This study forms part of the preparation of communities for HIV-preventive vaccine trials in South Africa. On the basis of the assumption that attitudes to any HIV vaccine or vaccine trials will partly be influenced by experiences of vaccination in general, this study aimed to investigate knowledge of, attitudes to, and experiences of vaccination…
Lindegger, Graham; Quayle, Michael; Ndlovu, Moses
Many attempts have been made or are ongoing for HIV prevention and HIV cure. Many successes are in the list, particularly for HIV drugs, recently proposed also for prevention. However, no eradication of infection has been achieved so far with any drug. Further, a residual immune dysregulation associated to chronic immune activation and incomplete restoration of B and T cell subsets, together with HIV DNA persistence in reservoirs, are still unmet needs of the highly active antiretroviral therapy, causing novel “non-AIDS related” diseases that account for a higher risk of death even in virologically suppressed patients. These “ART unmet needs” represent a problem, which is expected to increase by ART roll out. Further, in countries such as South Africa, where six millions of individuals are infected, ART appears unable to contain the epidemics. Regretfully, all the attempts at developing a preventative vaccine have been largely disappointing. However, recent therapeutic immunization strategies have opened new avenues for HIV treatment, which might be exploitable also for preventative vaccine approaches. For example, immunization strategies aimed at targeting key viral products responsible of virus transmission, activation, and maintenance of virus reservoirs may intensify drug efficacy and lead to a functional cure providing new perspectives also for prevention and future virus eradication strategies. However, this approach imposes new challenges to the scientific community, vaccine developers, and regulatory bodies, such as the identification of novel immunological and virological biomarkers to assess efficacy end-points, taking advantage from the natural history of infection and exploiting lessons from former trials. This review will focus first on recent advancement of therapeutic strategies, then on the progresses made in preventative approaches, discussing concepts, and problems for the way ahead for the development of vaccines for HIV treatment and prevention. PMID:25250026
Ensoli, Barbara; Cafaro, Aurelio; Monini, Paolo; Marcotullio, Simone; Ensoli, Fabrizio
Background Even in the era of highly active antiretroviral therapy (HAART), HIV-infected subjects are at higher risk of complications from vaccine-preventable diseases than those uninfected. The current international guidelines strongly recommend that these patients should receive all the routine childhood vaccinations. Although these children represent an appropriate target for immunization, the available data indicate suboptimal coverage rates. Methods To evaluate seroprotection/seropositivity rates and vaccination coverage against the common vaccine-preventable diseases, all patients with vertically transmitted HIV-1 infection who attended San Martino Hospital were enrolled. Blood samples were collected for testing antibodies against diphtheria, tetanus, hepatitis A and B viruses by Enzyme-Linked ImmunoSorbent Assay and polioviruses by microneutralization test. In order to assess immunization coverage, retrospectively was recorded the vaccination history collecting data from Regional Immunization Database. Results A total of 39 perinatally HIV-1 infected patients were included in the study. At the time of serum was obtained, the mean age was 18,1 years (range: 6-28). The median CD4+ T-lymphocyte count was 702 cells/mm(3) (2-1476 cells/mm(3)). Twenty-nine (74.4%) patients were found with HIV RNA load < 50 copies/mL. The proportion of subjects with protective anti-tetanus and anti-HBs were 43.6% and 30.8%, respectively. Seroprotection rates about 20% against rubella and measles were found, less than 20% against all the other antigens investigated. In particular, all patients resulted susceptible to mumps. High immunization rates were observed for polio and HBV (100% and 92.3%, respectively) and suboptimal for diphtheria-tetanus (84.6%). For the other recommended vaccines the rates were generally low. None of the patients received varicella vaccine doses. Conclusions As in the HAART era the vertically acquired HIV infection has become a chronic treatable disease, the vaccine-induced long-term protection plays an increasingly significant role; despite good initial response to primary vaccination, subsequent decline and loss of detectable antibodies may be prevented by additional strategies for booster doses of vaccines in adolescents and young adults. PMID:25483544
