot replicate in primary human monocyte-derived macrophages because they trigger innate sensors leading to nuclear translocation of NF-κB and IRF3, the production of soluble type 1 IFN and induction of an antiviral state. Depletion of CPSF6 with short hairpin RNA expression allows wild-type virus to trigger innate sensors and IFN production. In each case, suppressed replication is rescued by IFN-receptor blockade, demonstrating a role for IFN in restriction. IFN production is dependent on viral reverse transcription but not integration, indicating that a viral reverse transcription product comprises the HIV-1 pathogen-associated molecular pattern. Finally, we show that we can pharmacologically induce wild-type HIV-1 infection to stimulate IFN secretion and an antiviral state using a non-immunosuppressive cyclosporine analogue. We conclude that HIV-1 has evolved to use CPSF6 and cyclophilins to cloak its replication, allowing evasion of innate immune sensors and induction of a cell-autonomous innate immune response in primary human macrophages.
Kisler, Kimberly A.; Williams, John K.
2013-01-01
Background HIV prevention has rarely explored the impact of childhood sexual abuse (CSA) across health domains among African American men who have sex with men and women (MSMW). Early sexual experiences may influence perceptions of gender roles, sexual identity, and risks for HIV/AIDS. The attribute of masculinity is commonly associated with strength and success. However, a legacy of racism and oppression may pose challenges for African American men in achieving gender-based milestones. Instead, proxies for success may include masculinity constructs with hypersexual posturing and prowess that contradict sexual health messages. Methods Two groups, each meeting twice for 90-minutes, of HIV-positive African American MSMW participated in discussions focusing on masculinity and sexual experiences. Participants were bisexual HIV-positive African American men who engaged in unprotected sex and had histories of CSA. Discussions were recorded, transcribed, and analyzed using consensual qualitative research and a constant comparison qualitative method. Results Participant mean age was 40.5 years (n=16). Majority had a high school education (69%), half were unemployed, and almost two-thirds earned less than $20,000 annually. Three themes, each with two subthemes, emerged that described the sociocultural context for engaging in high-risk sexual behaviors, and included: 1) the importance of inhabiting a “traditional” masculine gender role with: a) general and b) sexual masculine traits; 2) the influence of conceptions of masculinity on sexual identity with the associations: a) between being gay and being effeminate and b) between being gay and being HIV-positive, and; 3) CSA experiences with: a) appraisal of CSA and b) early sexual experiences as rites of passage. Conclusion Attempts to be masculine may contribute to high-risk sexual behaviors. Research needs to explore how early sexual experiences shape perceptions of masculinity and masculinity's influence on receiving health messages for African American MSMW who may prioritize a specific image over sexual risk reduction PMID:24443705
2014-01-01
Background There is a huge interest by faith-based organizations (FBOs) in sub-Saharan Africa and elsewhere in HIV prevention interventions that build on the religious aspects of being. Successful partnerships between the public health services and FBOs will require a better understanding of the conceptual framing of HIV prevention by FBOS to access for prevention intervention, those concepts the churches of various denominations and their members would support or endorse. This study investigated the conceptual framing of HIV prevention among church youths in Botswana; - a country with one of the highest HIV prevalence in the world. Method Participants were 213 Pentecostal church members (67% female; age range 12 to 23 years; median age = 19 years). We engaged the participants in a mixed-method inductive process to collect data on their implicit framing of HIV prevention concepts, taking into account the centrality of religion concepts to them and the moderating influences of age, gender and sexual experience. After, we analysed the data using multi-dimensional scaling (MDS) and hierarchical cluster analysis (HCA) to map the ways the church youths framed HIV prevention. Results The findings suggest the church youth to conceptually frame their HIV prevention from both faith-oriented and secular-oriented perspectives, while prioritizing the faith-oriented concepts based on biblical teachings and future focus. In their secular-oriented framing of HIV prevention, the church youths endorsed the importance to learn the facts about HIV and AIDS, understanding of community norms that increased risk for HIV and prevention education. However, components of secular-oriented framing of HIV prevention concepts were comparatively less was well differentiated among the youths than with faith-oriented framing, suggesting latent influences of the church knowledge environment to undervalue secular oriented concepts. Older and sexually experienced church youths in their framing of HIV prevention valued future focus and prevention education less than contrasting peer cohorts, suggesting their greater relative risk for HIV infection. Conclusion A prospective HIV prevention intervention with the Pentecostal church youths would combine both faith and secular informed concepts. It also would need to take into account the ways in which these youth interpret secular-oriented health concepts in the context of their religious beliefs. PMID:24593140
Posch, Wilfried; Cardinaud, Sylvain; Hamimi, Chiraz; Fletcher, Adam; Mühlbacher, Annelies; Loacker, Klaus; Eichberger, Paul; Dierich, Manfred P.; Pancino, Gianfranco; Lass-Flörl, Cornelia; Moris, Arnaud; Saez-Cirion, Asier; Wilflingseder, Doris
2014-01-01
Background Control of HIV is suggested to depend on potent effector functions of the virus-specific CD8+ T-cell response. Antigen opsonization can modulate the capture of antigen, its presentation, and the priming of specific CD8+ T-cell responses. Objective We have previously shown that opsonization of retroviruses acts as an endogenous adjuvant for dendritic cell (DC)–mediated induction of specific cytotoxic T lymphocytes (CTLs). However, in some HIV-positive subjects, high levels of antibodies and low levels of complement fragments coat the HIV surface. Methods Therefore we analyzed the effect of IgG opsonization on the antigen-presenting capacity of DCs by using CD8+ T-cell proliferation assays after repeated prime boosting, by measuring the antiviral activity against HIV-infected autologous CD4+ T cells, and by determining IFN-γ secretion from HIV-specific CTL clones. Results We find that DCs exposed to IgG-opsonized HIV significantly decreased the HIV-specific CD8+ T-cell response compared with the earlier described efficient CD8+ T-cell activation induced by DCs loaded with complement-opsonized HIV. DCs exposed to HIV bearing high surface IgG levels after incubation in plasma from HIV-infected subjects acted as weak stimulators for HIV-specific CTL clones. In contrast, HIV opsonized with plasma from patients exhibiting high complement and low IgG deposition on the viral surface favored significantly higher activation of HIV-specific CD8+ T-cell clones. Conclusion Our ex vivo and in vitro observations provide the first evidence that IgG opsonization of HIV is associated with a decreased CTL-stimulatory capacity of DCs. PMID:23063584
The stochastic dance of early HIV infection
NASA Astrophysics Data System (ADS)
Merrill, Stephen J.
2005-12-01
The stochastic nature of early HIV infection is described in a series of models, each of which captures aspects of the dance of HIV during the early stages of infection. It is to this highly variable target that the immune response must respond. The adaptability of the various components of the immune response is an important aspect of the system's operation, as the nature of the pathogens that the response will be required to respond to and the order in which those responses must be made cannot be known beforehand. As HIV infection has direct influence over cells responsible for the immune response, the dance predicts that the immune response will be also in a variable state of readiness and capability for this task of adaptation. The description of the stochastic dance of HIV here will use the tools of stochastic models, and for the most part, simulation. The justification for this approach is that the early stages and the development of HIV diversity require that the model to be able to describe both individual sample path and patient-to-patient variability. In addition, as early viral dynamics are best described using branching processes, the explosive growth of these models both predicts high variability and rapid response of HIV to changes in system parameters.In this paper, a basic viral growth model based on a time dependent continuous-time branching process is used to describe the growth of HIV infected cells in the macrophage and lymphocyte populations. Immigration from the reservoir population is added to the basic model to describe the incubation time distribution. This distribution is deduced directly from the modeling assumptions and the model of viral growth. A system of two branching processes, one in the infected macrophage population and one in the infected lymphocyte population is used to provide a description of the relationship between the development of HIV diversity as it relates to tropism (host cell preference). The role of the immune response to HIV and HIV infected cells is used to describe the movement of the infection from a few infected macrophages to a disease of infected CD4+ T lymphocytes.
Predominate HIV1-specific IgG activity in various mucosal compartments of HIV1-infected individuals.
Lü, F X
2000-10-01
Evaluating mucosal humoral immunity is important for understanding local immunity induced by HIV infection or vaccination and designing prophylactic strategies. To characterize the mucosal humoral immunity following HIV infection, the levels of immunoglobulins (Igs), antibodies (Abs), and HIV1-specific Ab activity were evaluated in cervicovaginal secretions (CVS), saliva, breast milk, and sera of HIV-infected individuals. HIV1-specific IgG activity was significantly higher than that of IgA in CVS, saliva, and breast milk. The highest HIV1-specific IgG activity was found in breast milk. The data suggest that anti-HIV1 Abs in CVS were most likely serum derived. However, HIV1-specific Abs in saliva and breast milk were mainly locally produced. The prevalence of HIV1-specific Abs in seropositive subjects was 97% for IgG and 95% for IgA in CVS, 100% for IgG and 80% for IgA in saliva, and 59% for IgG and 94% for IgA in breast milk. These data provide evidence for both a better understanding of the nature of humoral mucosal responses after HIV1 infection and the development of strategies to induce desirable functional mucosal immunity for preventing HIV transmission. Copyright 2000 Academic Press.
Kill: Boosting HIV-specific immune responses
Trautmann, Lydie
2016-01-01
Purpose of review Increasing evidences suggest that purging the latent HIV reservoir in virally-suppressed individuals will require both the induction of viral replication from its latent state and the elimination of these reactivated HIV infected cells (“Shock and Kill” strategy). Boosting potent HIV-specific CD8 T cells is a promising way to achieve an HIV cure. Recent findings Recent studies provided the rationale for developing immune interventions to increase the numbers, function and location of HIV-specific CD8 T cells to purge HIV reservoirs. Multiple approaches are being evaluated including very early suppression of HIV replication in acute infection, adoptive cell transfer, therapeutic vaccination or use of immunomodulatory molecules. New assays to measure the killing and antiviral function of induced HIV-specific CD8 T cells have been developed to assess the efficacy of these new approaches. The strategies combining HIV reactivation and immunobased therapies to boost HIV-specific CD8 T cells can be tested in in vivo and in silico models to accelerate the design of new clinical trials. Summary New immunobased strategies are explored to boost HIV-specific CD8 T cells able to purge the HIV-infected cells with the ultimate goal of achieving spontaneous control of viral replication without antiretroviral treatment. PMID:27054280
Influence of faith-based organisations on HIV prevention strategies in Africa: a systematic review.
Ochillo, Marylyn A; van Teijlingen, Edwin; Hind, Martin
2017-09-01
The HIV/AIDS epidemic remains of global significance and there is a need to target sub-Saharan Africa since it is the hardest hit region worldwide. Religion and more specifically faith-based organisations can have an effect on socio-cultural factors that increase or decrease the risk of infection; and offer preventative interventions to the wider community. To understand the influence of faith-based organisations on HIV prevention in Africa. The main search engine of a British university 'mysearch' was used as this incorporates all relevant databases. Studies were also retrieved by searches within Google scholar, PubMed and reference lists of included papers were hand searched. The authors assessed the relevance of each article separately against the inclusion criteria. The data extraction form was piloted by the first author and cross-checked by the other authors. Seven studies met all inclusion criteria and were reviewed. Seven individual themes were identified. However, for the purposes of focus within this paper only two themes were focused on. Given the accessibility of faith-based organisations (FBOs) and the coverage of religion among the population, FBOs are potentially important players in HIV prevention. Therefore, more resources and support should be given to support their health promotion strategies.
Professional ideologies and the development of syringe exchange: Wales as a case study.
Keene, J M; Stimson, G V
1997-12-01
This paper is derived from an evaluative study of HIV prevention programs for drug injectors across Wales. It considers how different professional territories and ideologies, concepts of drug misuse and models of HIV prevention may influence policy development. The research involved monitoring the introduction and development of agency and community based syringe exchange schemes and initiatives taken by community pharmacists. Interviews with staff, managers and administrators, and descriptions of service history, development and delivery inform the discussion. HIV prevention varied in different areas of Wales depending on the particular professional group involved, local ideologies regarding drug use treatment, and the extent to which HIV prevention was seen either as a specialist area of expertise and specific remit of drug workers or a generic health care task. Drug agencies with an abstinence policy rejected syringe exchange; instead, prevention in those areas developed in ad hoc ways as health care workers and pharmacists attempted to develop a community based service. Drug agencies with a pre-existing harm minimisation model easily integrated syringe exchange into their work and played the major part in establishing the service, but there was difficulty in extending it beyond their professional caseloads. As there were disincentives to use treatment agencies, and their catchment areas were limited, these factors influenced effective service provision.
Yu, Donglei; Wild, Carl T; Martin, David E; Morris-Natschke, Susan L; Chen, Chin-Ho; Allaway, Graham P; Lee, Kuo-Hsiung
2005-06-01
Although HIV infection is now primarily treated with reverse transcriptase and protease inhibitors, HIV therapy must look toward new drugs with novel mechanism(s) of action to both improve efficacy and address the growing problem of drug resistance. Using natural products as a source of biologically active compounds, our drug discovery program has successfully optimised the natural product betulinic acid to the first-in-class maturation inhibitor 3-O-(3',3'-dimethylsuccinyl)-betulinic acid (DSB). DSB's unique viral target has been identified as a late step in Gag processing. Specifically, it inhibits the cleavage of the capsid precursor, CA-SP1, resulting in a block to the processing of mature capsid protein leading to a defect in viral core condensation. DSB represents a unique class of anti-HIV compounds that inhibit virus maturation and provide additional opportunities for anti-HIV therapy. In this review, the discovery of DSB and its mode of action are summarised. Anti-AIDS Agents part 64. For part 63 in the series, see YU D, LEE KH: Recent progress and prospects on plant-derived anti-HIV agents and analogs. In: Medicinal Chemistry of Bioactive Natural Products. XT Liang, WS Fang (Eds), Wiley, New York, USA (2005) (In Press).
The Influence of Community Members on Participation by Youth in an HIV Vaccine Trial in Tanzania
Mbunda, Theodora; Tarimo, Edith A. M.; Bakari, Muhammad; Sandström, Eric; Kulane, Asli
2016-01-01
In sub-Saharan Africa, the burden of HIV is high among young people and it is of the utmost importance that they be recruited into vaccination trials. Since community members influence the willingness of young people to participate in the vaccination trials, ascertaining their opinions is essential to overcoming barriers to such participation. Here, in seven focus group discussions we explored the views of 44 community members identified as someone they felt close by youth in Tanzania. The transcripts of these discussions were examined using content analysis. Our participants expressed that community members would be directly involved in the decisions of young people about whether or not to participate in an HIV vaccine trial. In general, they felt that community members would provide social support for youth during the trial and perceived that youth might have misconceptions concerning the vaccine and trial process. The participants pointed out structural factors such as substance use, poverty, stigma and unemployment that are barriers to participation. In conclusion, involvement of community members could be an integral part of the recruitment and retention of young people in HIV vaccine trials in Tanzania. PMID:27997617
Rolon, Maria Luisa; Syvertsen, Jennifer L.; Robertson, Angela M.; Rangel, M. Gudelia; Martinez, Gustavo; Ulibarri, Monica D.; Servin, Argentina
2013-01-01
Among female sex workers who use drugs, the experience of having children and its effect on HIV risk behaviors remains underexplored. We draw from a study of 214 female sex workers and their intimate non-commercial partners in Tijuana and Ciudad Juárez, México (n = 428), approximately 30% of whom have children living with them. During qualitative interviews with 41 of these couples, having children emerged as an important topic. Children influenced partners’ lives and HIV-related risk behaviors in positive and negative ways. Couples perceived that children strengthened their relationships. Concern for children’s well-being motivated couples to contemplate healthier lifestyle changes. However, childrearing costs motivated sex work and structural constraints prevented couples from enacting lifestyle changes. Case studies illustrate these themes and highlight implications for couple- and family-based harm reduction interventions. Specifically, our results suggest a need for economic alternatives to sex work while working with families to develop risk reduction skills. PMID:23418131
FIV diversity: FIV Ple subtype composition may influence disease outcome in African lions.
Troyer, Jennifer L; Roelke, Melody E; Jespersen, Jillian M; Baggett, Natalie; Buckley-Beason, Valerie; MacNulty, Dan; Craft, Meggan; Packer, Craig; Pecon-Slattery, Jill; O'Brien, Stephen J
2011-10-15
Feline immunodeficiency virus (FIV) infects domestic cats and at least 20 additional species of non-domestic felids throughout the world. Strains specific to domestic cat (FIV(Fca)) produce AIDS-like disease progression, sequelae and pathology providing an informative model for HIV infection in humans. Less is known about the immunological and pathological influence of FIV in other felid species although multiple distinct strains of FIV circulate in natural populations. As in HIV-1 and HIV-2, multiple diverse cross-species infections may have occurred. In the Serengeti National Park, Tanzania, three divergent subtypes of lion FIV (FIV(Ple)) are endemic, whereby 100% of adult lions are infected with one or more of these strains. Herein, the relative distribution of these subtypes in the population are surveyed and, combined with observed differences in lion mortality due to secondary infections based on FIV(Ple) subtypes, the data suggest that FIV(Ple) subtypes may have different patterns of pathogenicity and transmissibility among wild lion populations. Copyright © 2011 Elsevier B.V. All rights reserved.
Polpitiya Arachchige, Sachith; Henke, Wyatt; Pramanik, Ankita; Kalamvoki, Maria; Stephens, Edward B
2018-01-15
Virus-encoded proteins that impair or shut down specific host cell functions during replication can be used as probes to identify potential proteins/pathways used in the replication of viruses from other families. We screened nine proteins from herpes simplex virus 1 (HSV-1) for the ability to enhance or restrict human immunodeficiency virus type 1 (HIV-1) replication. We show that several HSV-1 proteins (glycoprotein M [gM], US3, and UL24) potently restricted the replication of HIV-1. Unlike UL24 and US3, which reduced viral protein synthesis, we observed that gM restriction of HIV-1 occurred through interference with the processing and transport of gp160, resulting in a significantly reduced level of mature gp120/gp41 released from cells. Finally, we show that an HSV-1 gM mutant lacking the majority of the C-terminal domain (HA-gM[Δ345-473]) restricted neither gp160 processing nor the release of infectious virus. These studies identify proteins from heterologous viruses that can restrict viruses through novel pathways. IMPORTANCE HIV-1 infection of humans results in AIDS, characterized by the loss of CD4 + T cells and increased susceptibility to opportunistic infections. Both HIV-1 and HSV-1 can infect astrocytes and microglia of the central nervous system (CNS). Thus, the identification of HSV-1 proteins that directly restrict HIV-1 or interfere with pathways required for HIV-1 replication could lead to novel antiretroviral strategies. The results of this study show that select viral proteins from HSV-1 can potently restrict HIV-1. Further, our results indicate that the gM protein of HSV-1 restricts HIV-1 through a novel pathway by interfering with the processing of gp160 and its incorporation into virus maturing from the cell. Copyright © 2018 American Society for Microbiology.
H Logie, Carmen; Perez-Brumer, Amaya; Jenkinson, Jesse; Madau, Veli; Nhlengethwa, Winnie; Baral, Stefan
2018-05-30
Swaziland has among the highest national adult HIV prevalence globally. There is limited knowledge of HIV vulnerabilities and prevention engagement among lesbian, gay, bisexual and transgender (LGBT) persons in the context of Swaziland's criminalization of consensual same-sex practices. This study explored social processes of marginalization to assess how they could potentiate HIV vulnerabilities and limit engagement in HIV prevention services. Additionally, we assessed positive change to better understand existing strategies employed by LGBT persons to challenge these HIV prevention barriers. Guided by community-based research methodology and conducted in Mbabane and Manzini, Swaziland, data were collected by LGBT peer-research assistants (PRA) in collaboration with an LGBT community organization in Manzini. Semi-structured interviews were conducted by trained PRAs and explored HIV prevention, including experiences of stigma and coping. Audio files were transcribed verbatim, translated to English, and analyzed using thematic techniques. Among participants (n = 51; mean age: 26.47, SD: 4.68), 40 self-identifed as gay or lesbian (78.4%), 11 bisexual (22.6%), and 12 (23.5%) identified as transgender. Findings highlighted three primary processes of marginalization and positive change in structural, community, and internal domains. First, structural marginalization, which included criminalization, healthcare discrimination, and a scarcity of LGBT tailored HIV prevention resources was challenged by grassroots networks created to access and share specific HIV resources with LGBT persons and the Ministry of Health. Second, community marginalization included stigma and multi-dimensional forms of violence, however, this was met with LGBT persons providing mutual peer support, including for accessing HIV testing services. Thirdly, internal marginalization comprised of self-stigma and associated sexual risk practices was contrasted with coping strategies focused on self-acceptance, stemming from social support and leading to healthcare utilization. Jointly, these findings can inform the implementation of community-based and rights affirming HIV prevention and care cascade strategies that improve coverage of services with LGBT persons in Swaziland.
GHARTEY, Jeny; KOVACS, Andrea; BURK, Robert D.; MASSAD, L. Stewart; MINKOFF, Howard; XIE, Xianhong; D’SOUZA, Gypsyamber; XUE, Xiaonan; WATTS, D. Heather; LEVINE, Alexandra M.; EINSTEIN, Mark H.; COLIE, Christine; ANASTOS, Kathryn; ELTOUM, Isam-Eldin; HEROLD, Betsy C.; PALEFSKY, Joel M.; STRICKLER, Howard D.
2014-01-01
Objective Plasma HIV RNA levels have been associated with risk of human papillomavirus (HPV) and cervical neoplasia in HIV-seropositive women. However, little is known regarding local genital tract HIV RNA levels and their relation with cervical HPV and neoplasia. Design/Methods In an HIV-seropositive women’s cohort with semi-annual follow-up, we conducted a nested case-control study of genital tract HIV RNA levels and their relation with incident high-grade squamous intraepithelial lesions sub-classified as severe (severe HSIL), as provided for under the Bethesda 2001 classification system. Specifically, 66 incident severe HSIL were matched to 130 controls by age, CD4+ count, HAART use, and other factors. We also studied HPV prevalence, incident detection, and persistence in a random sample of 250 subjects. Results Risk of severe HSIL was associated with genital tract HIV RNA levels (odds ratio comparing HIV RNA ≥ the median among women with detectable levels versus undetectable [ORVL] 2.96; 95% CI: 0.99–8.84; Ptrend=0.03). However, this association became non-significant (Ptrend=0.51) following adjustment for plasma HIV RNA levels. There was also no association between genital tract HIV RNA levels and the prevalence of any HPV or oncogenic HPV. However, the incident detection of any HPV (Ptrend=0.02) and persistence of oncogenic HPV (Ptrend=0.04) were associated with genital tract HIV RNA levels, after controlling plasma HIV RNA levels. Conclusion These prospective data suggest that genital tract HIV RNA levels are not a significant independent risk factor for cervical pre-cancer in HIV-seropositive women, but leave open the possibility that they may modestly influence HPV infection, an early stage of cervical tumoriogenesis. PMID:24694931
Kessler, Jason; Myers, Julie E.; Nucifora, Kimberly A.; Mensah, Nana; Kowalski, Alexis; Sweeney, Monica; Toohey, Christopher; Khademi, Amin; Shepard, Colin; Cutler, Blayne; Braithwaite, R. Scott
2013-01-01
Background New York City (NYC) remains an epicenter of the HIV epidemic in the United States. Given the variety of evidence-based HIV prevention strategies available and the significant resources required to implement each of them, comparative studies are needed to identify how to maximize the number of HIV cases prevented most economically. Methods A new model of HIV disease transmission was developed integrating information from a previously validated micro-simulation HIV disease progression model. Specification and parameterization of the model and its inputs, including the intervention portfolio, intervention effects and costs were conducted through a collaborative process between the academic modeling team and the NYC Department of Health and Mental Hygiene. The model projects the impact of different prevention strategies, or portfolios of prevention strategies, on the HIV epidemic in NYC. Results Ten unique interventions were able to provide a prevention benefit at an annual program cost of less than $360,000, the threshold for consideration as a cost-saving intervention (because of offsets by future HIV treatment costs averted). An optimized portfolio of these specific interventions could result in up to a 34% reduction in new HIV infections over the next 20 years. The cost-per-infection averted of the portfolio was estimated to be $106,378; the total cost was in excess of $2 billion (over the 20 year period, or approximately $100 million per year, on average). The cost-savings of prevented infections was estimated at more than $5 billion (or approximately $250 million per year, on average). Conclusions Optimal implementation of a portfolio of evidence-based interventions can have a substantial, favorable impact on the ongoing HIV epidemic in NYC and provide future cost-saving despite significant initial costs. PMID:24058465
Koblavi-Dème, Stéphania; Maurice, Chantal; Yavo, Daniel; Sibailly, Toussaint S.; N′guessan, Kabran; Kamelan-Tano, Yvonne; Wiktor, Stefan Z.; Roels, Thierry H.; Chorba, Terence; Nkengasong, John N.
2001-01-01
To evaluate serologic testing algorithms for human immunodeficiency virus (HIV) based on a combination of rapid assays among persons with HIV-1 (non-B subtypes) infection, HIV-2 infection, and HIV-1–HIV-2 dual infections in Abidjan, Ivory Coast, a total of 1,216 sera with known HIV serologic status were used to evaluate the sensitivity and specificity of four rapid assays: Determine HIV-1/2, Capillus HIV-1/HIV-2, HIV-SPOT, and Genie II HIV-1/HIV-2. Two serum panels obtained from patients recently infected with HIV-1 subtypes B and non-B were also included. Based on sensitivity and specificity, three of the four rapid assays were evaluated prospectively in parallel (serum samples tested by two simultaneous rapid assays) and serial (serum samples tested by two consecutive rapid assays) testing algorithms. All assays were 100% sensitive, and specificities ranged from 99.4 to 100%. In the prospective evaluation, both the parallel and serial algorithms were 100% sensitive and specific. Our results suggest that rapid assays have high sensitivity and specificity and, when used in parallel or serial testing algorithms, yield results similar to those of enzyme-linked immunosorbent assay-based testing strategies. HIV serodiagnosis based on rapid assays may be a valuable alternative in implementing HIV prevention and surveillance programs in areas where sophisticated laboratories are difficult to establish. PMID:11325995
Suryawanshi, Gajendra W.; Hoffmann, Alexander
2015-01-01
Human immunodeficiency virus-1 (HIV-1) employs accessory proteins to evade innate immune responses by neutralizing the anti-viral activity of host restriction factors. Apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G, A3G) and bone marrow stromal cell antigen 2 (BST2) are host resistance factors that potentially inhibit HIV-1 infection. BST2 reduces viral production by tethering budding HIV-1 particles to virus producing cells, while A3G inhibits the reverse transcription (RT) process and induces viral genome hypermutation through cytidine deamination, generating fewer replication competent progeny virus. Two HIV-1 proteins counter these cellular restriction factors: Vpu, which reduces surface BST2, and Vif, which degrades cellular A3G. The contest between these host and viral proteins influences whether HIV-1 infection is established and progresses towards AIDS. In this work, we present an age-structured multi-scale viral dynamics model of in vivo HIV-1 infection. We integrated the intracellular dynamics of anti-viral activity of the host factors and their neutralization by HIV-1 accessory proteins into the virus/cell population dynamics model. We calculate the basic reproductive ratio (Ro) as a function of host-viral protein interaction coefficients, and numerically simulated the multi-scale model to understand HIV-1 dynamics following host factor-induced perturbations. We found that reducing the influence of Vpu triggers a drop in Ro, revealing the impact of BST2 on viral infection control. Reducing Vif’s effect reveals the restrictive efficacy of A3G in blocking RT and in inducing lethal hypermutations, however, neither of these factors alone is sufficient to fully restrict HIV-1 infection. Interestingly, our model further predicts that BST2 and A3G function synergistically, and delineates their relative contribution in limiting HIV-1 infection and disease progression. We provide a robust modeling framework for devising novel combination therapies that target HIV-1 accessory proteins and boost antiviral activity of host factors. PMID:26385832
Rosenfeld, Dana; Ridge, Damien; Catalan, Jose; Delpech, Valerie
2016-08-01
Studies of disclosure amongst older people living with HIV (PLWH) are uninformed by critical social-gerontological approaches that can help us to appreciate how older PLWH see and treat age as relevant to disclosure of their HIV status. These approaches include an ethnomethodologically-informed social constructionism that explores how 'the' life course (a cultural framework depicting individuals' movement through predictable developmental stages from birth to death) is used as an interpretive resource for determining self and others' characteristics, capacities, and social circumstances: a process Rosenfeld and Gallagher (2002) termed 'lifecoursing'. Applying this approach to our analysis of 74 life-history interviews and three focus groups with older (aged 50+) people living with HIV in the United Kingdom, we uncover the central role that lifecoursing plays in participants' decision-making surrounding disclosure of their HIV to their children and/or older parents. Analysis of participants' accounts uncovered four criteria for disclosure: the relevance of their HIV to the other, the other's knowledge about HIV, the likelihood of the disclosure causing the other emotional distress, and the other's ability to keep the disclosed confidential. To determine if these criteria were met in relation to specific children and/or elders, participants engaged in lifecoursing, evaluating the other's knowledge of HIV, and capacity to appropriately manage the disclosure, by reference to their age. The use of assumptions about age and life-course location in decision-making regarding disclosure of HIV reflects a more nuanced engagement with age in the disclosure decision-making process than has been captured by previous research into HIV disclosure, including on the part of people aging with HIV. Copyright © 2016 Elsevier Inc. All rights reserved.
Brander, Christian; Yang, Otto O.; Jones, Norman G.; Lee, Yun; Goulder, Philip; Johnson, R. Paul; Trocha, Alicja; Colbert, David; Hay, Christine; Buchbinder, Susan; Bergmann, Cornelia C.; Zweerink, Hans J.; Wolinsky, Steven; Blattner, William A.; Kalams, Spyros A.; Walker, Bruce D.
1999-01-01
Immune escape from cytotoxic T-lymphocyte (CTL) responses has been shown to occur not only by changes within the targeted epitope but also by changes in the flanking sequences which interfere with the processing of the immunogenic peptide. However, the frequency of such an escape mechanism has not been determined. To investigate whether naturally occurring variations in the flanking sequences of an immunodominant human immunodeficiency virus type 1 (HIV-1) Gag CTL epitope prevent antigen processing, cells infected with HIV-1 or vaccinia virus constructs encoding different patient-derived Gag sequences were tested for recognition by HLA-A*0201-restricted, p17-specific CTL. We found that the immunodominant p17 epitope (SL9) and its variants were efficiently processed from minigene expressing vectors and from six HIV-1 Gag variants expressed by recombinant vaccinia virus constructs. Furthermore, SL9-specific CTL clones derived from multiple donors efficiently inhibited virus replication when added to HLA-A*0201-bearing cells infected with primary or laboratory-adapted strains of virus, despite the variability in the SL9 flanking sequences. These data suggest that escape from this immunodominant CTL response is not frequently accomplished by changes in the epitope flanking sequences. PMID:10559335
Exploring the membrane fusion mechanism through force-induced disassembly of HIV-1 six-helix bundle
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gao, Kai; Beijing Key Laboratory of Noncoding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101; University of Chinese Academy of Sciences, Beijing 100049
Enveloped virus, such as HIV-1, employs membrane fusion mechanism to invade into host cell. HIV-1 gp41 ectodomain uses six-helix bundle configuration to accomplish this process. Using molecular dynamic simulations, we confirmed the stability of this six-helix bundle by showing high occupancy of hydrogen bonds and hydrophobic interactions. Key residues and interactions important for the bundle integration were characterized by force-induced unfolding simulations of six-helix bundle, exhibiting the collapse order of these groups of interactions. Moreover, our results in some way concerted with a previous theory that the formation of coiled-coil choose a route which involved cooperative interactions between the N-terminalmore » and C-terminal helix. -- Highlights: •Unfolding of HIV-1 gp41 six-helix bundle is studied by molecular dynamics simulations. •Specific interactions responsible for the stability of HIV-1 envelope post-fusion conformation were identified. •The gp41 six-helix bundle transition inducing membrane fusion might be a cooperative process of the three subunits.« less
Topp, Stephanie M; Chipukuma, Julien M
2016-01-01
Background In sub-Saharan Africa, large amounts of funding continue to be directed towards HIV-specific care and treatment, often with claims of ‘health system strengthening’ effect. Such claims rarely account for the impact on human relationships and decisions that are core to functional health systems. This research examined how establishment of externally funded HIV services influenced trusting relationships in Zambian health centres. Methods An in-depth, multicase study included four health centres selected for urban, peri-urban and rural characteristics. Case data included healthcare worker (HCW) interviews (60); patient interviews (180); direct observation of facility operations (2 weeks/centre) and key informant interviews (14) which were recorded and transcribed verbatim. Thematic analysis adopted inductive and deductive coding guided by a framework incorporating concepts of workplace trust, patient–provider trust, intrinsic and extrinsic motivation. Results HIV service scale-up impacted trust in positive and negative ways. Investment in HIV-specific infrastructure, supplies and quality assurance mechanisms strengthened workplace trust, HCW motivation and patient–provider trust in HIV departments in the short-term. In the health centres more broadly and over time, however, non-governmental organisation-led investment and support of HIV departments reinforced HCW's perceptions of the government as uninterested or unable to provide a quality work environment. Exacerbating existing perceptions of systemic workplace inequity and nepotism, uneven distribution of personal and professional opportunities related to HIV service establishment contributed to interdepartmental antagonism and reinforced workplace practices designed to protect individual HCW's interests. Conclusions Findings illustrate long-term negative effects of the vertical HIV resourcing and support structures which failed to address and sometimes exacerbated HCW (dis)trust with their own government and supervisors. The short-term and long-term effects of weakened workplace trust on HCWs' motivation and performance signal the importance of understanding how such relationships play a role in generating virtuous or perverse cycles of actor interactions, with implications for service outcomes. PMID:28588985
Jochmans, Dirk; Anders, Maria; Keuleers, Inge; Smeulders, Liesbeth; Kräusslich, Hans-Georg; Kraus, Günter; Müller, Barbara
2010-10-15
Current antiretroviral therapy against human immunodeficiency virus (HIV-1) reduces viral load and thereby prevents viral spread, but it cannot eradicate proviral genomes from infected cells. Cells in immunological sanctuaries as well as cells producing low levels of virus apparently contribute to a reservoir that maintains HIV persistence in the presence of highly active antiretroviral therapy. Thus, accelerated elimination of virus producing cells may represent a complementary strategy to control HIV infection. Here we sought to exploit HIV protease (PR) related cytotoxicity in order to develop a strategy for drug induced killing of HIV producing cells. PR processes the viral Gag and Gag-Pol polyproteins during virus maturation, but is also implicated in killing of virus producing cells through off-target cleavage of host proteins. It has been observed previously that micromolar concentrations of certain non-nucleoside reverse transcriptase inhibitors (NNRTIs) can stimulate intracellular PR activity, presumably by enhancing Gag-Pol dimerization. Using a newly developed cell-based assay we compared the degree of PR activation displayed by various NNRTIs. We identified inhibitors showing higher potency with respect to PR activation than previously described for NNRTIs, with the most potent compounds resulting in ~2-fold increase of the Gag processing signal at 250 nM. The degree of enhancement of intracellular Gag processing correlated with the compound's ability to enhance RT dimerization in a mammalian two-hybrid assay. Compounds were analyzed for their potential to mediate specific killing of chronically infected MT-4 cells. Levels of cytotoxicity on HIV infected cells determined for the different NNRTIs corresponded to the relative degree of drug induced intracellular PR activation, with CC50 values ranging from ~0.3 μM to above the tested concentration range (10 μM). Specific cytotoxicity was reverted by addition of PR inhibitors. Two of the most active compounds, VRX-480773 and GW-678248, were also tested in primary human cells and mediated cytotoxicity on HIV-1 infected peripheral blood mononuclear cells. These data present proof of concept for targeted drug induced elimination of HIV producing cells. While NNRTIs themselves may not be sufficiently potent for therapeutic application, the results provide a basis for the development of drugs exploiting this mechanism of action.
2010-01-01
Background Current antiretroviral therapy against human immunodeficiency virus (HIV-1) reduces viral load and thereby prevents viral spread, but it cannot eradicate proviral genomes from infected cells. Cells in immunological sanctuaries as well as cells producing low levels of virus apparently contribute to a reservoir that maintains HIV persistence in the presence of highly active antiretroviral therapy. Thus, accelerated elimination of virus producing cells may represent a complementary strategy to control HIV infection. Here we sought to exploit HIV protease (PR) related cytotoxicity in order to develop a strategy for drug induced killing of HIV producing cells. PR processes the viral Gag and Gag-Pol polyproteins during virus maturation, but is also implicated in killing of virus producing cells through off-target cleavage of host proteins. It has been observed previously that micromolar concentrations of certain non-nucleoside reverse transcriptase inhibitors (NNRTIs) can stimulate intracellular PR activity, presumably by enhancing Gag-Pol dimerization. Results Using a newly developed cell-based assay we compared the degree of PR activation displayed by various NNRTIs. We identified inhibitors showing higher potency with respect to PR activation than previously described for NNRTIs, with the most potent compounds resulting in ~2-fold increase of the Gag processing signal at 250 nM. The degree of enhancement of intracellular Gag processing correlated with the compound's ability to enhance RT dimerization in a mammalian two-hybrid assay. Compounds were analyzed for their potential to mediate specific killing of chronically infected MT-4 cells. Levels of cytotoxicity on HIV infected cells determined for the different NNRTIs corresponded to the relative degree of drug induced intracellular PR activation, with CC50 values ranging from ~0.3 μM to above the tested concentration range (10 μM). Specific cytotoxicity was reverted by addition of PR inhibitors. Two of the most active compounds, VRX-480773 and GW-678248, were also tested in primary human cells and mediated cytotoxicity on HIV-1 infected peripheral blood mononuclear cells. Conclusion These data present proof of concept for targeted drug induced elimination of HIV producing cells. While NNRTIs themselves may not be sufficiently potent for therapeutic application, the results provide a basis for the development of drugs exploiting this mechanism of action. PMID:20950436
Noden, Bruce H; Gomes, Aurelio; Ferreira, Aldina
2010-10-01
The interactions between religious affiliation, education, HIV knowledge, and HIV-related sexual behaviors among African church youth are poorly understood. In this socio-demographic study, 522 unmarried youth 12-28 years old in rural central Mozambique were surveyed with a structured questionnaire. Using binary logistic regression analysis, we used religious affiliation and education to measure influence on (1) HIV transmission and prevention knowledge and attitudes and (2) HIV-related sexual behaviors among youth. Religiously affiliated males were more likely than non-religious males to know when a condom should be used, respond correctly to HIV transmission questions and respond with less stigma to HIV-related scenarios. Increased levels of education among males corresponded significantly to increased knowledge of condom usage and HIV prevention strategies and less likelihood to respond with stigma. Only education levels influenced young female responses. Religious affiliation and education had minimal effects on sexual activity, condom usage, and multiple partnerships. African Independent Church/Zionist males were 1.6 times more likely to be sexually inexperienced than non-religious males but were also significantly less likely to use condoms (0.23, p=0.024). Non-religious youth were most likely to have visited sex workers and did not use condoms. These results suggest that religious affiliation, possibly as the result of educational opportunities afforded by religious-affiliated schools, is contributing to increased HIV transmission and prevention knowledge among youth in rural Central Mozambique but not influencing HIV-related sexual behavior. The need exists to strengthen the capacity of religious congregations to teach about HIV/AIDS and target non-religious youth with HIV transmission and prevention information.
Gamba, Elia; Mori, Mattia; Kovalenko, Lesia; Giannini, Alessia; Sosic, Alice; Saladini, Francesco; Fabris, Dan; Mély, Yves; Gatto, Barbara; Botta, Maurizio
2018-02-10
In this report, we present a new benzoxazole derivative endowed with inhibitory activity against the HIV-1 nucleocapsid protein (NC). NC is a 55-residue basic protein with nucleic acid chaperone properties, which has emerged as a novel and potential pharmacological target against HIV-1. In the pursuit of novel NC-inhibitor chemotypes, we performed virtual screening and in vitro biological evaluation of a large library of chemical entities. We found that compounds sharing a benzoxazolinone moiety displayed putative inhibitory properties, which we further investigated by considering a series of chemical analogues. This approach provided valuable information on the structure-activity relationships of these compounds and, in the process, demonstrated that their anti-NC activity could be finely tuned by the addition of specific substituents to the initial benzoxazolinone scaffold. This study represents the starting point for the possible development of a new class of antiretroviral agents targeting the HIV-1 NC protein. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
HIV-associated Prospective Memory Impairment Increases Risk of Dependence in Everyday Functioning
Woods, Steven Paul; Iudicello, Jennifer E.; Moran, Lisa M.; Carey, Catherine L.; Dawson, Matthew S.; Grant, Igor
2007-01-01
HIV infection is associated with impairments in prospective memory (ProM), an aspect of episodic memory that refers to the ability to execute a future intention, such as remembering to take a medication at a specific time. The current study sought to examine the relationship between HIV-associated ProM impairment and the successful management of independent activities of daily living (IADLs). In a cohort of 66 HIV-infected individuals, ProM accounted for a significant proportion of variance in self-reported IADL dependence over and above that which was explained by retrospective memory and current affective distress. Analysis of component cognitive processes revealed that the relationship between HIV-associated ProM deficits and IADL dependence was driven by impaired cue detection and self-initiated intention retrieval. Results were not better explained by demographic factors, HIV disease severity, psychiatric comorbidity, or substance use. Collectively, these data support the potential incremental ecological validity of ProM as a predictor of dependence in IADLs among persons living with HIV infection. PMID:18211160
Microbicides for the Treatment of Sexually Transmitted HIV Infections
Singh, Onkar; Garg, Tarun; Rath, Goutam; Goyal, Amit K.
2014-01-01
Approximately 34 million people were living with human immunodeficiency virus (HIV-1) at the end of 2011. From the last two decades, researchers are actively involved in the development of an effective HIV-1 treatment, but the results intended are still doubtful about the eradication of HIV. The HIV-1 virus has gone from being an “inherently untreatable” infectious agent to the one liable to be affected by a range of approved therapies. Candidate microbicides have been developed to target specific steps in the process of viral transmission. Microbicides are self-administered agents that can be applied to vaginal or rectal mucosal surfaces with the aim of preventing, or reducing, the transmission of sexually transmitted infections (STIs) including HIV-1. The development of efficient, widely available, and low-cost microbicides to prevent sexually transmitted HIV infections should be given high priority. In this review, we studied the various forms of microbicides, their mechanism of action, and their abundant approaches to control the transmission of sexually transmitted infections (STIs). PMID:26556193
[Tuberculosis in HIV-infected and AIDS patients].
Rakhmanova, A G; Stepanova, E V; Romanova, E I; Evseeva, I D
2003-01-01
The course of the combined infection (tuberculosis plus HIV-infection) has been analysed in 41 patients. Of them, 24 patients developed tuberculosis in the presence of HIV-infection (group 1) and 17 were infected with HIV when they already had tuberculosis running up to 5 years. HIV-infection in group 1 ran a more severe course, the patients developed generalized, disseminated and complicated forms of tuberculosis with more frequent lethal outcome. 39 patients of both groups received specific antituberculous therapy including 1-5 drugs. A response to treatment was achieved in 23 (60%) patients (52 and 47.8% at early and late HIV-infection stages, respectively). Treatment failure was explained by development of severe opportunistic infections and secondary diseases (generalized cytomegalovirus infection, advanced candidiasis, toxoplasmosis), poor compliance, asocial life style, advanced tuberculosis process, late diagnosis, inadequate treatment. It is shown that in late HIV-infection positive results of treatment can be expected only in early detection of tuberculosis and active long-term treatment.
Giri, J A; Gregoresky, J; Silguero, P; García Messina, O; Planes, N
2001-01-01
Several studies had previously demonstrated the high sensitivity and specificity of JCV DNA detection in CSF by PCR. This paper reported the implementation of a simple PCR procedure to detect JCV in the CSF in a cohort of HIV-1 infected patients from Argentina. Years ago, the confirmatory diagnosis of this disease was made by in-situ hybridization or immunohistochemistry techniques on brain biopsies. The PCR procedure described here improves the diagnosis of PML because it is simple and noninvasive, and allows the differential diagnosis of PML from other neurological syndromes associated with AIDS. Many recent studies report a significant benefit of combined antiretroviral therapy on the survival of HIV patients without clear neurological improvements. A negative correlation has been described between the concentration of JCV in the CSF and survival time in HIV-1 infected patients, and the level of immune depression may influence JCV replication. This suggests that a single CSF JCV viral load determination during the course of PML disease progression may be of prognostic value for managing HIV patients.
Onono, Maricianah; Blat, Cinthia; Miles, Sondra; Steinfeld, Rachel; Wekesa, Pauline; Bukusi, Elizabeth A.; Owuor, Kevin; Grossman, Daniel; Cohen, Craig R.; Newmann, Sara J.
2015-01-01
Objective To determine if a health talk on family planning (FP) by community clinic health assistants (CCHAs) will improve knowledge, attitudes and behavioral intentions about contraception in HIV-infected individuals. Methods A 15-min FP health talk was given by CCHAs in six rural HIV clinics to a sample of 49 HIV-infected men and women. Effects of the health talk were assessed through a questionnaire administered before the health talk and after completion of the participant's clinic visit. Results Following the health talk, there was a significant increase in knowledge about contraceptives (p < .0001), side-effects (p < .0001), and method-specific knowledge about IUCDs (p < .001), implants (p < .0001), and injectables (p < .05). Out of 31 women and 18 men enrolled, 14 (45%) women and 6 (33%) men intended to try a new contraceptive. Participant attitudes toward FP were high before and after the health talk (median 4 of 4). Conclusion A health talk delivered by CCHAs can increase knowledge of contraception and promote the intention to try new more effective contraception among HIV-infected individuals. Practice implications FP health talks administered by lay-health providers to HIV-infected individuals as they wait for HIV services can influence FP knowledge and intention to use FP. PMID:24316053
Onono, Maricianah; Blat, Cinthia; Miles, Sondra; Steinfeld, Rachel; Wekesa, Pauline; Bukusi, Elizabeth A; Owuor, Kevin; Grossman, Daniel; Cohen, Craig R; Newmann, Sara J
2014-03-01
To determine if a health talk on family planning (FP) by community clinic health assistants (CCHAs) will improve knowledge, attitudes and behavioral intentions about contraception in HIV-infected individuals. A 15-min FP health talk was given by CCHAs in six rural HIV clinics to a sample of 49 HIV-infected men and women. Effects of the health talk were assessed through a questionnaire administered before the health talk and after completion of the participant's clinic visit. Following the health talk, there was a significant increase in knowledge about contraceptives (p<.0001), side-effects (p<.0001), and method-specific knowledge about IUCDs (p<.001), implants (p<.0001), and injectables (p<.05). Out of 31 women and 18 men enrolled, 14 (45%) women and 6 (33%) men intended to try a new contraceptive. Participant attitudes toward FP were high before and after the health talk (median 4 of 4). A health talk delivered by CCHAs can increase knowledge of contraception and promote the intention to try new more effective contraception among HIV-infected individuals. FP health talks administered by lay-health providers to HIV-infected individuals as they wait for HIV services can influence FP knowledge and intention to use FP. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Spielberg, Freya; Wood, Robert; Binson, Diane; Woods, William J.; Goldbaum, Gary M.
2009-01-01
Objectives. We studied the HIV risk behaviors of patrons of the 3 commercial sex venues for men in Seattle, Washington. Methods. We conducted cross-sectional, observational surveys in 2004 and 2006 by use of time–venue cluster sampling with probability proportional to size. Surveys were anonymous and self-reported. We analyzed the 2004 data to identify patron characteristics and predictors of risk behaviors and compared the 2 survey populations. Results. Fourteen percent of respondents reported a previous HIV-positive test, 14% reported unprotected anal intercourse, and 9% reported unprotected anal intercourse with a partner of unknown or discordant HIV status during the current commercial sex venue visit. By logistic regression, recent unprotected anal intercourse outside of a commercial sex venue was independently associated with unprotected anal intercourse. Sex venue site and patron drug use were strongly associated with unprotected anal intercourse at the crude level. The 2004 and 2006 survey populations did not differ significantly in demographics or behaviors. Conclusions. Patron and venue-specific characteristics factors may each influence the frequency of HIV risk behaviors in commercial sex venues. Future research should evaluate the effect of structural and individual-level interventions on HIV transmission. PMID:19218174
Immune activation and paediatric HIV-1 disease outcome.
Roider, Julia M; Muenchhoff, Maximilian; Goulder, Philip J R
2016-03-01
The paediatric HIV epidemic is changing. Over the past decade, new infections have substantially reduced, whereas access to antiretroviral therapy (ART) has increased. Overall this success means that numbers of children living with HIV are climbing. In addition, the problems observed in adult infection resulting from chronic inflammation triggered by persistent immune activation even following ART mediated suppression of viral replication are magnified in children infected from birth. Features of immune ontogeny favour low immune activation in early life, whereas specific aspects of paediatric HIV infection tend to increase it. A subset of ART-naïve nonprogressing children exists in whom normal CD4 cell counts are maintained in the setting of persistent high viremia and yet in the context of low immune activation. This sooty mangabey-like phenotype contrasts with nonprogressing adult infection which is characterized by the expression of protective HLA class I molecules and low viral load. The particular factors contributing to raised or lowered immune activation in paediatric infection, which ultimately influence disease outcome, are discussed. Novel strategies to circumvent the unwanted long-term consequences of HIV infection may be possible in children in whom natural immune ontogeny in early life militates against immune activation. Defining the mechanisms underlying low immune activation in natural HIV infection would have applications beyond paediatric HIV.
Lemos, Diana; Hosek, Sybil G.
2014-01-01
Abstract This article describes the influence of a group-based behavioral intervention for adolescents and young adults newly diagnosed with HIV (Project ACCEPT) on four dimensions of HIV-related stigma—personalized stigma, disclosure concerns, negative self-image, and concern with public attitudes about people with HIV—as measured by the Berger HIV Stigma Scale. Stigma was addressed in a holistic manner during the intervention by providing HIV/AIDS-related information, facilitating the acquisition of coping skills, and providing contact with other youth living with HIV in order to improve social support. Fifty youth (28 male, 22 female; mean age=19.24 years) newly diagnosed with HIV from four geographically diverse clinics participated in a one-group pretest-posttest design study whereby they received the intervention over a 12-week period, and completed assessments at baseline, post-intervention, and 3-month follow-up. Results from the combined sample (males and females) revealed overall reductions in stigma in three dimensions: personalized stigma, disclosure concerns, and negative self-image, although only the combined-sample effects for negative self-image were maintained at 3-month follow-up. Gender-specific analyses revealed that the intervention reduced stigma for males across all four dimensions of stigma, with all effects being maintained to some degree at the 3-month follow-up. Only personalized stigma demonstrated a decrease for females, although this effect was not maintained at the 3-month follow-up; while the other three types of stigma increased at post-intervention and 3-month follow-up. Findings are discussed in terms of gender specific outcomes and the need for a different type of intervention to reduce stigma for young women. PMID:25216106
Patel, Shabnum; Lam, Sharon; Cruz, Conrad Russell; Wright, Kaylor; Cochran, Christina; Ambinder, Richard F; Bollard, Catherine M
2016-03-01
Allogeneic hematopoietic stem cell transplantation (HSCT) can potentially cure human immunodeficiency virus (HIV) by eliminating infected recipient cells, particularly in the context of technologies that may confer HIV resistance to these stem cells. But, to date, the Berlin patient remains the only case of HIV cure despite multiple attempts to eradicate infection with HSCT. One approach to improve this is to administer virus-specific T cells, a strategy that has proven success in preventing other infections after transplantation. Although we have reported that broadly HIV-specific T cells can be expanded from HIV+ patients, allogeneic transplantations only contain virus-naïve T cells. Modifying this approach for the allogeneic setting requires a robust, reproducible platform that can expand HIV-specific cells from the naïve pool. Hence, we hypothesized that HIV-specific T cells could be primed ex vivo from seronegative individuals to effectively target HIV. Here, we show that ex vivo-primed and expanded HIV-specific T cells released IFNγ in response to HIV antigens and that these cells have enhanced ability to suppress replication in vitro. This is the first demonstration of ex vivo priming and expansion of functional, multi-HIV antigen-specific T cells from HIV-negative donors, which has implications for use of allogeneic HSCT as a functional HIV cure. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
Day, Cheryl L; Abrahams, Deborah A; Harris, Levelle D; van Rooyen, Michele; Stone, Lynnett; de Kock, Marwou; Hanekom, Willem A
2017-09-15
Coinfection with HIV is the single greatest risk factor for reactivation of latent Mycobacterium tuberculosis infection (LTBI) and progression to active tuberculosis disease. HIV-associated dysregulation of adaptive immunity by depletion of CD4 Th cells most likely contributes to loss of immune control of LTBI in HIV-infected individuals, although the precise mechanisms whereby HIV infection impedes successful T cell-mediated control of M. tuberculosis have not been well defined. To further delineate mechanisms whereby HIV impairs protective immunity to M. tuberculosis , we evaluated the frequency, phenotype, and functional capacity of M. tuberculosis -specific CD4 T cells in HIV-infected and HIV-uninfected adults with LTBI. HIV infection was associated with a lower total frequency of cytokine-producing M. tuberculosis -specific CD4 T cells, and preferential depletion of a discrete subset of M. tuberculosis -specific IFN-γ + IL-2 - TNF-α + CD4 T cells. M. tuberculosis -specific CD4 T cells in HIV-infected individuals expressed significantly higher levels of Ki67, compared with HIV-uninfected individuals, thus indicating recent activation and turnover of these cells in vivo. The ex vivo proliferative capacity of M. tuberculosis -specific CD4 T cells was markedly impaired in HIV-infected individuals, compared with HIV-uninfected individuals. Moreover, HIV infection was associated with increased M. tuberculosis Ag-induced CD4 T cell death ex vivo, indicating a possible mechanism contributing to impaired proliferative capacity of M. tuberculosis -specific CD4 T cells in HIV-infected individuals. These data provide new insights into the parameters of M. tuberculosis -specific CD4 T cell immunity that are impaired in HIV-infected individuals with LTBI, which may contribute to their increased risk of developing active tuberculosis disease. Copyright © 2017 by The American Association of Immunologists, Inc.
Towner, Senna L; Dolcini, M Margaret; Harper, Gary W
2015-05-01
Relationship dynamics develop early in life and are influenced by social environments. STI/HIV prevention programs need to consider romantic relationship dynamics that contribute to sexual health. The aim of this study was to examine monogamous patterns, commitment, and trust in African American adolescent romantic relationships. The authors also focused on the differences in these dynamics between and within gender. The way that such dynamics interplay in romantic relationships has the potential to influence STI/HIV acquisition risk. In-depth interviews were conducted with 28 African American adolescents aged 14 to 21 living in San Francisco. Our results discuss data related to monogamous behaviors, expectations, and values; trust and respect in romantic relationships; commitment to romantic relationships; and outcomes of mismatched relationship expectations. Incorporating gender-specific romantic relationships dynamics can enhance the effectiveness of prevention programs.
Carvajal, Felipe; Vallejos, Maricarmen; Walters, Beth; Contreras, Nataly; Hertz, Marla I; Olivares, Eduardo; Cáceres, Carlos J; Pino, Karla; Letelier, Alejandro; Thompson, Sunnie R; López-Lastra, Marcelo
2016-07-01
The 5' leader of the HIV-1 genomic RNA is a multifunctional region that folds into secondary/tertiary structures that regulate multiple processes during viral replication including translation initiation. In this work, we examine the internal ribosome entry site (IRES) located in the 5' leader that drives translation initiation of the viral Gag protein under conditions that hinder cap-dependent translation initiation. We show that activity of the HIV-1 IRES relies on ribosomal protein S25 (eS25). Additionally, a mechanistic and mutational analysis revealed that the HIV-1 IRES is modular in nature and that once the 40S ribosomal subunit is recruited to the IRES, translation initiates without the need of ribosome scanning. These findings elucidate a mechanism of initiation by the HIV-1 IRES whereby a number of highly structured sites present within the HIV-1 5' leader leads to the recruitment of the 40S subunit directly at the site of initiation of protein synthesis. © 2016 Federation of European Biochemical Societies.
Carvajal, Felipe; Vallejos, Maricarmen; Walters, Beth A.; Contreras, Nataly; Hertz, Marla I.; Olivares, Eduardo; Cáceres, C. Joaquín; Pino, Karla; Letelier, Alejandro; Thompson, Sunnie R.; López-Lastra, Marcelo
2016-01-01
The 5′leader of the HIV-1 genomic RNA is a multifunctional region that folds into secondary/tertiary structures that regulate multiple processes during viral replication including translation initiation. In this work we examine the internal ribosome entry site (IRES) located in the 5′leader that drives translation initiation of the viral Gag protein under conditions that hinder cap-dependent translation initiation. We show that activity of the HIV-1 IRES relies on ribosomal protein S25 (eS25). Additionally, a mechanistic and mutational analysis revealed that the HIV-1 IRES is modular in nature and that once the 40S ribosomal subunit is recruited to the IRES, translation initiates without the need of ribosome scanning. These findings elucidate a mechanism of initiation by the HIV-1 IRES whereby a number of highly structured sites present within the HIV-1 5′leader leads to the recruitment of the 40S subunit directly at the site of initiation of protein synthesis. PMID:27191820
Martin-Gayo, Enrique; Buzon, Maria Jose; Ouyang, Zhengyu; Hickman, Taylor; Cronin, Jacqueline; Pimenova, Dina; Walker, Bruce D; Lichterfeld, Mathias; Yu, Xu G
2015-06-01
The majority of HIV-1 elite controllers (EC) restrict HIV-1 replication through highly functional HIV-1-specific T cell responses, but mechanisms supporting the evolution of effective HIV-1-specific T cell immunity in these patients remain undefined. Cytosolic immune recognition of HIV-1 in conventional dendritic cells (cDC) can facilitate priming and expansion of HIV-1-specific T cells; however, HIV-1 seems to be able to avoid intracellular immune recognition in cDCs in most infected individuals. Here, we show that exposure of cDCs from EC to HIV-1 leads to a rapid and sustained production of type I interferons and upregulation of several interferon-stimulated effector genes. Emergence of these cell-intrinsic immune responses was associated with a reduced induction of SAMHD1 and LEDGF/p75, and an accumulation of viral reverse transcripts, but inhibited by pharmacological blockade of viral reverse transcription or siRNA-mediated silencing of the cytosolic DNA sensor cGAS. Importantly, improved cell-intrinsic immune recognition of HIV-1 in cDCs from elite controllers translated into stronger abilities to stimulate and expand HIV-1-specific CD8 T cell responses. These data suggest an important role of cell-intrinsic type I interferon secretion in dendritic cells for the induction of effective HIV-1-specific CD8 T cells, and may be helpful for eliciting functional T cell immunity against HIV-1 for preventative or therapeutic clinical purposes.
Shah, Monica R; Cook, Nakela; Wong, Renee; Hsue, Priscilla; Ridker, Paul; Currier, Judith; Shurin, Susan
2015-02-24
The clinical challenges confronting patients with human immunodeficiency virus (HIV) have shifted from acquired immunodeficiency syndrome (AIDS)-related illnesses to chronic diseases, such as coronary artery disease, chronic lung disease, and chronic anemia. With the growing burden of HIV-related heart, lung, and blood (HLB) disease, the National Heart, Lung, and Blood Institute (NHLBI) recognizes it must stimulate and support HIV-related HLB research. Because HIV offers a natural, accelerated model of common pathological processes, such as inflammation, HIV-related HLB research may yield important breakthroughs for all patients with HLB disease. This paper summarizes the cardiovascular recommendations of an NHLBI Working Group, Advancing HIV/AIDS Research in Heart, Lung, and Blood Diseases, charged with identifying scientific priorities in HIV-related HLB disease and developing recommendations to promote multidisciplinary collaboration among HIV and HLB investigators. The working group included multidisciplinary sessions, as well as HLB breakout sessions for discussion of disease-specific issues, with common themes about scientific priorities and strategies to stimulate HLB research emerging in all 3 groups. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Bogart, Laura M.; Wagner, Glenn; Galvan, Frank H.; Banks, Denedria
2009-01-01
Background Medical mistrust is prevalent among African Americans and may influence health care behaviors such as treatment adherence. We examined whether a specific form of medical mistrust – HIV conspiracy beliefs (e.g., HIV is genocide against African Americans) – was associated with antiretroviral treatment nonadherence among African American men with HIV. Methods On baseline surveys, 214 African American men with HIV reported their agreement with 9 conspiracy beliefs, socio-demographic characteristics, depression symptoms, substance use, disease characteristics, medical mistrust, and health care barriers. Antiretroviral medication adherence was monitored electronically for one-month post-baseline among 177 men in the baseline sample. Results Confirmatory factor analysis revealed two distinct conspiracy belief subscales: genocidal beliefs (e.g., HIV is manmade) and treatment-related beliefs (e.g., people who take antiretroviral treatments are human guinea pigs for the government). Both subscales were related to nonadherence in bivariate tests. In a multivariate logistic regression, only treatment-related conspiracies were associated with a lower likelihood of optimal adherence at one-month follow-up (Odds ratio = 0.60, 95% confidence interval = 0.37 to 0.96, p < 0.05). Conclusions HIV conspiracy beliefs, especially those related to treatment mistrust, can contribute to health disparities by discouraging appropriate treatment behavior. Adherence-promoting interventions targeting African Americans should openly address such beliefs. PMID:19952767
Frew, Paula M; Parker, Kimberly; Vo, Linda; Haley, Danielle; O'Leary, Ann; Diallo, Dazon Dixon; Golin, Carol E; Kuo, Irene; Soto-Torres, Lydia; Wang, Jing; Adimora, Adaora A; Randall, Laura A; Del Rio, Carlos; Hodder, Sally
2016-08-17
We sought to understand the multilevel syndemic factors that are concurrently contributing to the HIV epidemic among women living in the US. We specifically examined community, network, dyadic, and individual factors to explain HIV vulnerability within a socioecological framework. We gathered qualitative data (120 interviews and 31 focus groups) from a subset of women ages 18-44 years (N = 2,099) enrolled in the HPTN 064 HIV seroincidence estimation study across 10 US communities. We analyzed data from 4 diverse locations: Atlanta, New York City (the Bronx), Raleigh, and Washington, DC. Data were thematically coded using grounded theory methodology. Intercoder reliability was assessed to evaluate consistency of team-based coding practices. The following themes were identified at 4 levels including 1) exosystem (community): poverty prevalence, discrimination, gender imbalances, community violence, and housing challenges; 2) mesosystem (network): organizational social support and sexual concurrency; 3) microsystem (dyadic): sex exchange, interpersonal social support, intimate partner violence; and 4) individual: HIV/STI awareness, risk taking, and substance use. A strong theme emerged with over 80 % of responses linked to the fundamental role of financial insecurity underlying risk-taking behavioral pathways. Multilevel syndemic factors contribute to women's vulnerability to HIV in the US. Financial insecurity is a predominant theme, suggesting the need for tailored programming for women to reduce HIV risk. Clinicaltrials.gov, NCT00995176.
Bousman, C A; Cherner, M; Ake, C; Letendre, S; Atkinson, J H; Patterson, T L; Grant, I; Everall, I P
2009-12-01
Research comparing the independent and combined contextual effects of methamphetamine dependence (METH) and HIV-infection (HIV) on mood and sexual behavior among men who have sex with men (MSM) has been sparse and inconsistent. This study examined the contextual influence of METH, HIV-infection and their combination on mood states and sexual behavior. 175 non-monogamous MSM concordant or discordant for METH and HIV were included. Multivariate analysis was conducted to examine mood and sexual behavior differences between groups, as well as to elucidate the relationship between mood and sexual risk behavior and explore the potential moderator (i.e. contextual) effects of METH and/or HIV on this relationship. METH+/HIV+ participants reported condom use less than 25% of the time whereas METH-/HIV+ participants reported condom use 51-75% of the time. METH+ and HIV+ status were associated with higher depression and confusion scores. Univariate regressions revealed negative relationships between mood states (depression, tension, anger, fatigue and confusion) and condom use. Neither METH nor HIV status moderated the relationships between negative mood and condom use. Results are derived from cross-sectional data, sample sizes for each of the four groups were relatively small, and condom use could not be linked to specific sexual practices and/or partner types. METH dependence, HIV seropositivity, and negative moods are associated with reduced condom use among non-monogamous MSM. Independent effects of METH dependence and negative mood on condom use suggest that sexual risk reduction interventions for MSM should incorporate multi-faceted approaches, including substance abuse and mental health treatment.
Nonhuman TRIM5 Variants Enhance Recognition of HIV-1-Infected Cells by CD8+ T Cells
Jimenez-Moyano, Esther; Ruiz, Alba; Kløverpris, Henrik N.; Rodriguez-Plata, Maria T.; Peña, Ruth; Blondeau, Caroline; Selwood, David L.; Izquierdo-Useros, Nuria; Moris, Arnaud; Clotet, Bonaventura; Goulder, Philip; Towers, Greg J.
2016-01-01
ABSTRACT Tripartite motif-containing protein 5 (TRIM5) restricts human immunodeficiency virus type 1 (HIV-1) in a species-specific manner by uncoating viral particles while activating early innate responses. Although the contribution of TRIM5 proteins to cellular immunity has not yet been studied, their interactions with the incoming viral capsid and the cellular proteasome led us to hypothesize a role for them. Here, we investigate whether the expression of two nonhuman TRIM5 orthologs, rhesus TRIM5α (RhT5) and TRIM-cyclophilin A (TCyp), both of which are potent restrictors of HIV-1, could enhance immune recognition of infected cells by CD8+ T cells. We illustrate how TRIM5 restriction improves CD8+ T-cell-mediated HIV-1 inhibition. Moreover, when TRIM5 activity was blocked by the nonimmunosuppressive analog of cyclosporine (CsA), sarcosine-3(4-methylbenzoate)–CsA (SmBz-CsA), we found a significant reduction in CD107a/MIP-1β expression in HIV-1-specific CD8+ T cells. This finding underscores the direct link between TRIM5 restriction and activation of CD8+ T-cell responses. Interestingly, cells expressing RhT5 induced stronger CD8+ T-cell responses through the specific recognition of the HIV-1 capsid by the immune system. The underlying mechanism of this process may involve TRIM5-specific capsid recruitment to cellular proteasomes and increase peptide availability for loading and presentation of HLA class I antigens. In summary, we identified a novel function for nonhuman TRIM5 variants in cellular immunity. We hypothesize that TRIM5 can couple innate viral sensing and CD8+ T-cell activation to increase species barriers against retrovirus infection. IMPORTANCE New therapeutics to tackle HIV-1 infection should aim to combine rapid innate viral sensing and cellular immune recognition. Such strategies could prevent seeding of the viral reservoir and the immune damage that occurs during acute infection. The nonhuman TRIM5 variants, rhesus TRIM5α (RhT5) and TRIM-cyclophilin A (TCyp), are attractive candidates owing to their potency in sensing HIV-1 and blocking its activity. Here, we show that expression of RhT5 and TCyp in HIV-1-infected cells improves CD8+ T-cell-mediated inhibition through the direct activation of HIV-1-specific CD8+ T-cell responses. We found that the potency in CD8+ activation was stronger for RhT5 variants and capsid-specific CD8+ T cells in a mechanism that relies on TRIM5-dependent particle recruitment to cellular proteasomes. This novel mechanism couples innate viral sensing with cellular immunity in a single protein and could be exploited to develop innovative therapeutics for control of HIV-1 infection. PMID:27440884
Goulder, P.J.R.; Sewell, A.K.; Lalloo, D.G.; Price, D.A.; Whelan, J.A.; Evans, J.; Taylor, G.P.; Luzzi, G.; Giangrande, P.; Phillips, R.E.; McMichael, A.J.
1997-01-01
Primary human immunodeficiency virus (HIV) infection is controlled principally by HIV-specific cytotoxic T lymphocytes (CTL) to a steady-state level of virus load, which strongly influences the ultimate rate of progression to disease. Epitope selection by CTL may be an important determinant of the degree of immune control over the virus. This report describes the CTL responses of two HLA-identical hemophiliac brothers who were exposed to identical batches of Factor VIII and became seropositive within 10 wk of one another. Both have HLA-A*0201. The CTL responses of the two siblings were very dissimilar, one donor making strong responses to two epitopes within p17 Gag (HLA-A*0201–restricted SLYNTVATL and HLA-A3–restricted RLRPGGKKK). The sibling responded to neither epitope, but made strong responses to two epitopes presented by HLA-B7. This was not the result of differences in presentation of the epitopes. However, mutations in both immunodominant epitopes of the p17 Gag responder were seen in proviral sequences of the nonresponder. We then documented the CTL responses to two HLA-A*0201–restricted epitopes, in Gag (SLYNTVATL) and Pol (ILKEPVHGV) in 22 other HIV-infected donors with HLA-A*0201. The majority (71%) generated responses to the Gag epitope. In the 29% of donors failing to respond to the Gag epitope in standard assays, there was evidence of low frequency memory CTL responses using peptide stimulation of PBMC, and most of these donors also showed mutations in or around the Gag epitope. We concluded that HLA class I genotype determines epitope selection initially but that mutation in immunodominant epitopes can profoundly alter the pattern of CTL response. PMID:9126923
Kirstein, Lynn M.; Mellors, John W.; Rinaldo, Charles R.; Margolick, Joseph B.; Giorgi, Janis V.; Phair, John P.; Dietz, Edith; Gupta, Phalguni; Sherlock, Christopher H.; Hogg, Robert; Montaner, J. S. G.; Muñoz, Alvaro
1999-01-01
We conducted two studies to determine the potential influence of delays in blood processing, type of anticoagulant, and assay method on human immunodeficiency virus type 1 (HIV-1) RNA levels in plasma. The first was an experimental study in which heparin- and EDTA-anticoagulated blood samples were collected from 101 HIV-positive individuals and processed to plasma after delays of 2, 6, and 18 h. HIV-1 RNA levels in each sample were then measured by both branched-DNA (bDNA) and reverse transcriptase PCR (RT-PCR) assays. Compared to samples processed within 2 h, the loss (decay) of HIV-1 RNA in heparinized blood was significant (P < 0.05) but small after 6 h (bDNA assay, −0.12 log10 copies/ml; RT-PCR, −0.05 log10 copies/ml) and after 18 h (bDNA assay, −0.27 log10 copies/ml; RT-PCR, −0.15 log10 copies/ml). Decay in EDTA-anticoagulated blood was not significant after 6 h (bDNA assay, −0.002 log10 copies/ml; RT-PCR, −0.02 log10 copies/ml), but it was after 18 h (bDNA assay, −0.09 log10 copies/ml; RT-PCR, −0.09 log10 copies/ml). Only 4% of samples processed after 6 h lost more than 50% (≥0.3 log10 copies/ml) of the HIV-1 RNA, regardless of the anticoagulant or the assay that was used. The second study compared HIV-1 RNA levels in samples from the Multicenter AIDS Cohort Study (MACS; samples were collected in heparin-containing tubes in 1985, had a 6-h average processing delay, and were assayed by bDNA assay) and the British Columbia Drug Treatment Program (BCDTP) (collected in EDTA- or acid citrate dextrose-containing tubes in 1996 and 1997, had a 2-h maximum processing delay, and were assayed by RT-PCR). HIV-1 RNA levels in samples from the two cohorts were not significantly different after adjusting for CD4+-cell count and converting bDNA assay values to those corresponding to the RT-PCR results. In summary, the decay of HIV-1 RNA measured in heparinized blood after 6 h was small (−0.05 to −0.12 log10 copies/ml), and the minor impact of this decay on HIV-1 RNA concentrations in archived plasma samples of the MACS was confirmed by the similarity of CD4+-cell counts and assay-adjusted HIV-1 RNA concentrations in the MACS and BCDTP. PMID:10405379
He, Huan; Xue, Jing; Wang, Weiming; Liu, Lihong; Ye, Chaobaihui; Cong, Zhe; Kimata, Jason T; Qin, Chuan; Zhou, Paul
2017-03-01
Human immunodeficiency virus type 1 (HIV-1)-based lentiviral vectors efficiently transduce genes to human, but not rhesus, primary T cells and hematopoietic stem cells (HSCs). The poor transduction of HIV-1 vectors to rhesus cells is mainly due to species-specific restriction factors such as rhesus TRIM5α. Previously, several strategies to modify HIV-1 vectors were developed to overcome rhesus TRIM5α restriction. While the modified HIV-1 vectors efficiently transduce rhesus HSCs, they remain suboptimal for rhesus primary T cells. Recently, HIV-1 variants that encode combinations of LNEIE mutations in capsid (CA) protein and SIVmac239 Vif were found to replicate efficiently in rhesus primary T cells. Thus, the present study tested whether HIV-1 vectors packaged by a packaging construct containing these CA substitutions could efficiently transduce both human and rhesus primary CD4 T cells. To accomplish this, LNEIE mutations were made in the packaging construct CEMΔ8.9, and recombinant HIV-1 vectors packaged by Δ8.9 WT or Δ8.9 LNEIE were generated. Transduction rates, CA stability, and vector integration in CEMss-CCR5 and CEMss-CCR5-rhTRIM5α/green fluorescent protein cells, as well as transduction rates in human and rhesus primary CD4 T cells by Δ8.9 WT or Δ8.9 LNEIE-packaged HIV-1 vectors, were compared. Finally, the influence of rhesus TRIM5α variations in transduction rates to primary CD4 T cells from a cohort of 37 Chinese rhesus macaques was studied. While it maintains efficient transduction for human T-cell line and primary CD4 T cells, Δ8.9 LNEIE-packaged HIV-1 vector overcomes rhesus TRIM5α-mediated CA degradation, resulting in significantly higher transduction efficiency of rhesus primary CD4 T cells than Δ8.9 WT-packaged HIV-1 vector. Rhesus TRIM5α variations strongly influence transduction efficiency of rhesus primary CD4 T cells by both Δ8.9 WT or Δ8.9 LNEIE-packaged HIV-1 vectors. Thus, it is concluded that Δ8.9 LNEIE-packaged HIV-1 vector overcomes rhesus TRIM5α restriction and efficiently transduces both human and rhesus primary T cells.
He, Huan; Xue, Jing; Wang, Weiming; Liu, Lihong; Ye, Chaobaihui; Cong, Zhe; Kimata, Jason T.; Qin, Chuan; Zhou, Paul
2017-01-01
Human immunodeficiency virus type 1 (HIV-1)-based lentiviral vectors efficiently transduce genes to human, but not rhesus, primary T cells and hematopoietic stem cells (HSCs). The poor transduction of HIV-1 vectors to rhesus cells is mainly due to species-specific restriction factors such as rhesus TRIM5α. Previously, several strategies to modify HIV-1 vectors were developed to overcome rhesus TRIM5α restriction. While the modified HIV-1 vectors efficiently transduce rhesus HSCs, they remain suboptimal for rhesus primary T cells. Recently, HIV-1 variants that encode combinations of LNEIE mutations in capsid (CA) protein and SIVmac239 Vif were found to replicate efficiently in rhesus primary T cells. Thus, the present study tested whether HIV-1 vectors packaged by a packaging construct containing these CA substitutions could efficiently transduce both human and rhesus primary CD4 T cells. To accomplish this, LNEIE mutations were made in the packaging construct CEMΔ8.9, and recombinant HIV-1 vectors packaged by Δ8.9 WT or Δ8.9 LNEIE were generated. Transduction rates, CA stability, and vector integration in CEMss-CCR5 and CEMss-CCR5-rhTRIM5α/green fluorescent protein cells, as well as transduction rates in human and rhesus primary CD4 T cells by Δ8.9 WT or Δ8.9 LNEIE-packaged HIV-1 vectors, were compared. Finally, the influence of rhesus TRIM5α variations in transduction rates to primary CD4 T cells from a cohort of 37 Chinese rhesus macaques was studied. While it maintains efficient transduction for human T-cell line and primary CD4 T cells, Δ8.9 LNEIE-packaged HIV-1 vector overcomes rhesus TRIM5α-mediated CA degradation, resulting in significantly higher transduction efficiency of rhesus primary CD4 T cells than Δ8.9 WT-packaged HIV-1 vector. Rhesus TRIM5α variations strongly influence transduction efficiency of rhesus primary CD4 T cells by both Δ8.9 WT or Δ8.9 LNEIE-packaged HIV-1 vectors. Thus, it is concluded that Δ8.9 LNEIE-packaged HIV-1 vector overcomes rhesus TRIM5α restriction and efficiently transduces both human and rhesus primary T cells. PMID:28042947
2018-01-01
ABSTRACT Vaccine-elicited humoral immune responses comprise an array of antibody forms and specificities, with only a fraction contributing to protective host immunity. Elucidation of antibody effector functions responsible for protective immunity against human immunodeficiency virus type 1 (HIV-1) acquisition is a major goal for the HIV-1 vaccine field. Immunoglobulin A (IgA) is an important part of the host defense against pathogens; however, little is known about the role of vaccine-elicited IgA and its capacity to mediate antiviral functions. To identify the antiviral functions of HIV-1-specific IgA elicited by vaccination, we cloned HIV-1 envelope-specific IgA monoclonal antibodies (MAbs) by memory B cell cultures from peripheral blood mononuclear cells from an RV144 vaccinee and produced two IgA clonal cell lines (HG129 and HG130) producing native, nonrecombinant IgA MAbs. The HG129 and HG130 MAbs mediated phagocytosis by monocytes, and HG129 blocked HIV-1 Env glycoprotein binding to galactosylceramide, an alternative HIV-1 receptor. These findings elucidate potential antiviral functions of vaccine-elicited HIV-1 envelope-specific IgA that may act to block HIV-1 acquisition at the portal of entry by preventing HIV-1 binding to galactosylceramide and mediating antibody Fc receptor-mediated virion phagocytosis. Furthermore, these findings highlight the complex and diverse interactions of vaccine-elicited IgA with pathogens that depend on IgA fine specificity and form (e.g., multimeric or monomeric) in the systemic circulation and mucosal compartments. IMPORTANCE Host-pathogen interactions in vivo involve numerous immune mechanisms that can lead to pathogen clearance. Understanding the nature of antiviral immune mechanisms can inform the design of efficacious HIV-1 vaccine strategies. Evidence suggests that both neutralizing and nonneutralizing antibodies can mediate some protection against HIV in animal models. Although numerous studies have characterized the functional properties of HIV-1-specific IgG, more studies are needed on the functional attributes of HIV-1-specific IgA, specifically for vaccine-elicited IgA. Characterization of the functional properties of HIV-1 Env-specific IgA monoclonal antibodies from human vaccine clinical trials are critical toward understanding the capacity of the host immune response to block HIV-1 acquisition. PMID:29321320
Palmer, Clovis S; Palchaudhuri, Riya; Albargy, Hassan; Abdel-Mohsen, Mohamed; Crowe, Suzanne M
2018-01-01
An emerging paradigm in immunology suggests that metabolic reprogramming and immune cell activation and functions are intricately linked. Viral infections, such as HIV infection, as well as cancer force immune cells to undergo major metabolic challenges. Cells must divert energy resources in order to mount an effective immune response. However, the fact that immune cells adopt specific metabolic programs to provide host defense against intracellular pathogens and how this metabolic shift impacts immune cell functions and the natural course of diseases have only recently been appreciated. A clearer insight into how these processes are inter-related will affect our understanding of several fundamental aspects of HIV persistence. Even in patients with long-term use of anti-retroviral therapies, HIV infection persists and continues to cause chronic immune activation and inflammation, ongoing and cumulative damage to multiple organs systems, and a reduction in life expectancy. HIV-associated fundamental changes to the metabolic machinery of the immune system can promote a state of "inflammaging", a chronic, low-grade inflammation with specific immune changes that characterize aging, and can also contribute to the persistence of HIV in its reservoirs. In this commentary, we will bring into focus evolving concepts on how HIV modulates the metabolic machinery of immune cells in order to persist in reservoirs and how metabolic reprogramming facilitates a chronic state of inflammation that underlies the development of age-related comorbidities. We will discuss how immunometabolism is facilitating the changing paradigms in HIV cure research and outline the novel therapeutic opportunities for preventing inflammaging and premature development of age-related conditions in HIV + individuals.
Laher, Faatima; Ranasinghe, Srinika; Porichis, Filippos; Mewalal, Nikoshia; Pretorius, Karyn; Ismail, Nasreen; Buus, Søren; Stryhn, Anette; Carrington, Mary; Walker, Bruce D.; Ndung'u, Thumbi
2017-01-01
ABSTRACT Immune control of viral infections is heavily dependent on helper CD4+ T cell function. However, the understanding of the contribution of HIV-specific CD4+ T cell responses to immune protection against HIV-1, particularly in clade C infection, remains incomplete. Recently, major histocompatibility complex (MHC) class II tetramers have emerged as a powerful tool for interrogating antigen-specific CD4+ T cells without relying on effector functions. Here, we defined the MHC class II alleles for immunodominant Gag CD4+ T cell epitopes in clade C virus infection, constructed MHC class II tetramers, and then used these to define the magnitude, function, and relation to the viral load of HIV-specific CD4+ T cell responses in a cohort of untreated HIV clade C-infected persons. We observed significantly higher frequencies of MHC class II tetramer-positive CD4+ T cells in HIV controllers than progressors (P = 0.0001), and these expanded Gag-specific CD4+ T cells in HIV controllers showed higher levels of expression of the cytolytic proteins granzymes A and B. Importantly, targeting of the immunodominant Gag41 peptide in the context of HLA class II DRB1*1101 was associated with HIV control (r = −0.5, P = 0.02). These data identify an association between HIV-specific CD4+ T cell targeting of immunodominant Gag epitopes and immune control, particularly the contribution of a single class II MHC-peptide complex to the immune response against HIV-1 infection. Furthermore, these results highlight the advantage of the use of class II tetramers in evaluating HIV-specific CD4+ T cell responses in natural infections. IMPORTANCE Increasing evidence suggests that virus-specific CD4+ T cells contribute to the immune-mediated control of clade B HIV-1 infection, yet there remains a relative paucity of data regarding the role of HIV-specific CD4+ T cells in shaping adaptive immune responses in individuals infected with clade C, which is responsible for the majority of HIV infections worldwide. Understanding the contribution of HIV-specific CD4+ T cell responses in clade C infection is particularly important for developing vaccines that would be efficacious in sub-Saharan Africa, where clade C infection is dominant. Here, we employed MHC class II tetramers designed to immunodominant Gag epitopes and used them to characterize CD4+ T cell responses in HIV-1 clade C infection. Our results demonstrate an association between the frequency of HIV-specific CD4+ T cell responses targeting an immunodominant DRB1*11-Gag41 complex and HIV control, highlighting the important contribution of a single class II MHC-peptide complex to the immune response against HIV-1 infections. PMID:28077659
HIV-specific CD8+ T cells: serial killers condemned to die?