Sticchi, Laura; Bruzzone, Bianca; Caligiuri, Patrizia; Rappazzo, Emanuela; Lo Casto, Michele; De Hoffer, Laura; Gustinetti, Giulia; Viscoli, Claudio; Di Biagio, Antonio
The advent of pre-exposure prophylaxis (PrEP) and treatment as prevention (TasP) as means of HIV prevention raises issues of justice concerning how most fairly and equitably to apportion resources in support of the burgeoning variety of established HIV treatment and prevention measures and further HIV research, including HIV vaccine research. We apply contemporary approaches to social justice to assess the ethical justification for allocating resources in support of HIV vaccine research given competing priorities to support broad implementation of HIV treatment and prevention measures, including TasP and PrEP. We argue that there is prima facie reason to believe that a safe and effective preventive HIV vaccine would offer a distinct set of ethically significant benefits not provided by current HIV treatment or prevention methods. It is thereby possible to justify continued support for HIV vaccine research despite tension with priorities for treatment, prevention, and other research. We then consider a counter-argument to such a justification based on the uncertainty of successfully developing a safe and effective preventive HIV vaccine. Finally, we discuss how HIV vaccine research might now be ethically designed and conducted given the new preventive options of TasP and PrEP, focusing on the ethically appropriate standard of prevention for HIV vaccine trials. PMID:24033297
Bailey, Theodore C.; Sugarman, Jeremy
A deterministic mathematical model for the transmission dynamics of HIV infection in the presence of a preventive vaccine is considered. Although the equilibria of the model could not be expressed in closed form, their existence and threshold conditions for their stability are theoretically investigated. It is shown that the disease-free equilibrium is locally-asymptotically stable if the basic reproductive number R<1 (thus, HIV disease can be eradicated from the community) and unstable if R>1 (leading to the persistence of HIV within the community). A robust, positivity-preserving, non-standard finite-difference method is constructed and used to solve the model equations. In addition to showing that the anti-HIV vaccine coverage level and the vaccine-induced protection are critically important in reducing the threshold quantity R, our study predicts the minimum threshold values of vaccine coverage and efficacy levels needed to eradicate HIV from the community.
Gumel, A. B.; Moghadas, S. M.; Mickens, R. E.
Researchers and sponsors are required to assist HIV prevention trial participants to remain HIV-uninfected by ensuring access to prevention services. Ethics guidelines require that these HIV risk-reduction services be state of the art. This and related ethics recommendations have been intensely debated. This descriptive study aimed to identify actual HIV prevention practices for two HIV vaccine trials at five South African sites, to explore whether actual practices meet guideline recommendations and to discuss implications for practices and ethics guidelines. Practices were examined through a review of site documents and interviews with site staff and network representatives, as well as community advisory board and research ethics committee representatives. A thematic analysis of HIV prevention practices, perspectives and perceived challenges was undertaken. Findings indicated that there was a high degree of correspondence between actual practices in South African HIV vaccine trials and guideline recommendations. Key challenges for implementing prevention services were identified as partnerships, provider-promotion of services and participant uptake of services. Practices deviated most from guidelines with regard to the description of prevention plans in informed consent forms. Recommendations are made for both practices and ethics guidelines. PMID:25031609
Phase 1 preventive HIV vaccine trials are often designed as randomized, double-blind studies with the inclusion of placebo recipients. Careful consideration is needed to determine when the inclusion of placebo recipients is highly advantageous and when it is optional for achieving the study objectives of assessing vaccine safety, tolerability and immunogenicity. The inclusion of placebo recipients is generally important to form a reference group that ensures fair evaluation and interpretation of subjective study endpoints, or endpoints whose levels may change due to exposures besides vaccination. In some settings, however, placebo recipients are less important because other data sources and tools are available to achieve the study objectives. PMID:25454855
Huang, Yunda; Karuna, Shelly T; Janes, Holly; Frahm, Nicole; Nason, Martha; Edlefsen, Paul T; Kublin, James G; Corey, Lawrence; McElrath, M Juliana; Gilbert, Peter B
We evaluated replication-defective poxvirus vectors (modified vaccinia Ankara [MVA] and fowlpox [FPV]) in a homologous and heterologous vector prime-boost vaccination regimen containing matching HIV inserts (MVA-HIV and FPV-HIV) given at months 0, 1, 3, 5 and 7 in 150 healthy HIV-negative vaccinia-naïve participants. FPV-HIV alone was poorly immunogenic, while the high dose (109 pfu/2ml) of MVA-HIV alone elicited maximal responses after two injections: CD4+ and CD8+ T-cell responses in 26/55 (47.3%) and 5/60 (8.3%) of participants, respectively and IFN-? ELISpot responses in 28/62 (45.2%). The infrequent CD8+ T-cell responses following MVA-HIV priming were boosted only by the heterologous (FPV-HIV) construct in 14/27 [51.9%] of participants post-4th vaccination. Alternatively, HIV envelope-specific binding antibodies were demonstrated in approximately two-thirds of recipients of the homologous boosting regimen, but in less than 20% of subjects after the heterologous vector boost. Thus, a heterologous poxvirus vector prime-boost regimen can induce an HIV-specific CD8+ T-cell and CD4+ T-cell responses, which may be an important feature of an optimal regimen for preventive HIV vaccination. PMID:21216311
Keefer, Michael C.; Frey, Sharon E.; Elizaga, Marnie; Metch, Barbara; De Rosa, Stephen C.; Barroso, Paulo F.; Tomaras, Georgia; Cardinali, Massimo; Goepfert, Paul; Kalichman, Artur; Philippon, Valérie; McElrath, M. Juliana; Jin, Xia; Ferrari, Guido; Defawe, Olivier D.; Mazzara, Gail P.; Montefiori, David; Pensiero, Michael; Panicali, Dennis L.; Corey, Lawrence
HIV prevention research has been facing increasing ethical and operational challenges. Factors influencing the design and conduct of HIV prevention trials include a rapidly changing evidence base, new biomedical prevention methods and modalities being tested, a large diversity of countries, sites and populations affected by HIV and participating in trials, and challenges of developing and making available products that will be feasible and affordable for at-risk populations. To discuss these challenges, a meeting, Ethical considerations around novel combination prevention modalities in HIV prevention and vaccine trials in resource-limited settings, was convened by NIH/NIAID/Division of AIDS on April 22-23, 2013. Several themes emerged from the meeting: (1) because of both trial design and ethical complexities, choosing prevention packages and designing combination prevention research trials will need to be evaluated on a case by case basis in different clinical trials, countries, and health systems; (2) multilevel stakeholder engagement from the beginning is vital to a fair and transparent process and also to designing ethical and relevant trials; (3) research should generally be responsive to a host country's needs, and sponsors and stakeholders should work together to address potential barriers to future access; and finally, (4) another meeting including a broader group of stakeholders is needed to address many of the outstanding ethical issues raised by this meeting. We offer an overview of the meeting and the key discussion points and recommendations to help guide the design and conduct of future HIV prevention and vaccine research in resource-limited settings. PMID:25117930
Garner, Samual A; Anude, Chuka J; Adams, Elizabeth; Dawson, Liza
Observed seroincidence and prevalence rates in male-to-female (MTF) transgender individuals highlight the need for effective targeted HIV prevention strategies for this community. In order to develop an effective vaccine that can be used by transgender women, researchers must understand and address existing structural issues that present barriers to this group's participation in HIV vaccine clinical trials. Overcoming barriers to participation is important for ensuring HIV vaccine acceptability and efficacy for the MTF transgender community. To explore barriers and facilitators to MTF transgender participation in preventive HIV vaccine clinical trials, the HIV Vaccine Trials Network conducted focus groups among transgender women in four urban areas (Atlanta, Boston, Philadelphia, and San Francisco). Barriers and facilitators to engagement of transgender women in preventive HIV vaccine clinical trials led to the following recommendations: (a) transgender cultural competency training, (b) creating trans-friendly environments, (c) true partnerships with local trans-friendly organizations and health care providers, (d) protocols that focus on transgender specific issues, and (e) data collection and tracking of transgender individuals. These results have implications for the conduct of HIV vaccine trials, as well as engagement of transgender women in research programs in general. PMID:23446435
Andrasik, Michele Peake; Yoon, Ro; Mooney, Jessica; Broder, Gail; Bolton, Marcus; Votto, Teress; Davis-Vogel, Annet