Petrovas, Constantinos; Mueller, Yvonne M; Katsikis, Peter D
2004-04-01
An increasing body of evidence supports a key role for cytotoxic CD8+ T cells (CTL) in controlling HIV infection. Although a vigorous HIV-specific CD8+ T cell response is raised during the primary infection, these cells ultimately fail to control virus and prevent disease progression. The failure of CTL to control HIV infection has been attributed to a number of strategies HIV employs to evade the immune system. Recently, intrinsic defects in the CTL themselves have been proposed to contribute to the failure of CTL to control HIV. HIV-specific CD8+ T cells differ in their effector/memory phenotype from other virus-specific CD8+ T cells indicating that their differentiation status differs. This altered differentiation may affect effector functions as well as homing properties of these cells. Other studies have indicated that activation of HIV-specific CTL may be impaired and this contributes to their dysfunction. The effector function of these CTL may also be affected. There are conflicting reports about their ability to kill, whereas IFNgamma production does not appear to be impaired in these cells. In this review we focus on recent work indicating that apoptosis may be an important mechanism through which HIV evades the CTL response. In particular, HIV-specific CD8+ T cells are highly susceptible to CD95/Fas-induced apoptosis. This leads to the hypothesis that virus-specific cytotoxic T cells can be eliminated upon binding CD95L/FasL on HIV-infected cells. Understanding the intrinsic defects of CTL in HIV infection could lead to new therapeutic strategies and optimized vaccination protocols that enhance the HIV-specific cytotoxic response.
Kegeles, Susan M; Rebchook, Gregory; Tebbetts, Scott; Arnold, Emily
2015-04-17
Since the scale-up of HIV/AIDS prevention evidence-based interventions (EBIs) has not been simple, it is important to examine processes that occur in the translation of the EBIs into practice that affect successful implementation. The goal of this paper is to examine facilitators and barriers to effective implementation that arose among 72 community-based organizations as they moved into practice a multilevel HIV prevention intervention EBI, the Mpowerment Project, for young gay and bisexual men. CBOs that were implementing the Mpowerment Project participated in this study and were assessed at baseline, and 6-months, 1 year, and 2 years post-baseline. Semi-structured telephone interviews were conducted separately with individuals at each CBO. Study data came from 647 semi-structured interviews and extensive notes and commentaries from technical assistance providers. Framework Analysis guided the analytic process. Barriers and facilitators to implementation was the overarching thematic framework used across all the cases in our analysis. Thirteen themes emerged regarding factors that influence the successful implementation of the MP. These were organized into three overarching themes: HIV Prevention System Factors, Community Factors, and Intervention Factors. The entire HIV Prevention System, including coordinators, supervisors, executive directors, funders, and national HIV prevention policies, all influenced implementation success. Other Prevention System Factors that affected the effective translation of the EBI into practice include Knowledge About Intervention, Belief in the Efficacy of the Intervention, Desire to Change Existing Prevention Approach, Planning for Intervention Before Implementation, Accountability, Appropriateness of Individuals for Coordinator Positions, Evaluation of Intervention, and Organizational Stability. Community Factors included Geography and Sociopolitical Climate. Intervention Factors included Intervention Characteristics and Adaptation Issues. The entire ecological system in which an EBI occurs affects implementation. It is imperative to focus capacity-building efforts on getting individuals at different levels of the HIV Prevention System into alignment regarding understanding and believing in the program's goals and methods. For a Prevention Support System to be maximally useful, it must address facilitators or barriers to implementation, address the right people, and use modalities to convey information that are acceptable for users of the system.
Qualitative features of the HIV-specific CD8+ T-cell response associated with immunologic control.
Hersperger, Adam R; Migueles, Stephen A; Betts, Michael R; Connors, Mark
2011-05-01
Over the past 2 years, a clearer picture has emerged regarding the properties of HIV-specific CD8+ T cells associated with immunologic control of HIV replication. These properties represent a potential mechanism by which rare patients might control HIV replication in the absence of antiretroviral therapy. This review addresses the background and recent findings that have lead to our current understanding of these mechanism(s). Patients with immunologic control of HIV are not distinguished by targeted specificities, or greater numbers or breadth of their HIV-specific CD8+ T-cell response. For this reason, recent work has focused greater attention on qualitative features of this response. The qualitative features most closely associated with immunologic control of HIV are related to the granule-exocytosis-mediated elimination of HIV-infected CD4 T cells. The ability of HIV-specific CD8+ T cells to increase their contents of proteins known to mediate cytotoxicity, such as granzyme B and perforin, appears to be a critical means by which HIV-specific cytotoxic capacity is regulated. Investigation from multiple groups has now focused upon HIV-specific CD8+ T-cell granule-exocytosis-mediated cytotoxicity as a correlate of immunologic control of HIV. In the near future, a more detailed understanding of the qualities associated with immunologic control may provide critical insights regarding the necessary features of a response that should be stimulated by immunotherapies or T-cell-based vaccines.
Risky Decision Making Assessed With the Gambling Task in Adults with HIV
Hardy, David J.; Hinkin, Charles H.; Castellon, Steven A.; Levine, Andrew J.; Lam, Mona N.
2010-01-01
Decision making was assessed using a laboratory gambling task in 67 adults with the Human Immunodeficiency Virus (HIV+) and in 19 HIV-seronegative (HIV−) control participants. Neurocognitive test performance across several domains was also analyzed to examine potential cognitive mechanisms of gambling task performance. As predicted, the HIV+ group performed worse on the gambling task, indicating greater risky decision making. Specifically, the HIV+ group selected more cards from the “risky” or disadvantageous deck that included relatively large payoffs but infrequent large penalties. The control group also selected such risky cards but quickly learned to avoid them. Exploratory analyses also indicated that in the HIV+ group, but not in the control group, gambling task performance was correlated with Stroop Interference performance and long delay free recall on the California Verbal Learning Test, suggesting the role of inhibitory processes and verbal memory in the poorer gambling task performance in HIV. These findings indicate the usefulness of the gambling task as a laboratory tool to examine risky decision making and cognition in the HIV population. PMID:16719628
HIV-1 Antibody Neutralization Breadth Is Associated with Enhanced HIV-Specific CD4+ T Cell Responses
Soghoian, Damien Z.; Lindqvist, Madelene; Ghebremichael, Musie; Donaghey, Faith; Carrington, Mary; Seaman, Michael S.; Kaufmann, Daniel E.; Walker, Bruce D.
2015-01-01
ABSTRACT Antigen-specific CD4+ T helper cell responses have long been recognized to be a critical component of effective vaccine immunity. CD4+ T cells are necessary to generate and maintain humoral immune responses by providing help to antigen-specific B cells for the production of antibodies. In HIV infection, CD4+ T cells are thought to be necessary for the induction of Env-specific broadly neutralizing antibodies. However, few studies have investigated the role of HIV-specific CD4+ T cells in association with HIV neutralizing antibody activity in vaccination or natural infection settings. Here, we conducted a comprehensive analysis of HIV-specific CD4+ T cell responses in a cohort of 34 untreated HIV-infected controllers matched for viral load, with and without neutralizing antibody breadth to a panel of viral strains. Our results show that the breadth and magnitude of Gag-specific CD4+ T cell responses were significantly higher in individuals with neutralizing antibodies than in those without neutralizing antibodies. The breadth of Gag-specific CD4+ T cell responses was positively correlated with the breadth of neutralizing antibody activity. Furthermore, the breadth and magnitude of gp41-specific, but not gp120-specific, CD4+ T cell responses were significantly elevated in individuals with neutralizing antibodies. Together, these data suggest that robust Gag-specific CD4+ T cells and, to a lesser extent, gp41-specific CD4+ T cells may provide important intermolecular help to Env-specific B cells that promote the generation or maintenance of Env-specific neutralizing antibodies. IMPORTANCE One of the earliest discoveries related to CD4+ T cell function was their provision of help to B cells in the development of antibody responses. Yet little is known about the role of CD4+ T helper responses in the setting of HIV infection, and no studies to date have evaluated the impact of HIV-specific CD4+ T cells on the generation of antibodies that can neutralize multiple different strains of HIV. Here, we addressed this question by analyzing HIV-specific CD4+ T cell responses in untreated HIV-infected persons with and without neutralizing antibodies. Our results indicate that HIV-infected persons with neutralizing antibodies have significantly more robust CD4+ T cell responses targeting Gag and gp41 proteins than individuals who lack neutralizing antibodies. These associations suggest that Gag- and gp41-specific CD4+ T cell responses may provide robust help to B cells for the generation or maintenance of neutralizing antibodies in natural HIV-infection. PMID:26656715
Thinking about "Think Again" in Canada: assessing a social marketing HIV/AIDS prevention campaign.
Lombardo, Anthony P; Léger, Yves A
2007-06-01
The Canadian "Think Again" social marketing HIV/AIDS prevention campaign, adapted from an American effort, encourages gay men to rethink their assumptions about their partners' HIV statuses and the risks of unsafe sex with them. To improve future efforts, existing HIV/AIDS prevention initiatives require critical reflection. While a formal evaluation of this campaign has been carried out elsewhere, here we use the campaign as a social marketing case study to illustrate its strengths and weaknesses, as a learning tool for other campaigns. After describing the campaign and its key results, we assess how it utilized central tenets of the social marketing process, such as formative research and the marketing mix. We then speak to the importance of theoretical influence in campaign design and the need to account for social-contextual factors in safer sex decision making. We conclude with a summary of the lessons learned from the assessment of this campaign.
AIDS-related stigma and social interaction: Puerto Ricans living with HIV/AIDS.
Varas-Díaz, Nelson; Serrano-García, Irma; Toro-Alfonso, José
2005-02-01
People living with HIV/AIDS are stigmatized. Although personal and social consequences of this stigmatization have been documented, research regarding its impact on social interactions is scarce. Latinos, and Puerto Ricans in particular, have voiced concern regarding AIDS stigma. The authors investigated the key role of social interaction in the process of stigmatization through in-depth, semistructured interviews in a sample of 30 Puerto Ricans living with HIV/AIDS. Participants reported instances in which AIDS stigma negatively influenced social interactions with family, friends, sexual partners, coworkers, and health professionals. Some of the consequences they described were loss of social support, persecution, isolation, job loss, and problems accessing health services. Findings support the need for interventions to address AIDS stigma and its consequences.
Reed, Elizabeth; Khoshnood, Kaveh; Blankenship, Kim M.; Fisher, Celia B.
2014-01-01
Female sex workers (FSW) from Andhra Pradesh, India who had participated in HIV research were interviewed to examine participant perspectives on research ethics. Content analysis indicated that aspects of the consent process, staff gender and demeanor, study environment, survey content, time requirements for study participation, and perceived FSW community support for research were key factors influencing whether FSW perceived their confidentiality and privacy had been maintained, and whether they felt the study was conducted respectfully. Findings suggest that partnership with community-based organizations and investigation of participant’s experiences in HIV prevention research can provide critical information to best inform research ethics protocols, a particular priority among research studies with highly stigmatized populations, such as FSW. PMID:24572080
Webel, Allison R; Perazzo, Joseph D; Dawson-Rose, Carol; Smith, Carolyn; Nicholas, Patrice K; Rivero-Méndez, Marta; Solís-Báez, Solymar S; Eller, Lucille Sanzero; Johnson, Mallory O; Corless, Inge B; Lindgren, Teri; Holzemer, William L; Kemppainen, Jeanne K; Reid, Paula; Mogobe, Keitshokile Dintle; Matshediso, Ella; Nokes, Kathleen; Portillo, Carmen J
2017-10-01
Globally, people living with HIV (PLWH) are at remarkably high risk for developing chronic comorbidities. While exercise and healthy eating reduce and mitigate chronic comorbidites, PLWH like many others, often fail to engage in recommended levels. We qualitatively examined the perspectives and contextual drivers of diet and exercise reported by PLWH and their health care providers. Two hundred and six participants across eight sites in the United States, Puerto Rico and Botswana described one overarching theme, Arranging Priorities, and four subthemes Defining Health, Perceived Importance of Diet and Exercise, Competing Needs, and Provider Influence. People living with HIV and their health care providers recognize the importance of eating a healthy diet and engaging in regular exercise. Yet there are HIV-specific factors limiting these behaviors that should be addressed. Health care providers have an important, and often underutilized opportunity to support PLWH to make improvements to their exercise and diet behavior. Copyright © 2017 Elsevier Inc. All rights reserved.
[Discrimination and homophobia associated to the human immunodeficiency virus epidemic].
Orozco-Núñez, Emanuel; Alcalde-Rabanal, Jacqueline Elizabeth; Ruiz-Larios, José Arturo; Sucilla-Pérez, Héctor; García-Cerde, Rodrigo
2015-01-01
To describe a political mapping on discrimination and homophobia associated to human immunodeficiency virus (HIV) in the context of public institutions in Mexico. The political mapping was conducted in six Mexican states. Stakeholders who were involved in HIV actions from public and private sectors were included. Semistructured interviews were applied to explore homophobia and discrimination associated with HIV. Information was systematized using the Policy Maker software, which is a good support for analyzing health policies. Discriminatory and homophobic practices in the public domain occurred, damaging people´s integrity via insults, derision and hate crimes. Most stakeholders expressed a supportive position to prevent discrimination and homophobia and some of them had great influence on policy-making decisions. It was found that state policy frameworks are less specific in addressing these issues. Homophobia and discrimination associated to HIV are still considered problematic in Mexico. Homophobia is a very sensitive issue that requires further attention. Also, an actual execution of governmental authority requires greater enforcement of laws against discrimination and homophobia.
An Automated HIV-1 Env-Pseudotyped Virus Production for Global HIV Vaccine Trials
Fuss, Martina; Mazzotta, Angela S.; Sarzotti-Kelsoe, Marcella; Ozaki, Daniel A.; Montefiori, David C.; von Briesen, Hagen; Zimmermann, Heiko; Meyerhans, Andreas
2012-01-01
Background Infections with HIV still represent a major human health problem worldwide and a vaccine is the only long-term option to fight efficiently against this virus. Standardized assessments of HIV-specific immune responses in vaccine trials are essential for prioritizing vaccine candidates in preclinical and clinical stages of development. With respect to neutralizing antibodies, assays with HIV-1 Env-pseudotyped viruses are a high priority. To cover the increasing demands of HIV pseudoviruses, a complete cell culture and transfection automation system has been developed. Methodology/Principal Findings The automation system for HIV pseudovirus production comprises a modified Tecan-based Cellerity system. It covers an area of 5×3 meters and includes a robot platform, a cell counting machine, a CO2 incubator for cell cultivation and a media refrigerator. The processes for cell handling, transfection and pseudovirus production have been implemented according to manual standard operating procedures and are controlled and scheduled autonomously by the system. The system is housed in a biosafety level II cabinet that guarantees protection of personnel, environment and the product. HIV pseudovirus stocks in a scale from 140 ml to 1000 ml have been produced on the automated system. Parallel manual production of HIV pseudoviruses and comparisons (bridging assays) confirmed that the automated produced pseudoviruses were of equivalent quality as those produced manually. In addition, the automated method was fully validated according to Good Clinical Laboratory Practice (GCLP) guidelines, including the validation parameters accuracy, precision, robustness and specificity. Conclusions An automated HIV pseudovirus production system has been successfully established. It allows the high quality production of HIV pseudoviruses under GCLP conditions. In its present form, the installed module enables the production of 1000 ml of virus-containing cell culture supernatant per week. Thus, this novel automation facilitates standardized large-scale productions of HIV pseudoviruses for ongoing and upcoming HIV vaccine trials. PMID:23300558
Cooperativity of HIV-Specific Cytolytic CD4 T Cells and CD8 T Cells in Control of HIV Viremia
Johnson, Susan; Eller, Michael; Teigler, Jeffrey E.; Maloveste, Sebastien M.; Schultz, Bruce T.; Soghoian, Damien Z.; Lu, Richard; Oster, Alexander F.; Chenine, Agnès-Laurence; Alter, Galit; Dittmer, Ulf; Marovich, Mary; Robb, Merlin L.; Michael, Nelson L.; Bolton, Diane
2015-01-01
ABSTRACT CD4+ T cells play a pivotal role in the control of chronic viral infections. Recently, nontraditional CD4+ T cell functions beyond helper effects have been described, and a role for cytolytic CD4+ T cells in the control of HIV infection has been suggested. We define here the transcriptional, phenotypic, and functional profiles of HIV-specific cytolytic CD4+ T cells. Fluidigm BioMark and multiparameter flow cytometric analysis of HIV-specific cytolytic CD4+ T cells revealed a distinct transcriptional signature compared to Th1 CD4+ cells but shared similar features with HIV-specific cytolytic CD8+ T cells. Furthermore, HIV-specific cytolytic CD4+ T cells showed comparable killing activity relative to HIV-specific CD8+ T cells and worked cooperatively in the elimination of virally infected cells. Interestingly, we found that cytolytic CD4+ T cells emerge early during acute HIV infection and tightly follow acute viral load trajectory. This emergence was associated to the early viral set point, suggesting an involvement in early control, in spite of CD4 T cell susceptibility to HIV infection. Our data suggest cytolytic CD4+ T cells as an independent subset distinct from Th1 cells that show combined activity with CD8+ T cells in the long-term control of HIV infection. IMPORTANCE The ability of the immune system to control chronic HIV infection is of critical interest to both vaccine design and therapeutic approaches. Much research has focused on the effect of the ability of CD8+ T cells to control the virus, while CD4+ T cells have been overlooked as effectors in HIV control due to the fact that they are preferentially infected. We show here that a subset of HIV-specific CD4+ T cells cooperate in the cytolytic control of HIV replication. Moreover, these cells represent a distinct subset of CD4+ T cells showing significant transcriptional and phenotypic differences compared to HIV-specific Th1 cells but with similarities to CD8+ T cells. These findings are important for our understanding of HIV immunopathology. PMID:25972560
Adapting an Evidence-Based HIV-Prevention Intervention for Women in Domestic Violence Shelters
Cavanaugh, Courtenay E.; Campbell, Jacquelyn; Braxton, Nikia; Harvey, Jenna; Wingood, Gina
2016-01-01
Objective Despite the documented intersection of intimate partner violence and HIV, there is a paucity of evidence-based HIV prevention interventions for female survivors of intimate partner violence in the United States. This paper describes the adaptation of an effective HIV prevention intervention, Sisters Informing Sisters about Topics on AIDS (SISTA), for women in domestic violence shelters and the steps taken to improve the adapted intervention’s implementation. Method The adaptation process was guided by the ADAPT-ITT framework and data collected from directors, direct client service providers, and residents of two domestic violence shelters located in urban areas, as well as topical experts. Results Eleven of 12 shelter staff (92%) reported that HIV interventions had never been implemented at their shelter and 64% reported they had not provided residents with educational brochures about HIV prevention. Changes made to adapt SISTA for this population and enhance the implementation of the intervention included reducing the intervention’s duration; adding education about the intersection of intimate partner violence, substance use, and HIV; and adding an HIV risk assessment and safety plan. Conclusions Next steps will include implementing the adapted intervention and evaluating its perceived acceptability and efficacy, and assessing whether contextual factors influence the intervention’s implementation. PMID:27398257
Junglen, Angela G; Smith, Brian C; Coleman, Jennifer A; Pacella, Maria L; Boarts, Jessica M; Jones, Tracy; Feeny, Norah C; Ciesla, Jeffrey A; Delahanty, Douglas L
2017-11-01
People living with HIV (PLWH) have extensive interpersonal trauma histories and higher rates of posttraumatic stress disorder (PTSD) than the general population. Prolonged exposure (PE) therapy is efficacious in reducing PTSD across a variety of trauma samples; however, research has not examined factors that influence how PTSD symptoms change during PE for PLWH. Using multi-level modeling, we examined the potential moderating effect of number of previous trauma types experienced, whether the index trauma was HIV-related or not, and years since HIV diagnosis on PTSD symptom reduction during a 10-session PE protocol in a sample of 51 PLWH. In general, PTSD symptoms decreased linearly throughout the PE sessions. Experiencing more previous types of traumatic events was associated with a slower rate of PTSD symptom change. In addition, LOCF analyses found that participants with a non-HIV-related versus HIV-related index trauma had a slower rate of change for PTSD symptoms over the course of PE. However, analyses of raw data decreased this finding to marginal. Years since HIV diagnosis did not impact PTSD symptom change. These results provide a better understanding of how to tailor PE to individual clients and aid clinicians in approximating the rate of symptom alleviation. Specifically, these findings underscore the importance of accounting for trauma history and index trauma type when implementing a treatment plan for PTSD in PLWH.
Fuster-Ruizdeapodaca, Maria J; Molero, Fernando; Holgado, Francisco Pablo; Mayordomo, Sonia
2014-09-01
This study analyzes the mediating role of social identity in the relationship between enacted stigma and internalized stigma and quality of life of people with HIV. A total of 557 people with HIV participated in this study. Participants were recruited from hospitals and non-governmental organizations. Questionnaires measuring perceived stigma (Berger's HIV Stigma Scale), social identity (Cameron's three factor identity scale), and quality of life (Ruiz and Baca's Quality of Life Questionnaire) were administered. The instruments were adapted for use with the Spanish population. Structural equation modeling (SEM) was used to test the mediation model, and multigroup SEM was conducted to evaluate its invariance. Both enacted stigma and internalized stigma had a negative influence on the quality of life of people with HIV, but this influence occurred in different ways. Enacted stigma had a direct negative influence on quality of life. No dimension of group identity protected people with HIV from its negative influence. However, the negative influence of internalized stigma was totally mediated by some dimensions of group identification, mainly through in-group affect. Group identification not only did not protect people with HIV from the negative effects of stigmatization, but it may even be detrimental in the case of internalized stigma. This suggests that in highly stigmatized groups, the salience of identity is negative and worsens the members' opinion of their own group. This argues for different kinds of intervention to improve the quality of life of people with HIV.
Leitman, Ellen M; Thobakgale, Christina F; Adland, Emily; Ansari, M Azim; Raghwani, Jayna; Prendergast, Andrew J; Tudor-Williams, Gareth; Kiepiela, Photini; Hemelaar, Joris; Brener, Jacqui; Tsai, Ming-Han; Mori, Masahiko; Riddell, Lynn; Luzzi, Graz; Jooste, Pieter; Ndung'u, Thumbi; Walker, Bruce D; Pybus, Oliver G; Kellam, Paul; Naranbhai, Vivek; Matthews, Philippa C; Gall, Astrid; Goulder, Philip J R
2017-11-06
Recent studies have suggested greater HIV cure potential among infected children than adults. A major obstacle to HIV eradication in adults is that the viral reservoir is largely comprised of HIV-specific cytotoxic T lymphocyte (CTL) escape variants. We here evaluate the potential for CTL in HIV-infected slow-progressor children to play an effective role in "shock-and-kill" cure strategies. Two distinct subgroups of children were identified on the basis of viral load. Unexpectedly, in both groups, as in adults, HIV-specific CTL drove the selection of escape variants across a range of epitopes within the first weeks of infection. However, in HIV-infected children, but not adults, de novo autologous variant-specific CTL responses were generated, enabling the pediatric immune system to "corner" the virus. Thus, even when escape variants are selected in early infection, the capacity in children to generate variant-specific anti-HIV CTL responses maintains the potential for CTL to contribute to effective shock-and-kill cure strategies in pediatric HIV infection. © 2017 Leitman et al.
Amutah, Ndidiamaka N; Gifuni, Jacqueline; Wesley, Yvonne
2016-01-01
The purpose of this qualitative secondary data analysis is to examine the major influencers on mothers with HIV in their childbearing decisions, as well as how those influencers shape conversations with clinicians and health-care providers regarding HIV treatment and prevention. The original study gained insight into the reproductive decision-making of mothers with HIV. By analyzing a subsample of 15 interviews from an original cohort of 25 participants in the earlier study, three major themes were identified as follows: (1) family members, not health-care providers, influence reproductive decisions; (2) negative attitudes toward subsequent pregnancies are mainly due to HIV transmission; and (3) birth control decisions were predominately supported by family members, while health-care providers were not consulted.
Radfar, Seyed Ramin; Sedaghat, Abbas; Banihashemi, Arash Tehrani; Gouya, Mohammadmehdi; Rawson, Richard A
2014-08-01
Identifying factors, which influence health behaviors is critical to designing appropriate and effective preventive programs. Human immunodeficiency virus (HIV) transmission is highly related to people behaviors and understanding factors influencing healthy behaviors among Iranian people living with HIVs (PLHIVs)/acquired immunodeficiency syndrome (AIDS) is very important to tailor an effective response to HIV/AIDS epidemic. This study was conducted as a qualitative study by methods of focus group discussion and in-depth interview in six provinces of Iran with 64 PLHIVs to determine factors influence engagement in positive prevention. Knowledge and education, feelings of responsibility and positive prevention practices were identified as the primary domains of engagement. These domains were found to be influenced by feelings of ostracism and frustration, poverty, barriers to disclosure of HIV status, access to and utilization of drug abuse treatment services and antiretroviral therapy, adherence to treatment, age, religiousness, sex work, singleness, and incarceration. Designing new interventions and updating current interventions directed toward the aforementioned factors should be addressed by responsible Iranian authorities in order to have a national effective response on the HIV/AIDS epidemic.
Moussa, Sandrine; Jenabian, Mohammad-Ali; Gody, Jean Chrysostome; Léal, Josiane; Grésenguet, Gérard; Le Faou, Alain; Bélec, Laurent
2013-01-01
Background We evaluated whether B cell-derived immune defenses of the gastro-intestinal tract are activated to produce HIV-specific antibodies in children continuously exposed to HIV via breast-feeding. Methods Couples of HIV-1-infected mothers (n = 14) and their breastfed non HIV-infected (n = 8) and HIV-infected (n = 6) babies, and healthy HIV-negative mothers and breastfed babies (n = 10) as controls, were prospectively included at the Complexe Pédiatrique of Bangui, Central African Republic. Immunoglobulins (IgA, IgG and IgM) and anti-gp160 antibodies from mother’s milk and stools of breastfed children were quantified by ELISA. Immunoaffinity purified anti-gp160 antibodies were characterized functionally regarding their capacity to reduce attachment and/or infection of R5- and X4- tropic HIV-1 strains on human colorectal epithelial HT29 cells line or monocyte-derived-macrophages (MDM). Results The levels of total IgA and IgG were increased in milk of HIV-infected mothers and stools of HIV-exposed children, indicating the activation of B cell-derived mucosal immunity. Breast milk samples as well as stool samples from HIV-negative and HIV-infected babies exposed to HIV by breast-feeding, contained high levels of HIV-specific antibodies, mainly IgG antibodies, less frequently IgA antibodies, and rarely IgM antibodies. Relative ratios of excretion by reference to lactoferrin calculated for HIV-specific IgA, IgG and IgM in stools of HIV-exposed children were largely superior to 1, indicating active production of HIV-specific antibodies by the intestinal mucosa. Antibodies to gp160 purified from pooled stools of HIV-exposed breastfed children inhibited the attachment of HIV-1NDK on HT29 cells by 63% and on MDM by 77%, and the attachment of HIV-1JRCSF on MDM by 40%; and the infection of MDM by HIV-1JRCSF by 93%. Conclusions The intestinal mucosa of children exposed to HIV by breast-feeding produces HIV-specific antibodies harbouring in vitro major functional properties against HIV. These observations lay the conceptual basis for the design of a prophylactic vaccine against HIV in exposed children. PMID:23704905
Necroptosis Takes Place in Human Immunodeficiency Virus Type-1 (HIV-1)-Infected CD4+ T Lymphocytes
Pan, Ting; Wu, Shuangxin; He, Xin; Luo, Haihua; Zhang, Yijun; Fan, Miaomiao; Geng, Guannan; Ruiz, Vivian Clarke; Zhang, Jim; Mills, Lisa; Bai, Chuan; Zhang, Hui
2014-01-01
Human immunodeficiency virus type 1 (HIV-1) infection is characterized by progressive depletion of CD4+ T lymphocytes and dysfunction of the immune system. The numbers of CD4+ T lymphocytes in the human body are maintained constantly by homeostatic mechanisms that failed during HIV-1 infection, resulting in progressive loss of CD4+ T cells mainly via apoptosis. Recently, a non-apoptotic form of necrotic programmed cell death, named necroptosis, has been investigated in many biological and pathological processes. We then determine whether HIV-1-infected cells also undergo necroptosis. In this report, we demonstrate that HIV-1 not only induces apoptosis, but also mediates necroptosis in the infected primary CD4+ T lymphocytes and CD4+ T-cell lines. Necroptosis-dependent cytopathic effects are significantly increased in HIV-1-infected Jurkat cells that is lack of Fas-associated protein-containing death domain (FADD), indicating that necroptosis occurs as an alternative cell death mechanism in the absence of apoptosis. Unlike apoptosis, necroptosis mainly occurs in HIV-infected cells and spares bystander damage. Treatment with necrostatin-1(Nec-1), a RIP1 inhibitor that specifically blocks the necroptosis pathway, potently restrains HIV-1-induced cytopathic effect and interestingly, inhibits the formation of HIV-induced syncytia in CD4+ T-cell lines. This suggests that syncytia formation is mediated, at least partially, by necroptosis-related processes. Furthermore, we also found that the HIV-1 infection-augmented tumor necrosis factor-alpha (TNF-α) plays a key role in inducing necroptosis and HIV-1 Envelope and Tat proteins function as its co-factors. Taken together,necroptosis can function as an alternative cell death pathway in lieu of apoptosis during HIV-1 infection, thereby also contributing to HIV-1-induced cytopathic effects. Our results reveal that in addition to apoptosis, necroptosis also plays an important role in HIV-1-induced pathogenesis. PMID:24714696
HIV-1 co-receptor usage: influence on mother-to-child transmission and pediatric infection.
Cavarelli, Mariangela; Scarlatti, Gabriella
2011-01-27
Viral CCR5 usage is not a predictive marker of mother to child transmission (MTCT) of HIV-1. CXCR4-using viral variants are little represented in pregnant women, have an increased although not significant risk of transmission and can be eventually also detected in the neonates. Genetic polymorphisms are more frequently of relevance in the child than in the mother. However, specific tissues as the placenta or the intestine, which are involved in the prevalent routes of infection in MTCT, may play an important role of selective barriers. The virus phenotype of the infected children, like that of adults, can evolve from R5 to CXCR4-using phenotype or remain R5 despite clinical progression to overt immune deficiency. The refined classification of R5 viruses into R5(narrow) and R5(broad) resolves the enigma of the R5 phenotype being associated with the state of immune deficiency. Studies are needed to address more in specific the relevance of these factors in HIV-1 MTCT and pediatric infection of non-B subtypes.
HIV-1 co-receptor usage:influence on mother-to-child transmission and pediatric infection
2011-01-01
Viral CCR5 usage is not a predictive marker of mother to child transmission (MTCT) of HIV-1. CXCR4-using viral variants are little represented in pregnant women, have an increased although not significant risk of transmission and can be eventually also detected in the neonates. Genetic polymorphisms are more frequently of relevance in the child than in the mother. However, specific tissues as the placenta or the intestine, which are involved in the prevalent routes of infection in MTCT, may play an important role of selective barriers. The virus phenotype of the infected children, like that of adults, can evolve from R5 to CXCR4-using phenotype or remain R5 despite clinical progression to overt immune deficiency. The refined classification of R5 viruses into R5narrow and R5broad resolves the enigma of the R5 phenotype being associated with the state of immune deficiency. Studies are needed to address more in specific the relevance of these factors in HIV-1 MTCT and pediatric infection of non-B subtypes. PMID:21284900
Reasons why persons living with HIV include individuals in their chosen families.
Grant, Joan S; Vance, David E; Keltner, Norman L; White, Worawan; Raper, James L
2013-01-01
HIV influences those with the disease as well as their families and social relationships. The chosen families of persons living with HIV (PLWH) provide structure, social support, and security. Our study identified reasons why PLWH included specific individuals in their chosen families (or families of choice). This mixed-method design used a convenience sample of 150 PLWH, ages 19-68 years. Self-reported reasons for including specific individuals in their chosen families were love and acceptance (n = 135; 90.0%), support (n = 100; 66.7%), blood and family ties (n = 37; 24.7%), and commonality (n = 28; 18.7%). Demographic and personal characteristics were unrelated to these themes, supporting the conclusion that reasons for choosing family members are universal across these variables. These findings emphasize the need for health care providers to encourage the development of friendships and relationships between PLWH and those who provide love and acceptance, support, blood/familial ties, and common interests. Copyright © 2013 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.
Effects of HIV and childhood trauma on brain morphometry and neurocognitive function.
Spies, Georgina; Ahmed-Leitao, Fatima; Fennema-Notestine, Christine; Cherner, Mariana; Seedat, Soraya
2016-04-01
A wide spectrum of neurocognitive deficits characterises HIV infection in adults. HIV infection is additionally associated with morphological brain abnormalities affecting neural substrates that subserve neurocognitive function. Early life stress (ELS) also has a direct influence on brain morphology. However, the combined impact of ELS and HIV on brain structure and neurocognitive function has not been examined in an all-female sample with advanced HIV disease. The present study examined the effects of HIV and childhood trauma on brain morphometry and neurocognitive function. Structural data were acquired using a 3T Magnetom MRI scanner, and a battery of neurocognitive tests was administered to 124 women: HIV-positive with ELS (n = 32), HIV-positive without ELS (n = 30), HIV-negative with ELS (n = 31) and HIV-negative without ELS (n = 31). Results revealed significant group volumetric differences for right anterior cingulate cortex (ACC), bilateral hippocampi, corpus callosum, left and right caudate and left and right putamen. Mean regional volumes were lowest in HIV-positive women with ELS compared to all other groups. Although causality cannot be inferred, findings also suggest that alterations in the left frontal lobe, right ACC, left hippocampus, corpus callosum, left and right amygdala and left caudate may be associated with poorer neurocognitive performance in the domains of processing speed, attention/working memory, abstraction/executive functions, motor skills, learning and language/fluency with these effects more pronounced in women living with both HIV and childhood trauma. This study highlights the potential contributory role of childhood trauma to brain alterations and neurocognitive decline in HIV-infected individuals.
Thapa, Subash; Hannes, Karin; Cargo, Margaret; Buve, Anne; Aro, Arja R; Mathei, Catharina
A scoping review of grey and peer-reviewed literature was conducted to develop a conceptual framework to illustrate mechanisms involved in reducing HIV stigma and increasing HIV test uptake. We followed a three-step approach to exploring the literature: developing concepts, organizing and categorizing concepts, and synthesizing concepts into a framework. The framework contains four types of intervention strategies: awareness creation, influencing normative behavior, providing support, and developing regulatory laws. The awareness creation strategy generally improves knowledge and the influencing normative behavior strategy changes stigmatizing attitudes and behaviors, and subsequently, increases HIV test uptake. Providing support and development of regulatory law strategies changes actual stigmatizing behaviors of the people, and subsequently, increases HIV test uptake. The framework further outlines that the mechanisms described are influenced by the interaction of various social-contextual and individual factors. The framework sheds new light on the effects of HIV stigma-reduction intervention strategies and HIV test uptake. Copyright © 2017 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.
2011-01-01
Background The process of HIV-1 genomic RNA (gRNA) encapsidation is governed by a number of viral encoded components, most notably the Gag protein and gRNA cis elements in the canonical packaging signal (ψ). Also implicated in encapsidation are cis determinants in the R, U5, and PBS (primer binding site) from the 5' untranslated region (UTR). Although conventionally associated with nuclear export of HIV-1 RNA, there is a burgeoning role for the Rev/RRE in the encapsidation process. Pleiotropic effects exhibited by these cis and trans viral components may confound the ability to examine their independent, and combined, impact on encapsidation of RNA into HIV-1 viral particles in their innate viral context. We systematically reconstructed the HIV-1 packaging system in the context of a heterologous murine leukemia virus (MLV) vector RNA to elucidate a mechanism in which the Rev/RRE system is central to achieving efficient and specific encapsidation into HIV-1 viral particles. Results We show for the first time that the Rev/RRE system can augment RNA encapsidation independent of all cis elements from the 5' UTR (R, U5, PBS, and ψ). Incorporation of all the 5' UTR cis elements did not enhance RNA encapsidation in the absence of the Rev/RRE system. In fact, we demonstrate that the Rev/RRE system is required for specific and efficient encapsidation commonly associated with the canonical packaging signal. The mechanism of Rev/RRE-mediated encapsidation is not a general phenomenon, since the combination of the Rev/RRE system and 5' UTR cis elements did not enhance encapsidation into MLV-derived viral particles. Lastly, we show that heterologous MLV RNAs conform to transduction properties commonly associated with HIV-1 viral particles, including in vivo transduction of non-dividing cells (i.e. mouse neurons); however, the cDNA forms are episomes predominantly in the 1-LTR circle form. Conclusions Premised on encapsidation of a heterologous RNA into HIV-1 viral particles, our findings define a functional HIV-1 packaging system as comprising the 5' UTR cis elements, Gag, and the Rev/RRE system, in which the Rev/RRE system is required to make the RNA amenable to the ensuing interaction between Gag and the canonical packaging signal for subsequent encapsidation. PMID:21702950
Nelson, LaRon E; Wilton, Leo; Agyarko-Poku, Thomas; Zhang, Nanhua; Aluoch, Marilyn; Thach, Chia T; Owiredu Hanson, Samuel; Adu-Sarkodie, Yaw
2015-06-01
Ghanaian men who have sex with men (MSM) have a high HIV seroprevalence, but despite a critical need to address this public health concern, research evidence has been extremely limited on influences on sexual risk behavior among MSM in Ghana. To investigate associations between HIV/STD knowledge, HIV stigma, and sexual behaviors in a sample of MSM in Ghana, we conducted a secondary data analysis of cross-sectional survey data from a non-probability sample of Ghanaian MSM (N = 137). Nearly all the men (93%) had more than one current sex partner (M = 5.11, SD = 7.4). Of those reported partners, the average number of current female sexual partners was 1.1 (SD = 2.6). Overall, knowledge levels about HIV and STDs were low, and HIV stigma was high. There was no age-related difference in HIV stigma. Younger MSM (≤25 years) used condoms less often for anal and vaginal sex than did those over 25. Relative frequency of condom use for oral sex was lower in younger men who had higher STD knowledge and also was lower in older men who reported high HIV stigma. Knowledge and stigma were not associated with condom use for anal or vaginal sex in either age group. These descriptive data highlight the need for the development of intervention programs that address HIV/STD prevention knowledge gaps and reduce HIV stigma in Ghanaian communities. Intervention research in Ghana should address age-group-specific HIV prevention needs of MSM youth. © 2015 Wiley Periodicals, Inc.
Nanomedicines for HIV therapy.
Siccardi, Marco; Martin, Philip; McDonald, Tom O; Liptrott, Neill J; Giardiello, Marco; Rannard, Steve; Owen, Andrew
2013-02-01
Heterogeneity in response to HIV treatments has been attributed to several causes including variability in pharmacokinetic exposure. Nanomedicine applications have a variety of advantages compared with traditional formulations, such as the potential to increase bioavailability and specifically target the site of action. Our group is focusing on the development of nanoformulations using a closed-loop design process in which nanoparticle optimization (disposition, activity and safety) is a continuous process based on experimental pharmacological data from in vitro and in vivo models. Solid drug nanoparticles, polymer-based drug-delivery carriers as well as nanoemulsions are nanomedicine options with potential application to improve antiretroviral deployment.
Goodkin, Karl; Miller, Eric N; Cox, Christopher; Reynolds, Sandra; Becker, James T; Martin, Eileen; Selnes, Ola A; Ostrow, David G; Sacktor, Ned C
2017-09-01
The demographics of the HIV epidemic in the USA have shifted towards older age. We aimed to establish the relationship between the processes of ageing and HIV infection in neurocognitive impairment. With longitudinal data from the Multicenter AIDS Cohort Study, a long-term prospective cohort study of the natural and treated history of HIV infection among men who have sex with men in the USA, we examined the effect of ageing, HIV infection (by disease stage), and their interaction on five neurocognitive domains: information processing speed, executive function, episodic memory, working memory, and motor function. We controlled for duration of serostatus in a subanalysis, as well as comorbidities and other factors that affect cognition. Analyses were by linear mixed models for longitudinal data. 5086 participants (47 886 visits) were included in the analytic sample (2278 HIV-seropositive participants contributed 20 477 visits and 2808 HIV-seronegative control participants contributed 27 409 visits). In an a-priori multivariate analysis with control variables including comorbidities and time since seroconversion, significant, direct negative effects of ageing were noted on all neurocognitive domains (p<0·0001 for all). Similar effects were noted for late-stage HIV disease progression on information processing speed (p=0·002), executive function (p<0·0001), motor function (p<0·0001), and working memory (p=0·001). Deleterious interaction effects were also noted in the domains of episodic memory (p=0·03) and motor function (p=0·02). A greater than expected effect of ageing on episodic memory and motor function with advanced stages of HIV infection suggests that these two domains are most susceptible to the progression of neurocognitive impairment caused by ageing in individuals with HIV. This deficit pattern suggests differential damage to the hippocampus and basal ganglia (specifically nigrostriatal pathways). Older individuals with HIV infection should be targeted for regular screening for HIV-associate neurocognitive disorder, particularly with tests referable to the episodic memory and motor domains. National Institute of Mental Health. Copyright © 2017 Elsevier Ltd. All rights reserved.