Background South Africa is a major hub of HIV prevention trials, with plans for a licensure trial to start in 2015. The appropriate standards of care and of prevention in HIV vaccine trials are complex and debated issues and ethical guidelines offer some direction. However, there has been limited empirical exploration of South African stakeholders’ perspectives on ethical guidance related to prevention and care in HIV vaccine trials. Methods Site staff, Community Advisory Board members and Research Ethics Committee members involved with current HIV vaccine trials in South Africa were invited to participate in an exploration of their views. A questionnaire listed 10 care and 10 prevention recommendations drawn from two widely available sets of ethical guidelines for biomedical HIV prevention trials. Respondents (n?=?98) rated each recommendation on five dimensions: “Familiarity with”, “Ease of Understanding”, “Ease of Implementing”, “Perceived Protection”, and “Agreement with” each ethical recommendation. The ratings were used to describe stakeholder perspectives on dimensions for each recommendation. Dimension ratings were averaged across the five dimensions and used as an indication of overall merit for each recommendation. Differences were explored across dimensions, between care-oriented and prevention-oriented recommendations, and between stakeholder groups. Results Both care and prevention recommendations were rated highly overall, with median ratings well above the scale midpoint. In general, informed consent recommendations were most positively rated. Care-related recommendations were rated significantly more positively than prevention-related recommendations, with the five lowest-rated recommendations being prevention-related. The most problematic dimension across all recommendations was “Ease of Implementing,” and the least problematic was “Agreement with,” suggesting the most pressing stakeholder concerns are practical rather than theoretical; that is, respondents agree with but see barriers to the attainment of these recommendations. Conclusions We propose that prevention recommendations be prioritized for refinement, especially those assigned bottom-ranking scores for “Ease of Implementing”, and/ or “Ease of Understanding” in order to assist vaccine stakeholders to better comprehend and implement these recommendations. Further qualitative research could also assist to better understand nuances in stakeholder reservations about implementing such recommendations. PMID:24981027
Abstract The HIV prevention landscape is evolving rapidly, and future efficacy trials of candidate vaccines, which remain the best long-term option for stemming the HIV epidemic, will be conducted in the context of partially effective nonvaccine prevention modalities. It is essential that these trials provide for valid and efficient evaluation of vaccine efficacy and immune correlates. The availability of partially effective prevention modalities presents opportunities to study their interactions with vaccines to maximally reduce HIV incidence. This article proposes an approach for conducting future vaccine efficacy trials in the context of background use of partially effective nonvaccine prevention modalities, and for conducting future vaccine efficacy trials that provide nonvaccine prevention modalities in one or more of the randomized study groups. Strategies are discussed for responding to emerging evidence on nonvaccine prevention modalities during ongoing vaccine trials. Next-generation HIV vaccine efficacy trials will almost certainly be more complex in their design and implementation but may become more relevant to at-risk populations and better suited to the ultimate goal of reducing HIV incidence at the population level. PMID:23597282
Gilbert, Peter; Buchbinder, Susan; Kublin, James; Sobieszczyk, Magdalena E.; Hammer, Scott M.
Purpose of the review Here we highlight the latest advances in HIV vaccine concepts that will expand our knowledge on how to elicit effective acquisition-prevention and/or control of SIV replication in the NHP model. Recent findings In the context of the promising analyses from the RV144 Thai Trial and the effective control of SIV replication exerted by rhCMV-(SIV) elicited EM CD8 T cells, the HIV field has recently shifted toward vaccine concepts that combine protection from acquisition with effective control of SIV replication. Current studies in the NHP model have demonstrated the efficacy of HIV-neutralizing antibodies via passive transfer, the potential importance of the CD4 Tfh subset, the ability to effectively model the RV144 vaccine trial and the capacity of an Ad26 prime and MVA boost to elicit Env-specific antibody and cellular responses that both limit acquisition and control heterologous SIVmac251 challenge. Summary The latest work in the NHP model suggests that the next generation HIV-1 vaccines should aim to provoke a comprehensive adaptive immune response for both prevention of SIV acquisition as well as control of replication in break through infection. PMID:23666390
Lynch, Rebecca; Yamamoto, Takuya; McDermott, Adrian B
In November 2010, the iPrEx study reported that pre-exposure prophylaxis (PrEP) with daily tenofovir disoproxil fumarate/emtricitabine reduced HIV infections by 44% among men who have sex with men and subsequent trials corroborated efficacy among heterosexual men and women. During regularly scheduled follow-up visits from January-March 2011, participants in an ongoing phase 2b vaccine efficacy trial completed an anonymous web survey about PrEP. Among 376 respondents, 17% reported they were very likely to use PrEP in the next year. Non-white participants were more likely to use PrEP. Among those with some level of interest, intent to use PrEP was greatest if the drug were available through the clinical trial or health insurance. Most (91%) believed taking PrEP would not change their willingness to stay in the vaccine trial and few thought it would affect recruitment. As key stakeholders, currently enrolled trial participants can offer vital input about emerging prevention technologies that may affect the design of future HIV vaccine and non-vaccine prevention trials. PMID:23614998
Fuchs, Jonathan D.; Sobieszczyk, Magdalena E.; Madenwald, Tamra; Grove, Doug; Karuna, Shelly T.; Andrasik, Michele; Sherwat, Adam; Broder, Gail; Mayer, Kenneth; Koblin, Beryl; Hammer, Scott
The human immunodeficiency virus (HIV) burden in women continues to increase, and heterosexual contact is now the most common route of infection worldwide. Effective protection of women against HIV-1 infection may require a vaccine specifically targeting mucosal immune responses in the female genital tract (FGT). To achieve this goal, a much better understanding of the immunology of the FGT is needed. Here we review the architecture of the immune system of the FGT, recent studies of potential methods to achieve the goal of mucosal protection in women, including systemic-prime, mucosal-boost, FGT-tropic vectors and immune response altering adjuvants. Advances in other fields that enhance our understanding of female genital immune correlates and the interplay between hormonal and immunological systems may also help to achieve protection of women from HIV infection. PMID:25408686
Rafferty, Hannah; Sibeko, Sengeziwe; Rowland-Jones, Sarah
Developing and disseminating a preventive HIV vaccine is a primary scientific and public health objective. However, little is known about HIV vaccine acceptability in the high prevalence setting of South Africa—where young adults are likely to be targeted in early dissemination efforts. In 2007, we conducted six focus groups (n=42) with South Africans aged 18-24 years old. We used a deductive framework approach to identify key motivators and barriers to future HIV vaccine uptake. Participants identified HIV testing, HIV stigma, mistrust of the health care system, and concerns about sexual disinhibition as barriers to vaccine uptake. For women, family members and friends were strong motivators for vaccine uptake, while men were more likely to see vaccines as an opportunity to stop using HIV prevention strategies such as condoms and partner reductions. Implications of these findings for developing HIV vaccine dissemination strategies and policy in South Africa are discussed. PMID:19509123
Sayles, Jennifer N.; Macphail, Catherine L.; Newman, Peter A.; Cunningham, William E.
The past few years have witnessed many promising advances in HIV prevention strategies involving pre-exposure prophylaxis approaches. Some may now wonder whether an HIV vaccine is still needed, and whether developing one is even possible. The partial efficacy reported in the RV144 trial and the encouraging results of the accompanying immune correlates analysis suggest that an effective HIV vaccine is achievable. These successes have provided a large impetus and guidance for conducting more HIV vaccine trials. A key lesson learned from RV144 is that assessment of HIV acquisition is now a feasible and valuable primary objective for HIV preventive vaccine trials. In this article we review how RV144 and other HIV vaccine efficacy trials have instructed the field and highlight some of the HIV vaccine concepts in clinical development. After a long and significant investment, HIV vaccine clinical research is paying off in the form of valuable lessons that, if applied effectively, will accelerate the path toward a safe and effective vaccine. Together with other HIV prevention approaches, preventive and therapeutic HIV vaccines will be invaluable tools in bringing the epidemic to an end. PMID:24033299
Day, Tracey A.; Kublin, James G.