Golin, Carol E; Knight, Kevin; Carda-Auten, Jessica; Gould, Michele; Groves, Jennifer; L White, Becky; Bradley-Bull, Steve; Amola, Kemi; Fray, Niasha; Rosen, David L; Mugavaro, Michael J; Pence, Brian W; Flynn, Patrick M; Wohl, David
2016-09-06
Policy-makers promote a seek, test, treat and retain (STTR) strategy to expand HIV testing, support linkage and engagement in care, and enhance the continuous use of antiretroviral therapy for those HIV-infected. This HIV prevention strategy is particularly appropriate in correctional settings where HIV screening and treatment are routinely available yet many HIV-infected individuals have difficulty sustaining sufficient linkage and engagement in care, disease management, and viral suppression after prison release. Our research team developed Project imPACT (individuals motivated to Participate in Adherence, Care and Treatment), a multi-component approach for HIV-Infected recently incarcerated individuals that specifically targets their care linkage, retention, and medication adherence by addressing multiple barriers to care engagement after release. The ultimate goals of this intervention are to improve the health of HIV-infected individuals recently released from prison and reduce HIV transmission to their communities by maintaining viral suppression. This paper describes the intervention and technology development processes, based on best practices for intervention development and process evaluation. These processes included: 1) identifying the target population; 2) clarifying the theoretical basis for intervention design; 3) describing features of its foundational interventions; 4) conducting formative qualitative research; 5) integrating and adapting foundational interventions to create and refine intervention content based on target audience feedback. These stages along with the final intervention product are described in detail. The intervention is currently being evaluation and a two arm randomized, controlled trial in two US state prison systems. Based on a literature review, qualitative research, integration of proven interventions and behavioral theory, the final imPACT intervention focused on the transition period two to three months before and three months after prison release. It emphasized pre-release readiness, pre- and post-release supportive non-judgmental counseling, linking individuals to a HIV care clinic and technological supports through videos and text messages. This article provides a useful model for how researchers can develop, test, and refine multi-component interventions to address HIV care linkage, retention and adherence. NCT01629316 , first registered 6-4-2012; last updated 6-9-2015.
Wilson, I B; Kaplan, S
2000-12-15
Although previous work that considered a variety of chronic conditions has shown that higher quality physician-patient communication care is related to better health outcomes, the quality of physician-patient communication itself for patients with HIV disease has not been well studied. To determine the relationship of patient, visit, physician, and physician practice characteristics to two measures of physician-patient communication for patients with HIV disease. Cross-sectional survey of physicians and patients. Cohort study enrolling patients from throughout eastern Massachusetts. 264 patients with HIV disease and their their primary HIV physicians (n = 69). Two measures of physician-patient communication were used, a five-item general communication measure (Cronbach's alpha = 0.93), and a four-item HIV-specific communication measure that included items about alcohol, drug use, and sexual behaviors (Cronbach's alpha = 0.92). The mean age of patients was 39. 5 years, 24% patients were women, 31.1% were nonwhite, and 52% indicated same-sex contact as their principal HIV risk factor. The mean age of physicians was 39.1 years, 33.3% were female, 39.7% were specialists, and 25.0% self-identified as gay, lesbian, or bisexual. In multivariable models relating patient and visit characteristics to general communication, longer reported visit length (p<.0001), longer duration of the physician-patient relationship (p =.02), and female gender (p =.04) were significantly associated with better communication. The interaction of patient gender and visit length was also significant (p =.02); longer visit length was more strongly associated with better general communication for male than female patients. In similar models relating patient and visit characteristics to HIV-specific communication, longer visit length (p <.0001) and less advanced disease stage (p =.009) were associated with better communication. In multivariable models relating physician and practice characteristics to general communication no variables were significant. However, both female physician gender (p =.002) and gay/lesbian/bisexual sexual preference (p =.003) were significantly associated with better HIV-specific communication. In this study, female and homosexual physicians provided higher quality HIV-specific communication than male and heterosexual physicians. Better understanding the processes by which female and homosexual physicians achieve higher quality communication may help other physicians communicate more effectively. Health care providers and third-party payers should be aware that shorter visits may compromise physician-patient communication, and that this effect may be more consequential for male patients.
Differences in HIV vaccine acceptability between genders
Kakinami, Lisa; Newman, Peter A.; Lee, Sung-Jae; Duan, Naihua
2010-01-01
The development of safe and efficacious preventive HIV vaccines offers the best long-term hope of controlling the AIDS pandemic. Nevertheless, suboptimal uptake of safe and efficacious vaccines that already exist suggest that HIV vaccine acceptability cannot be assumed, particularly among communities most vulnerable to HIV. The present study aimed to identify barriers and motivators to future HIV vaccine acceptability among low socioeconomic, ethnically diverse men and women in Los Angeles County. Participants completed a cross-sectional survey assessing their attitudes and beliefs regarding future HIV vaccines. Hypothetical HIV vaccine scenarios were administered to determine HIV vaccine acceptability. Two-sided t-tests were performed, stratified by gender, to examine the association between vaccine acceptability and potential barriers and motivators. Barriers to HIV vaccine acceptability differed between men and women. For women, barriers to HIV vaccine acceptability were related to their intimate relationships (p <0.05), negative experiences with health care providers (p <0.05) and anticipated difficulties procuring insurance (p <0.01). Men were concerned that the vaccine would weaken the immune system (p <0.005) or would affect their HIV test results (p <0.05). Motivators for women included the ability to conceive a child without worrying about contracting HIV (p <0.10) and support from their spouse/significant other for being vaccinated (p <0.10). Motivators for men included feeling safer with sex partners (p <0.05) and social influence from friends to get vaccinated (p <0.005). Family support for HIV immunization was a motivator for both men and women (p <0.10). Gender-specific interventions may increase vaccine acceptability among men and women at elevated risk for HIV infection. Among women, interventions need to focus on addressing barriers due to gendered power dynamics in relationships and discrimination in health care. Among men, education that addresses fears and misconceptions about adverse effects of HIV vaccination on health and the importance of vaccination as one component of integrated HIV prevention may increase vaccine acceptability. PMID:18484322
Aidala, Angela A; Wilson, Michael G; Shubert, Virginia; Gogolishvili, David; Globerman, Jason; Rueda, Sergio; Bozack, Anne K; Caban, Maria; Rourke, Sean B
2016-01-01
Accumulating evidence suggests responses to HIV that combine individual-level interventions with those that address structural or contextual factors that influence risks and health outcomes of infection. Housing is such a factor. Housing occupies a strategic position as an intermediate structural factor, linking "upstream" economic, social, and cultural determinants to the more immediate physical and social environments in which everyday life is lived. The importance of housing status for HIV prevention and care has been recognized, but much of this attention has focused on homeless individuals as a special risk group. Analyses have less often addressed community housing availability and conditions as factors influencing population health or unstable, inadequate, or unaffordable housing as a situation or temporary state. A focus on individual-level characteristics associated with literal homelessness glosses over social, economic, and policy drivers operating largely outside any specific individual's control that affect housing and residential environments and the health resources or risk exposures such contexts provide. We examined the available empirical evidence on the association between housing status (broadly defined), medical care, and health outcomes among people with HIV and analyzed results to inform future research, program development, and policy implementation. We searched 8 electronic health and social science databases from January 1, 1996, through March 31, 2014, using search terms related to housing, dwelling, and living arrangements and HIV and AIDS. We contacted experts for additional literature. We selected articles if they were quantitative analyses published in English, French, or Spanish that included at least 1 measure of housing status as an independent variable and at least 1 health status, health care, treatment adherence, or risk behavior outcome among people with HIV in high-income countries. We defined housing status to include consideration of material or social dimensions of housing adequacy, stability, and security of tenure. Two independent reviewers performed data extraction and quality appraisal. We used the Cochrane Risk of Bias Tool for randomized controlled trials and a modified version of the Newcastle Ottawa Quality Appraisal Tool for nonintervention studies. In our quality appraisal, we focused on issues of quality for observational studies: appropriate methods for determining exposure and measuring outcomes and methods to control confounding. Searches yielded 5528 references from which we included 152 studies, representing 139,757 HIV-positive participants. Most studies were conducted in the United States and Canada. Studies examined access and utilization of HIV medical care, adherence to antiretroviral medications, HIV clinical outcomes, other health outcomes, emergency department and inpatient utilization, and sex and drug risk behaviors. With rare exceptions, across studies in all domains, worse housing status was independently associated with worse outcomes, controlling for a range of individual patient and care system characteristics. Lack of stable, secure, adequate housing is a significant barrier to consistent and appropriate HIV medical care, access and adherence to antiretroviral medications, sustained viral suppression, and risk of forward transmission. Studies that examined the history of homelessness or problematic housing years before outcome assessment were least likely to find negative outcomes, homelessness being a potentially modifiable contextual factor. Randomized controlled trials and observational studies indicate an independent effect of housing assistance on improved outcomes for formerly homeless or inadequately housed people with HIV. Housing challenges result from complex interactions between individual vulnerabilities and broader economic, political, and legal structural determinants of health. The broad structural processes sustaining social exclusion and inequality seem beyond the immediate reach of HIV interventions, but changing housing and residential environments is both possible and promising.
2013-01-01
Background Despite Sub-Saharan Africa (SSA) being the epicenter of the HIV epidemic, uptake of HIV testing is not optimal. While qualitative studies have been undertaken to investigate factors influencing uptake of HIV testing, systematic reviews to provide a more comprehensive understanding are lacking. Methods Using Noblit and Hare’s meta-ethnography method, we synthesised published qualitative research to understand factors enabling and deterring uptake of HIV testing in SSA. We identified 5,686 citations out of which 56 were selected for full text review and synthesised 42 papers from 13 countries using Malpass’ notion of first-, second-, and third-order constructs. Results The predominant factors enabling uptake of HIV testing are deterioration of physical health and/or death of sexual partner or child. The roll-out of various HIV testing initiatives such as ‘opt-out’ provider-initiated HIV testing and mobile HIV testing has improved uptake of HIV testing by being conveniently available and attenuating fear of HIV-related stigma and financial costs. Other enabling factors are availability of treatment and social network influence and support. Major barriers to uptake of HIV testing comprise perceived low risk of HIV infection, perceived health workers’ inability to maintain confidentiality and fear of HIV-related stigma. While the increasingly wider availability of life-saving treatment in SSA is an incentive to test, the perceived psychological burden of living with HIV inhibits uptake of HIV testing. Other barriers are direct and indirect financial costs of accessing HIV testing, and gender inequality which undermines women’s decision making autonomy about HIV testing. Despite differences across SSA, the findings suggest comparable factors influencing HIV testing. Conclusions Improving uptake of HIV testing requires addressing perception of low risk of HIV infection and perceived inability to live with HIV. There is also a need to continue addressing HIV-related stigma, which is intricately linked to individual economic support. Building confidence in the health system through improving delivery of health care and scaling up HIV testing strategies that attenuate social and economic costs of seeking HIV testing could also contribute towards increasing uptake of HIV testing in SSA. PMID:23497196
Factors influencing intent to get pregnant in HIV-infected women living in the southern USA.
Sowell, R L; Murdaugh, C L; Addy, C L; Moneyham, L; Tavokoli, A
2002-04-01
This descriptive study sought to identify factors that influence HIV-infected women's intent to get pregnant. Interviews were conducted with a convenience sample of n = 322 HIV-infected women at risk for pregnancy. Participants were predominantly African-American (84.4%), single (57.9%), and ranged in age from 17 to 48 years. Forty per cent (n = 128) of the women had been pregnant since becoming HIV-positive. Potential factors influencing intent to get pregnant that were examined included demographic characteristics, HIV-related factors and personal beliefs and attitudes. In simple logistic regression models, younger age, increased motivation for child bearing, decreased perceived threat of HIV, decreased HIV symptomatology, higher traditional gender role orientation, and greater avoidance coping were all associated with greater intent to get pregnant. Following a model selection procedure, motivation for child bearing (OR = 16.05, 95% CI 7.95, 30.41) and traditional sex roles (OR = 4.49, 95% CI 1.44, 13.55) were significantly associated with greater intent to get pregnant. Traditional gender role orientation and motivation for childbearing are significant factors in predicting intent to get pregnant among HIV-infected women. These factors, as well as other non HIV-related factors, need to be routinely assessed by health care providers in developing plans of care for HIV-infected women.
Eba, Patrick M.; Lim, HyeYoung
2017-01-01
Abstract Introduction: AIDS is a leading cause of death among adolescents in sub-Saharan Africa. Yet, legal, policy and social barriers continue to restrict their access to HIV services. In recent years, access to independent HIV testing and treatment for adolescents has gained increased attention. The 2013 WHO Guidance on HIV testing and counselling and care for adolescents living with HIV (WHO Guidance) calls for reviewing legal and regulatory frameworks to facilitate adolescents’ access to comprehensive HIV services. As of 31 March 2017, some 28 countries in sub-Saharan Africa have adopted HIV-specific legislation. But there is limited understanding of the provisions of these laws on access to HIV services for adolescents and their implication on efforts to scale up HIV prevention, testing, treatment and care among this population. Methods: A desk review of 28 HIV-specific laws in sub-Saharan Africa complemented with the review of HIV testing policies in four countries using human rights norms and key public health recommendations from the 2013 WHO Guidance. These recommendations call on countries to (i) lower the age of consent to HIV testing and counselling and allow mature adolescents who have not reached the age of consent to independently access HIV testing, (ii) ensure access to HIV counselling for adolescents, (iii) protect the confidentiality of adolescents living with HIV and (iv) facilitate access to HIV treatment for adolescents living with HIV. Results: Most HIV-specific laws fail to take into account human rights principles and public health recommendations for facilitating adolescents’ access to HIV services. None of the countries with HIV-specific laws has adopted all four recommendations for access to HIV services for adolescents. Discrepancies exist between HIV laws and national policy documents. Inadequate and conflicting provisions in HIV laws are likely to hinder access to HIV testing, counselling and treatment for adolescents. Conclusions: Efforts to end legal barriers to access to HIV services for adolescents in sub-Saharan Africa should address HIV-specific laws. Restrictive provisions in these laws should be reformed, and their protective norms effectively implemented including by translating them into national policies and ensuring sensitization and training of healthcare workers and communities. This study reiterates the need for action in all countries across Africa and beyond to review their laws and policies to create an enabling environment to accelerate access to HIV prevention, testing and treatment services for adolescents. PMID:28799324
Unraveling HIV protease flaps dynamics by Constant pH Molecular Dynamics simulations.
Soares, Rosemberg O; Torres, Pedro H M; da Silva, Manuela L; Pascutti, Pedro G
2016-08-01
The active site of HIV protease (HIV-PR) is covered by two flaps. These flaps are known to be essential for the catalytic activity of the HIV-PR, but their exact conformations at the different stages of the enzymatic pathway remain subject to debate. Understanding the correct functional dynamics of the flaps might aid the development of new HIV-PR inhibitors. It is known that, the HIV-PR catalytic efficiency is pH-dependent, likely due to the influence of processes such as charge transfer and protonation/deprotonation of ionizable residues. Several Molecular Dynamics (MD) simulations have reported information about the HIV-PR flaps. However, in MD simulations the protonation of a residue is fixed and thus it is not possible to study the correlation between conformation and protonation state. To address this shortcoming, this work attempts to capture, through Constant pH Molecular Dynamics (CpHMD), the conformations of the apo, substrate-bound and inhibitor-bound HIV-PR, which differ drastically in their flap arrangements. The results show that the HIV-PR flaps conformations are defined by the protonation of the catalytic residues Asp25/Asp25' and that these residues are sensitive to pH changes. This study suggests that the catalytic aspartates can modulate the opening of the active site and substrate binding. Copyright © 2016 Elsevier Inc. All rights reserved.
Communicating about microbicides with women in mind: tailoring messages for specific audiences
Sidibe, Sekou; Pack, Allison P; Tolley, Elizabeth E; Ryan, Elizabeth; Mackenzie, Caroline; Bockh, Emily; Githuka, George
2014-01-01
Introduction Current HIV prevention options are unrealistic for most women; however, HIV prevention research has made important strides, including on-going development of antiretroviral-based vaginal microbicide gels. Nevertheless, social-behavioural research suggests that women's ability to access and use new HIV prevention technologies will be strongly influenced by a range of socio-cultural, gender and structural factors which should be addressed by communications and marketing strategies, so that these products can be positioned in ways that women can use them. Methods Based on an extensive literature review and in-country policy consultation, consisting of approximately 43 stakeholders, we describe barriers and facilitators to HIV prevention, including potential microbicide use, for four priority audiences of Kenyan women (female sex workers [FSWs], women in stable and discordant relationships, and sexually active single young women). We then describe how messages that position microbicides might be tailored for each audience of women. Results We reviewed 103 peer-reviewed articles and reports. In Kenya, structural factors and gender inequality greatly influence HIV prevention for women. HIV risk perception and the ability to consistently use condoms and other prevention products often vary by partner type. Women in stable relationships find condom use challenging because they connote a lack of trust. However, women in other contexts are often able to negotiate condom use, though they may face challenges with consistent use. These women include FSWs who regularly use condoms with their casual clients, young women in the initial stages of a sexual relationship and discordant couples. Thus, we consider two approaches to framing messages aimed at increasing general awareness of microbicides – messages that focus strictly on HIV prevention and ones that focus on other benefits of microbicides such as increased pleasure, intimacy or sexual empowerment, in addition to HIV prevention. Conclusions If carefully tailored, microbicide communication materials may facilitate product use by women who do not currently use any HIV prevention method. Conversely, message tailoring for women with high-risk perception will help ensure that microbicides are used as additional protection, together with condoms. PMID:25224612
Communicating about microbicides with women in mind: tailoring messages for specific audiences.
Sidibe, Sekou; Pack, Allison P; Tolley, Elizabeth E; Ryan, Elizabeth; Mackenzie, Caroline; Bockh, Emily; Githuka, George
2014-01-01
Current HIV prevention options are unrealistic for most women; however, HIV prevention research has made important strides, including on-going development of antiretroviral-based vaginal microbicide gels. Nevertheless, social-behavioural research suggests that women's ability to access and use new HIV prevention technologies will be strongly influenced by a range of socio-cultural, gender and structural factors which should be addressed by communications and marketing strategies, so that these products can be positioned in ways that women can use them. Based on an extensive literature review and in-country policy consultation, consisting of approximately 43 stakeholders, we describe barriers and facilitators to HIV prevention, including potential microbicide use, for four priority audiences of Kenyan women (female sex workers [FSWs], women in stable and discordant relationships, and sexually active single young women). We then describe how messages that position microbicides might be tailored for each audience of women. We reviewed 103 peer-reviewed articles and reports. In Kenya, structural factors and gender inequality greatly influence HIV prevention for women. HIV risk perception and the ability to consistently use condoms and other prevention products often vary by partner type. Women in stable relationships find condom use challenging because they connote a lack of trust. However, women in other contexts are often able to negotiate condom use, though they may face challenges with consistent use. These women include FSWs who regularly use condoms with their casual clients, young women in the initial stages of a sexual relationship and discordant couples. Thus, we consider two approaches to framing messages aimed at increasing general awareness of microbicides - messages that focus strictly on HIV prevention and ones that focus on other benefits of microbicides such as increased pleasure, intimacy or sexual empowerment, in addition to HIV prevention. If carefully tailored, microbicide communication materials may facilitate product use by women who do not currently use any HIV prevention method. Conversely, message tailoring for women with high-risk perception will help ensure that microbicides are used as additional protection, together with condoms.
Laher, Faatima; Ranasinghe, Srinika; Porichis, Filippos; Mewalal, Nikoshia; Pretorius, Karyn; Ismail, Nasreen; Buus, Søren; Stryhn, Anette; Carrington, Mary; Walker, Bruce D; Ndung'u, Thumbi; Ndhlovu, Zaza M
2017-04-01
Immune control of viral infections is heavily dependent on helper CD4 + T cell function. However, the understanding of the contribution of HIV-specific CD4 + T cell responses to immune protection against HIV-1, particularly in clade C infection, remains incomplete. Recently, major histocompatibility complex (MHC) class II tetramers have emerged as a powerful tool for interrogating antigen-specific CD4 + T cells without relying on effector functions. Here, we defined the MHC class II alleles for immunodominant Gag CD4 + T cell epitopes in clade C virus infection, constructed MHC class II tetramers, and then used these to define the magnitude, function, and relation to the viral load of HIV-specific CD4 + T cell responses in a cohort of untreated HIV clade C-infected persons. We observed significantly higher frequencies of MHC class II tetramer-positive CD4 + T cells in HIV controllers than progressors ( P = 0.0001), and these expanded Gag-specific CD4 + T cells in HIV controllers showed higher levels of expression of the cytolytic proteins granzymes A and B. Importantly, targeting of the immunodominant Gag41 peptide in the context of HLA class II DRB1*1101 was associated with HIV control ( r = -0.5, P = 0.02). These data identify an association between HIV-specific CD4 + T cell targeting of immunodominant Gag epitopes and immune control, particularly the contribution of a single class II MHC-peptide complex to the immune response against HIV-1 infection. Furthermore, these results highlight the advantage of the use of class II tetramers in evaluating HIV-specific CD4 + T cell responses in natural infections. IMPORTANCE Increasing evidence suggests that virus-specific CD4 + T cells contribute to the immune-mediated control of clade B HIV-1 infection, yet there remains a relative paucity of data regarding the role of HIV-specific CD4 + T cells in shaping adaptive immune responses in individuals infected with clade C, which is responsible for the majority of HIV infections worldwide. Understanding the contribution of HIV-specific CD4 + T cell responses in clade C infection is particularly important for developing vaccines that would be efficacious in sub-Saharan Africa, where clade C infection is dominant. Here, we employed MHC class II tetramers designed to immunodominant Gag epitopes and used them to characterize CD4 + T cell responses in HIV-1 clade C infection. Our results demonstrate an association between the frequency of HIV-specific CD4 + T cell responses targeting an immunodominant DRB1*11-Gag41 complex and HIV control, highlighting the important contribution of a single class II MHC-peptide complex to the immune response against HIV-1 infections. Copyright © 2017 American Society for Microbiology.
Decker, Michele R; Tomko, Catherine; Wingo, Erin; Sawyer, Anne; Peitzmeier, Sarah; Glass, Nancy; Sherman, Susan G
2017-08-01
Female sex workers (FSWs) are an important population for HIV acquisition and transmission. Their risks are shaped by behavioral, sexual network, and structural level factors. Violence is pervasive and associated with HIV risk behavior and infection, yet interventions to address the dual epidemics of violence and HIV among FSWs are limited. We used participatory methods to develop a brief, trauma-informed intervention, INSPIRE (Integrating Safety Promotion with HIV Risk Reduction), to improve safety and reduce HIV risk for FSWs. A quasi-experimental, single group pretest-posttest study evaluated intervention feasibility, acceptability and efficacy among FSWs in Baltimore, MD, most of whom were drug-involved (baseline n = 60; follow-up n = 39 [65%]; non-differential by demographics or outcomes). Qualitative data collected at follow-up contextualizes findings. Based on community partnership and FSW input, emergent goals included violence-related support, connection with services, and buffering against structural forces that blame FSWs for violence. Qualitative and quantitative results demonstrate feasibility and acceptability. At follow-up, improvements were seen in avoidance of client condom negotiation (p = 0.04), and frequency of sex trade under the influence of drugs or alcohol (p = 0.04). Women's safety behavior increased (p < 0.001). Participants improved knowledge and use of sexual violence support (p < 0.01) and use of intimate partner violence support (p < 0.01). By follow-up, most respondents (68.4%) knew at least one program to obtain assistance reporting violence to police. Over the short follow-up period, client violence increased. In reflecting on intervention acceptability, participants emphasized the value of a safe and supportive space to discuss violence. This brief, trauma-informed intervention was feasible and highly acceptable to FSWs. It prompted safety behavior, mitigated sex trade under the influence, and bolstered confidence in condom negotiation. INSPIRE influenced endpoints deemed valuable by community partners, specifically improving connection to support services and building confidence in the face of myths that falsely blame sex workers for violence. Violence persisted; prevention also requires targeting perpetrators, and longer follow-up durations as women acquire safety skills. This pilot study informs scalable interventions that address trauma and its impact on HIV acquisition and care trajectories for FSWs. Addressing violence in the context of HIV prevention is feasible, acceptable to FSWs, and can improve safety and reduce HIV risk, thus supporting FSW health and human rights.
Reproductive Health Decision-Making in Perinatally HIV-Infected Adolescents and Young Adults
Wiener, Lori; Zadeh, Sima; Albright, Jamie; Mellins, Claude Ann; Mancilla, Michael; Tepper, Vicki; Trexler, Connie; Purdy, Julia; Osherow, Janet; Lovelace, Susan; Kapetanovic, Suad
2013-01-01
With widespread access to antiretroviral therapy in the United States, many perinatally HIV-infected (PHIV+) children are surviving into adolescence and adulthood, becoming sexually active and making decisions about their reproductive health. The literature focusing on the reproductive decisions of individuals behaviorally infected with HIV can serve as a springboard for understanding the decision-making process of PHIV+ youth. Yet, there are many differences that critically distinguish reproductive health and related decision-making of PHIV+ youth. Given the potential public health implications of their reproductive decisions, better understanding of factors influencing the decision-making process is needed to help inform the development of salient treatment and prevention interventions. To begin addressing this understudied area, a “think tank” session, comprised of clinicians, medical providers, and researchers with expertise in the area of adolescent HIV, was held in Bethesda, MD, on September 21, 2011. The focus was to explore what is known about factors that influence the reproductive decision-making of PHIV+ adolescents and young adults, determine what important data are needed in order to develop appropriate intervention for PHIV+ youth having children, and to recommend future directions for the field in terms of designing and carrying out collaborative studies. In this report, we summarize the findings from this meeting. The paper is organized around the key themes that emerged, including utilizing a developmental perspective to create an operational definition of reproductive decision-making, integration of psychosocial services with medical management, and how to design future research studies. Case examples are presented and model program components proposed. PMID:22736033
Reproductive health decision-making in perinatally HIV-infected adolescents and young adults.
Fair, Cynthia; Wiener, Lori; Zadeh, Sima; Albright, Jamie; Mellins, Claude Ann; Mancilla, Michael; Tepper, Vicki; Trexler, Connie; Purdy, Julia; Osherow, Janet; Lovelace, Susan; Kapetanovic, Suad
2013-07-01
With widespread access to antiretroviral therapy in the United States, many perinatally HIV-infected (PHIV+) children are surviving into adolescence and adulthood, becoming sexually active and making decisions about their reproductive health. The literature focusing on the reproductive decisions of individuals behaviorally infected with HIV can serve as a springboard for understanding the decision-making process of PHIV+ youth. Yet, there are many differences that critically distinguish reproductive health and related decision-making of PHIV+ youth. Given the potential public health implications of their reproductive decisions, better understanding of factors influencing the decision-making process is needed to help inform the development of salient treatment and prevention interventions. To begin addressing this understudied area, a "think tank" session, comprised of clinicians, medical providers, and researchers with expertise in the area of adolescent HIV, was held in Bethesda, MD, on September 21, 2011. The focus was to explore what is known about factors that influence the reproductive decision-making of PHIV+ adolescents and young adults, determine what important data are needed in order to develop appropriate intervention for PHIV+ youth having children, and to recommend future directions for the field in terms of designing and carrying out collaborative studies. In this report, we summarize the findings from this meeting. The paper is organized around the key themes that emerged, including utilizing a developmental perspective to create an operational definition of reproductive decision-making, integration of psychosocial services with medical management, and how to design future research studies. Case examples are presented and model program components proposed.
King, Elizabeth J; Maman, Suzanne; Bowling, J Michael; Moracco, Kathryn E; Dudina, Viktoria
2013-10-01
Stigma associated with HIV and risk behaviors is known to be a barrier to health care access for many populations. Less is known about female sex workers (FSW) in Russia, a population that is especially vulnerable to HIV-infection, and yet hard-to-reach for service providers. We administered a questionnaire to 139 FSW to better understand how stigma and discrimination influence HIV service utilization. Logistic regression analysis indicated that HIV-related stigma is negatively associated with uptake of HIV testing, while sex work-related stigma is positively associated with HIV testing. HIV-positive FSW are more likely than HIV-negative FSW to experience discrimination in health care settings. While decreasing societal stigma should be a long-term goal, programs that foster inclusion of marginalized populations in Russian health care settings are urgently needed.
Higgins, D L; O'Reilly, K; Tashima, N; Crain, C; Beeker, C; Goldbaum, G; Elifson, C S; Galavotti, C; Guenther-Grey, C
1996-01-01
The AIDS Community Demonstration Projects provided community-level HIV prevention interventions to historically hard-to-reach groups at high risk for HIV infection. The projects operated under a common research protocol which encompassed formative research, intervention delivery, process evaluation, and outcome evaluation. A formative research process specifically focusing on intervention development was devised to assist project staff in identifying, prioritizing, accessing, and understanding the intervention target groups. This process was central to the creation of interventions that were acceptable and unique to the target populations. Intended to be rapid, the process took 6 months to complete. Drawn from the disciplines of anthropology, community psychology, sociology, and public health, the formative research process followed distinct steps which included (a) defining the populations at high-risk for HIV; (b) gathering information about these populations through interviews with persons who were outside of, but who had contact with, the target groups (such as staff from the health department and alcohol and drug treatment facilities, as well as persons who interacted in an informal manner with the target groups, such as clerks in neighborhood grocery stores and bartenders); (c) interviewing people with access to the target populations (gatekeepers), and conducting observations in areas where these high-risk groups were reported to gather (from previous interviews); (d) interviewing members of these groups at high risk for HIV infection or transmission; and (e) systematically integrating information throughout the process. Semistructured interview schedules were used for all data collection in this process. This standardized systematic method yielded valuable information about the focal groups in each demonstration project site. The method, if adopted by others, would assist community intervention specialists in developing interventions that are culturally appropriate and meaningful to their respective target populations. PMID:8862154
Isolation of HIV-1-Neutralizing Mucosal Monoclonal Antibodies from Human Colostrum
Friedman, James; Alam, S. Munir; Shen, Xiaoying; Xia, Shi-Mao; Stewart, Shelley; Anasti, Kara; Pollara, Justin; Fouda, Genevieve G.; Yang, Guang; Kelsoe, Garnett; Ferrari, Guido; Tomaras, Georgia D.; Haynes, Barton F.; Liao, Hua-Xin
2012-01-01
Background Generation of potent anti-HIV antibody responses in mucosal compartments is a potential requirement of a transmission-blocking HIV vaccine. HIV-specific, functional antibody responses are present in breast milk, and these mucosal antibody responses may play a role in protection of the majority of HIV-exposed, breastfeeding infants. Therefore, characterization of HIV-specific antibodies produced by B cells in milk could guide the development of vaccines that elicit protective mucosal antibody responses. Methods We isolated B cells from colostrum of an HIV-infected lactating woman with a detectable neutralization response in milk and recombinantly produced and characterized the resulting HIV-1 Envelope (Env)-specific monoclonal antibodies (mAbs). Results The identified HIV-1 Env-specific colostrum mAbs, CH07 and CH08, represent two of the first mucosally-derived anti-HIV antibodies yet to be reported. Colostrum mAb CH07 is a highly-autoreactive, weakly-neutralizing gp140-specific mAb that binds to linear epitopes in the gp120 C5 region and gp41 fusion domain. In contrast, colostrum mAb CH08 is a nonpolyreactive CD4-inducible (CD4i) gp120-specific mAb with moderate breadth of neutralization. Conclusions These novel HIV-neutralizing mAbs isolated from a mucosal compartment provide insight into the ability of mucosal B cell populations to produce functional anti-HIV antibodies that may contribute to protection against virus acquisition at mucosal surfaces. PMID:22624058
Cultural considerations in theories of adolescent development: a case study from Botswana.
Ntsayagae, Esther; Sabone, Motshedise; Mogobe, Keitshokile D; Seboni, Naomi M; Sebego, Miriam; Brown, Marie Scott
2008-01-01
Western studies of adolescent development are beginning to corporate not only the traditional ideas of nature and nurture, but also contextual factors such as culture, ecology and historical time. This article explores how adolescent development is influenced by both a specific culture (Botswana) and a specific ecological situation (the rampant HIV pandemic in that country). A case study of late adolescents living in this pandemic in Botswana helps broaden our traditional views of adolescent development.
Gwadz, Marya; Cleland, Charles M; Kutnick, Alexandra; Leonard, Noelle R; Ritchie, Amanda S; Lynch, Laura; Banfield, Angela; McCright-Gill, Talaya; Del Olmo, Montserrat; Martinez, Belkis
2016-01-01
The Centers for Disease Control and Prevention recommends persons at high risk for HIV infection in the United States receive annual HIV testing to foster early HIV diagnosis and timely linkage to health care. Heterosexuals make up a significant proportion of incident HIV infections (>25%) but test for HIV less frequently than those in other risk categories. Yet factors that promote or impede annual HIV testing among heterosexuals are poorly understood. The present study examines individual/attitudinal-, social-, and structural-level factors associated with past-year HIV testing among heterosexuals at high risk for HIV. Participants were African-American/Black and Hispanic heterosexual adults (N = 2307) residing in an urban area with both high poverty and HIV prevalence rates. Participants were recruited by respondent-driven sampling in 2012-2015 and completed a computerized structured assessment battery covering background factors, multi-level putative facilitators of HIV testing, and HIV testing history. Separate logistic regression analysis for males and females identified factors associated with past-year HIV testing. Participants were mostly male (58%), African-American/Black (75%), and 39 years old on average (SD = 12.06 years). Lifetime homelessness (54%) and incarceration (62%) were common. Half reported past-year HIV testing (50%) and 37% engaged in regular, annual HIV testing. Facilitators of HIV testing common to both genders included sexually transmitted infection (STI) testing or STI diagnosis, peer norms supporting HIV testing, and HIV testing access. Among women, access to general medical care and extreme poverty further predicted HIV testing, while recent drug use reduced the odds of past-year HIV testing. Among men, past-year HIV testing was also associated with lifetime incarceration and substance use treatment. The present study identified gaps in rates of HIV testing among heterosexuals at high risk for HIV, and both common and gender-specific facilitators of HIV testing. Findings suggest a number of avenues for increasing HIV testing rates, including increasing the number and types of settings offering high-quality HIV testing; promoting STI as well as HIV testing; better integrating STI and HIV testing systems; implementing peer-driven social/behavioral intervention approaches to harness the positive influence of social networks and reduce unfavorable shared peer norms; and specialized approaches for women who use drugs.
Religion and HIV/AIDS Stigma: Considerations for the Nursing Profession
Reyes-Estrada, Marcos; Varas-Díaz, Nelson; Martínez-Sarson, Miluska T.
2016-01-01
Nurses’ stigmatization of people living with HIV/AIDS hinders effective health care provisions for this sector of the population. Scientific literature on HIV/AIDS stigma has emphasized cognitive, individual, and interpersonal factors that are relevant to the understanding of the stigmatization process among health care professionals (e.g. a health care professional’s accuracy in knowledge of the workings of the virus, effectiveness of emotion management, degree of proximity to the stigmatized group, etc.). However, researchers have also examined the socio-structural factors underlying stigma, and religion has consequently emerged as a social phenomenon that may foster it. The role of religion among professional nurses who specifically service people living with HIV/AIDS remains understudied. Focusing on evidence-based literature, we discuss the relationship between religion and HIV/AIDS stigma, explore potential implications of this relationship for the nursing profession, and make recommendations for stigma-reducing interventions. PMID:26858806
HIV incidence and CDC's HIV prevention budget: an exploratory correlational analysis.
Holtgrave, David R; Kates, Jennifer
2007-01-01
The central evaluative question about a national HIV prevention program is whether that program affects HIV incidence. Numerous factors may influence incidence, including public investment in HIV prevention. Few studies, however, have examined the relationship between public investment and the HIV epidemic in the United States. This 2006 exploratory analysis examined the period from 1978 through 2006 using a quantitative, lagged, correlational analysis to capture the relationship between national HIV incidence and Centers for Disease Control and Prevention's HIV prevention budget in the United States over time. The analyses suggest that early HIV incidence rose in advance of the nation's HIV prevention investment until the mid-1980s (1-year lag correlation, r=0.972, df=2, p <0.05). From that point on, it appears that the nation's investment in HIV prevention became a strong correlate of HIV incidence (1-year lag correlation, r=-0.905, df=18, p <0.05). This exploratory study provides correlational evidence of a relationship between U.S. HIV incidence and the federal HIV prevention budget over time, and calls for further analysis of the role of funding and other factors that may influence the direction of a nation's HIV epidemic.
HIV-Associated Cognitive Impairment in Perinatally Infected Children: A Meta-analysis.
Phillips, Nicole; Amos, Taryn; Kuo, Caroline; Hoare, Jacqueline; Ipser, Jonathan; Thomas, Kevin G F; Stein, Dan J
2016-11-01
Research shows, conclusively, that perinatal HIV infection has negative effects on cognitive functioning of children and adolescents. However, the extent of these cognitive impairments is unknown. Current literature does not document specific cognitive domains most affected in HIV-infected children and adolescents. To systematically review and meta-analyze the degree of cognitive impairment, and the specific cognitive domains affected, in children and adolescents with perinatally acquired HIV infection. We systematically searched 5 electronic bibliographic databases, namely: PubMed, PsychINFO, Academic Search Premier, Scopus, and WorldCat, by using a search protocol specifically designed for this study. Studies were selected on the basis of set a priori eligibility criteria. Titles, abstracts, and full texts were assessed by 2 independent reviewers. Data from included studies were extracted into Microsoft Excel by 2 independent reviewers. Twenty-two studies were identified for inclusion in the systematic review and of this, 6 studies were included in the meta-analysis. Results from the meta-analysis indicated that working memory and executive function were the domains most affected by the HIV virus. Only 27% of the included studies were suitable to enter into the meta-analysis. There was significant geographic bias in published studies, with only 32% (7/22) of included studies from sub-Saharan Africa. The evidence supports an association between HIV infection in children and adolescents and cognitive impairment in the domains of working memory, executive function and processing speed, with effect size estimates also providing some support for deficits in visual memory and visual-spatial ability. Copyright © 2016 by the American Academy of Pediatrics.
Buttolph, Jasmine; Inwani, Irene; Agot, Kawango; Cleland, Charles M; Cherutich, Peter; Kiarie, James N; Osoti, Alfred; Celum, Connie L; Baeten, Jared M; Nduati, Ruth; Kinuthia, John; Hallett, Timothy B; Alsallaq, Ramzi; Kurth, Ann E
2017-03-08
Nearly three decades into the epidemic, sub-Saharan Africa (SSA) remains the region most heavily affected by human immunodeficiency virus (HIV), with nearly 70% of the 34 million people living with HIV globally residing in the region. In SSA, female and male youth (15 to 24 years) are at a disproportionately high risk of HIV infection compared to adults. As such, there is a need to target HIV prevention strategies to youth and to tailor them to a gender-specific context. This protocol describes the process for the multi-staged approach in the design of the MP3 Youth pilot study, a gender-specific, combination, HIV prevention intervention for youth in Kenya. The objective of this multi-method protocol is to outline a rigorous and replicable methodology for a gender-specific combination HIV prevention pilot study for youth in high-burden settings, illustrating the triangulated methods undertaken to ensure that age, sex, and context are integral in the design of the intervention. The mixed-methods, cross-sectional, longitudinal cohort pilot study protocol was developed by first conducting a systematic review of the literature, which shaped focus group discussions around prevention package and delivery options, and that also informed age- and sex- stratified mathematical modeling. The review, qualitative data, and mathematical modeling created a triangulated evidence base of interventions to be included in the pilot study protocol. To design the pilot study protocol, we convened an expert panel to select HIV prevention interventions effective for youth in SSA, which will be offered in a mobile health setting. The goal of the pilot study implementation and evaluation is to apply lessons learned to more effective HIV prevention evidence and programming. The combination HIV prevention package in this protocol includes (1) offering HIV testing and counseling for all youth; (2) voluntary medical circumcision and condoms for males; (3) pre-exposure prophylaxis (PrEP), conditional cash transfer (CCT), and contraceptives for females; and (4) referrals for HIV care among those identified as HIV-positive. The combination package platform selected is mobile health teams in an integrated services delivery model. A cross-sectional analysis will be conducted to determine the uptake of the interventions. To determine long-term impact, the protocol outlines enrolling selected participants in mutually exclusive longitudinal cohorts (HIV-positive, PrEP, CCT, and HIV-negative) followed by using mobile phone text messages (short message service, SMS) and in-person surveys to prospectively assess prevention method uptake, adherence, and risk compensation behaviors. Cross-sectional and sub-cohort analyses will be conducted to determine intervention packages uptake. The literature review, focus groups, and modeling indicate that offering age- and gender- specific combination HIV prevention interventions that include biomedical, behavioral, and structural interventions can have an impact on HIV risk reduction. Implementing this protocol will show the feasibility of delivering these services at scale. The MP3 Youth study is one of the few combination HIV prevention intervention protocols incorporating youth- and gender-specific interventions in one delivery setting. Lessons learned from the design of the protocol can be incorporated into the national guidance for combination HIV prevention for youth in Kenya and other high-burden SSA settings. ClinicalTrials.gov NCT01571128; http://clinicaltrials.gov/ct2/show/NCT01571128?term=MP3+youth&rank=1 (Archived by WebCite at http://www.webcitation.org/6nmioPd54). ©Jasmine Buttolph, Irene Inwani, Kawango Agot, Charles M Cleland, Peter Cherutich, James N Kiarie, Alfred Osoti, Connie L Celum, Jared M Baeten, Ruth Nduati, John Kinuthia, Timothy B Hallett, Ramzi Alsallaq, Ann E Kurth. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 08.03.2017.
HIV infection impairs Th1 and Th17 Mycobacterium tuberculosis-specific T cell responses
Murray, Lyle W; Satti, Iman; Meyerowitz, Jodi; Jones, Matthew; Willberg, Christian B; Ussher, James E; Goedhals, Dominique; Hurst, Jacob; Phillips, Rodney E; McShane, Helen
2018-01-01
Background HIV-infected individuals have a higher risk of developing active tuberculosis than HIV-uninfected individuals, but the mechanisms underpinning this are unclear. We hypothesized that depletion of specific components of Mycobacterium tuberculosis (M.tb)-specific CD4+ and CD8+ T cell responses contributed to this increased risk. Methods M.tb-specific T cell responses in 147 HIV-infected and 44 HIV-uninfected control subjects in a TB-endemic setting in Bloemfontein, South Africa were evaluated. Using a whole-blood flow cytometry assay, we measured expression of IFNγ, TNFα, IL-2 and IL-17 in CD4+ and CD8+ T cells in response to M.tb antigens (PPD, ESAT-6/CFP-10 (EC) and DosR regulon-encoded α-crystallin (Rv2031c)). Results Fewer HIV-infected individuals had detectable CD4+ and CD8+ T cell responses to PPD and Rv2031c than HIV-uninfected subjects. M.tb-specific T cells showed distinct patterns of cytokine expression comprising both Th1 (CD4 and CD8) and Th17 (CD4) cytokines, the latter at highest frequency for Rv2031c. Th17 antigen-specific responses to all antigens tested were specifically impaired in HIV-infected individuals. Conclusions HIV-associated impairment of CD4+ and CD8+ M.tb-specific T cell responses is antigen-specific, particularly impacting responses to PPD and Rv2031c. Preferential depletion of Th17 cytokine-expressing CD4+ T cells suggests this T cell subset may be key to TB susceptibility in HIV-infected individuals. PMID:29546381
Towner, Senna L.; Dolcini, M. Margaret; Harper, Gary W.
2013-01-01
Relationship dynamics develop early in life and are influenced by social environments. STI/HIV prevention programs need to consider romantic relationship dynamics that contribute to sexual health. The aim of this study was to examine monogamous patterns, commitment, and trust in African American adolescent romantic relationships. The authors also focused on the differences in these dynamics between and within gender. The way that such dynamics interplay in romantic relationships has the potential to influence STI/HIV acquisition risk. In-depth interviews were conducted with 28 African American adolescents aged 14 to 21 living in San Francisco. Our results discuss data related to monogamous behaviors, expectations, and values; trust and respect in romantic relationships; commitment to romantic relationships; and outcomes of mismatched relationship expectations. Incorporating gender-specific romantic relationships dynamics can enhance the effectiveness of prevention programs. PMID:26691404
Newcomb, Michael D; Locke, Thomas F; Goodyear, Rodney K
2003-08-01
This study determined how adverse childhood experiences influenced risky sexual behavior in a community sample of Latina adolescents in Los Angeles (N = 904) within a modified ecodevelopmental perspective. Psychosocial, sociocultural, and environmental mediators of the relations between childhood experiences and risky sexual behavior were tested. Many direct and mediated paths were revealed using structural equation modeling. Childhood maltreatment was associated with risk sexual practices, including more partners, less condom use, more frequent intercourse, and less HIV testing. Drug use and general self-efficacy mediated several relationships. Reducing childhood maltreatment reduced HIV risk and improved psychosocial functioning. Many factors tested did not influence HIV risk. Much of what is known about HIV risk among other populations may not apply to young Latina women.
Amutah, Ndidiamaka N.; Gifuni, Jacqueline; Wesley, Yvonne
2016-01-01
The purpose of this qualitative secondary data analysis is to examine the major influencers on mothers with HIV in their childbearing decisions, as well as how those influencers shape conversations with clinicians and health-care providers regarding HIV treatment and prevention. The original study gained insight into the reproductive decision-making of mothers with HIV. By analyzing a subsample of 15 interviews from an original cohort of 25 participants in the earlier study, three major themes were identified as follows: (1) family members, not health-care providers, influence reproductive decisions; (2) negative attitudes toward subsequent pregnancies are mainly due to HIV transmission; and (3) birth control decisions were predominately supported by family members, while health-care providers were not consulted. PMID:27158227
Sikweyiya, Yandisa M; Jewkes, Rachel; Dunkle, Kristin
2014-01-01
To date, whilst there have been many published studies exploring the links between masculinity and HIV, not much work has been done to explore how an HIV-positive diagnosis impacts men's sense of masculinity and contextualizing the masculinities as fluid and changing. To explore how human immunodeficiency virus (HIV) impacts the lives of men and their constructions of masculinity through interviews with 18 men living with HIV. Qualitative study involving conveniently and purposively selected black South African adult men who lived with HIV. In-depth interviews were conducted with 18 men who resided in Johannesburg and Mthatha, South Africa. Our analysis suggests that the performance of risky masculinity may influence the acquisition of HIV. Yet, it also reveals that HIV can have a significant effect on men and their masculinities. Men's constructions of harmful notions of hegemonic masculinity pre-HIV diagnosis negatively affected their help-seeking behavior and coping and adjustment to living with HIV, post-diagnosis. The dominant discourse that men are strong and healthy visibly presented challenges for men when faced with an HIV-positive status. They interpreted HIV diagnosis as a loss, a sign of failure as a man, and evidence of an inability to retain control. Being sick undermined their ability to perform roles expected of them, and this led to feelings of powerlessness, worthlessness, and distress. Interventions with men living with HIV need to provide safe spaces for men to critically explore gender and constructions of social identities and the pressures these place on men and implications for their health. With this approach, harmful constructions of masculinities may be challenged and mitigated, and this process may render men amenable to change.
Sikweyiya, Yandisa M.; Jewkes, Rachel; Dunkle, Kristin
2014-01-01
Background To date, whilst there have been many published studies exploring the links between masculinity and HIV, not much work has been done to explore how an HIV-positive diagnosis impacts men's sense of masculinity and contextualizing the masculinities as fluid and changing. Objective To explore how human immunodeficiency virus (HIV) impacts the lives of men and their constructions of masculinity through interviews with 18 men living with HIV. Design Qualitative study involving conveniently and purposively selected black South African adult men who lived with HIV. In-depth interviews were conducted with 18 men who resided in Johannesburg and Mthatha, South Africa. Results Our analysis suggests that the performance of risky masculinity may influence the acquisition of HIV. Yet, it also reveals that HIV can have a significant effect on men and their masculinities. Men's constructions of harmful notions of hegemonic masculinity pre-HIV diagnosis negatively affected their help-seeking behavior and coping and adjustment to living with HIV, post-diagnosis. The dominant discourse that men are strong and healthy visibly presented challenges for men when faced with an HIV-positive status. They interpreted HIV diagnosis as a loss, a sign of failure as a man, and evidence of an inability to retain control. Being sick undermined their ability to perform roles expected of them, and this led to feelings of powerlessness, worthlessness, and distress. Conclusions Interventions with men living with HIV need to provide safe spaces for men to critically explore gender and constructions of social identities and the pressures these place on men and implications for their health. With this approach, harmful constructions of masculinities may be challenged and mitigated, and this process may render men amenable to change. PMID:25280735
Chacón, Lucía; Mateos, María Luisa; Holguín, África
2017-07-01
Despite the high specificity of fourth-generation enzyme immunoassays (4th-gen-EIA) for screening during HIV diagnosis, their positive predictive value is low in populations with low HIV prevalence. Thus, screening should be optimized to reduce false positive results. The influence of sample cutoff (S/CO) values by a 4th-gen-EIA with the false positive rate during the routine HIV diagnosis in a low HIV prevalence population was evaluated. A total of 30,201 sera were tested for HIV diagnosis using Abbott Architect ® HIV-Ag/Ab-Combo 4th-gen-EIA at a hospital in Spain during 17 months. Architect S/CO values were recorded, comparing the HIV-1 positive results following Architect interpretation (S/CO≥1) with the final HIV-1 diagnosis by confirmatory tests (line immunoassay, LIA and/or nucleic acid test, NAT). ROC curve was also performed. Among the 30,201 HIV performed tests, 256 (0.85%) were positive according to Architect interpretation (S/CO≥1) but only 229 (0.76%) were definitively HIV-1 positive after LIA and/or NAT. Thus, 27 (10.5%) of 256 samples with S/CO≥1 by Architect were false positive diagnose. The false positive rate decreased when the S/CO ratio increased. All 19 samples with S/CO ≤10 were false positives and all 220 with S/CO>50 true HIV-positives. The optimal S/CO cutoff value provided by ROC curves was 32.7. No false negative results were found. We show that very low S/CO values during HIV-1 screening using Architect can result HIV negative after confirmation by LIA and NAT. The false positive rate is reduced when S/CO increases. Copyright © 2017 Elsevier B.V. All rights reserved.
Karnasuta, Chitraporn; Vasan, Sandhya; Rerks-Ngarm, Supachai; Pitisuttithum, Punnee; Madnote, Sirinan; Savadsuk, Hathairat; Rittiroongrad, Surawach; Puangkaew, Jiraporn; Phogat, Sanjay; Tartaglia, James; Sinangil, Faruk; de Souza, Mark S.; Excler, Jean-Louis; Kim, Jerome H.; Robb, Merlin L.; Michael, Nelson L.; Ngauy, Viseth; O'Connell, Robert J.; Karasavvas, Nicos
2018-01-01
Sexual transmission is the principal driver of the human immunodeficiency virus (HIV) pandemic. Understanding HIV vaccine-induced immune responses at mucosal surfaces can generate hypotheses regarding mechanisms of protection, and may influence vaccine development. The RV144 (ClinicalTrials.gov NCT00223080) efficacy trial showed protection against HIV infections but mucosal samples were not collected, therefore, the contribution of mucosal antibodies to preventing HIV-1 acquisition is unknown. Here, we report the generation, magnitude and persistence of antibody responses to recombinant gp120 envelope and antigens including variable one and two loop scaffold antigens (gp70V1V2) previously shown to correlate with risk in RV144. We evaluated antibody responses to gp120 A244gD and gp70V1V2 92TH023 (both CRF01_AE) and Case A2 (subtype B) in cervico-vaginal mucus (CVM), seminal plasma (SP) and rectal secretions (RS) from HIV-uninfected RV144 vaccine recipients, who were randomized to receive two late boosts of ALVAC-HIV/AIDSVAX®B/E, AIDSVAX®B/E, or ALVAC-HIV alone at 0 and 6 months. Late vaccine boosting increased IgG geometric mean titers (GMT) to gp120 A244gD in AIDSVAX®B/E and ALVAC-HIV/AIDSVAX®B/E CVM (28 and 17 fold, respectively), followed by SP and RS. IgG to gp70V1V2 92TH023 increased in AIDSVAX®B/E and ALVAC-HIV/AIDSVAX®B/E CVM (11–17 fold) and SP (2 fold) two weeks post first boost. IgG to Case A2 was only detected in AIDSVAX®B/E and ALVAC-HIV/AIDSVAX®B/E CVM. Mucosal IgG to gp120 A244gD (CVM, SP, RS), gp70V1V2 92TH023 (CVM, SP), and Case A2 (CVM) correlated with plasma IgG levels (p<0.001). Although the magnitude of IgG responses declined after boosting, anti-gp120 A244gD IgG responses in CVM persisted for 12 months post final vaccination. Further studies in localization, persistence and magnitude of envelope specific antibodies (IgG and dimeric IgA) in anogenital secretions will help determine their role in preventing mucosal HIV acquisition. PMID:29702672
Walther, Joseph B; Jang, Jeong-Woo; Hanna Edwards, Ashley A
2018-01-01
Unlike traditional media, social media systems often present information of different types from different kinds of contributors within a single message pane, a juxtaposition of potential influences that challenges traditional health communication processing. One type of social media system, question-and-answer advice systems, provides peers' answers to health-related questions, which yet other peers read and rate. Responses may appear good or bad, responders may claim expertise, and others' aggregated evaluations of an answer's usefulness may affect readers' judgments. An experiment explored how answer feasibility, expertise claims, and user-generated ratings affected readers' assessments of advice about anonymous HIV testing. Results extend the heuristic-systematic model of persuasion (Chaiken, 1980) and warranting theory (Walther & Parks, 2002). Information that is generally associated with both systematic and heuristic processes influenced readers' evaluations. Moreover, content-level cues affected judgments about message sources unexpectedly. When conflicting cues were present, cues with greater warranting value (consensus user-generated ratings) had greater influence on outcomes than less warranted cues (self-promoted expertise). Findings present a challenge to health professionals' concerns about the reliability of online health information systems.
Harper, Gary W.; Tyler, April Timmons; Bruce, Douglas; Graham, Louis; Wade, Ryan M.
2016-01-01
Black gay and bisexual young men carry a disproportionate burden of HIV in the United States. This study explored Black gay and bisexual young men living with HIV’s identification and interpretation of race-specific cultural messages regarding substance use, sexual activity, and condom use. A total of 36 Black gay and bisexual young men living with HIV (ages 16-24, mean=20.6 years) from four geographically diverse regions of the US participated in qualitative in-depth interviews. Results from this study elucidate the ways in which these young men interpret various forms of race-specific cultural messages and experiences regarding substance use, sexual activity, and condom use. Participants discussed cultural messages and experiences promoting and discouraging condoms and substance use. Regarding sexual activity, only messages and experiences promoting sex were reported. Across all three categories, messages and experiences promoting risk were predominant. Data further revealed that socially transmitted cultural messages received by young men emanated from multiple sources, such as family, peers, sexual partners, community/neighborhood, and the broader society. Race-specific cultural messages and experiences should be addressed in interventions for this population, and programs should assist young men in developing a critical consciousness regarding these messages and experiences in order to promote health and well-being. PMID:27883219
Luo, Xinlong; Yang, Wei; Gao, Guangxia
2018-07-01
Human immunodeficiency virus type 1 (HIV-1) can infect nondividing cells via passing through the nuclear pore complex. The nuclear membrane-imbedded protein SUN2 was recently reported to be involved in the nuclear import of HIV-1. Whether SUN1, which shares many functional similarities with SUN2, is involved in this process remained to be explored. Here we report that overexpression of SUN1 specifically inhibited infection by HIV-1 but not that by simian immunodeficiency virus (SIV) or murine leukemia virus (MLV). Overexpression of SUN1 did not affect reverse transcription but led to reduced accumulation of the 2-long-terminal-repeat (2-LTR) circular DNA and integrated viral DNA, suggesting a block in the process of nuclear import. HIV-1 CA was mapped as a determinant for viral sensitivity to SUN1. Treatment of SUN1-expressing cells with cyclosporine (CsA) significantly reduced the sensitivity of the virus to SUN1, and an HIV-1 mutant containing CA-G89A, which does not interact with cyclophilin A (CypA), was resistant to SUN1 overexpression. Downregulation of endogenous SUN1 inhibited the nuclear entry of the wild-type virus but not that of the G89A mutant. These results indicate that SUN1 participates in the HIV-1 nuclear entry process in a manner dependent on the interaction of CA with CypA. IMPORTANCE HIV-1 infects both dividing and nondividing cells. The viral preintegration complex (PIC) can enter the nucleus through the nuclear pore complex. It has been well known that the viral protein CA plays an important role in determining the pathways by which the PIC enters the nucleus. In addition, the interaction between CA and the cellular protein CypA has been reported to be important in the selection of nuclear entry pathways, though the underlying mechanisms are not very clear. Here we show that both SUN1 overexpression and downregulation inhibited HIV-1 nuclear entry. CA played an important role in determining the sensitivity of the virus to SUN1: the regulatory activity of SUN1 toward HIV-1 relied on the interaction between CA and CypA. These results help to explain how SUN1 is involved in the HIV-1 nuclear entry process. Copyright © 2018 American Society for Microbiology.
Accounts from the field: a public relations perspective on global AIDS/HIV.
Bardhan, Nilanjana R
2002-01-01
This study is a theoretical as well as empirical exploration of the power and cultural differentials that mark and construct various intersecting discourses, specifically media discourse, on global AIDS/HIV. It applies the language and concepts of public relations to understand how the press coverage of the pandemic is associated with the variables that impact the newsmaking process as well as the public and policy implications of macro news frames generated over time. Theoretical work in the areas of agenda setting and news framing also instruct the conceptual framework of this analysis. Narrative analysis is used as a methodology to qualitatively analyze three pools of accounts-from people either living with AIDS/HIV, involved in AIDS/HIV work, or discursively engaged in the media construction of the pandemic; from transnational wire service journalists who cover the issue at global and regional levels; and policy shapers and communicators who are active at the global level. These three communities of respondents represent important stakeholders in the AIDS/HIV issue. The findings are analyzed from a public relations standpoint. Perhaps the most important finding of this study is that the public relations approaches used to address AIDS/HIV related issues need to be grounded in context-specific research and communicative practices that bring out the lived realities of AIDS/HIV at grassroots levels. The findings also posit that those situated at critical junctions between various stakeholders need to cultivate a finely balanced understanding of the etic and emic intersections and subjectivities of global/local AIDS/HIV.
Sakane, Naoki; Kwon, Hye-Sook; Pagans, Sara; Kaehlcke, Katrin; Mizusawa, Yasuhiro; Kamada, Masafumi; Lassen, Kara G.; Chan, Jonathan; Greene, Warner C.; Schnoelzer, Martina; Ott, Melanie
2011-01-01
The essential transactivator function of the HIV Tat protein is regulated by multiple posttranslational modifications. Although individual modifications are well characterized, their crosstalk and dynamics of occurrence during the HIV transcription cycle remain unclear. We examine interactions between two critical modifications within the RNA-binding domain of Tat: monomethylation of lysine 51 (K51) mediated by Set7/9/KMT7, an early event in the Tat transactivation cycle that strengthens the interaction of Tat with TAR RNA, and acetylation of lysine 50 (K50) mediated by p300/KAT3B, a later process that dissociates the complex formed by Tat, TAR RNA and the cyclin T1 subunit of the positive transcription elongation factor b (P-TEFb). We find K51 monomethylation inhibited in synthetic Tat peptides carrying an acetyl group at K50 while acetylation can occur in methylated peptides, albeit at a reduced rate. To examine whether Tat is subject to sequential monomethylation and acetylation in cells, we performed mass spectrometry on immunoprecipitated Tat proteins and generated new modification-specific Tat antibodies against monomethylated/acetylated Tat. No bimodified Tat protein was detected in cells pointing to a demethylation step during the Tat transactivation cycle. We identify lysine-specific demethylase 1 (LSD1/KDM1) as a Tat K51-specific demethylase, which is required for the activation of HIV transcription in latently infected T cells. LSD1/KDM1 and its cofactor CoREST associates with the HIV promoter in vivo and activate Tat transcriptional activity in a K51-dependent manner. In addition, small hairpin RNAs directed against LSD1/KDM1 or inhibition of its activity with the monoamine oxidase inhibitor phenelzine suppresses the activation of HIV transcription in latently infected T cells. Our data support the model that a LSD1/KDM1/CoREST complex, normally known as a transcriptional suppressor, acts as a novel activator of HIV transcription through demethylation of K51 in Tat. Small molecule inhibitors of LSD1/KDM1 show therapeutic promise by enforcing HIV latency in infected T cells. PMID:21876670
Goldenberg, Tamar; Stephenson, Rob
2015-01-01
Background Gay, bisexual, and other men who have sex with men account for a disproportionate burden of HIV incidence in the United States, with one-third to two-thirds of these new HIV infections occurring within main partnerships. Early initiation and adherence to highly active antiretroviral treatment is a key factor in treating and preventing the transmission of HIV; however, the average rate of adherence in the United States is low. Social support has been examined as a source of improving health for people experiencing a variety of chronic health conditions. This study aims to understand perceptions of how dyadic HIV care could influence partner-specific support for same-sex male couples with a goal of improving adherence. Methods Data were collected from 5 focus group (n = 35) discussions with gay and bisexual men in same-sex male relationships in Atlanta, GA. Participants discussed perceptions of how dyadic HIV care would impact partner support among serodiscordant and seroconcordant HIV-positive same-sex male couples. Verbatim transcripts were segmented thematically and systematically analyzed to examine patterns. Results Participants described how dyadic HIV care can facilitate emotional, informational, and instrumental support at various stages across the continuum of care, depending on partner dynamics. Participants stated that dyadic HIV care can provide an additional “sense of togetherness” and “solidarity” that helps to “alleviate stress.” Conclusions Results suggest that dyadic approaches for HIV care across the continuum may be useful in promoting partner support and improving adherence. Future research should further examine dyadic interventions for HIV treatment among same-sex male couples. PMID:25867781
Garcia, Jonathan; Parker, Caroline; Parker, Richard G; Wilson, Patrick A; Philbin, Morgan M; Hirsch, Jennifer S
2015-01-01
Black men who have sex with men (BMSM) experience among the highest rates of HIV infection in the United States. We conducted a community-based ethnography in New York City to identify the structural and environmental factors that influence BMSMs vulnerability to HIV and their engagement with HIV prevention services. Methods included participant observation at community-based organizations (CBOs) in New York City, in-depth interviews with 31 BMSM, and 17 key informant interviews. Our conceptual framework shows how creating and sustaining safe spaces could be a critical environmental approach to reduce vulnerability to HIV among BMSM. Participant observation, in-depth and key informant interviews revealed that fear and mistrust characterized men's relation to social and public institutions, such as churches, schools, and the police. This fear and mistrust created HIV vulnerability among the BMSM in our sample by challenging engagement with services. Our findings suggest that to be successful, HIV prevention efforts must address these structural and environmental vulnerabilities. Among the CBOs that we studied, "safe spaces" emerged as an important tool for addressing these environmental vulnerabilities. CBOs used safe spaces to provide social support, to address stigma, to prepare men for the workforce, and to foster a sense of community among BMSM. In addition, safe spaces were used for HIV and STI testing and treatment campaigns. Our ethnographic findings suggest that safe spaces represent a promising but so far under-utilized part of HIV prevention infrastructure. Safe spaces seem integral to high impact comprehensive HIV prevention efforts, and may be considered more appropriately as part of HIV capacity-building rather than being nested within program-specific funding structures.
Ohmine, Seiga; Singh, Raman Deep; Marks, David L; Meyer, Melissa A; Pagano, Richard E; Ikeda, Yasuhiro
2013-01-01
TRIM5α (tripartite motif 5α) acts as a pattern recognition receptor specific for the retrovirus capsid lattice and blocks infection by HIV-1 immediately after entry. However, the precise mechanisms underlying this rapid recognition of viral components remain elusive. Here, we analyzed the influence of viral exposure on TRIM5α. Total internal reflection fluorescence microscopy and lipid flotation assays revealed rapid recruitment of a TRIM5α subpopulation to the plasma membrane (PM) upon exposure to vesicular stomatitis virus-G-pseudotyped HIV-1 viral-like particles (VLPs), but not to envelope (Env)-less HIV-1 VLPs. TRIM5α signals were frequently colocalized with those of HIV-1 capsid at the PM. Exposure to HIV-1 Env-pseudotyped HIV-1 vectors also triggered translocation of endogenous TRIM5α to lipid microdomains within human T cells. Similarly, clustering of lipid microdomains by a glycosphingolipid stereoisomer resulted in rapid TRIM5α recruitment to the PM. Of note, recruitment of endogenous rhesus TRIM5α to the PM prior to HIV-1 infection significantly increased the potency of viral restriction. Our data therefore suggest the importance of TRIM5α recruitment to the PM for TRIM5α-mediated innate immune sensing and restriction of retroviral infection. Copyright © 2013 S. Karger AG, Basel.
Patel, Mickey V; Ghosh, Mimi; Fahey, John V; Ochsenbauer, Christina; Rossoll, Richard M; Wira, Charles R
2014-07-01
Whether the concentrations of antiviral proteins, and anti-HIV activity, within human vaginal secretions change across the menstrual cycle is unknown. Using a menstrual cup, vaginal secretions from pre-menopausal women were recovered at the proliferative (d6-8), mid-cycle (d13-15), and secretory (d21-23) stages of the menstrual cycle. Antiviral protein concentration was determined by ELISA, and anti-HIV activity assessed using the TZM-bl reporter cell line. CCL20, RANTES, elafin, HBD2, SDF-1α, and IL-8 levels were detectable in the secretions. Vaginal secretions had anti-HIV activity against specific clade B strains of HIV, with significant inhibition of IIIB and increased infectivity of transmitted/founder CH077.t. No significant differences in either antiviral protein concentration or anti-HIV activity with respect to menstrual cycle stage were measured, but marked differences were observed in both parameters over the course of the cycle between different women and in consecutive cycles from the same woman. The vagina contains a complement of antiviral proteins. The variation in anti-HIV activity demonstrates that immune protection in the vagina is not constant. Intra- and interindividual variations suggest that factors in addition to sex hormones influence antiviral protection. Lastly, the menstrual cup is a new model for recovering undiluted vaginal secretions from women throughout their reproductive life. © 2014 John Wiley & Sons Ltd.
Gloyd, Stephen; Wagenaar, Bradley H; Woelk, Godfrey B; Kalibala, Samuel
2016-01-01
HIV programme data from routine health information systems (RHIS) and personal health information (PHI) provide ample opportunities for secondary data analysis. However, these data pose unique opportunities and challenges for use in health system monitoring, along with process and impact evaluations. Analyses focused on retrospective case reviews of four of the HIV-related studies published in this JIAS supplement. We identify specific opportunities and challenges with respect to the secondary analysis of RHIS and PHI data. Challenges working with both HIV-related RHIS and PHI included missing, inconsistent and implausible data; rapidly changing indicators; systematic differences in the utilization of services; and patient linkages over time and different data sources. Specific challenges among RHIS data included numerous registries and indicators, inconsistent data entry, gaps in data transmission, duplicate registry of information, numerator-denominator incompatibility and infrequent use of data for decision-making. Challenges specific to PHI included the time burden for busy providers, the culture of lax charting, overflowing archives for paper charts and infrequent chart review. Many of the challenges that undermine effective use of RHIS and PHI data for analyses are related to the processes and context of collecting the data, excessive data requirements, lack of knowledge of the purpose of data and the limited use of data among those generating the data. Recommendations include simplifying data sources, analysis and reporting; conducting systematic data quality audits; enhancing the use of data for decision-making; promoting routine chart review linked with simple patient tracking systems; and encouraging open access to RHIS and PHI data for increased use.
Rouhani, Shada A; O'Laughlin, Kelli N; Faustin, Zikama M; Tsai, Alexander C; Kasozi, Julius; Ware, Norma C
2017-08-01
Little is known about the factors that encourage or discourage refugees to test for HIV, or to access and adhere to HIV care. In non-refugee populations, social support has been shown to influence HIV testing and utilisation of services. The present study enrolled HIV-infected refugees on anti-retroviral therapy (ART) in Uganda, who participated in qualitative interviews on HIV testing, treatment, and adherence. Interviews were analysed for themes about four types of social support: emotional, informational, instrumental, and appraisal support. A total of 61 interviews were analysed. Four roles for these types of social support were identified: (1) informational support encouraged refugees to test for HIV; (2) emotional support helped refugees cope with a diagnosis of HIV; (3) instrumental support facilitated adherence to ART and (4) after diagnosis, HIV-infected refugees provided informational and emotional support to encourage other refugees to test for HIV. These results suggest that social support influences HIV testing and treatment among refugees. Future interventions should capitalise on social support within a refugee settlement to facilitate testing and treatment.
Socioecological Influences on Community Involvement in HIV Vaccine Research
Frew, Paula M.; Archibald, Matthew; Hixson, Brooke; del Rio, Carlos
2011-01-01
Objective This study investigated socioecological factors influencing HIV vaccine research participation among communities living in geographic areas with high HIV prevalence and high poverty rates. Methods We surveyed a sample of 453 adults ≥ 18 years from areas of high poverty and high HIV prevalence in metro Atlanta and differentiated the effects of individual-, social/organizational-, and community-level characteristics on participation in HIV vaccine research via multilevel modeling techniques that incorporated questionnaire, program, and census data. Results Models that adjusted for both individual-level covariates (such as race, gender, attitudes, and beliefs concerning HIV research), social/organizational- and community-level factors such as local HIV prevalence rates, revealed that the extent of HIV prevention-related programs and services in census tracts contributed to individuals’ likelihood of participation in an HIV vaccine study. Additionally, neighborhood-based organizations offering HIV medical and treatment programs, support groups, and services (e.g., food, shelter, and clothing) encourage greater HIV vaccine research participation. Conclusions The findings support the hypothesis that community-level factors facilitate participation in HIV vaccine research independent of both individual- and social/organizational-level factors. PMID:21722689
Wardle, Margaret C.; Gonzalez, Raul; Bechara, Antoine; Martin-Thormeyer, Eileen M.
2013-01-01
HIV+ substance-dependent individuals (SDIs) show emotional distress and executive impairment, but in isolation these poorly predict sexual risk. We hypothesized that an executive measure sensitive to emotional aspects of judgment (Iowa Gambling Task; IGT) would identify HIV+ SDIs whose sexual risks were influenced by emotional distress. We assessed emotional distress and performance on several executive tasks in 190 HIV+ SDIs. IGT performance interacted significantly with emotional distress, such that only in better performers were distress and risk related. Our results are interpreted using the somatic marker hypothesis and indicate that the IGT identifies HIV+ SDIs for whom psychological distress influences HIV risk. PMID:20480423
Hussen, Sophia A; Bowleg, Lisa; Sangaramoorthy, Thurka; Malebranche, David J
2012-01-01
Black men in the USA experience disproportionately high rates of HIV infection, particularly in the Southeastern part of the country. We conducted 90 qualitative in-depth interviews with Black men living in the state of Georgia and analysed the transcripts using Sexual Script Theory to: (1) characterise the sources and content of sexual scripts that Black men were exposed to during their childhood and adolescence and (2) describe the potential influence of formative scripts on adult HIV sexual risk behaviour. Our analyses highlighted salient sources of cultural scenarios (parents, peers, pornography, sexual education and television), interpersonal scripts (early sex- play, older female partners, experiences of child abuse) and intrapsychic scripts that participants described. Stratification of participant responses based on sexual-risk behaviour revealed that lower- and higher-risk men described exposure to similar scripts during their formative years; however, lower-risk men reported an ability to cognitively process and challenge the validity of risk-promoting scripts that they encountered. Implications for future research are discussed.
Kovacsics, Colleen E.; Vance, Patricia J.; Collman, Ronald G.
2015-01-01
ABSTRACT Expression of the cytoprotective enzyme heme oxygenase-1 (HO-1) is significantly reduced in the brain prefrontal cortex of HIV-positive individuals with HIV-associated neurocognitive disorders (HAND). Furthermore, this HO-1 deficiency correlates with brain viral load, markers of macrophage activation, and type I interferon responses. In vitro, HIV replication in monocyte-derived macrophages (MDM) selectively reduces HO-1 protein and RNA expression and induces production of neurotoxic levels of glutamate; correction of this HO-1 deficiency reduces neurotoxic glutamate production without an effect on HIV replication. We now demonstrate that macrophage HO-1 deficiency, and the associated neurotoxin production, is a conserved feature of infection with macrophage-tropic HIV-1 strains that correlates closely with the extent of replication, and this feature extends to HIV-2 infection. We further demonstrate that this HO-1 deficiency does not depend specifically upon the HIV-1 accessory genes nef, vpr, or vpu but rather on HIV replication, even when markedly limited. Finally, antiretroviral therapy (ART) applied to MDM after HIV infection is established does not prevent HO-1 loss or the associated neurotoxin production. This work defines a predictable relationship between HIV replication, HO-1 loss, and neurotoxin production in MDM that likely reflects processes in place in the HIV-infected brains of individuals receiving ART. It further suggests that correcting this HO-1 deficiency in HIV-infected MDM could provide neuroprotection above that provided by current ART or proposed antiviral therapies directed at limiting Nef, Vpr, or Vpu functions. The ability of HIV-2 to reduce HO-1 expression suggests that this is a conserved phenotype among macrophage-tropic human immunodeficiency viruses that could contribute to neuropathogenesis. IMPORTANCE The continued prevalence of HIV-associated neurocognitive disorders (HAND) underscores the need for adjunctive therapy that targets the neuropathological processes that persist in antiretroviral therapy (ART)-treated HIV-infected individuals. To this end, we previously identified one such possible process, a deficiency of the antioxidative and anti-inflammatory enzyme heme oxygenase-1 (HO-1) in the brains of individuals with HAND. In the present study, our findings suggest that the HO-1 deficiency associated with excess glutamate production and neurotoxicity in HIV-infected macrophages is a highly conserved phenotype of macrophage-tropic HIV strains and that this phenotype can persist in the macrophage compartment in the presence of ART. This suggests a plausible mechanism by which HIV infection of brain macrophages in ART-treated individuals could exacerbate oxidative stress and glutamate-induced neuronal injury, each of which is associated with neurocognitive dysfunction in infected individuals. Thus, therapies that rescue the HO-1 deficiency in HIV-infected individuals could provide additional neuroprotection to ART. PMID:26269184
Current lead natural products for the chemotherapy of human immunodeficiency virus (HIV) infection.
De Clercq, E
2000-09-01
A large variety of natural products have been described as anti-HIV agents, and for a portion thereof the target of interaction has been identified. Cyanovirin-N, a 11-kDa protein from Cyanobacterium (blue-green alga) irreversibly inactivates HIV and also aborts cell-to-cell fusion and transmission of HIV, due to its high-affinity interaction with gp120. Various sulfated polysaccharides extracted from seaweeds (i.e., Nothogenia fastigiata, Aghardhiella tenera) inhibit the virus adsorption process. Ingenol derivatives may inhibit virus adsorption at least in part through down-regulation of CD4 molecules on the host cells. Inhibition of virus adsorption by flavanoids such as (-)epicatechin and its 3-O-gallate has been attributed to an irreversible interaction with gp120 (although these compounds are also known as reverse transcriptase inhibitors). For the triterpene glycyrrhizin (extracted from the licorice root Glycyrrhiza radix) the mode of anti-HIV action may at least in part be attributed to interference with virus-cell binding. The mannose-specific plant lectins from Galanthus, Hippeastrum, Narcissus, Epipac tis helleborine, and Listera ovata, and the N-acetylgl ucosamine-specific lectin from Urtica dioica would primarily be targeted at the virus-cell fusion process. Various other natural products seem to qualify as HIV-cell fusion inhibitors: the siamycins [siamycin I (BMY-29304), siamycin II (RP 71955, BMY 29303), and NP-06 (FR901724)] which are tricyclic 21-amino-acid peptides isolated from Streptomyces spp that differ from one another only at position 4 or 17 (valine or isoleucine in each case); the betulinic acid derivative RPR 103611, and the peptides tachyplesin and polyphemusin which are highly abundant in hemocyte debris of the horseshoe crabs Tachypleus tridentatus and Limulus polyphemus, i.e., the 18-amino-acid peptide T22 from which T134 has been derived. Both T22 and T134 have been shown to block T-tropic X4 HIV-1 strains through a specific antagonism with the HIV corecept or CXCR4. A number of natural products have been reported to interact with the reverse transcriptase, i.e., baicalin, avarol, avarone, psychotrine, phloroglucinol derivatives, and, in particular, calanolides (from the tropical rainforest tree, Calophyllum lanigerum) and inophyllums (from the Malaysian tree, Calophyllum inophyllum). The natural marine substance illimaquinone would be targeted at the RNase H function of the reverse transcriptase. Curcumin (diferuloylmethane, from turmeric, the roots/rhizomes of Curcuma spp), dicaffeoylquinic and dicaffeoylt artaric acids, L-chicoric acid, and a number of fungal metabolites (equisetin, phomasetin, oteromycin, and integric acid) have all been proposed as HIV-1 integrase inhibitors. Yet, we have recently shown that L-c hicoric acid owes its anti-HIV activity to a specific interaction with the viral envelope gp120 rather than integrase. A number of compounds would be able to inhibit HIV-1 gene expression at the transcription level: the flavonoid chrysin (through inhibition of casein kinase II, the antibacter ial peptides melittin (from bee venom) and cecropin, and EM2487, a novel substance produced by Streptomyces. (ABSTRACT TRUNCATED)
Lamers, S L; Fogel, G B; Liu, E S; Nolan, D J; Salemi, M; Barbier, A E; Rose, R; Singer, E J; McGrath, M S
2017-07-01
HIV cure research is increasingly focused on anatomical tissues as sites for residual HIV replication during combined antiretroviral therapy (cART). Tissue-based HIV could contribute to low-level immune activation and viral rebound over the course of infection and could also influence the development of diseases, such as atherosclerosis, neurological disorders and cancers. cART-treated subjects have a decreased and irregular presence of HIV among tissues, which has resulted in a paucity of actual evidence concerning how or if HIV persists, replicates and evolves in various anatomical sites during therapy. In this study, we pooled 1806 HIV envelope V3 loop sequences from twenty-six tissue types (seventy-one total tissues) of six pre-cART subjects, four subjects with an unknown cART history who died with profound AIDS, and five subjects who died while on cART with an undetectable plasma viral load. A computational approach was used to assess sequences for their ability to utilize specific cellular coreceptors (R5, R5 and X4, or X4). We found that autopsied tissues obtained from virally suppressed cART+ subjects harbored both integrated and expressed viruses with similar coreceptor usage profiles to subjects with no or ineffective cART therapy (i.e., significant plasma viral load at death). The study suggests that tissue microenvironments provide a sanctuary for the continued evolution of HIV despite cART. Copyright © 2017 Elsevier B.V. All rights reserved.
McKay, Virginia R; Margaret Dolcini, M; Hoffer, Lee D
2017-12-01
Evidence-based intervention (EBI) de-adoption and its influence on public health organizations are largely unexplored within public health implementation research. However, a recent shift in support for HIV prevention EBIs by the Centers for Disease Control and Prevention provides an opportunity to explore EBI de-adoption. The current mixed-method study examines EBI de-adoption and the subsequent impact on a community-based organization (CBO) dedicated to HIV prevention. We conducted a case study with a CBO implementing RESPECT, an HIV prevention EBI, over 5 years (2010-2014), but then de-adopted the intervention. We collected archival data documenting RESPECT implementation and conducted two semi-structured interviews with RESPECT staff (N = 5). Using Fixsen and colleagues' implementation framework, we developed a narrative of RESPECT implementation, delivery, and de-adoption and a thematic analysis to understand additional consequences of RESPECT de-adoption. Discontinuation of RESPECT activities unfolded in a process over time, requiring effort by RESPECT staff. RESPECT de-adoption had wide-reaching influences on individual staff, interactions between the staff and the community, the agency overall, and for implementation of future EBIs. We propose a revision of the implementation framework, incorporating EBI de-adoption as a phase of the implementation cycle. Furthermore, EBI de-adoption may have important, unintended consequences and can inform future HIV prevention strategies and guide research focusing on EBI de-adoption.
Criminal law and HIV testing: empirical analysis of how at-risk individuals respond to the law.
Lee, Sun Goo
2014-01-01
This Note assesses the effect of laws that specifically criminalize behaviors that expose others to the human immunodeficiency virus (HIV). This Note examines the relationship between HIV testing decisions by high-risk individuals and the existence of these HIV-specific statutes, as well as the amount of media coverage related to them. One of the main reasons public health experts criticize criminalization of HIV-exposing behavior is that it may discourage at-risk individuals from undergoing HIV testing. This argument, however, remains empirically untested to date. This study quantitatively examines whether at-risk individuals living in jurisdictions with HIV-specific statutes are less likely to report having been tested for HIV in the past year compared to those living in jurisdictions without HIV-specific statutes. Regression analysis is conducted using data collected in the United States over a seven-year span. The results show that at-risk individuals residing in states with HIV-specific statutes are no less likely to report having been tested for HIV than those who live in other states. However, the number of people who reported that they had been tested for HIV is inversely correlated with the frequency of newspaper coverage of criminalization of HIV-exposing behavior. These findings imply that at-risk individuals' HIV testing is associated with media coverage of criminalizing HIV-exposing behavior. The negative impact that criminal law has on HIV testing rates could be a serious public health threat. Testing is often the initial step in public health interventions that most effectively modify the risky behavior of HIV-positive individuals. The adverse consequence of criminalization should weigh heavily in the design and application of criminal sanctions for HIV-exposing behavior. In addition, future research should further explore the relationships between criminalization, media coverage of criminalization, and HIV testing decisions for a more nuanced understanding of the consequences of criminalization.