While the human immunodeficiency virus (HIV)/AIDS pandemic continues, the incidence of HIV infections has fallen because of the deployment of antiretroviral drugs and multiple prevention modalities. To achieve a durable end to the pandemic, a vaccine remains essential. Recent advances in vaccinology offer new promise for an effective HIV vaccine. PMID:25151483
Fauci, Anthony S; Folkers, Gregory K; Marston, Hilary D
Sexual mucosal transmission of HIV-1 is the most common means of spread of HIV\\/AIDS throughout the world. Although it may\\u000a be reasonable to assume that a vaccine that works to eliminate viral replication in the systemic lymphoid tissue may be partially\\u000a protective, there is still a reasonable belief that a vaccine that engenders high level of immune defenses at mucosal
Background HIV vaccine trials generally require that pregnant women are excluded from participation, and contraceptive methods must be used to prevent pregnancy during the trial. However, access to quality services and misconceptions associated with contraceptive methods may impact on their effective use in developing countries. We describe the pattern of contraceptive use in a multi-site phase I/IIa HIV Vaccine trial in East Africa (Uganda, Kenya and Tanzania) and factors that may have influenced their use during the trial. Methods Pregnancy prevention counseling was provided to female participants during informed consent process and at each study visit. Participants' methods of contraception used were documented. Methods of contraceptives were provided on site. Pregnancy testing was done at designated visits during the trial. Obstacles to contraceptive use were identified and addressed at each visit. Results Overall, 103 (31.8%) of a total of 324 enrolled volunteers were females. Female participants were generally young with a mean age of 29(±7.2), married (49.5%) and had less than high school education (62.1%). Hormonal contraceptives were the most common method of contraception (58.3%) followed by condom use (22.3%). The distribution of methods of contraception among the three sites was similar except for more condom use and less abstinence in Uganda. The majority of women (85.4%) reported to contraceptive use prior to screening. The reasons for not using contraception included access to quality services, insufficient knowledge of certain methods, and misconceptions. Conclusion Although hormonal contraceptives were frequently used by females participating in the vaccine trial, misconceptions and their incorrect use might have led to inconsistent use resulting in undesired pregnancies. The study underscores the need for an integrated approach to pregnancy prevention counseling during HIV vaccine trials. Trial Registration ClinicalTrials.gov NCT00123968 PMID:19360102
Kibuuka, Hannah; Guwatudde, David; Kimutai, Robert; Maganga, Lucas; Maboko, Leonard; Watyema, Cecilia; Sawe, Fredrick; Shaffer, Douglas; Matsiko, Dickson; Millard, Monica; Michael, Nelson; Wabwire-Mangen, Fred; Robb, Merlin
All current human immunodeficiency virus (HIV) vaccine candidates contain multiple viral components and elicit antibodies that react positively in licensed HIV diagnostic tests, which contain similar viral products. Thus, vaccine trial participants could be falsely diagnosed as infected with HIV. Additionally, uninfected, seropositive vaccinees may encounter long-term social and economic harms. Moreover, this also interferes with early detection of true HIV infections during preventive HIV vaccine trials. An HIV-seropositive test result among uninfected vaccine trial participants is a major public health concern for volunteers who want to participate in future HIV vaccine trials. Based on the increased number of HIV vaccines being tested globally, it is essential to differentiate vaccine- from virus-induced antibodies. Using a whole-HIV-genome phage display library, we identified conserved sequences in Env-gp41 and Gag-p6 which are recognized soon after infection, do not contain protective epitopes, and are not part of most current HIV vaccines. We established a new HIV serodetection assay based on these peptides. To date, this assay, termed HIV-SELECTEST, demonstrates >99% specificity and sensitivity. Importantly, in testing of plasma samples from multiple HIV vaccine trials, uninfected trial participants scored negative, while all intercurrent infections were detected within 1 to 3 months of HIV infection. The new HIV-SELECTEST is a simple but robust diagnostic tool for easy implementation in HIV vaccine trials and blood banks worldwide. PMID:16474117
Khurana, Surender; Needham, James; Mathieson, Bonnie; Rodriguez-Chavez, Isaac R.; Catanzaro, Andrew T.; Bailer, Robert T.; Kim, Jerome; Polonis, Vicky; Cooper, David A.; Guerin, Jan; Peterson, Michael L.; Gurwith, Marc; Nguyen, Nga; Graham, Barney S.; Golding, Hana