Immunotherapy with an HIV-DNA Vaccine in Children and Adults
Palma, Paolo; Gudmundsdotter, Lindvi; Finocchi, Andrea; Eriksson, Lars E.; Mora, Nadia; Santilli, Veronica; Aquilani, Angela; Manno, Emma C.; Zangari, Paola; Romiti, Maria Luisa; Montesano, Carla; Grifoni, Alba; Brave, Andreas; Ljungberg, Karl; Blomberg, Pontus; Bernardi, Stefania; Sandström, Eric; Hejdeman, Bo; Rossi, Paolo; Wahren, Britta
2014-01-01
Therapeutic HIV immunization is intended to induce new HIV-specific cellular immune responses and to reduce viral load, possibly permitting extended periods without antiretroviral drugs. A multigene, multi-subtype A, B, C HIV-DNA vaccine (HIVIS) has been used in clinical trials in both children and adults with the aim of improving and broadening the infected individuals’ immune responses. Despite the different country locations, different regimens and the necessary variations in assays performed, this is, to our knowledge, the first attempt to compare children’s and adults’ responses to a particular HIV vaccine. Ten vertically HIV-infected children aged 4–16 years were immunized during antiretroviral therapy (ART). Another ten children were blindly recruited as controls. Both groups continued their antiretroviral treatment during and after vaccinations. Twelve chronically HIV-infected adults were vaccinated, followed by repeated structured therapy interruptions (STI) of their antiretroviral treatment. The adult group included four controls, receiving placebo vaccinations. The HIV-DNA vaccine was generally well tolerated, and no serious adverse events were registered in any group. In the HIV-infected children, an increased specific immune response to Gag and RT proteins was detected by antigen-specific lymphoproliferation. Moreover, the frequency of HIV-specific CD8+ T-cell lymphocytes releasing perforin was significantly higher in the vaccinees than the controls. In the HIV-infected adults, increased CD8+ T-cell responses to Gag, RT and viral protease peptides were detected. No augmentation of HIV-specific lymphoproliferative responses were detected in adults after vaccination. In conclusion, the HIV-DNA vaccine can elicit new HIV-specific cellular immune responses, particularly to Gag antigens, in both HIV-infected children and adults. Vaccinated children mounted transient new HIV-specific immune responses, including both CD4+ T-cell lymphoproliferation and late CD8+ T-cell responses. In the adult cohort, primarily CD8+ T-cell responses related to MHC class I alleles were noted. However, no clinical benefits with respect to viral load reduction were ascribable to the vaccinations alone. No severe adverse effects related to the vaccine were found in either cohort, and no virological failures or drug resistances were detected. PMID:26344746
Conformations of the HIV-1 protease: A crystal structure data set analysis.
Palese, Luigi Leonardo
2017-11-01
The HIV protease is an important drug target for HIV/AIDS therapy, and its structure and function have been extensively investigated. This enzyme performs an essential role in viral maturation by processing specific cleavage sites in the Gag and Gag-Pol precursor polyproteins so as to release their mature forms. This 99 amino acid aspartic protease works as a homodimer, with the active site localized in a central cavity capped by two flexible flap regions. The dimer presents closed or open conformations, which are involved in the substrate binding and release. Here the results of the analysis of a HIV-1 protease data set containing 552 dimer structures are reported. Different dimensionality reduction methods have been used in order to get information from this multidimensional database. Most of the structures in the data set belong to two conformational clusters. An interesting observation that comes from the analysis of these data is that some protease sequences are localized preferentially in specific areas of the conformational landscape of this protein. Copyright © 2017 Elsevier B.V. All rights reserved.
Wang, Chao; Li, Xue; Yu, Fei; Lu, Lu; Jiang, Xifeng; Xu, Xiaoyu; Wang, Huixin; Lai, Wenqing; Zhang, Tianhong; Zhang, Zhenqing; Ye, Ling; Jiang, Shibo; Liu, Keliang
2016-08-26
Peptides derived from the N-terminal heptad repeat (NHR) of HIV-1 gp41 can be potent inhibitors against viral entry when presented in a nonaggregating trimeric coiled-coil conformation via the introduction of exogenous trimerization motifs and intermolecular disulfide bonds. We recently discovered that crosslinking isopeptide bridges within the de novo helical trimers added exceptional resistance to unfolding. Herein, we attempted to optimize (CCIZN17)3, a representative disulfide bond-stabilized chimeric NHR-trimer, by incorporating site-specific interhelical isopeptide bonds as the redox-sensitive disulfide surrogate. In this process, we systematically examined the effect of isopeptide bond position and molecular sizes of auxiliary trimeric coiled-coil motif and NHR fragments on the antiviral potency of these NHR-trimers. Pleasingly, (IZ14N24N)3 possessed promising inhibitory activity against HIV-1 infection and markedly increased proteolytic stability relative to its disulfide-tethered counterpart, suggesting good potential for further development as an effective antiviral agent for treatment of HIV-1 infection.
Wang, Chao; Li, Xue; Yu, Fei; Lu, Lu; Jiang, Xifeng; Xu, Xiaoyu; Wang, Huixin; Lai, Wenqing; Zhang, Tianhong; Zhang, Zhenqing; Ye, Ling; Jiang, Shibo; Liu, Keliang
2016-01-01
Peptides derived from the N-terminal heptad repeat (NHR) of HIV-1 gp41 can be potent inhibitors against viral entry when presented in a nonaggregating trimeric coiled-coil conformation via the introduction of exogenous trimerization motifs and intermolecular disulfide bonds. We recently discovered that crosslinking isopeptide bridges within the de novo helical trimers added exceptional resistance to unfolding. Herein, we attempted to optimize (CCIZN17)3, a representative disulfide bond-stabilized chimeric NHR-trimer, by incorporating site-specific interhelical isopeptide bonds as the redox-sensitive disulfide surrogate. In this process, we systematically examined the effect of isopeptide bond position and molecular sizes of auxiliary trimeric coiled-coil motif and NHR fragments on the antiviral potency of these NHR-trimers. Pleasingly, (IZ14N24N)3 possessed promising inhibitory activity against HIV-1 infection and markedly increased proteolytic stability relative to its disulfide-tethered counterpart, suggesting good potential for further development as an effective antiviral agent for treatment of HIV-1 infection. PMID:27562370
Ahuja, Sunil K; Kulkarni, Hemant; Catano, Gabriel; Agan, Brian K; Camargo, Jose F; He, Weijing; O'Connell, Robert J; Marconi, Vincent C; Delmar, Judith; Eron, Joseph; Clark, Robert A; Frost, Simon; Martin, Jeffrey; Ahuja, Seema S; Deeks, Steven G; Little, Susan; Richman, Douglas; Hecht, Frederick M; Dolan, Matthew J
2008-01-01
The basis for the extensive variability seen in the reconstitution of CD4+ T cell counts in HIV-infected individuals receiving highly active antiretroviral therapy (HAART) is not fully known. Here, we show that variations in CCL3L1 gene dose and CCR5 genotype, but not major histocompatibility complex HLA alleles, influence immune reconstitution, especially when HAART is initiated at <350 CD4+ T cells/mm3. The CCL3L1-CCR5 genotypes favoring CD4+ T cell recovery are similar to those that blunted CD4+ T cell depletion during the time before HAART became available (pre-HAART era), suggesting that a common CCL3L1-CCR5 genetic pathway regulates the balance between pathogenic and reparative processes from early in the disease course. Hence, CCL3L1-CCR5 variations influence HIV pathogenesis even in the presence of HAART and, therefore, may prospectively identify subjects in whom earlier initiation of therapy is more likely to mitigate immunologic failure despite viral suppression by HAART. Furthermore, as reconstitution of CD4+ cells during HAART is more sensitive to CCL3L1 dose than to CCR5 genotypes, CCL3L1 analogs might be efficacious in supporting immunological reconstitution. PMID:18376407
Lapinski, Maria Knight; Randall, Liisa M; Peterson, Mark; Peterson, Amy; Klein, Katherine A
2009-09-01
This article reports the results of a small-scale quasi-experiment that tested the efficacy of the Prevention Options for Positives intervention. The experiment tested for the outcomes of group sessions combined with individual-level counseling (ILC) versus ILC-only for men who have sex with men who are HIV positive. Both arms of the intervention were based on behavior change theory and dealt specifically with communication outcomes. The results indicate that the group- and individual-level interventions combined have a greater impact on risk communication behaviors with main partners than did the ILC-only sessions. group-session/ILC participants were more likely to decide not to have sex if they were drunk or high, and more likely to tell their partner and ask their partner about HIV status than were participants in the ILC groups. Knowledge about HIV was relatively high, and there was little change across groups. The Prevention Options for Positives intervention influenced the relative importance of various referent groups, but normative beliefs were not affected. The implications of these findings for communication practice and research with HIV-positive men who have sex with men are addressed.
Williams, John K; Glover, Dorie A; Wyatt, Gail E; Kisler, Kimberly; Liu, Honghu; Zhang, Muyu
2013-08-01
HIV transmission risk is high among men who have sex with men and women (MSMW), and it is further heightened by a history of childhood sexual abuse (CSA) and current traumatic stress or depression. Yet, traumatic stress is rarely addressed in HIV interventions. We tested a stress-focused sexual risk reduction intervention for African American MSMW with CSA histories. This randomized controlled trial compared a stress-focused sexual risk reduction intervention with a general health promotion intervention. Sexual risk behaviors, psychological symptoms, stress biomarkers (urinary cortisol and catecholamines), and neopterin (an indicator of HIV progression) were assessed at baseline and at 3- and 6-month follow-ups. Both interventions decreased and sustained reductions in sexual risk and psychological symptoms. The stress-focused intervention was more efficacious than the general health promotion intervention in decreasing unprotected anal insertive sex and reducing depression symptoms. Despite randomization, baseline group differences in CSA severity, psychological symptoms, and biomarkers were found and linked to subsequent intervention outcomes. Although interventions designed specifically for HIV-positive African American MSMW can lead to improvements in health outcomes, future research is needed to examine factors that influence intervention effects.
Parker, Caroline M; Garcia, Jonathan; Philbin, Morgan M; Wilson, Patrick A; Parker, Richard G; Hirsch, Jennifer S
2017-03-01
Black men who have sex with men in the USA face disproportionate incidence rates of HIV. This paper presents findings from an ethnographic study conducted in New York City that explored the structural and socio-cultural factors shaping men's sexual relationships with the goal of furthering understandings of their HIV-related vulnerability. Methods included participant observation and in-depth interviews with 31 Black men who have sex with men (three times each) and 17 key informants. We found that HIV vulnerability is perceived as produced through structural inequalities including economic insecurity, housing instability, and stigma and discrimination. The theoretical concepts of social risk, intersectional stigma, and the social production of space are offered as lenses through which to analyse how structural inequalities shape HIV vulnerability. We found that social risk shaped HIV vulnerability by influencing men's decisions in four domains: 1) where to find sexual partners, 2) where to engage in sexual relationships, 3) what kinds of relationships to seek, and 4) whether to carry and to use condoms. Advancing conceptualisations of social risk, we show that intersectional stigma and the social production of space are key processes through which social risk generates HIV vulnerability among Black men who have sex with men.
Parker, Caroline M.; Garcia, Jonathan; Philbin, Morgan M.; Wilson, Patrick A.; Parker, Richard G.; Hirsch, Jennifer S.
2017-01-01
Black men who have sex with men in the USA face disproportionate incidence rates of HIV. This paper presents findings from an ethnographic study conducted in New York City that explored the structural and socio-cultural factors shaping men’s sexual relationships with the goal of furthering understandings of their HIV-related vulnerability. Methods included participant observation and in-depth interviews with 31 Black men who have sex with men (three times each) and 17 key informants. We found that HIV vulnerability is perceived as produced through structural inequalities including economic insecurity, housing instability, and stigma and discrimination. The theoretical concepts of social risk, intersectional stigma, and the social production of space are offered as lenses through which to analyse how structural inequalities shape HIV vulnerability. We found that social risk shaped HIV vulnerability by influencing men’s decisions in four domains: 1) where to find sexual partners, 2) where to engage in sexual relationships, 3) what kinds of relationships to seek, and 4) whether to carry and to use condoms. Advancing conceptualisations of social risk, we show that intersectional stigma and the social production of space are key processes through which social risk generates HIV vulnerability among Black men who have sex with men. PMID:27550415
Bekalu, Mesfin Awoke; Eggermont, Steven; Viswanath, K Vish
2017-06-01
Three-and-a-half decades on, no cure or vaccine is yet on the horizon for HIV, making effective behavior change communication (BCC) the key preventive strategy. Despite considerable success, HIV/AIDS BCC efforts have long been criticized for their primary focus on the individual-level field of influence, drawing on the more reductionist view of causation at the individual level. In view of this, we conducted a series of studies that employed a household survey, field experiment, and textual content analysis, and explored the macro-social-level effects of HIV/AIDS-related media and messages on HIV/AIDS cognitive and affective outcomes in Ethiopia. Against a backdrop of epidemiological and socioecological differences, urban versus rural residence has emerged as an important community-level factor that impacts HIV/AIDS-related media and message consumption processes and associated outcomes. The central thread crossing through the six studies included in this paper demonstrates that urban and rural people in high HIV prevalence contexts differ in their concern about and information needs on HIV/AIDS, HIV/AIDS-related media use, and HIV/AIDS-related cognitive and affective outcomes, as well as in their reaction to differently designed/framed HIV prevention messages. This paper proposes that HIV prevention media and message effects in high epidemic situations should be considered from a larger community-level perspective and calls for a socioecological approach to AIDS communication in the hard-hit sub-Saharan Africa. With a number of concrete recommendations to current and future HIV/AIDS BCC efforts in the region, the study joins an emerging body of health communication literature and theorizing that suggests the need to consider media and message effects from a macro-social perspective.
The Influence of Community Context on How Coalitions Achieve HIV-Preventive Structural Change
ERIC Educational Resources Information Center
Reed, Sarah J.; Miller, Robin Lin; Francisco, Vincent T.
2014-01-01
Community coalition action theory (CCAT) depicts the processes and factors that affect coalition formation, maintenance, institutionalization, actions, and outcomes. CCAT proposes that community context affects coalitions at every phase of development and operation. We analyzed data from 12 "Connect to Protect" coalitions using inductive…
Francica, Joseph R; Sheng, Zizhang; Zhang, Zhenhai; Nishimura, Yoshiaki; Shingai, Masashi; Ramesh, Akshaya; Keele, Brandon F; Schmidt, Stephen D; Flynn, Barbara J; Darko, Sam; Lynch, Rebecca M; Yamamoto, Takuya; Matus-Nicodemos, Rodrigo; Wolinsky, David; Nason, Martha; Valiante, Nicholas M; Malyala, Padma; De Gregorio, Ennio; Barnett, Susan W; Singh, Manmohan; O'Hagan, Derek T; Koup, Richard A; Mascola, John R; Martin, Malcolm A; Kepler, Thomas B; Douek, Daniel C; Shapiro, Lawrence; Seder, Robert A
2015-04-10
Developing predictive animal models to assess how candidate vaccines and infection influence the ontogenies of Envelope (Env)-specific antibodies is critical for the development of an HIV vaccine. Here we use two nonhuman primate models to compare the roles of antigen persistence, diversity and innate immunity. We perform longitudinal analyses of HIV Env-specific B-cell receptor responses to SHIV(AD8) infection and Env protein vaccination with eight different adjuvants. A subset of the SHIV(AD8)-infected animals with higher viral loads and greater Env diversity show increased neutralization associated with increasing somatic hypermutation (SHM) levels over time. The use of adjuvants results in increased ELISA titres but does not affect the mean SHM levels or CDR H3 lengths. Our study shows how the ontogeny of Env-specific B cells can be tracked, and provides insights into the requirements for developing neutralizing antibodies that should facilitate translation to human vaccine studies.
Broadly neutralizing antibody specificities detected in the genital tract of HIV-1 infected women.
Mkhize, Nonhlanhla N; Durgiah, Raveshni; Ashley, Vicki; Archary, Derseree; Garrett, Nigel J; Karim, Quarraisha Abdool; Karim, Salim S Abdool; Moore, Penny L; Yates, Nicole; Passmore, Jo-Ann S; Tomaras, Georgia D; Morris, Lynn
2016-04-24
Broadly neutralizing antibodies (bNAbs) targeting conserved epitopes on the HIV envelope glycoprotein have been identified in blood from HIV-1 infected women. We investigated whether antibodies in the genital tract from these women share similar epitope specificities and functional profiles as those in blood. Immunoglobulin (Ig)G and IgA antibodies were isolated from cervicovaginal lavages or Softcups from 13 HIV-infected women in the CAPRISA cohort using Protein G and Peptide M, respectively. Binding antibodies to envelope antigens were quantified by ELISA and binding antibody multiplex assay. Neutralizing antibody titers and epitope targets were measured using the TZM-bl assay with Env-pseudotyped wild-type and mutated viruses. HIV-specific IgG, but not IgA, was detected in genital secretions and the ratio of total IgG to HIV-specific IgG was similar to plasma. HIV-specific IgG reacted with multiple envelope antigens, including V1V2, gp120, gp140 and gp41. Two women had high plasma titers of HIV-specific IgG3 which was also detected in their genital tract samples. IgG from the genital tract had neutralizing activity against both Tier 1 and Tier 2 primary HIV-isolates. Antibodies targeting well known glycan epitopes and the membrane proximal region of gp41 were detected in genital secretions, and matched specificities in plasma. Women with plasma bNAbs have overlapping specificities in their genital secretions, indicating that these predominantly IgG isotype antibodies may transudate from blood to the genital tract. These data provide evidence that induction of systemic HIV-specific bNAbs can lead to antiviral immunity at the portal of entry.
Alcohol and HIV Effects on the Immune System
Bagby, Gregory J.; Amedee, Angela M.; Siggins, Robert W.; Molina, Patricia E.; Nelson, Steve; Veazey, Ronald S.
2015-01-01
HIV disease and alcohol independently influence the human immune system, so it stands to reason that, together, their influence may be additive. Here, we review the evidence that alcohol can exacerbate HIV’s influence on the immune system, thereby affecting disease progression and transmission. We focus particularly on alcohol’s effect on the mucosal immune system in the tissues of the gastrointestinal tract, the genital tract and the lungs, all of which play a role in transmission and progression of HIV disease. PMID:26695751
Brawner, Bridgette M; Jemmott, Loretta Sweet; Wingood, Gina; Reason, Janaiya; Mack, Niya
Heterosexually active Black adolescents with mental illnesses are at increased risk for sexually transmitted infections (STIs), including HIV. However, few HIV/STI prevention interventions exist for this demographic. We held seven focus groups (N = 33) to elucidate social, cultural, and psychological factors that influence HIV/STI risk-related sexual behaviors in this understudied population. Seven themes emerged: (a) Blackness and media portrayals, (b) Blackness as a source of cultural resilience and pride, (c) psychosocial determinants of condom use, (d) consequences of engaging in sexual activity, (e) attitudes and beliefs toward sexual behaviors, (f) benefits of sexual activity, and (g) coping mechanisms. Participants also supported the feasibility of and interest in HIV/STI prevention programs integrated with mental health treatment. Transportation, potential breaches of confidentiality, and time were noted barriers to participation. Psychoeducational, skills-based programs are needed to address the sequelae of mental illnesses as they relate to the sexual decision-making process in adolescents. Copyright © 2017 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.
HIV/AIDS Risk and Prevention Issues Among Inuit Living in Nunavut Territory of Canada.
Kumar, Alexander
HIV infections occur across the Arctic but their incidence among aboriginal populations varies vastly. At the time this research was initiated there were no data on their occurrence, risk of HIV/AIDS or preventive strategies among Inuit living in the Nunavut territory of Canada. This review is the first to assess the risk of HIV infection among Inuit and evaluate current prevention strategies among Canadian-Inuit populations. The contents of this article are based on the author's own research, undertaken during 3 visits to the Canadian Arctic and the published literature. Disproportionately high rates of Chlamydia and Gonorrhoea within Inuit communities confirm the potential threat of silent HIV transmission. Inuit awareness of HIV/AIDS issues remains inadequate. It is easy to blame distorted perceptions fuelled by the media, religious influence and socio-cultural factors. Aboriginal and Inuit groups, including youth, women and injection drug abusers are at increased risk of infection. The adaptability of proven prevention methods including condom use and male circumcision are discussed. Access to treatment, adherence and resistance issues in the North Canada, require attention. HIV/AIDS poses a considerable threat to Canadian Inuit public health. The most important problem to be addressed is Inuit lack of awareness and understanding of HIV. Education is the single most effective means of prevention. Inuit-specific and culture-sensitive interventions are recommended. Further research opportunities exist to investigate Inuit understanding over HIV/AIDS issues and to assess local prevention efforts. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
Auerbach, Judith D; Smith, Laramie R
2015-06-01
Although substance use continues to be a significant component of HIV risk among women worldwide, to date, relatively little attention has been paid in research, services, or policy to substance-involved women (SIW). HIV acquisition for SIW stems from transmission risks directly related to substance use and risks associated with sexual activity in which power to negotiate risk and safety are influenced by dynamics of male partnerships, sex work, and criminalization (of both drug use and sex work), among other factors. As such, HIV risk for SIW resides as much in the environment—physical, social, cultural, economic, and political—in which drug use occurs as it does from transmission-related behaviors of individual women. To reduce HIV infections among SIW, it is important to specify the interaction of individual- and environmental-level factors, including, but not limited to those related to women's own substance use, that can and ought to be changed. This involves theorizing about the interplay of gender, substance use, and HIV risk, and incorporating that theoretical understanding into intervention design and evaluation. A review of the published literature focused on HIV prevention among SIW revealed a general lack of theoretical and conceptual foundation specific to the gender-related and environmental drivers of HIV in this population. Greater theoretical linkages to intersectionality and syndemic approaches are recommended to better identify and target relevant mechanisms by which the interplay of gender dynamics and substance use potentiate the likelihood of HIV acquisition and transmission among SIW.
HIV-1 concentrations in human breast milk before and after weaning
Kuhn, Louise; Kim, Hae-Young; Walter, Jan; Thea, Donald M.; Sinkala, Moses; Mwiya, Mwiya; Kankasa, Chipepo; Decker, Don; Aldrovandi, Grace M.
2015-01-01
Concentrations of HIV-1 RNA and DNA in mucosal compartments influence the risk of sexual transmission and mother-to-child transmission of HIV-1. Breast milk production is physiologically regulated such that supply is a function of infant demand but whether demand also influences HIV-1 dynamics in breast milk is unknown. We tested whether minor and major changes in feeding frequency influence breast milk viral concentrations in 958 HIV-1-infected women, who were followed with their infants for 24 months as part of a trial in Lusaka, Zambia. Women were randomized to wean abruptly at 4 months or to continue breastfeeding for a duration of their own choosing. Two weeks after breastfeeding cessation i.e. weaning (4.5 months) HIV-1 concentrations in breast milk were substantially higher (median RNA 2,708 copies/ml and DNA 14 copies/ml) than if breastfeeding continued (median RNA <50 copies/ml and DNA <1 copy/ml, p<0.0001). Among those continuing breastfeeding, HIV-1 concentrations in milk were higher if breastfeeding was non-exclusive (median RNA 293 copies/ml and DNA 2 copies/ml, p=0.0006). Elevated milk viral concentrations after stopping breastfeeding explained higher than expected rates of late postnatal HIV transmission in those who weaned early. Changes in the frequency of breastfeeding peri-weaning and with non-exclusive breastfeeding influenced milk viral concentrations. This may explain the reduced risk of HIV-1 transmission associated with exclusive breastfeeding and may explain why early weaning does not achieve the magnitude of HIV prevention predicted by models. Our results support continuation of maternal antiretroviral drug interventions over the full duration of time when any breast milk exposures are likely to occur after planned weaning. PMID:23596203
Zhou, Tao; Dang, Ying; Zheng, Yong-Hui
2014-03-01
The HIV-1 Env glycoprotein is folded in the endoplasmic reticulum (ER), which is necessary for viral entry and replication. Currently, it is still unclear how this process is regulated. The glycoprotein folding in the ER is controlled by the ER-associated protein degradation (ERAD) pathway, which specifically targets misfolded proteins for degradation. Previously, we reported that HIV-1 replication is restricted in the human CD4(+) T cell line CEM.NKR (NKR). To understand this mechanism, we first analyzed cellular protein expression in NKR cells and discovered that levels of the mitochondrial translocator protein TSPO were upregulated by ∼64-fold. Notably, when NKR cells were treated with TSPO antagonist PK-11195, Ro5-4864, or diazepam, HIV restriction was completely disrupted, and TSPO knockdown by short hairpin RNAs (shRNAs) achieved a similar effect. We next analyzed viral protein expression, and, interestingly, we discovered that Env expression was specifically inhibited. Both TSPO knockdown and treatment with TSPO antagonist could restore Env expression in NKR cells. We further discovered that Env proteins were rapidly degraded and that kifunensine, an ERAD pathway inhibitor, could restore Env expression and viral replication, indicating that Env proteins were misfolded and degraded through the ERAD pathway in NKR cells. We also knocked out the TSPO gene in 293T cells using CRISPR/Cas9 (clustered, regularly interspaced, short palindromic repeat [CRISPR]/CRISPR-associated-9) technology and found that TSPO could similarly inhibit Env expression in these cells. Taken together, these results demonstrate that TSPO inhibits Env protein expression through the ERAD pathway and suggest that mitochondria play an important role in regulating the Env folding process. The HIV-1 Env glycoprotein is absolutely required for viral infection, and an understanding of its expression pathway in infected cells will identify new targets for antiretroviral therapies. Env proteins are folded in the ER and secreted through the classical secretory pathway. The Env folding process involves extensive cross-linking of 10 Cys residues by disulfide bond formation and heavy N-glycosylation on ∼30 Asn residues. Currently, it is still unclear how this process is regulated. Here, we studied this mechanism in the HIV nonpermissive human CD4(+) T cell line CEM.NKR. We found that Env proteins were rapidly degraded through a cellular pathway that specifically targets misfolded proteins, resulting in inhibition of Env expression. Importantly, we have identified a mitochondrial translocator protein, TSPO, which could trigger this degradation by interfering with the Env folding process. Further characterization of TSPO antiviral activity will reveal a novel antiretroviral mechanism that targets the Env protein.
Exploring sexual risk taking among American Indian adolescents through protection motivation theory.
Chambers, Rachel; Tingey, Lauren; Mullany, Britta; Parker, Sean; Lee, Angelita; Barlow, Allison
2016-09-01
This paper examines decision-making around sexual behavior among reservation-based American Indian youth. Focus group discussions were conducted with youth ages 13-19 years old. Through these discussions, we explored youth's knowledge, attitudes and behaviors related to sexual risk taking through the lens of the protection motivation theory to inform the adaptation of an evidence-based HIV prevention intervention. Findings suggest that condom use self-efficacy and HIV prevention knowledge is low, vulnerability to sexually transmitted infections is lacking and alcohol plays a significant role in sexual risk taking in this population. In addition, parental monitoring and peer influence may contribute to or protect against sexual risk taking. Results suggest that future HIV prevention interventions should be delivered to gender-specific peer groups, include a parental component, teach sexual health education and communication skills, integrate substance-use prevention, and work to remove stigma around obtaining and using condoms.
The response of religious congregations to the spiritual needs of people living with HIV/AIDS.
Somlai, A M; Heckman, T G; Kelly, J A; Mulry, G W; Multhauf, K E
1997-01-01
Investigates the perceptions and responses of members of five diverse religious congregations to the spiritual needs of people living with AIDS, the impact of AIDS on membership participation, and the beliefs held by different congregations regarding AIDS. Evaluates and compares the AIDS-related perceptions of 204 participants in five congregations (Buddhists, Catholic, Fundamental Christians, Protestants, and Unitarians). Results indicated that congregations differed in how their members responded to the spiritual needs of people living with HIV/AIDS, the level of influence AIDS had on membership participation in formal religions, and whether AIDS was seen as the result of sinful behavior or divine retribution. Concludes that the congregational differences appeared consistent with the core beliefs of the faith communities. Suggests that clergy and congregations need to take specific steps to provide spiritual support to people living with HIV/AIDS consistent with their history of caregiving to all people regardless of the crisis situation.
Leddy, Anna M; Kerrigan, Deanna; Kennedy, Caitlin E; Mbwambo, Jessie; Likindikoki, Samuel; Underwood, Carol R
2018-03-16
Female sex workers experience high rates of gender-based violence and HIV. Alcohol has been shown to facilitate women's risk of both gender-based violence and HIV; however, little research has explored how aspects of the sex work environment shape this risk. Drawing on structuration theory, this study explored how social conduct is patterned across time and space within the sex work environment to influence alcohol consumption, gender-based violence and HIV risk among female sex workers. Qualitative in-depth interviews were conducted with 24 female sex workers enrolled in an ongoing community randomised controlled trial of a combination HIV prevention intervention in Iringa, Tanzania. Data were analysed using both inductive and deductive approaches. Findings reveal how routine interactions between female sex workers and their clients occur at three moments of time and space during the sex exchange process to facilitate alcohol consumption and increase women's risk of gender-based violence and HIV. Findings also highlight how sex workers utilise collective agency to address aspects of the sex work environment that place them at risk of alcohol abuse, gender-based violence and HIV. Implications for future interventions to prevent gender-based violence and HIV among female sex workers in Tanzania and similar contexts are discussed.
Pan, Xin; Zhang, Alice; Henderson, Gail E; Rennie, Stuart; Liu, Chuncheng; Cai, Weiping; Wu, Feng; Tucker, Joseph D
2017-12-13
Traditional, complementary, and alternative medicine (TCAM) has been used by some people living with HIV (PLHIV) in an attempt to cure HIV. This article reviews the main factors influencing their decision to choose TCAM to cure HIV and discusses implications for HIV cure research. Those who decide to pursue traditional, complementary, and alternative medical cures may be influenced by the health system, cultural, and social dynamics, and their own individual beliefs and preferences. These same factors may impact participation in HIV cure research. People who search for traditional, complementary, and alternative medical cures may face special challenges as they are recruited, consented, and retained within HIV cure research studies. To address these potential challenges, we have suggested solutions focusing on culturally tailored communication and education, formative social science research, and community partnerships with key stakeholders. The social conditions that have promoted traditional, complementary and alternative medical cures will likely impact how PLHIV participate and experience HIV remission trials. Despite the potential challenges, it will be crucial to involve those who have previously sought out traditional cures for HIV in HIV cure research.
Kaida, Angela; Laher, Fatima; Strathdee, Steffanie A.; Money, Deborah; Janssen, Patricia A.; Hogg, Robert S.; Gray, Glenda
2010-01-01
Objective Preventing unintended pregnancy among HIV-positive women constitutes a critical and cost-effective approach to primary prevention of mother-to-child transmission of HIV and is a global public health priority for addressing the desperate state of maternal and child health in HIV hyper-endemic settings. We sought to investigate whether the prevalence of contraceptive use and method preferences varied by HIV status and receipt of highly active antiretroviral therapy (HAART) among women in Soweto, South Africa. Methods We used survey data from 563 sexually active, non-pregnant women (18–44 years) recruited from the Perinatal HIV Research Unit in Soweto (May–December, 2007); 171 women were HIV-positive and receiving HAART (median duration of use = 31 months; IQR = 28, 33), 178 were HIV-positive and HAART-naïve, and 214 were HIV-negative. Medical record review was conducted to confirm HIV status and clinical variables. Logistic regression models estimated adjusted associations between HIV status, receipt of HAART, and contraceptive use. Results Overall, 78% of women reported using contraception, with significant variation by HIV status: 86% of HAART users, 82% of HAART-naïve women, and 69% of HIV-negative women (p<0.0001). In adjusted models, compared with HIV-negative women, women receiving HAART were significantly more likely to use contraception while HAART-naïve women were non-significantly more likely (AOR: 2.40; 95% CI: 1.25, 4.62 and AOR: 1.59; 95% CI: 0.88, 2.85; respectively). Among HIV-positive women, HAART users were non-significantly more likely to use contraception compared with HAART-naïve women (AOR: 1.55; 95% CI: 0.84, 2.88). Similar patterns held for specific use of barrier (primarily male condoms), permanent, and dual protection contraceptive methods. Conclusion Among HIV-positive women receiving HAART, the observed higher prevalence of contraceptive use overall and condoms in particular promises to yield fewer unintended pregnancies and reduced risks of vertical and sexual HIV transmission. These findings highlight the potential of integrated HIV and reproductive health services to positively impact maternal, partner, and child health. PMID:21079770
Kaida, Angela; Laher, Fatima; Strathdee, Steffanie A; Money, Deborah; Janssen, Patricia A; Hogg, Robert S; Gray, Glenda
2010-11-05
Preventing unintended pregnancy among HIV-positive women constitutes a critical and cost-effective approach to primary prevention of mother-to-child transmission of HIV and is a global public health priority for addressing the desperate state of maternal and child health in HIV hyper-endemic settings. We sought to investigate whether the prevalence of contraceptive use and method preferences varied by HIV status and receipt of highly active antiretroviral therapy (HAART) among women in Soweto, South Africa. We used survey data from 563 sexually active, non-pregnant women (18-44 years) recruited from the Perinatal HIV Research Unit in Soweto (May-December, 2007); 171 women were HIV-positive and receiving HAART (median duration of use = 31 months; IQR = 28, 33), 178 were HIV-positive and HAART-naïve, and 214 were HIV-negative. Medical record review was conducted to confirm HIV status and clinical variables. Logistic regression models estimated adjusted associations between HIV status, receipt of HAART, and contraceptive use. Overall, 78% of women reported using contraception, with significant variation by HIV status: 86% of HAART users, 82% of HAART-naïve women, and 69% of HIV-negative women (p<0.0001). In adjusted models, compared with HIV-negative women, women receiving HAART were significantly more likely to use contraception while HAART-naïve women were non-significantly more likely (AOR: 2.40; 95% CI: 1.25, 4.62 and AOR: 1.59; 95% CI: 0.88, 2.85; respectively). Among HIV-positive women, HAART users were non-significantly more likely to use contraception compared with HAART-naïve women (AOR: 1.55; 95% CI: 0.84, 2.88). Similar patterns held for specific use of barrier (primarily male condoms), permanent, and dual protection contraceptive methods. Among HIV-positive women receiving HAART, the observed higher prevalence of contraceptive use overall and condoms in particular promises to yield fewer unintended pregnancies and reduced risks of vertical and sexual HIV transmission. These findings highlight the potential of integrated HIV and reproductive health services to positively impact maternal, partner, and child health.
Latest animal models for anti-HIV drug discovery.
Sliva, Katja
2015-02-01
HIV research is limited by the fact that lentiviruses are highly species specific. The need for appropriate models to promote research has led to the development of many elaborate surrogate animal models. This review looks at the history of animal models for HIV research. Although natural animal lentivirus infections and chimeric viruses such as chimera between HIV and simian immunodeficiency virus and simian-tropic HIV are briefly discussed, the main focus is on small animal models, including the complex design of the 'humanized' mouse. The review also traces the historic evolution and milestones as well as depicting current models and future prospects for HIV research. HIV research is a complex and challenging task that is highly manpower-, money- and time-consuming. Besides factors such as hypervariability and latency, the lack of appropriate animal models that exhibit and recapitulate the entire infectious process of HIV, is one of the reasons behind the failure to eliminate the lentivirus from the human population. This obstacle has led to the exploitation and further development of many sophisticated surrogate animal models for HIV research. While there is no animal model that perfectly mirrors and mimics HIV infections in humans, there are a variety of host species and viruses that complement each other. Combining the insights from each model, and critically comparing the results obtained with data from human clinical trials should help expand our understanding of HIV pathogenesis and drive future drug development.
Maintenance of HIV-Specific Memory B-Cell Responses in Elite Controllers Despite Low Viral Burdens.
Buckner, Clarisa M; Kardava, Lela; Zhang, Xiaozhen; Gittens, Kathleen; Justement, J Shawn; Kovacs, Colin; McDermott, Adrian B; Li, Yuxing; Sajadi, Mohammad M; Chun, Tae-Wook; Fauci, Anthony S; Moir, Susan
2016-08-01
Human immunodeficiency virus (HIV)-specific B-cell responses in infected individuals are maintained by active HIV replication. Suppression of viremia by antiretroviral therapy (ART) leads to quantitative and qualitative changes that remain unclear. Accordingly, B-cell responses were investigated in elite controllers (ECs), who maintain undetectable HIV levels without ART, and in individuals whose viremia was suppressed by ART. Despite a higher HIV burden in the ART group, compared with the EC group, frequencies of HIV-specific B cells were higher in the EC group, compared with those in the ART group. However, the initiation of ART in several ECs was associated with reduced frequencies of HIV-specific B cells, suggesting that responses are at least in part sustained by HIV replication. Furthermore, B-cell responses to tetanus toxin but not influenza hemagglutinin in the ART group were lower than those in the EC group. Thus, the superior HIV-specific humoral response in ECs versus ART-treated individuals is likely due to a more intact humoral immune response in ECs and/or distinct responses to residual HIV replication. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Qian, Yi-Wen; Li, Chuan; Jiang, Ai-Ping; Ge, Shengfang; Gu, Ping; Fan, Xianqun; Li, Tai-Sheng; Jin, Xia; Wang, Jian-Hua; Wang, Zhi-Liang
2016-10-28
Approximately 70% of HIV-1 infected patients acquire ocular opportunistic infections and manifest eye disorders during the course of their illness. The mechanisms by which pathogens invade the ocular site, however, are unclear. Under normal circumstances, vascular endothelium and retinal pigment epithelium (RPE), which possess a well developed tight junction complex, form the blood-retinal barrier (BRB) to prevent pathogen invasion. We hypothesize that disruption of the BRB allows pathogen entry into ocular sites. The hypothesis was tested using in vitro models. We discovered that human RPE cells could bind to either HIV-1 gp120 glycoproteins or HIV-1 viral particles. Furthermore, the binding was mediated by dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) expressed on RPE cells. Upon gp120 binding to DC-SIGN, cellular NF-κB signaling was triggered, leading to the induction of matrix metalloproteinases, which subsequently degraded tight junction proteins and disrupted the BRB integrity. DC-SIGN knockdown or prior blocking with a specific antibody abolished gp120-induced matrix metalloproteinase expression and reduced the degradation of tight junction proteins. This study elucidates a novel mechanism by which HIV, type 1 invades ocular tissues and provides additional insights into the translocation or invasion process of ocular complication-associated pathogens. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Lin, Ying-Chuan; Perryman, Alexander L.; Olson, Arthur J.; Torbett, Bruce E.; Elder, John H.; Stout, C. David
2011-01-01
A chimeric feline immunodeficiency virus (FIV) protease (PR) has been engineered that supports infectivity but confers sensitivity to the human immunodeficiency virus (HIV) PR inhibitors darunavir (DRV) and lopinavir (LPV). The 6s-98S PR has five replacements mimicking homologous residues in HIV PR and a sixth which mutated from Pro to Ser during selection. Crystal structures of the 6s-98S FIV PR chimera with DRV and LPV bound have been determined at 1.7 and 1.8 Å resolution, respectively. The structures reveal the role of a flexible 90s loop and residue 98 in supporting Gag processing and infectivity and the roles of residue 37 in the active site and residues 55, 57 and 59 in the flap in conferring the ability to specifically recognize HIV PR drugs. Specifically, Ile37Val preserves tertiary structure but prevents steric clashes with DRV and LPV. Asn55Met and Val59Ile induce a distinct kink in the flap and a new hydrogen bond to DRV. Ile98Pro→Ser and Pro100Asn increase 90s loop flexibility, Gln99Val contributes hydrophobic contacts to DRV and LPV, and Pro100Asn forms compensatory hydrogen bonds. The chimeric PR exhibits a comparable number of hydrogen bonds, electrostatic interactions and hydrophobic contacts with DRV and LPV as in the corresponding HIV PR complexes, consistent with IC50 values in the nanomolar range. PMID:21636894
ERIC Educational Resources Information Center
Burnett, Audrey J.; Sabato, Todd M.; Walter, Katherine Ott; Kerr, Dianne L.; Wagner, Laurie; Smith, Amy
2013-01-01
HIV, AIDS, STIs, and unwanted pregnancy continue to impact young adults in the U.S. at a disproportionate rate, particularly during the college years. Attributional style (i.e., locus of control) influences one's HIV risk. Internal locus of control indicates a lower risk of HIV infection, whereas an external locus of control signals an increased…
ERIC Educational Resources Information Center
Burnett, Audrey J.; Sabato, Todd M.; Wagner, Laurie; Smith, Amy
2014-01-01
HIV, AIDS, STIs, and unwanted pregnancy continue to impact young adults in the U. S. at a disproportionate rate, particularly during the college years. Attributional style (i.e., locus of control) influences one's HIV risk. Internal locus of control indicates a lower risk of HIV infection, whereas external locus of control signals an…
Lambdin, Barrot; Kanweka, William; Inambao, Mubiana; Mwananyanda, Lawrence; Shah, Heena; Linton, Sabriya; Wong, Frank; Luisi, Nicole; Tichacek, Amanda; Kalowa, James; Chomba, Elwyn; Allen, Susan
2011-01-01
Couples in sub-Saharan Africa are the largest group in the world at risk for HIV infection. Couples counseling and testing programs have been shown to reduce HIV transmission, but such programs remain rare in Africa. Before couples counseling and testing can become the norm, it is essential to increase demand for the services. We evaluated the effectiveness of several promotional strategies during a two -year program in Kitwe and Ndola, Zambia. The program attracted more than 7,600 couples through the use of radio broadcasts, billboards, and other strategies. The most effective recruiting technique was the use of local residents trained as “influence agents” to reach out to friends, neighbors, and others in their sphere of influence. Of the estimated 2.5 million new cases of HIV in adults and children in 2009, more than two-thirds occurred in sub-Saharan Africa.1 In Zambia, the prevalence of HIV among adults in urban and rural areas is estimated at 19 and 10 percent, respectively.2 Most HIV transmission in sub-Saharan Africa is heterosexual and occurs between cohabiting partners with discordant HIV test results3–5—that is, only one partner is HIV-positive. Thus, most new cases of HIV occur when someone infects his or her heterosexual partner. Sub-Saharan African couples with discordant HIV test results are the world’s largest risk group for HIV.6 Approximately 20 percent of Zambian couples have discordant HIV results, a rate consistent with estimates from Uganda, Rwanda, Tanzania, and Kenya.7–14 PMID:21821565
van Rooyen, Heidi; Tulloch, Olivia; Mukoma, Wanjiru; Makusha, Tawanda; Chepuka, Lignet; Knight, Lucia C; Peck, Roger B; Lim, Jeanette M; Muturi, Nelly; Chirwa, Ellen; Taegtmeyer, Miriam
2015-01-01
HIV self-testing (HIVST) has the potential to increase uptake of HIV testing among untested populations in sub-Saharan Africa and is on the brink of scale-up. However, it is unclear to what extent HIVST would be supported by stakeholders, what policy frameworks are in place and how variations between contexts might influence country-preparedness for scale-up. This qualitative study assessed the perceptions of HIVST among stakeholders in three sub-Saharan countries. Fifty-four key informant interviews were conducted in Kenya (n=16), Malawi (n=26) and South Africa (n=12) with government policy makers, academics, activists, donors, procurement specialists, laboratory practitioners and health providers. A thematic analysis was conducted in each country and a common coding framework allowed for inter-country analysis to identify common and divergent themes across contexts. Respondents welcomed the idea of an accurate, easy-to-use, rapid HIV self-test which could increase testing across all populations. High-risk groups, such as men, Men who have sex with men (MSM), couples and young people in particular, could be targeted through a range of health facility and community-based distribution points. HIVST is already endorsed in Kenya, and political support for scale-up exists in South Africa and Malawi. However, several caveats remain. Further research, policy and ensuing guidelines should consider how to regulate, market and distribute HIVST, ensure quality assurance of tests and human rights, and critically, link testing to appropriate support and treatment services. Low literacy levels in some target groups would also need context-specific consideration before scale up. World Health Organization (WHO) policy and regulatory frameworks are needed to guide the process in those areas which are new or specific to self-testing. Stakeholders in three HIV endemic sub-Saharan countries felt that HIVST will be an important complement to existing community and facility-based testing approaches if accompanied by the same essential components of any HIV testing service, including access to accurate information and linkages to care. While there is an increasingly positive global policy environment regarding HIVST, several implementation and social challenges limit scale-up. There is a need for further research to provide contextual and operational evidence that addresses concerns and contributes to normative WHO guidance.
Batraville, Laurie-Anne; Richard, Jonathan; Veillette, Maxime; Labbé, Annie-Claude; Alary, Michel; Guédou, Fernand; Kaufmann, Daniel E; Poudrier, Johanne; Finzi, Andrés; Roger, Michel
2014-11-01
Characterization of the immune correlates of protection against HIV infection is crucial for the development of preventive strategies. This study examined HIV-1 envelope (Env) glycoproteins, specifically immunoglobulin G (IgG), in systemic and mucosal compartments of female Beninese commercial sex workers (CSWs). Samples of 23 HIV-1-positive and 20 highly exposed HIV-1-seronegative (HESN) CSWs were studied. HIV-1 Env-specific IgG detection in sera and cervicovaginal lavages (CVLs) from the study population was done by cell-based ELISA. The HIV neutralizing activity was evaluated with a neutralization assay. The HIV-1-specific antibody-dependent cellular cytotoxicity (ADCC) response of the cohort was measured with a FACS-based assay evaluating the ADCC-mediated elimination of gp120-coated target cells. No anti-HIV-1 Env-specific IgG neutralizing or ADCC activities were detected in samples from HESN CSWs. Samples from HIV-1-infected CSWs presented ADCC activity in both sera and CVLs. Anti-Env IgG from sera and CVLs from HIV-1-infected CSWs preferentially recognized Env in its CD4-bound conformation. HIV-1-infected CSWs have ADCC-mediating IgG that preferentially recognizes Env in its CD4-bound conformation at the mucosal site.
Mitchell, Elizabeth O; Stewart, Greg; Bajzik, Olivier; Ferret, Mathieu; Bentsen, Christopher; Shriver, M Kathleen
2013-12-01
A multisite study was conducted to evaluate the performance of the Bio-Rad 4th generation GS HIV Combo Ag/Ab EIA versus Abbott 4th generation ARCHITECT HIV Ag/Ab Combo. The performance of two 3rd generation EIAs, Ortho Diagnostics Anti-HIV 1+2 EIA and Siemens HIV 1/O/2 was also evaluated. Study objective was comparison of analytical HIV-1 p24 antigen detection, sensitivity in HIV-1 seroconversion panels, specificity in blood donors and two HIV false reactive panels. Analytical sensitivity was evaluated with International HIV-1 p24 antigen standards, the AFFSAPS (pg/mL) and WHO 90/636 (IU/mL) standards; sensitivity in acute infection was compared on 55 seroconversion samples, and specificity was evaluated on 1000 negative blood donors and two false reactive panels. GS HIV Combo Ag/Ab demonstrated better analytical HIV antigen sensitivity compared to ARCHITECT HIV Ag/Ab Combo: 0.41 IU/mL versus 1.2 IU/mL (WHO) and 12.7 pg/mL versus 20.1 pg/mL (AFSSAPS); GS HIV Combo Ag/Ab EIA also demonstrated slightly better specificity compared to ARCHITECT HIV Ag/Ab Combo (100% versus 99.7%). The 4th generation HIV Combo tests detected seroconversion 7-11 days earlier than the 3rd generation HIV antibody only EIAs. Both 4th generation immunoassays demonstrated excellent performance in sensitivity, with the reduction of the serological window period (7-11 days earlier detection than the 3rd generation HIV tests). However, GS HIV Combo Ag/Ab demonstrated improved HIV antigen analytical sensitivity and slightly better specificity when compared to ARCHITECT HIV Ag/Ab Combo assay, with higher positive predictive values (PPV) for low prevalence populations. Copyright © 2013 Elsevier B.V. All rights reserved.
Ilinskaya, Anna; Dorjbal, Batsukh; Truong, Rosaline; Derse, David; Uchil, Pradeep D.; Heidecker, Gisela; Mothes, Walther
2013-01-01
Virus transmission can occur either by a cell-free mode through the extracellular space or by cell-to-cell transmission involving direct cell-to-cell contact. The factors that determine whether a virus spreads by either pathway are poorly understood. Here, we assessed the relative contribution of cell-free and cell-to-cell transmission to the spreading of the human immunodeficiency virus (HIV). We demonstrate that HIV can spread by a cell-free pathway if all the steps of the viral replication cycle are efficiently supported in highly permissive cells. However, when the cell-free path was systematically hindered at various steps, HIV transmission became contact-dependent. Cell-to-cell transmission overcame barriers introduced in the donor cell at the level of gene expression and surface retention by the restriction factor tetherin. Moreover, neutralizing antibodies that efficiently inhibit cell-free HIV were less effective against cell-to-cell transmitted virus. HIV cell-to-cell transmission also efficiently infected target T cells that were relatively poorly susceptible to cell-free HIV. Importantly, we demonstrate that the donor and target cell types influence critically the extent by which cell-to-cell transmission can overcome each barrier. Mechanistically, cell-to-cell transmission promoted HIV spread to more cells and infected target cells with a higher proviral content than observed for cell-free virus. Our data demonstrate that the frequently observed contact-dependent spread of HIV is the result of specific features in donor and target cell types, thus offering an explanation for conflicting reports on the extent of cell-to-cell transmission of HIV. PMID:23308151
Yates, Nicole L.; Liao, Hua-Xin; Fong, Youyi; deCamp, Allan; Vandergrift, Nathan A.; Williams, William T.; Alam, S. Munir; Ferrari, Guido; Yang, Zhi-yong; Seaton, Kelly E.; Berman, Phillip W.; Alpert, Michael D.; Evans, David T.; O’Connell, Robert J.; Francis, Donald; Sinangil, Faruk; Lee, Carter; Nitayaphan, Sorachai; Rerks-Ngarm, Supachai; Kaewkungwal, Jaranit; Pitisuttithum, Punnee; Tartaglia, James; Pinter, Abraham; Zolla-Pazner, Susan; Gilbert, Peter B.; Nabel, Gary J.; Michael, Nelson L.; Kim, Jerome H.; Montefiori, David C.; Haynes, Barton F.; Tomaras, Georgia D.
2014-01-01
HIV-1–specific immunoglobulin G (IgG) subclass antibodies bind to distinct cellular Fc receptors. Antibodies of the same epitope specificity but of a different subclass therefore can have different antibody effector functions. The study of IgG subclass profiles between different vaccine regimens used in clinical trials with divergent efficacy outcomes can provide information on the quality of the vaccine-induced B cell response. We show that HIV-1–specific IgG3 distinguished two HIV-1 vaccine efficacy studies (RV144 and VAX003 clinical trials) and correlated with decreased risk of HIV-1 infection in a blinded follow-up case-control study with the RV144 vaccine. HIV-1–specific IgG3 responses were not long-lived, which was consistent with the waning efficacy of the RV144 vaccine. These data suggest that specific vaccine-induced HIV-1 IgG3 should be tested in future studies of immune correlates in HIV-1 vaccine efficacy trials. PMID:24648342
Velloza, Jennifer; Watt, Melissa H.; Choi, Karmel W.; Abler, Laurie; Kalichman, Seth C.; Skinner, Donald; Pieterse, Desiree; Sikkema, Kathleen J.
2015-01-01
Alcohol-serving venues in South Africa are sites for high-risk behaviours that may lead to HIV transmission. Prevention and treatment interventions are sorely needed in these settings, but HIV-related stigma may limit their effectiveness. This study explored expressions of stigma among alcohol-serving venue patrons in Cape Town and examined the potential impact of stigma on HIV disclosure, testing, and treatment-seeking behaviours. A total of 92 in-depth interviews with male and female, Black and Coloured patrons were conducted. Transcripts were analysed via memo-writing and diagramming techniques. Many participants mentioned knowing other patrons living with HIV/AIDS (PLWH), and this visibility of HIV impacted expressions of HIV-related stigma. Participants discussed four forms of HIV-related stigma in the venues: fearing PLWH, fearing HIV acquisition, blaming others for spreading HIV, and isolating PLWH. HIV visibility and expressions of HIV-related stigma, particularly fear of isolation, influenced participants’ willingness to disclose their status. HIV-related stigma in the venues also appeared to indirectly influence testing and treatment-seeking behaviour outside the venue. Results suggest that efforts to change norms and reduce expressions of HIV-related stigma in alcohol-serving venues are necessary to successfully deliver tailored HIV prevention interventions and increase uptake of HIV testing and care in this important social setting. PMID:25630531
Riou, Catherine; Strickland, Natalie; Soares, Andreia P.; Corleis, Bjorn; Kwon, Douglas; Wherry, E. John; Wilkinson, Robert J.; Burgers, Wendy A.
2016-01-01
HIV-infected persons are at greater risk of developing tuberculosis (TB) even before profound CD4 loss occurs, suggesting that HIV alters CD4+T cell functions capable of containing bacterial replication. An effective immune response to Mycobacterium tuberculosis likely relies on the development of a balanced CD4 response, where distinct CD4+T helper subsets act in synergy to control the infection. To define the diversity of Mtb-specific CD4+Th subsets and determine whether HIV infection impacts such responses, the expression of lineage-defining transcription factors T-bet, Gata3, RORγt and Foxp3 was measured in Mtb-specific CD4+T cells in HIV-uninfected (n=20) and HIV-infected individuals (n=20) with latent TB infection. Our results show that upon 5 day restimulation in vitro, Mtb-specific CD4+T cells from healthy individuals have the ability to exhibit a broad spectrum of T helper subsets, defined by specific patterns of transcription factor co-expression. These transcription factor profiles were skewed in HIV-infected individuals where the proportion of T-bethighFoxp3+ Mtb-specific CD4+T cells was significantly decreased (p=0.002) compared to HIV-uninfected individuals, a change that correlated inversely with HIV viral load (p=0.0007) and plasma TNF-α (p=0.027). Our data demonstrate an important balance in T helper subset diversity defined by lineage-defining transcription factor co-expression profiles that is disrupted by HIV infection and suggest a role for HIV in impairing TB immunity by altering the equilibrium of Mtb-specific CD4+T helper subsets. PMID:26927799
Countervailing social network influences on problem behaviors among homeless youth.
Rice, Eric; Stein, Judith A; Milburn, Norweeta
2008-10-01
The impact of countervailing social network influences (i.e., pro-social, anti-social or HIV risk peers) on problem behaviors (i.e., HIV drug risk, HIV sex risk or anti-social behaviors) among 696 homeless youth was assessed using structural equation modeling. Results revealed that older youth were less likely to report having pro-social peers and were more likely to have HIV risk and anti-social peers. A longer time homeless predicted fewer pro-social peers, more anti-social peers, and more HIV risk peers. Heterosexual youth reported fewer HIV risk peers and more pro-social peers. Youth recruited at agencies were more likely to report pro-social peers. Having pro-social peers predicted less HIV sex risk behavior and less anti-social behavior. Having HIV risk peers predicted all problem behavior outcomes. Anti-social peers predicted more anti-social behavior. Once the association between anti-social and HIV risk peers was accounted for independently, having anti-social peers did not independently predict sex or drug risk behaviors.
Ackerman, Margaret E; Dugast, Anne-Sophie; McAndrew, Elizabeth G; Tsoukas, Stephen; Licht, Anna F; Irvine, Darrell J; Alter, Galit
2013-05-01
While development of an HIV vaccine that can induce neutralizing antibodies remains a priority, decades of research have proven that this is a daunting task. However, accumulating evidence suggests that antibodies with the capacity to harness innate immunity may provide some protection. While significant research has focused on the cytolytic properties of antibodies in acquisition and control, less is known about the role of additional effector functions. In this study, we investigated antibody-dependent phagocytosis of HIV immune complexes, and we observed significant differences in the ability of antibodies from infected subjects to mediate this critical effector function. We observed both quantitative differences in the capacity of antibodies to drive phagocytosis and qualitative differences in their FcγR usage profile. We demonstrate that antibodies from controllers and untreated progressors exhibit increased phagocytic activity, altered Fc domain glycosylation, and skewed interactions with FcγR2a and FcγR2b in both bulk plasma and HIV-specific IgG. While increased phagocytic activity may directly influence immune activation via clearance of inflammatory immune complexes, it is also plausible that Fc receptor usage patterns may regulate the immune response by modulating downstream signals following phagocytosis--driving passive degradation of internalized virus, release of immune modulating cytokines and chemokines, or priming of a more effective adaptive immune response.
Geographic distribution of HIV stigma among women of childbearing age in rural Kenya
Akullian, Adam; Kohler, Pamela; Kinuthia, John; Laserson, Kayla; Mills, Lisa A.; Okanda, John; Olilo, George; Ombok, Maurice; Odhiambo, Frank; Rao, Deepa; Wakefield, Jonathan; John-Stewart, Grace
2015-01-01
Objective(s) HIV stigma is considered to be a major driver of the HIV/AIDS pandemic, yet there is a limited understanding of its occurrence. We describe the geographic patterns of two forms of HIV stigma in a cross-sectional sample of women of childbearing age from western Kenya: internalized stigma (associated with shame) and externalized stigma (associated with blame). Design Geographic studies of HIV stigma provide a first step in generating hypotheses regarding potential community-level causes of stigma and may lead to more effective community-level interventions. Methods Spatial regression using generalized additive models and point pattern analyses using K-functions were used to assess the spatial scale(s) at which each form of HIV stigma clusters, and to assess whether the spatial clustering of each stigma indicator was present after adjustment for individual-level characteristics. Results There was evidence that externalized stigma (blame) was geographically heterogeneous across the study area, even after controlling for individual-level factors (P=0.01). In contrast, there was less evidence (P=0.70) of spatial trend or clustering of internalized stigma (shame). Conclusion Our results may point to differences in the underlying social processes motivating each form of HIV stigma. Externalized stigma may be driven more by cultural beliefs disseminated within communities, whereas internalized stigma may be the result of individual-level characteristics outside the domain of community influence. These data may inform community-level interventions to decrease HIV-related stigma, and thus impact the HIV epidemic. PMID:24835356
Formation of Personal HIV Disclosure Policies among HIV-Positive Men Who Have Sex with Men
2009-01-01
Abstract Given the increasing emphasis on “prevention with positives” programs designed to promote HIV transmission risk reduction among people living with HIV/AIDS, better understanding of influences upon serostatus disclosure in sexual situations is needed. Based on grounded theory analyses of individual interviews, this exploratory research hypothesizes and interprets how 15 HIV-positive men who have sex with men (MSM) formed personal HIV disclosure policies for sexual situations. Participants described five elements influencing development of their personal policies, including: (1) making sense of having been infected, (2) envisioning sex as an HIV-positive man, (3) sorting through feelings of responsibility for others, (4) responding to views of friends and the gay community, and (5) anticipating reactions and consequences of disclosure. The article concludes with implications for current initiatives for prevention with positives. PMID:19621994
Mohammadzadeh, Sara; Rajabibazl, Masoumeh; Fourozandeh, Mehdi; Rasaee, Mohammad Javad; Rahbarizadeh, Fatemeh; Mohammadi, Mohammad
2014-02-01
Phage display has a fundamental role in protein isolation and engineering. Isolated proteins produced with this method can be modified for specific binding and affinity. P24 is the most produced protein during human immune deficiency virus (HIV) replication; especially in the early steps of HIV-1 infection, its evaluation may have diagnostic values. To test the HIV-1 infection, p24 antigen assay appears to be a very promising alternative to RNA assays. In this study, we have generated a recombinant mouse single chain antibody fragment against p24 of the HIV-1 with the use of phage display technology. After isolation of antibody variable-region (V) gene of B cells extracted from the spleen of an immunized mouse, a library of single chain Fv fragments (scFv) was constructed. The library was used in a series of bio-panning processes against recombinant p24 protein expressed from Escherichia coli. The isolated scFv antibody specifically recognizes the HIV-1 capsid protein p24. The affinity constant of the isolated scFv antibody (MF85) was found to be 2×10(-9) M. Our studies showed that the MF85 scFV antibody has similar properties as that of monoclonal antibodies produced by the hybridoma technology.
Developing consumer involvement in rural HIV primary care programmes.
Mamary, Edward M; Toevs, Kim; Burnworth, Karla B; Becker, Lin
2004-06-01
As part of a broader medical and psychosocial needs assessment in a rural region of northern California, USA, five focus groups were conducted to explore innovative approaches to creating a system of consumer involvement in the delivery of HIV primary care services in the region. A total of five focus groups (n = 30) were conducted with clients from three of five counties in the region with the highest number of HIV patients receiving primary care. Participants were recruited by their HIV case managers. They were adults living with HIV, who were receiving health care, and who resided in a rural mountain region of northern California. Group discussions explored ideas for new strategies and examined traditional methods of consumer involvement, considering ways they could be adapted for a rural environment. Recommendations for consumer involvement included a multi-method approach consisting of traditional written surveys, a formal advisory group, and monthly consumer led social support/informal input groups. Specific challenges discussed included winter weather conditions, transportation barriers, physical limitations, confidentiality concerns, and needs for social support and education. A multiple-method approach would ensure more comprehensive consumer involvement in the programme planning process. It is also evident that methods for incorporating consumer involvement must be adapted to the specific context and circumstances of a given programme.
Hsu, Justine; Zinsou, Cyprien; Parkhurst, Justin; N'Dour, Marguerite; Foyet, Léger; Mueller, Dirk H
2013-01-01
Behavioural interventions have been widely integrated in HIV/AIDS social marketing prevention strategies and are considered valuable in settings with high levels of risk behaviours and low levels of HIV/AIDS awareness. Despite their widespread application, there is a lack of economic evaluations comparing different behaviour change communication methods. This paper analyses the costs to increase awareness and the cost-effectiveness to influence behaviour change for five interventions in Benin. Cost and cost-effectiveness analyses used economic costs and primary effectiveness data drawn from surveys. Costs were collected for provider inputs required to implement the interventions in 2009 and analysed by 'person reached'. Cost-effectiveness was analysed by 'person reporting systematic condom use'. Sensitivity analyses were performed on all uncertain variables and major assumptions. Cost-per-person reached varies by method, with public outreach events the least costly (US$2.29) and billboards the most costly (US$25.07). Influence on reported behaviour was limited: only three of the five interventions were found to have a significant statistical correlation with reported condom use (i.e. magazines, radio broadcasts, public outreach events). Cost-effectiveness ratios per person reporting systematic condom use resulted in the following ranking: magazines, radio and public outreach events. Sensitivity analyses indicate rankings are insensitive to variation of key parameters although ratios must be interpreted with caution. This analysis suggests that while individual interventions are an attractive use of resources to raise awareness, this may not translate into a cost-effective impact on behaviour change. The study found that the extensive reach of public outreach events did not seem to influence behaviour change as cost-effectively when compared with magazines or radio broadcasts. Behavioural interventions are context-specific and their effectiveness influenced by a multitude of factors. Further analyses using a quasi-experimental design would be useful to programme implementers and policy makers as they face decisions regarding which HIV prevention activities to prioritize.
Turan, Janet M.; Hatcher, Abigail H.; Medema-Wijnveen, José; Onono, Maricianah; Miller, Suellen; Bukusi, Elizabeth A.; Turan, Bulent; Cohen, Craig R.
2012-01-01
Background Childbirth with a skilled attendant is crucial for preventing maternal mortality and is an important opportunity for prevention of mother-to-child transmission of HIV. The Maternity in Migori and AIDS Stigma Study (MAMAS Study) is a prospective mixed-methods investigation conducted in a high HIV prevalence area in rural Kenya, in which we examined the role of women's perceptions of HIV-related stigma during pregnancy in their subsequent utilization of maternity services. Methods and Findings From 2007–2009, 1,777 pregnant women with unknown HIV status completed an interviewer-administered questionnaire assessing their perceptions of HIV-related stigma before being offered HIV testing during their first antenatal care visit. After the visit, a sub-sample of women was selected for follow-up (all women who tested HIV-positive or were not tested for HIV, and a random sample of HIV-negative women, n = 598); 411 (69%) were located and completed another questionnaire postpartum. Additional qualitative in-depth interviews with community health workers, childbearing women, and family members (n = 48) aided our interpretation of the quantitative findings and highlighted ways in which HIV-related stigma may influence birth decisions. Qualitative data revealed that health facility birth is commonly viewed as most appropriate for women with pregnancy complications, such as HIV. Thus, women delivering at health facilities face the risk of being labeled as HIV-positive in the community. Our quantitative data revealed that women with higher perceptions of HIV-related stigma (specifically those who held negative attitudes about persons living with HIV) at baseline were subsequently less likely to deliver in a health facility with a skilled attendant, even after adjusting for other known predictors of health facility delivery (adjusted odds ratio = 0.44, 95% CI 0.22–0.88). Conclusions Our findings point to the urgent need for interventions to reduce HIV-related stigma, not only for improving quality of life among persons living with HIV, but also for better health outcomes among all childbearing women and their families. Please see later in the article for the Editors' Summary. PMID:22927800
Church, Kathryn; Wringe, Alison; Lewin, Simon; Ploubidis, George B.; Fakudze, Phelele; Mayhew, Susannah H.
2015-01-01
Integrating reproductive health (RH) with HIV care is a policy priority in high HIV prevalence settings, despite doubts surrounding its feasibility and varying evidence of effects on health outcomes. The process and outcomes of integrated RH-HIV care were investigated in Swaziland, through a comparative case study of four service models, ranging from fully integrated to fully stand-alone HIV services, selected purposively within one town. A client exit survey (n=602) measured integrated care received and unmet family planning (FP) needs. Descriptive statistics were used to assess the degree of integration per clinic and client demand for services. Logistic regression modelling was used to test the hypothesis that clients at more integrated sites had lower unmet FP needs than clients in a stand-alone site. Qualitative methods included in-depth interviews with clients and providers to explore contextual factors influencing the feasibility of integrated RH-HIV care delivery; data were analysed thematically, combining deductive and inductive approaches. Results demonstrated that clinic models were not as integrated in practice as had been claimed. Fragmentation of HIV care was common. Services accessed per provider were no higher at the more integrated clinics compared to stand-alone models (p>0.05), despite reported demand. While women at more integrated sites received more FP and pregnancy counselling than stand-alone models, they received condoms (a method of choice) less often, and there was no statistical evidence of difference in unmet FP needs by model of care. Multiple contextual factors influenced integration practices, including provider de-skilling within sub-specialist roles; norms of task-oriented routinised HIV care; perceptions of heavy client loads; imbalanced client-provider interactions hindering articulation of RH needs; and provider motivation challenges. Thus, despite institutional support, factors related to the social context of care inhibited provision of fully integrated RH-HIV services in these clinics. Programmes should move beyond simplistic training and equipment provision if integrated care interventions are to be sustained. PMID:25978632
Rasheed, Suraiya; Yan, Jasper S; Lau, Alex; Chan, Arvan S
2008-08-20
HIV-infected patients develop multiple metabolic abnormalities including insulin resistance, lipodystrophy and dyslipidemia. Although progression of these disorders has been associated with the use of various protease inhibitors and other antiretroviral drugs, HIV-infected individuals who have not received these treatments also develop lipid abnormalities albeit to a lesser extent. How HIV alters lipid metabolism in an infected cell and what molecular changes are affected through protein interaction pathways are not well-understood. Since many genetic, epigenetic, dietary and other factors influence lipid metabolism in vivo, we have chosen to study genome-wide changes in the proteomes of a human T-cell line before and after HIV infection in order to circumvent computational problems associated with multiple variables. Four separate experiments were conducted including one that compared 14 different time points over a period of >3 months. By subtractive analyses of protein profiles overtime, several hundred differentially expressed proteins were identified in HIV-infected cells by mass spectrometry and each protein was scrutinized for its biological functions by using various bioinformatics programs. Herein, we report 18 HIV-modulated proteins and their interaction pathways that enhance fatty acid synthesis, increase low density lipoproteins (triglycerides), dysregulate lipid transport, oxidize lipids, and alter cellular lipid metabolism. We conclude that HIV replication alone (i.e. without any influence of antiviral drugs, or other human genetic factors), can induce novel cellular enzymes and proteins that are significantly associated with biologically relevant processes involved in lipid synthesis, transport and metabolism (p = <0.0002-0.01). Translational and clinical studies on the newly discovered proteins may now shed light on how some of these proteins may be useful for early diagnosis of individuals who might be at high risk for developing lipid-related disorders. The target proteins could then be used for future studies in the development of inhibitors for preventing lipid-metabolic anomalies. This is the first direct evidence that HIV-modulates production of proteins that are significantly involved in disrupting the normal lipid-metabolic pathways.
Pialoux, G; Excler, J L; Rivière, Y; Gonzalez-Canali, G; Feuillie, V; Coulaud, P; Gluckman, J C; Matthews, T J; Meignier, B; Kieny, M P
1995-03-01
The safety and the immunogenicity of a recombinant canarypox live vector expressing the human immunodeficiency virus type 1 (HIV-1) gp160 gene from the MN isolate, ALVAC-HIV (vCP125), followed by booster injections of a soluble recombinant hybrid envelope glycoprotein MN/LAI (rgp160), were evaluated in vaccinia-immune, healthy adults at low risk for acquiring HIV-1 infection. Volunteers (n = 20) received vCP125 (10(6) TCID50) at 0 and 1 month, followed randomly by rgp160 formulated in alum or in Freund's incomplete adjuvant (FIA) at 3 and 6 months. Local and systemic reactions were mild or moderate and resolved within the first 72 hr after immunization. No significant biological changes in routine tests were observed in any volunteer. Two injections of vCP125 did not elicit antibodies. Neutralizing antibodies (NA) against the HIV-1 MN isolate were detected in 65 and 90% of the subjects after the first and the second rgp 160 booster injections, respectively. Six months after the last boost, only 55% were still positive. Seven of 14 sera with the highest NA titers against MN weakly cross-neutralized the HIV-1 SF2 isolate; none had NA against the HIV-1 LAI or against a North American primary isolate. Specific lymphocyte T cell proliferation to rgp 160 was detected in 25% of the subjects after vCP125 and in all subjects after the first booster injection and 12 months after the first injection. An envelope-specific cytotoxic lymphocyte activity was found in 39% of the volunteers and characterized for some of them as CD3+, CD8+, MHC class I restricted. The adjuvant formulation did not influence significantly the immune responses.(ABSTRACT TRUNCATED AT 250 WORDS)
Dunham, Richard M; Cervasi, Barbara; Brenchley, Jason M; Albrecht, Helmut; Weintrob, Amy; Sumpter, Beth; Engram, Jessica; Gordon, Shari; Klatt, Nichole R; Frank, Ian; Sodora, Donald L; Douek, Daniel C; Paiardini, Mirko; Silvestri, Guido
2008-04-15
Decreased CD4(+) T cell counts are the best marker of disease progression during HIV infection. However, CD4(+) T cells are heterogeneous in phenotype and function, and it is unknown how preferential depletion of specific CD4(+) T cell subsets influences disease severity. CD4(+) T cells can be classified into three subsets by the expression of receptors for two T cell-tropic cytokines, IL-2 (CD25) and IL-7 (CD127). The CD127(+)CD25(low/-) subset includes IL-2-producing naive and central memory T cells; the CD127(-)CD25(-) subset includes mainly effector T cells expressing perforin and IFN-gamma; and the CD127(low)CD25(high) subset includes FoxP3-expressing regulatory T cells. Herein we investigated how the proportions of these T cell subsets are changed during HIV infection. When compared with healthy controls, HIV-infected patients show a relative increase in CD4(+)CD127(-)CD25(-) T cells that is related to an absolute decline of CD4(+)CD127(+)CD25(low/-) T cells. Interestingly, this expansion of CD4(+)CD127(-) T cells was not observed in naturally SIV-infected sooty mangabeys. The relative expansion of CD4(+)CD127(-)CD25(-) T cells correlated directly with the levels of total CD4(+) T cell depletion and immune activation. CD4(+)CD127(-)CD25(-) T cells were not selectively resistant to HIV infection as levels of cell-associated virus were similar in all non-naive CD4(+) T cell subsets. These data indicate that, during HIV infection, specific changes in the fraction of CD4(+) T cells expressing CD25 and/or CD127 are associated with disease progression. Further studies will determine whether monitoring the three subsets of CD4(+) T cells defined based on the expression of CD25 and CD127 should be used in the clinical management of HIV-infected individuals.
Reuter, H; Burgess, L J; Schneider, J; Van Vuuren, W; Doubell, A F
2006-02-01
To establish the influence of human immunodeficiency virus (HIV) infection on the histopathological features of patients presenting with tuberculous pericarditis. A prospective study was carried out at Tygerberg Academic Hospital, South Africa; 36 patients with large pericardial effusions had open pericardial biopsies under general anaesthesia and were included in the study. Patients underwent pericardiocentesis, followed by daily intermittent catheter drainage; a comprehensive diagnostic work-up (including histopathology of the pericardial tissue) was also performed. Histological tuberculous pericarditis was diagnosed according to predetermined criteria. Tuberculous pericarditis was identified in 25 patients, five of whom were HIV+. The presence of granulomatous inflammation (with or without necrosis) and/or Ziehl-Neelsen positivity yielded the best test results (sensitivity 64%, specificity 100% and diagnostic efficiency 75%). Co-infection with HIV impacts on the histopathological features of pericardial tuberculosis and leads to a decrease in the sensitivity of the test. In areas which have a high prevalence of tuberculosis, the combination of a sensitive test such as adenosine deaminase, chest X-ray and clinical features has a higher diagnostic efficiency than pericardial biopsy in diagnosing tuberculous pericarditis.
Go, Vivian F.; Latkin, Carl; Le Minh, Nguyen; Frangakis, Constantine; Ha, Tran Viet; Sripaipan, Teerada; Mo, Tran Thi; Davis, Wendy W.; Vu, Pham The; Quan, Vu Minh
2016-01-01
Stigma and perceived social support can influence the decision to disclose HIV positive status, especially for people who inject drugs (PWID). In this analysis, the association between social support and HIV disclosure among 336 newly diagnosed HIV-infected PWID in Northern Vietnam was assessed. One month after diagnosis, 34.8% of participants had not disclosed to anyone. Disclosure to anyone and to a family member specifically, was associated with baseline social support in the form of positive interactions and a history of incarceration. Disclosing to a family member was less likely among those who had unprotected sex in the previous 3 months. Disclosure to an injecting partner was more likely among those with a history of being in a drug treatment program, knowing someone on ART and believing that ART is safe. These data suggest that social support may facilitate disclosure among family members, including spouses, while disclosure to injecting partners is greater when PWID know that ART is a safe and viable option. PMID:25972071
Perception of risk of HIV/AIDS and sexual behaviour in Kenya.
Akwara, Priscilla A; Madise, Nyovani Janet; Hinde, Andrew
2003-07-01
The association between perception of risk of HIV infection and sexual behaviour remains poorly understood, although perception of risk is considered to be the first stage towards behavioural change from risk-taking to safer behaviour. Using data from the 1998 Kenya Demographic and Health Survey, logistic regression models were fitted to examine the direction and the strength of the association between perceived risk of HIV/AIDS and risky sexual behaviour in the last 12 months before the survey. The findings indicate a strong positive association between perceived risk of HIV/AIDS and risky sexual behaviour for both women and men. Controlling for sociodemographic, sexual exposure and knowledge factors such as age, marital status, education, work status, residence, ethnicity, source of AIDS information, specific knowledge of AIDS, and condom use to avoid AIDS did not change the direction of the association, but altered its strength slightly. Young and unmarried women and men were more likely than older and married ones to report risky sexual behaviour. Ethnicity was significantly associated with risky sexual behaviour, suggesting a need to identify the contextual and social factors that influence behaviour among Kenyan people.
Go, Vivian F; Latkin, Carl; Le Minh, Nguyen; Frangakis, Constantine; Ha, Tran Viet; Sripaipan, Teerada; Mo, Tran Thi; Davis, Wendy W; Vu, Pham The; Quan, Vu Minh
2016-01-01
Stigma and perceived social support can influence the decision to disclose HIV positive status, especially for people who inject drugs (PWID). In this analysis, the association between social support and HIV disclosure among 336 newly diagnosed HIV-infected PWID in Northern Vietnam was assessed. One month after diagnosis, 34.8 % of participants had not disclosed to anyone. Disclosure to anyone and to a family member specifically, was associated with baseline social support in the form of positive interactions and a history of incarceration. Disclosing to a family member was less likely among those who had unprotected sex in the previous 3 months. Disclosure to an injecting partner was more likely among those with a history of being in a drug treatment program, knowing someone on ART and believing that ART is safe. These data suggest that social support may facilitate disclosure among family members, including spouses, while disclosure to injecting partners is greater when PWID know that ART is a safe and viable option.
Madhivanan, Purnima; Krupp, Karl; Kulkarni, Vinay; Kulkarni, Sanjeevani; Vaidya, Neha; Shaheen, Reshma; Philpott, Sean; Fisher, Celia
2014-03-24
In India, approximately 49,000 women living with HIV become pregnant and deliver each year. While the government of India has made progress increasing the availability of prevention of mother-to-child transmission of HIV (PMTCT) services, only about one quarter of pregnant women received an HIV test in 2010, and about one-in-five that were found positive for HIV received interventions to prevent vertical transmission of HIV. Between February 2012 to March 2013, 14 HIV-positive women who had recently delivered a baby were recruited from HIV positive women support groups, Government of India Integrated Counseling and Testing Centers, and nongovernmental organizations in Mysore and Pune, India. In-depth interviews were conducted to examine their general experiences with antenatal healthcare; specific experiences around HIV counseling and testing; and perceptions about their care and follow-up treatment. Data were analyzed thematically using the human rights framework for HIV testing adopted by the United Nations and India's National AIDS Control Organization. While all of the HIV-positive women in the study received HIV and PMTCT services at a government hospital or antiretroviral therapy center, almost all reported attending a private clinic or hospital at some point in their pregnancy. According to the participants, HIV testing often occurred without consent; there was little privacy; breaches of confidentiality were commonplace; and denial of medical treatment occurred routinely. Among women living with HIV in this study, violations of their human rights occurred more commonly in private rather than public healthcare settings. There is an urgent need for capacity building among private healthcare providers to improve standards of practice with regard to informed consent process, HIV testing, patient confidentiality, treatment, and referral of pregnant women living with HIV.
ERIC Educational Resources Information Center
Yadav, Aman; Phillips, Michael M.; Lundeberg, Mary A.; Koehler, Matthew J.; Hilden, Katherine; Dirkin, Kathryn H.
2011-01-01
In this investigation we assessed whether different formats of media (video, text, and video + text) influenced participants' engagement, cognitive processing and recall of non-fiction cases of people diagnosed with HIV/AIDS. For each of the cases used in the study, we designed three informationally-equivalent versions: video, text, and video +…
Degroote, Sophie; Vogelaers, Dirk; Vandijck, Dominique M
2014-01-01
As infection with the Human Immunodeficiency Virus (HIV) has evolved to a chronic disease, perceived health-related quality of life (HRQoL) is becoming a prominent and important patient-reported outcome measure in HIV care. Literature discusses different factors influencing HRQoL in this population, however, currently no consensus exists about the main determinants. In this review a clear, up-to-date overview of the determinants influencing HRQOL among people living with HIV is provided. All studies published before July 2013 that identified determinants of HRQoL among people living with HIV in high-income countries, were considered in this narrative review. PubMed, Web of Science and The Cochrane Library were consulted using the keywords 'determinants', 'quality of life', 'HIV' and 'AIDS'. To be included, studies should have reported overall health and/or physical/mental health scores on a validated instrument and performed multivariable regression analyses to identify determinants that independently influence perceived HRQoL. In total, 49 studies were included for further analysis and they used a variety of HRQoL instruments: Medical Outcomes Study Short Form-36 or variants, Medical Outcomes Study-HIV, HIV Cost and Services Utilization Study measure, Multidimensional Quality of Life Questionnaire, HIV targeted quality of life instrument, Functional Assessment of Human Immunodeficiency Virus Infection, HIV Overview of Problems Evaluation System, EuroQol, Fanning Quality of Life scale, Health Index and PROQOL-HIV. In this review, the discussed determinants were thematically divided into socio-demographic, clinical, psychological and behavioural factors. Employment, immunological status, presence of symptoms, depression, social support and adherence to antiretroviral therapy were most frequently and consistently reported to be associated with HRQoL among people living with HIV. HRQoL among people living with HIV is influenced by several determinants. These determinants independently, but simultaneously impact perceived HRQoL. Most HRQoL instruments do not capture all key determinants. We recommend that the choice for an instrument should depend on the purpose of the HRQoL assessment.
Vanhommerig, Joost W; Bezemer, Daniela; Molenkamp, Richard; Van Sighem, Ard I; Smit, Colette; Arends, Joop E; Lauw, Fanny N; Brinkman, Kees; Rijnders, Bart J; Newsum, Astrid M; Bruisten, Sylvia M; Prins, Maria; Van Der Meer, Jan T; Van De Laar, Thijs J; Schinkel, Janke
2017-09-24
MSM are at increased risk for infection with HIV-1 and hepatitis C virus (HCV). Is HIV/HCV coinfection confined to specific HIV transmission networks? A HIV phylogenetic tree was constructed for 5038 HIV-1 subtype B polymerase (pol) sequences obtained from MSM in the AIDS therapy evaluation in the Netherlands cohort. We investigated the existence of HIV clusters with increased HCV prevalence, the HIV phylogenetic density (i.e. the number of potential HIV transmission partners) of HIV/HCV-coinfected MSM compared with HIV-infected MSM without HCV, and the overlap in HIV and HCV phylogenies using HCV nonstructural protein 5B sequences from 183 HIV-infected MSM with acute HCV infection. Five hundred and sixty-three of 5038 (11.2%) HIV-infected MSM tested HCV positive. Phylogenetic analysis revealed 93 large HIV clusters (≥10 MSM), 370 small HIV clusters (2-9 MSM), and 867 singletons with a median HCV prevalence of 11.5, 11.6, and 9.3%, respectively. We identified six large HIV clusters with elevated HCV prevalence (range 23.5-46.2%). Median HIV phylogenetic densities for MSM with HCV (3, interquartile range 1-7) and without HCV (3, interquartile range 1-8) were similar. HCV phylogeny showed 12 MSM-specific HCV clusters (clustersize: 2-39 HCV sequences); 12.7% of HCV infections were part of the same HIV and HCV cluster. We observed few HIV clusters with elevated HCV prevalence, no increase in the HIV phylogenetic density of HIV/HCV-coinfected MSM compared to HIV-infected MSM without HCV, and limited overlap between HIV and HCV phylogenies among HIV/HCV-coinfected MSM. Our data do not support the existence of MSM-specific sexual networks that fuel both the HIV and HCV epidemic.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Reiss, T.F.; Golden, J.