"No virus, no transmission." Studies have repeatedly shown that viral load (the quantity of virus present in blood and sexual secretions) is the strongest predictor of HIV transmission during unprotected sex or transmission from infected mother to child. Effective treatment lowers viral load to undetectable levels. If one could identify and treat all HIV-infected people immediately after infection, the HIV/AIDS epidemic would eventually disappear. Such a radical solution is currently unrealistic. In reality, not all people get tested, especially when they fear stigma and discrimination. Thus, not all HIV-infected individuals are known. Of those HIV-positive individuals for whom the diagnosis is known, not all of them have access to therapy, agree to be treated, or are taking therapy effectively. Some on effective treatment will stop, and in others, the development of resistance will lead to treatment failure. Furthermore, resources are limited: should we provide drugs to asymptomatic HIV-infected individuals without indication for treatment according to guidelines in order to prevent HIV transmission at the risk of diverting funding from sick patients in urgent need? In fact, the preventive potential of anti-HIV drugs is unknown. Modellers have tried to fill the gap, but models differ depending on assumptions that are strongly debated. Further, indications for antiretroviral treatments expand; in places like Vancouver and San Francisco, the majority of HIV-positive individuals are now under treatment, and the incidence of new HIV infections has recently fallen. However, correlation does not necessarily imply causation. Finally, studies in couples where one partner is HIV-infected also appear to show that treatment reduces the risk of transmission. More definite studies, where a number of communities are randomized to either receive the "test-and-treat" approach or continue as before, are now in evaluation by funding agencies. Repeated waves of testing would precisely measure the incidence of HIV infection. Such trials face formidable logistical, practical and ethical obstacles. However, without definitive data, the intuitive appeal of "test-and-treat" is unlikely to translate into action on a global scale. In the meantime, based on the available evidence, we must strive to provide treatment to all those in medical need under the current medical guidelines. This will lead to a decrease in HIV transmission while "test-and-treat" is fully explored in prospective clinical trials. PMID:21612619
Although the HIV incidence rate has slowed in some countries, HIV remains a serious health challenge, particularly in the developing world. The epidemic is increasingly feminised, with young women at high risk of acquiring the virus. There is thus a clear requirement for acceptable woman-initiated methods of HIV prevention. Foremost among these are vaginally-applied substances known as microbicides; early research into potential microbicides focussed on non-HIV-specific compounds such as surfactants and polyanionic entry inhibitors. However, proof of the microbicide concept as a viable prevention strategy was not provided until the CAPRISA 004 trial of a microbicide containing the HIV-specific antiretroviral tenofovir was completed in mid-2010. Confirmation of the proof of concept provided by CAPRISA 004 by at least two major trials will hopefully lead to licensure of the product by 2018. Parallel studies are planned to ascertain the feasibility of implementation of these products in the public sector with subsequent research focussed on appropriate and acceptable methods of delivery of the active ingredient, and to increase adherence through other delivery systems such as vaginal rings. PMID:22310825
of sexual activity Â· Condom skills education Â· Group-based interactive HIV prevention intervention #12;( SEETopics in hiv SUMMARY OF SUCCESSFUL STRATEGIES Condoms Used properly, condoms are up to 87 people about HIV, and in developing, implementing, and evaluating prevention programs 5. Male Condoms
HIV antibody (Ab) functions capable of preventing mucosal cell-free or cell-to-cell HIV transmission are critical for the development of effective prophylactic and therapeutic vaccines. In addition to CD4+ T cells, other potential HIV-target cell types including antigen-presenting cells (APCs) (dendritic cells, macrophages) residing at mucosal sites are infected. Moreover, the interactions between APCs and HIV lead to HIV cell-to-cell transmission. Recently discovered broadly neutralizing antibodies (NAbs) are able to neutralize a broad spectrum of HIV strains, inhibit cell-to-cell transfer, and efficiently protect from infection in the experimentally challenged macaque model. However, the 31% protection observed in the RV144 vaccine trial in the absence of detectable NAbs in blood samples pointed to the possible role of additional Ab inhibitory functions. Increasing evidence suggests that IgG Fc? receptor (Fc?R)-mediated inhibition of Abs present at the mucosal site may play a role in protection against HIV mucosal transmission. Moreover, mucosal IgA Abs may be determinant in protection against HIV sexual transmission. Therefore, defining Ab inhibitory functions that could lead to protection is critical for further HIV vaccine design. Here, we review different inhibitory properties of HIV-specific Abs and discuss their potential role in protection against HIV sexual transmission. PMID:24995008
Su, Bin; Moog, Christiane