Pneumocystis carinii pneumonia was suggested by a diffuse, bilateral pulmonary uptake of gallium-67 in an asymptomatic, homosexual male with the antibody to the immunodeficiency virus (HIV) who was undergoing staging evaluation for lymphoma clinically localized to a left inguinal lymph node. Chest radiograph and pulmonary function evaluation, including lung volumes, diffusing capacity and arterial blood gases, were within normal limits. Bronchoalveolar lavage revealed Pneumocystis carinii organisms. In this asymptomatic, HIV-positive patient, active alveolar infection, evidenced by abnormal gallium-67 scanning, predated pulmonary physiologic abnormalities. This observation raises questions concerning the natural history of this disease process and the specificity of physiologicmore » tests for excluding disease. It also has implications for the treatment of neoplasia in the HIV-positive patient population.« less
Sun, Yanqing; Qi, Li; Yang, Guangren; Gilbert, Peter B
2018-05-01
This article develops hypothesis testing procedures for the stratified mark-specific proportional hazards model with missing covariates where the baseline functions may vary with strata. The mark-specific proportional hazards model has been studied to evaluate mark-specific relative risks where the mark is the genetic distance of an infecting HIV sequence to an HIV sequence represented inside the vaccine. This research is motivated by analyzing the RV144 phase 3 HIV vaccine efficacy trial, to understand associations of immune response biomarkers on the mark-specific hazard of HIV infection, where the biomarkers are sampled via a two-phase sampling nested case-control design. We test whether the mark-specific relative risks are unity and how they change with the mark. The developed procedures enable assessment of whether risk of HIV infection with HIV variants close or far from the vaccine sequence are modified by immune responses induced by the HIV vaccine; this question is interesting because vaccine protection occurs through immune responses directed at specific HIV sequences. The test statistics are constructed based on augmented inverse probability weighted complete-case estimators. The asymptotic properties and finite-sample performances of the testing procedures are investigated, demonstrating double-robustness and effectiveness of the predictive auxiliaries to recover efficiency. The finite-sample performance of the proposed tests are examined through a comprehensive simulation study. The methods are applied to the RV144 trial. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Peifang, S.; Pira, G. L.; Fenoglio, D.; Harris, S.; Costa, M. G.; Venturino, V.; Dessì, V.; Layton, G.; Laman, J.; Huisman, J. G.; Manca, F.
1994-01-01
Recombinant virus-like particles (VLP), formed by the yeast Ty p1 protein, carrying the HIV gp120 V3 loop on their surface (V3-VLP) have been tested in vitro for immunogenicity and antigenicity by using VLP p1-specific human CD4+ T cell lines and clones. VLP-specific human T cell lines and clones were generated from normal individuals, indicating that VLP-specific precursor cells present in the peripheral lymphocyte pool can be induced to expand clonally upon antigen challenge in vitro, in the absence of previous immunization. It was also shown that V3-specific polyclonal antibodies enhance V3-VLP-induced activation of VLP-specific T cell clones. Antibody-dependent potentiation has been shown previously in other antigen systems, and it depends on enhanced uptake of complexed antigen by Fc receptor-positive antigen-presenting cells. Since in this case antigen is internalized by presenting cells as a complex, it can be inferred that a similar event of antibody-mediated antigen uptake can take place with V3-specific B cells, resulting in presentation by the B cells of T helper epitopes derived from processing of the VLP p1 moiety. This suggests that T helper cells specific for the carrier VLP p1 protein can be activated to provide help to V3-specific B cells in the presence of the appropriate antigen construct. PMID:7915974
Li, Jonathan Z.; Heisey, Andrea; Ahmed, Hayat; Wang, Hongying; Zheng, Lu; Carrington, Mary; Wrin, Terri; Schooley, Robert T.; Lederman, Michael M.; Kuritzkes, Daniel R.
2014-01-01
Objectives To evaluate the impact of therapeutic HIV vaccination on the HIV reservoir, and assess the relationship of the viral reservoir with HIV-specific immune status and viral rebound kinetics. Design Retrospective analysis of ACTG A5197, a randomized, placebo-controlled trial of a therapeutic rAd5 HIV-1 gag vaccine. Methods Participants received vaccine/placebo at weeks 0, 4, and 26 prior to a 16-week analytic treatment interruption (ATI) at week 38. Cell-associated HIV-1 RNA and DNA (CA-RNA and CA-DNA) and HIV-1 residual viremia (RV) were quantified at weeks 0, 8, and 38. HIV-specific CD4+/CD8+ activity were assessed by an intracellular cytokine staining assay. Results At study entry, CA-RNA and CA-DNA levels were correlated inversely with the numbers of HIV-specific CD4+ interferon-γ-producing cells (CA-RNA: r = −0.23, P=0.03 and CA-DNA: r = −0.28, P<0.01, N=93). Therapeutic HIV vaccination induced HIV-specific CD4+ activity, but did not significantly affect levels of CA-RNA or CA-DNA. Vaccine recipients with undetectable RV at week 8 had higher frequencies of HIV-specific CD4+ and CD8+ interferon-γ-producing cells (undetectable versus detectable RV: 277 versus 161 CD4+ cells/106 lymphocytes, P=0.03 and 1326 versus 669 CD8+ cells/106 lymphocytes, P=0.04). Pre-ATI CA-RNA and CA-DNA were associated with post-ATI plasma HIV set point (CA-RNA: r = 0.51, P<0.01 and CA-DNA: r = 0.47, P<0.01). Conclusions Vaccine-induced T-cell responses were associated with a modest transient effect on RV, but more potent immune responses and/or combination treatment with latency-reversing agents are needed to reduce the HIV reservoir. HIV reservoir measures may act as biomarkers of post-ATI viral rebound kinetics. PMID:25254301
Deliberative and spontaneous cognitive processes associated with HIV risk behavior
Ames, Susan L.; Stacy, Alan W.
2012-01-01
Dual process models of decision-making suggest that behavior is mediated by a spontaneous behavior selection process or by a more deliberative evaluation of behavioral options. We examined whether the deliberative system moderates the influence of spontaneous cognition on HIV-risk behaviors. A measure of spontaneous sex-related associations (word association), a measure of deliberative working memory capacity (operation span), and two measures of sexual behavior (condom use and multiple partners) were assessed in a cross-sectional study among 490 adult drug offenders. Significant effects were observed among men but not among women in two latent interaction models. In a novel finding, the accessibility of spontaneous safe sex-related associations was significantly more predictive of condom use among men with higher working memory capacity than among men with lower capacity. These results have implications for the design of interventions to promote safe sex practices. PMID:22331437
Grosse, V; Schulte, A; Weber, K; Mendila, M; Jacobs, R; Schmidt, R E; Heiken, H
2000-08-01
Visualization of antigen-specific T cells has become an important tool in studying immune responses. The aim of this study was to analyze CMV-specific CD4+ T cells in healthy and HIV-infected individuals. Peripheral blood mononuclear cells (PBMC) were examined for antigen-induced intracellular cytokine responses. We found significant numbers of CMV-specific CD4+ T cells detectable in most CMV-IgG+ HIV-1 infected individuals, whereas CMV-specific CD4+ T cells could not be demonstrated in CMV-IgG- patients. Median frequency of CMV-specific CD4+ T cells were lower in HIV-infected subjects who had been treated with highly active antiretroviral therapy (HAART) for more than 1 year than in untreated HIV-infected individuals. In patients under therapy for less than 1 year median CMV-specific CD4+ T cell responder frequency was higher than in subjects treated for more than 1 year but lower than in untreated subjects. HIV suppression with HAART might lead to a progressive reduction of CMV-specific CD4+ T cells indicating an efficient elimination of an opportunistic pathogen.
Herbeck, Joshua T; Rolland, Morgane; Liu, Yi; McLaughlin, Sherry; McNevin, John; Zhao, Hong; Wong, Kim; Stoddard, Julia N; Raugi, Dana; Sorensen, Stephanie; Genowati, Indira; Birditt, Brian; McKay, Angela; Diem, Kurt; Maust, Brandon S; Deng, Wenjie; Collier, Ann C; Stekler, Joanne D; McElrath, M Juliana; Mullins, James I
2011-08-01
HIV-1 transmission and viral evolution in the first year of infection were studied in 11 individuals representing four transmitter-recipient pairs and three independent seroconverters. Nine of these individuals were enrolled during acute infection; all were men who have sex with men (MSM) infected with HIV-1 subtype B. A total of 475 nearly full-length HIV-1 genome sequences were generated, representing on average 10 genomes per specimen at 2 to 12 visits over the first year of infection. Single founding variants with nearly homogeneous viral populations were detected in eight of the nine individuals who were enrolled during acute HIV-1 infection. Restriction to a single founder variant was not due to a lack of diversity in the transmitter as homogeneous populations were found in recipients from transmitters with chronic infection. Mutational patterns indicative of rapid viral population growth dominated during the first 5 weeks of infection and included a slight contraction of viral genetic diversity over the first 20 to 40 days. Subsequently, selection dominated, most markedly in env and nef. Mutants were detected in the first week and became consensus as early as day 21 after the onset of symptoms of primary HIV infection. We found multiple indications of cytotoxic T lymphocyte (CTL) escape mutations while reversions appeared limited. Putative escape mutations were often rapidly replaced with mutually exclusive mutations nearby, indicating the existence of a maturational escape process, possibly in adaptation to viral fitness constraints or to immune responses against new variants. We showed that establishment of HIV-1 infection is likely due to a biological mechanism that restricts transmission rather than to early adaptive evolution during acute infection. Furthermore, the diversity of HIV strains coupled with complex and individual-specific patterns of CTL escape did not reveal shared sequence characteristics of acute infection that could be harnessed for vaccine design.
Is HIV a model of accelerated or accentuated aging?
Pathai, Sophia; Bajillan, Hendren; Landay, Alan L; High, Kevin P
2014-07-01
Antiretroviral therapy has reduced the incidence of adverse events and early mortality in HIV-infected persons. Despite these benefits, important comorbidities that increase with age (eg, diabetes, cardiovascular disease, cancer, liver disease, and neurocognitive impairment) are more prevalent in HIV-infected persons than in HIV-uninfected persons at every age, and geriatric syndromes such as falls and frailty occur earlier in HIV-infected persons. This raises a critical research question: Does HIV accelerate aging through pathways and mechanisms common to the aging process or is HIV simply an additional risk factor for a wide number of chronic conditions, thus accentuating aging? Extensive literature review. The purpose of this review is to briefly outline the evidence that age-related clinical syndromes are exacerbated by HIV, examine the ways in which HIV is similar, and dissimilar from natural aging, and assess the validity of HIV as a model of premature aging. Specific biomarkers of aging are limited in HIV-infected hosts and impacted by antiretroviral therapy, and a high rate of modifiable life style confounders (eg, smoking, substance abuse, alcohol) and coinfections (eg, hepatitis) in HIV-infected participants. There is a need for validated biomarkers of aging in the context of HIV. Despite these differences, welldesigned studies of HIV-infected participants are likely to provide new opportunities to better understand the mechanisms that lead to aging and age-related diseases. © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Nguyen, Marie; Pean, Polidy; Lopalco, Lucia; Nouhin, Janin; Phoung, Viseth; Ly, Nary; Vermisse, Pierre; Henin, Yvette; Barré-Sinoussi, Françoise; Burastero, Samuele E; Reynes, Jean-Marc; Carcelain, Guislaine; Pancino, Gianfranco
2006-08-01
To study biological factors related to protection against HIV-1 infection in Cambodia, we recruited 48 partners of HIV-1-infected patients who remained uninfected (exposed uninfected individuals, EUs) despite unprotected sexual intercourse for more than 1 year and 49 unexposed controls (UCs). HIV-1-specific antibodies (IgA anti-gp41 and IgG anti-CD4-gp120 complex), T-cell responses, and cellular factors that may be involved in protection (peripheral blood mononuclear cell [PBMC] resistance to HIV-1 infection and beta-chemokine production) were evaluated. Anti-HIV-1 antibodies were higher in EUs than those in UCs (P = 0.01 and P = 0.04 for anti-gp41 and anti-CD4-gp120, respectively). We observed a decreased susceptibility to a primary Cambodian isolate, HIV-1KH019, in EU PBMCs as compared with UC PBMCs (P = 0.03). A weak T-cell response to one pool of HIV-1 Gag peptides was found by ELISpot in 1 of 19 EUs. Whereas T-cell specific immunity was not associated to protection, our results suggest that HIV-specific humoral immunity and reduced cell susceptibility to infection may contribute to protection against HIV-1 infection in Cambodian EUs.
Human Immunodeficiency Virus-Specific CD8+ T Cells in Human Breast Milk
Sabbaj, Steffanie; Edwards, Bradley H.; Ghosh, Mrinal K.; Semrau, Katherine; Cheelo, Sanford; Thea, Donald M.; Kuhn, Louise; Ritter, G. Douglas; Mulligan, Mark J.; Goepfert, Paul A.; Aldrovandi, Grace M.
2002-01-01
Breast-feeding infants of human immunodeficiency virus (HIV)-infected women ingest large amounts of HIV, but most escape infection. While the factors affecting transmission risk are poorly understood, HIV-specific cytotoxic T-lymphocyte (CTL) responses play a critical role in controlling HIV levels in blood. We therefore investigated the ability of breast milk cells (BMC) from HIV-infected women from the United States and Zambia to respond to HIV-1 peptides in a gamma interferon enzyme-linked immunospot assay. All (n = 11) HIV-infected women had responses to pools of Gag peptide (range, 105 to 1,400 spot-forming cells/million; mean = 718), 8 of 11 reacted to Pol, 7 reacted to Nef, and 2 of 5 reacted to Env. Conversely, of four HIV-negative women, none responded to any of the tested HIV peptide pools. Depletion and tetramer staining studies demonstrated that CD8+ T cells mediated these responses, and a chromium-release assay showed that these BMC were capable of lysing target cells in an HIV-specific manner. These data demonstrate the presence of HIV-specific major histocompatibility complex class I-restricted CD8+ CTLs in breast milk. Their presence suggests a role in limiting transmission and provides a rationale for vaccine strategies to enhance these responses. PMID:12097549
Dima, Alexandra L; Stutterheim, Sarah E; Lyimo, Ramsey; de Bruin, Marijn
2014-05-01
Disclosure of HIV status has been the focus of three decades of research, which have revealed its complex relations to many behaviors involved in HIV prevention and treatment, and exposed its central role in managing the HIV epidemic. The causes and consequences of disclosure acts have recently been the subject of several theoretical models. Although it is acknowledged that individual disclosure events are part of a broader process of disclosing one's HIV status to an increasing number of people, this process has received less theoretical attention. In quantitative studies of disclosure, researchers have often implicitly assumed that disclosure is a single unidimensional process appropriately measured via the total number of one's disclosure acts. However, there is also evidence that disclosure may have different causes and consequences depending on the types of actors involved (e.g. family members, friends) and on the presence or absence of the discloser's intention, suggesting that the unidimensionality assumption may not hold. We quantitatively examined the dimensionality of voluntary and involuntary disclosure to different categories of actors, using data collected via structured interviews in the spring of 2010 from 158 people living with HIV in Kilimanjaro, Tanzania. For voluntary disclosure, nonparametric item response analyses identified two multi-category clusters, family and community, and two single-category dimensions, partner and children. Involuntary disclosure consisted of several single- or two-category dimensions. Correlation analyses between the resulting disclosure dimensions and stigma and social support revealed distinct relationships for each disclosure dimension. Our results suggest that treating disclosure as a unidimensional construct is a simplification of disclosure processes that may lead to incorrect conclusions about disclosure correlates. We therefore recommend examining disclosure acts jointly to identify sample-specific dimensions before examining causes and consequences of disclosure. We propose a methodology for investigating disclosure processes, and recommend its adoption in future disclosure studies. Copyright © 2014 Elsevier Ltd. All rights reserved.
Foster, Pamela Payne; Cooper, Krista; Parton, Jason M; Meeks, John O
2011-04-01
This exploratory study sought to elicit information from rural Baptist leaders about their interest in HIV prevention activities within their congregation and other influencers in their human deficiency virus (HIV) prevention activities based on their geographical residence (urban vs rural). This study utilized both qualitative (in-depth interviews, N = 8) and quantitative (written survey, N = 56) methodologies (mixed method) in order to obtain pertinent information. A ministerial liaison was hired to assist in recruitment of participants within a statewide Baptist conference. Written surveys were distributed at a statewide meeting. The majority of participants (N = 50) in this study (89.3%) were receptive to conducting HIV/AIDS prevention activities within their congregations. The study also revealed rural/urban differences, including: interest in HIV/AIDS prevention, direct experiences with infected persons, or whether churches have a health-related ministry. Positive influencers of HIV/AIDS prevention in rural church leaders included either the participant or their spouse being in a health-related occupation, migratory patterns from larger metropolitan areas in other areas of the country to the rural south, and whether the church has a health-related ministry. Findings from this study are significant for a variety of reasons, including use of faith-based models for HIV/ AIDS capacity building and use of potential influencers on HIV/AIDS prevention in African Americans in the rural Deep South, where the epidemic is growing fastest. Future implications of this study might include expansion of faith-based models to include other denominations and health care providers as well of use of positive influencers to develop future HIV/AIDS intervention strategies.
Shmelkov, Evgeny; Krachmarov, Chavdar; Grigoryan, Arsen V.; Pinter, Abraham; Statnikov, Alexander; Cardozo, Timothy
2014-01-01
The extreme diversity of HIV-1 strains presents a formidable challenge for HIV-1 vaccine design. Although antibodies (Abs) can neutralize HIV-1 and potentially protect against infection, antibodies that target the immunogenic viral surface protein gp120 have widely variable and poorly predictable cross-strain reactivity. Here, we developed a novel computational approach, the Method of Dynamic Epitopes, for identification of neutralization epitopes targeted by anti-HIV-1 monoclonal antibodies (mAbs). Our data demonstrate that this approach, based purely on calculated energetics and 3D structural information, accurately predicts the presence of neutralization epitopes targeted by V3-specific mAbs 2219 and 447-52D in any HIV-1 strain. The method was used to calculate the range of conservation of these specific epitopes across all circulating HIV-1 viruses. Accurately identifying an Ab-targeted neutralization epitope in a virus by computational means enables easy prediction of the breadth of reactivity of specific mAbs across the diversity of thousands of different circulating HIV-1 variants and facilitates rational design and selection of immunogens mimicking specific mAb-targeted epitopes in a multivalent HIV-1 vaccine. The defined epitopes can also be used for the purpose of epitope-specific analyses of breakthrough sequences recorded in vaccine clinical trials. Thus, our study is a prototype for a valuable tool for rational HIV-1 vaccine design. PMID:24587168
Gill, Alexander J; Kovacsics, Colleen E; Vance, Patricia J; Collman, Ronald G; Kolson, Dennis L
2015-10-01
Expression of the cytoprotective enzyme heme oxygenase-1 (HO-1) is significantly reduced in the brain prefrontal cortex of HIV-positive individuals with HIV-associated neurocognitive disorders (HAND). Furthermore, this HO-1 deficiency correlates with brain viral load, markers of macrophage activation, and type I interferon responses. In vitro, HIV replication in monocyte-derived macrophages (MDM) selectively reduces HO-1 protein and RNA expression and induces production of neurotoxic levels of glutamate; correction of this HO-1 deficiency reduces neurotoxic glutamate production without an effect on HIV replication. We now demonstrate that macrophage HO-1 deficiency, and the associated neurotoxin production, is a conserved feature of infection with macrophage-tropic HIV-1 strains that correlates closely with the extent of replication, and this feature extends to HIV-2 infection. We further demonstrate that this HO-1 deficiency does not depend specifically upon the HIV-1 accessory genes nef, vpr, or vpu but rather on HIV replication, even when markedly limited. Finally, antiretroviral therapy (ART) applied to MDM after HIV infection is established does not prevent HO-1 loss or the associated neurotoxin production. This work defines a predictable relationship between HIV replication, HO-1 loss, and neurotoxin production in MDM that likely reflects processes in place in the HIV-infected brains of individuals receiving ART. It further suggests that correcting this HO-1 deficiency in HIV-infected MDM could provide neuroprotection above that provided by current ART or proposed antiviral therapies directed at limiting Nef, Vpr, or Vpu functions. The ability of HIV-2 to reduce HO-1 expression suggests that this is a conserved phenotype among macrophage-tropic human immunodeficiency viruses that could contribute to neuropathogenesis. The continued prevalence of HIV-associated neurocognitive disorders (HAND) underscores the need for adjunctive therapy that targets the neuropathological processes that persist in antiretroviral therapy (ART)-treated HIV-infected individuals. To this end, we previously identified one such possible process, a deficiency of the antioxidative and anti-inflammatory enzyme heme oxygenase-1 (HO-1) in the brains of individuals with HAND. In the present study, our findings suggest that the HO-1 deficiency associated with excess glutamate production and neurotoxicity in HIV-infected macrophages is a highly conserved phenotype of macrophage-tropic HIV strains and that this phenotype can persist in the macrophage compartment in the presence of ART. This suggests a plausible mechanism by which HIV infection of brain macrophages in ART-treated individuals could exacerbate oxidative stress and glutamate-induced neuronal injury, each of which is associated with neurocognitive dysfunction in infected individuals. Thus, therapies that rescue the HO-1 deficiency in HIV-infected individuals could provide additional neuroprotection to ART. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
HIV testing patterns among urban YMSM of color.
Leonard, Noelle R; Rajan, Sonali; Gwadz, Marya V; Aregbesola, Temi
2014-12-01
The heightened level of risk for HIV infection among Black and Latino young men who have sex with men (YMSM) is driven by multilevel influences. Using cross-sectional data, we examined HIV testing patterns among urban YMSM of color in a high-HIV seroprevalence area (ages 16 to 21 years). Self-reported frequency of testing was high, with 42% of youth reporting testing at a greater frequency than recommended guidelines. There were no differences between less frequent and more frequent testers on sexual risk behaviors. Most (80%) youth cited reassurance of HIV-negative status as a reason for testing. Further, over half of the sample reported numerous other reasons for HIV testing, which spanned individual, partner, social, and structural levels of influence. Approximately half of respondents indicated that peers, family members, and counselors influenced their motivation to get tested. Of concern, their first HIV test occurred approximately 2 years after their first sexual experience with another male. These results indicate the need to consider developmental issues as well as comprehensive, multilevel efforts to ensure that YMSM of color test at the Centers for Disease Control and Prevention-recommended frequency but not less than this or too frequently. © 2014 Society for Public Health Education.
HIV Testing Patterns Among Urban YMSM of Color
Leonard, Noelle R.; Ragan, Sonali; Gwadz, Marya V.; Aregbesola, Temi
2015-01-01
The heightened level of risk for HIV infection among African-American and Latino young men who have sex with men (YMSM) is driven by multi-level influences. Using cross-sectional data, we examined HIV testing patterns among urban YMSM of color in a high HIV sero-prevalence area (ages 16 to 21 years). Self-reported frequency of testing was high with 42% of youth reporting testing at a greater frequency than recommended guidelines. There were no differences between less frequent and high frequent testers on sexual risk behaviors. Most (80%) youth cited reassurance of HIV-negative status as a reason for testing. Further, over half of the sample reported numerous other reasons for HIV testing, which spanned individual, partner, social, and structural levels of influence. Approximately half of respondents indicated that peers, family members, and counselors influenced their motivation to get tested. Of concern, youths’ first HIV test occurred approximately two years after their first sexual experience with another male. These results indicate the need to consider developmental issues as well as for comprehensive, multi-level efforts to ensure that YMSM of color test at the CDC-recommended frequency, but not less than this or too frequently. PMID:24973260
Psychosocial influences on HIV-1 disease progression: neural, endocrine, and virologic mechanisms.
Cole, Steve W
2008-06-01
This review surveys empirical research pertinent to the hypothesis that activity of the hypothalamus-pituitary-adrenal (HPA) axis and/or the sympathetic nervous system (SNS) might mediate biobehavioral influences on HIV-1 pathogenesis and disease progression. Data are considered based on causal effects of neuroeffector molecules on HIV-1 replication, prospective relationships between neural/endocrine parameters and HIV-relevant biological or clinical markers, and correlational data consistent with in vivo neural/endocrine mediation in human or animal studies. Results show that HPA and SNS effector molecules can enhance HIV-1 replication in cellular models via effects on viral infectivity, viral gene expression, and the innate immune response to infection. Animal models and human clinical studies both provide evidence consistent with SNS regulation of viral replication, but data on HPA mediation are less clear. Regulation of leukocyte biology by neuroeffector molecules provides a plausible biological mechanism by which psychosocial factors might influence HIV-1 pathogenesis, even in the era of effective antiretroviral therapy. As such, neural and endocrine parameters might provide useful biomarkers for gauging the promise of behavioral interventions and suggest novel adjunctive strategies for controlling HIV-1 disease progression.
Women's Beliefs about Male Circumcision, HIV Prevention, and Sexual Behaviors in Kisumu, Kenya
Riess, Thomas H.; Achieng', Maryline M.; Bailey, Robert C.
2014-01-01
It is important to understand how women's sexual practices may be influenced by male circumcision (MC) as an HIV prevention effort. Women's beliefs about MC and sexual behaviour will likely influence the scale-up and uptake of medical MC. We conducted qualitative interviews with 30 sexually active women in Kisumu, Kenya. Women discussed MC related to perceived health benefits, condom use, sexual behaviour, knowledge of susceptibility to HIV and sexually transmitted infections (STIs), circumcision preference, and influence on circumcision uptake. Respondents had a good understanding of the partial protection of MC for acquisition of HIV for men. Women perceived circumcised men as cleaner, carrying fewer diseases, and taking more time to reach ejaculation. Male's circumcision status is a salient factor for women's sexual decision making, including partner choice, and condom use. It will be important that educational information affirms that MC provides only partial protection against female to male transmission of HIV and some STIs; that other HIV and STI prevention methods such as condoms need to be used in conjunction with MC; that MC does not preclude a man from having HIV; and that couples should develop plans for not having sex while the man is healing. PMID:24844845
[Review on the association between social culture and HIV prevalence among MSM in China].
He, Huijing; Lyu, Fan
2015-11-01
Social culture have significant influence on HIV transmission. Men who have sex with men (MSM), have their own sub-culture, by which made them very different with other population in social norm, behavior mode, as well as some HIV related behavior and the disease transmission risk. Up to date, study focused on the association between social culture and HIV transmission among MSM was limited, thus we reviewed relevant studies in the view of social culture and sub-culture of MSM, analyzed how social culture could potentially influence HIV transmission, and how sub-culture could affect MSM's friend-making, HIV risk behaviors in three aspects including social identity, social norm and social development. Furthermore, we provided some recommendations and suggestions on the future work.
Individual interviews with African-American women regarding condom use: a pilot study.
Hunter, Teressa Sanders
2010-07-01
African-American women between 25 and 34 years of age are disproportionately affected by HIV/AIDS. Current prevention techniques, including education, have not had a significant influence on decreasing the rates of HIV and increasing safer sexual practices among some African-American women. This pilot study is one step towards increasing the understanding of this serious problem and developing effective interventions to stem the tide of HIV infection in African-American women. A grounded theory approach was used to address the process that unmarried, heterosexual, African-American women used to negotiate condom use with their sexual partner. Major concepts, connections between the categories, and theoretical codes are identified in this study and can be used to predict, speculate, explain, and understand the reported behavior of African-American women in negotiating condom use with their sexual partner.
Dave, Rajnish S.
2011-01-01
Opiate-abusing individuals are in the top three risk-factor groups for HIV infection. In fact, almost 30% of HIV-infected individuals in the USA are reported to abuse opiates, highlighting the intersection of drugs of abuse with HIV/AIDS. Opiate-abusers are cognitively impaired and suffer from neurological dysfunctions that may lead to high-risk sexual behavior, poor adherence to antiretroviral regimens, and hepatitis-C virus infection. Collectively, these factors may contribute to accelerated HIV CNS disease progression. To understand the role of morphine in disease progression, we sought to determine whether morphine influences HIV-induced inflammation or viral replication in human monocyte-derived macrophages (h-mdms) and MAGI cells infected with HIV and exposed to morphine. Chronic morphine exposure of HIV-infected h-mdms led to significant alterations in secretion of IL-6 and MCP-2. Morphine enhanced IL-6 secretion and blunted MCP-2 secretion from HIV-infected h-mdms. However, exposure of HIV-infected h-mdms to morphine had no effect on TNF-α secretion. Morphine had no effect on later-stages of viral replication in HIV-infected h-mdms. Morphine had a potentially additive effect on the HIV-induced production of IL-6 and delayed HIV-induced MCP-2 production. These results suggest that in HIV-infected opiate abusers enhanced CNS inflammation might result even when HIV disease is controlled. PMID:22066570
Atun, Rifat A.; McKee, Martin; Drobniewski, Francis; Coker, Richard
2005-01-01
OBJECTIVE: To develop a methodology and an instrument that allow the simultaneous rapid and systematic examination of the broad public health context, the health care systems, and the features of disease-specific programmes. METHODS: Drawing on methodologies used for rapid situational assessments of vertical programmes for tackling communicable disease, we analysed programmes for the control human of immunodeficiency virus (HIV) and their health systems context in three regions in the Russian Federation. The analysis was conducted in three phases: first, analysis of published literature, documents and routine data from the regions; second, interviews with key informants, and third, further data collection and analysis. Synthesis of findings through exploration of emergent themes, with iteration, resulted in the identification of the key systems issues that influenced programme delivery. FINDINGS: We observed a complex political economy within which efforts to control HIV sit, an intricate legal environment, and a high degree of decentralization of financing and operational responsibility. Although each region displays some commonalities arising from the Soviet traditions of public health control, there are considerable variations in the epidemiological trajectories, cultural responses, the political environment, financing, organization and service delivery, and the extent of multisectoral work in response to HIV epidemics. CONCLUSION: Within a centralized, post-Soviet health system, centrally directed measures to enhance HIV control may have varying degrees of impact at the regional level. Although the central tenets of effective vertical HIV programmes may be present, local imperatives substantially influence their interpretation, operationalization and effectiveness. Systematic analysis of the context within which vertical programmes are embedded is necessary to enhance understanding of how the relevant policies are prioritized and translated to action. PMID:16283049
Hospers, Harm J.; van Empelen, Pepijn; Breukelen, Gerard van; Kok, Gerjo
2007-01-01
Determinants of intended condom use with steady and casual sex partners were examined among Dutch HIV-positive men who have sex with men (MSM) (N = 296). Given the proposition that safer sex behavior among HIV-positive people is a form of prosocial behavior, the present study extended the general framework of the Theory of Planned Behavior with Schwartz’s norm-activation theory and tested the assumption that personal norms would mediate the effects of other psychosocial factors on intended condom use for anal sex. In addition, it was hypothesized that, depending on the context in which sex occurs, specific motives for unprotected anal sex may have a negative influence on intended condom use and, as such, undermine a prosocial tendency to practice safer sex. Therefore, we also investigated the influence of sexual motives for unprotected anal sex on intended condom use with steady and casual sex partners. Results indicated that the Theory of Planned Behavior adequately predicted condom use intentions (for casual sex partners and steady sex partners, the explained variance was 52% and 53%, respectively). However, our proposed model of sexual decision-making significantly improved the prediction of behavioral intentions. For steady and casual sex partners, the assumption of the mediating role of personal norms on condom use intention was confirmed empirically. Additionally, sexual motives for unprotected anal sex exerted, as expected, a direct, negative effect on condom use intention with casual sex partners. The implications of the findings for future research and the development of HIV-prevention programs for HIV-positive MSM are discussed. PMID:17333328
Evans, Shenell D.; Williams, Bryman E.
2015-01-01
Transportation-related problems have been consistently reported as barriers to accessing and remaining in HIV medical care, particularly among African American women living in under-resourced areas. With emphasis on the Southern region of the United States, this commentary presents a brief overview of the HIV/AIDS epidemic among African Americans, barriers to remaining in HIV care, and pilot data from a study conducted among African American women living in Mississippi. A small focus group study was conducted to examine the relative influence of transportation-related barriers on attendance and motivation to attend HIV medical care appointments. Eight African American women (mean age of 43.50, SD = 10.82) who were engaged in medical care participated in one focus group session. Time since diagnosis ranged from 6 to 17 years. Participants reported transportation-related barriers that were generally consistent with previous research, including lack of personal transportation, limited financial resources to pay family and friends for transportation or gasoline, and inconveniences associated with sharing van services with other patients. Participants appeared to have learned how to successfully navigate these barriers in order to remain in care. Interestingly, participants reported significant fear of disclosure related to use of transportation services provided by insurance providers and community organizations. Specifically, many of the women indicated that family, friends, and neighbors questioned them about where they were going and why they used taxis. These types of encounters might influence whether individuals utilize available transportation services. Participants provided several recommendations for improving the transportation system. Additional research is warranted to obtain a more representative sampling of opinions among African American women living in under-resourced areas. PMID:26523160
Patel, Mickey V.; Ghosh, Mimi; Fahey, John V.; Ochsenbauer, Christina; Rossoll, Richard M.; Wira, Charles R.
2015-01-01
Problem Whether the concentrations of antiviral proteins, and anti-HIV activity, within human vaginal secretions changes across the menstrual cycle is unknown. Method of Study Using a menstrual cup, vaginal secretions from premenopausal women were recovered at the proliferative (d6–8), mid-cycle (d13–15) and secretory (d21–23) stages of the menstrual cycle. Antiviral protein concentration was determined by ELISA, and anti-HIV activity assessed using the TZM-bl reporter cell line. Results CCL20, RANTES, elafin, HBD2, SDF-1α and IL-8 levels were detectable in the secretions. Vaginal secretions had anti-HIV activity against specific clade B strains of HIV, with significant inhibition of IIIB and increased infectivity of transmitted/founder CH077.t. No significant differences in either antiviral protein concentration or anti-HIV activity with respect to menstrual cycle stage were measured, but marked differences were observed in both parameters over the course of the cycle between different women, and in consecutive cycles from the same woman. Conclusion The vagina contains a complement of antiviral proteins. The variation in anti-HIV activity demonstrates that immune protection in the vagina is not constant. Intra- and inter-individual variations suggest that factors in addition to sex hormones influence antiviral protection. Lastly, the menstrual cup is a new model for recovering undiluted vaginal secretions from women throughout their reproductive life. PMID:24806967
Manufacturing disability: HIV, women and the construction of difference.
Gagnon, Marilou; Stuart, Meryn
2009-01-01
In 1998, the US Supreme Court first held that asymptomatic HIV infection constituted a disability when it ruled on the case of Bragdon v. Abbott. The use of yet another label (disabled) to identify women living with HIV has been rarely (if ever) questioned. While we do value the use of this label as an anti-discriminatory strategy, we believe that there is a need to examine how language and more specifically, the use of words such as disability, limitation, and impairment may create new forms of identities for women living with HIV. Using this legal case as a starting point, the goal of this paper is to critically examine the 'fabrication' of asymptomatic HIV infection as a disability. Grounded in a feminist poststructuralist perspective, this paper exposes the relationship between language, social institutions, subjectivity, and power in the construction of difference. By doing so, it addresses the identification of women living with HIV/AIDS as disabled and the self-differentiation process that they must go through in order to live as normally as possible.
Identity management strategies among HIV-positive Colombian gay men in London.
Jaspal, Rusi; Williamson, Iain
2017-12-01
This study set out to explore the social-psychological aspects of living with HIV among a group of HIV-positive Colombian gay men in London, and the strategies that they deployed to manage ensuing threats to their identities. Focus group and individual interview data were collected from 14 Colombian gay men living with HIV, and were analysed using qualitative thematic analysis and identity process theory. The following themes are discussed: (1) identity struggles and conflicts in Colombia, (2), managing multiple layers of social stigma in England, and (3) changing interpersonal and intergroup dynamics, which highlight the inter-connections between sexual prejudice, sexual risk-taking and HIV stigma. Identity may be chronically threatened due to the multiple layers of stigma, which can limit the coping strategies available to individuals. Findings strongly support the need for action and programmes to highlight and tackle both racism and HIV stigma on the gay scene and to fund more specific resources for sub-communities of gay, bisexual and other men who have sex with men, which employ appropriately trained and culturally competent staff.
Bandali, Sarah
2014-01-01
The global fight against HIV is progressing; however, women living in rural areas particularly in sub-Saharan Africa (SSA) continue to face the devastating consequences of HIV and AIDS. Lack of knowledge and geographical barriers to HIV services are compounded by gender norms often limiting the negotiation of safe sexual practices among women living in rural areas. This paper discusses findings from a qualitative study conducted in rural areas of Mozambique examining factors that influenced women to engage in HIV risk-reduction practices. The findings from this study led to the emergence of an HIV and AIDS risk assessment and reduction (HARAR) model, which is described in detail. The model helps in understanding gender-related factors influencing men and women to engage in risk-reduction practices, which can be used as a framework in other settings to design more nuanced and contextual policies and programs. PMID:25089093
Islamic Influence on HIV Risk and Protection Among Central Asian Male Migrant Workers in Kazakhstan.
Shaw, Stacey A; McCrimmon, Tara; Mergenova, Gaukhar; Sultangaliyeva, Alma; El-Bassel, Nabila
2017-08-01
HIV incidence is increasing in Central Asia, where migrant workers experience risks for acquiring sexually transmitted HIV. As a social and structural factor that may influence perceptions and behavior, we examine how Islam shapes HIV risk and protection. Phenomenological qualitative interviews examine religion and contexts of HIV risk among 48 male Central Asian migrant workers residing in Almaty, Kazakhstan. Men described nonvaginal sex, alcohol use, premarital sex, and extramarital sex as forbidden or frowned upon. Religious networks were unlikely to discuss HIV risks, and some men viewed religious affiliation or practices as protective. Marital practices including neke (religious marriage), polygyny, and bride kidnapping may be linked to risk. Findings suggest adhering to Islamic ideals may be protective for some men, but for others, assumptions of protection may enhance risk. HIV prevention strategies among Central Asian migrants may be strengthened by attention to religious and cultural understandings of risk and protection.
Social capital and HIV risks among acculturating Asian Indian men in New York City.
Bhattacharya, Gauri
2005-12-01
This community-based, qualitative study explored social capital resources and their influences upon HIV risk behaviors in a sample of 17 heterosexual Asian Indian immigrant men residing in New York City. Our study defined social capital as the resources available to individuals and society through social relationships. At the family, peer, and community levels, social capital's influence appeared to reduce acculturative stress and HIV risks. However, participants who lacked sexually transmitted infection and HIV transmission knowledge and/or sought peer solidarity through adherence to negative peer norms (e.g., alcohol use with sex) had elevated sexual risks for HIV. These findings suggest the promise of a social capital approach in the development of HIV prevention programs, as well as the need for HIV risk and social capital researchers to examine multiple systems of social relationships in sociocultural context.
Nattabi, Barbara; Li, Jianghong; Thompson, Sandra C; Orach, Christopher G; Earnest, Jaya
2012-01-01
Background HIV-related stigma, among other factors, has been shown to have an impact on the desire to have children among people living with HIV (PLHIV). Our objective was to explore the experiences of HIV-related stigma among PLHIV in post-conflict northern Uganda, a region of high HIV prevalence, high infant and child mortality and low contraception use, and to describe how stigma affected the desires of PLHIV to have children in the future. Methods Semi-structured interviews were conducted with 26 PLHIV in Gulu district, northern Uganda. The interviews, conducted in Luo, the local language, were audio recorded, transcribed and then translated into English. Thematic data analysis was undertaken using NVivo8 and was underpinned by the “Conceptual Model of HIV/AIDS Stigma”. Results HIV-related stigma continues to affect the quality of life of PLHIV in Gulu district, northern Uganda, and also influences PLHIV's desire to have children. PLHIV in northern Uganda continue to experience stigma in various forms, including internal stigma and verbal abuse from community members. While many PLHIV desire to have children and are strongly influenced by several factors including societal and cultural obligations, stigma and discrimination also affect this desire. Several dimensions of stigma, such as types of stigma (received, internal and associated stigma), stigmatizing behaviours (abusing and desertion) and agents of stigmatization (families, communities and health systems), either directly, or indirectly, enhanced or reduced PLHIV's desire to have more children. Conclusion The social-cultural context within which PLHIV continue to desire to have children must be better understood by all health professionals who hope to improve the quality of PLHIV's lives. By delineating the stigma process, the paper proposes interventions for reducing stigmatization of PLHIV in northern Uganda in order to improve the quality of life and health outcomes for PLHIV and their children. PMID:22713256