Background Informed consent based on comprehension of potential risks and benefits is fundamental to the ethical conduct of clinical research. We explored mental models of candidate HIV vaccines and clinical trials that may impact on the feasibility and ethics of biomedical HIV prevention trials among men who have sex with men (MSM) in India. Methods A community-based research project was designed and implemented in partnership with community-based organizations serving MSM in Chennai and Mumbai. We conducted 12 focus groups (n?=?68) with diverse MSM and 14 key informant interviews with MSM community leaders/service providers using a semi-structured interview guide to explore knowledge and beliefs about HIV vaccines and clinical trials. Focus groups (60–90 minutes) and interviews (45–60 minutes) were conducted in participants’ native language (Tamil in Chennai; Marathi or Hindi in Mumbai), audio-taped, transcribed and translated into English. We explored focus group and interview data using thematic analysis and a constant comparative method, with a focus on mental models of HIV vaccines and clinical trials. Results A mental model of HIV vaccine-induced seropositivity as “having HIV” resulted in fears of vaccine-induced infection and HIV stigma. Some participants feared inactivated vaccines might “drink blood” and “come alive”. Pervasive preventive misconception was based on a mental model of prevention trials as interventions, overestimation of likely efficacy of candidate vaccines and likelihood of being assigned to the experimental group, with expectations of protective benefits and decreased condom use. Widespread misunderstanding and lack of acceptance of placebo and random assignment supported perceptions of clinical trials as “cheating”. Key informants expressed concerns that volunteers from vulnerable Indian communities were being used as “experimental rats” to benefit high-income countries. Conclusions Evidence-informed interventions that engage with shared mental models among potential trial volunteers, along with policies and funding mechanisms that ensure local access to products that demonstrate efficacy in trials, may support the safe and ethical implementation of HIV vaccine trials in India. PMID:23919283
A vaccine that can prevent the transmission of HIV-1 at the site of exposure to the host is one of the best hopes to control the HIV-1 pandemic. The trimeric envelope spike consisting of heterodimers, gp120 and gp41, is essential for virus entry and thus has been a key target for HIV-1 vaccine development. However, it has been extremely difficult to identify the types of antibodies required to block the transmission of various HIV-1 strains and the immunogens that can elicit such antibodies due to the high genetic diversity of the HIV-1 envelope. The modest efficacy of the gp120 HIV-1 vaccine used in the RV144 Thai trial, including the studies on the immune correlates of protection, and the discovery of vaccine-induced immune responses to certain signature regions of the envelope have shown that the gp120 variable loop 2 (V2) is an important region. Since there is evidence that the V2 region interacts with the integrin ?4?7 receptor of the host cell, and that this interaction might be important for virus capture, induction of antibodies against V2 loop could be postulated as one of the mechanisms to prevent the acquisition of HIV-1. Immunogens that can induce these antibodies should therefore be taken into consideration when designing HIV-1 vaccine formulations. PMID:24191938
Rao, Mangala; Peachman, Kristina K; Kim, Jiae; Gao, Guofen; Alving, Carl R; Michael, Nelson L; Rao, Venigalla B
Since the human immunodeficiency virus (HIV-1) pandemic began, few prophylactic vaccines have reached phase III trials. Only one has shown partial efficacy in preventing HIV-1 infection. The introduction of antiretroviral therapy (ART) has had considerable success in controlling infection and reducing transmission but in so doing has changed the nature of HIV-1 infection for those with access to ART. Access, compliance, and toxicity alongside the emergence of serious non-AIDS morbidity and the sometimes poor immune reconstitution in ART-treated patients have emphasized the need for additional therapies. Such therapy is intended to contribute to control of HIV-1 infection, permit structured treatment interruptions, or even establish a functional cure of permanently suppressed and controlled infection. Both immunotherapy and therapeutic vaccination have the potential to reach these goals. In this review, the latest developments in immunotherapy and therapeutic vaccination are discussed. PMID:24991420
Tanner, Helen; Dalgleish, Angus
have more tools to effectively prevent HIV than ever before. Since no single strategy provides complete protection or is right for all individuals, a combination of methods is needed to help reduce HIV transmission. CDC and its partners are currently pursuing a High-Impact Prevention approach to reducing the continued toll of HIV. This approach seeks to use the best mix of proven, cost-effective, and scalable interventions for high-risk populations and areas of the nation (see “Future of HIV Prevention ” fact sheet for information). Below is an overview of proven prevention strategies to date. HIV Testing and Linkage to Care HIV testing is the first critical step to ending the HIV epidemic in the United States, and CDC recommends that all Americans aged 13-64 get tested at least once for HIV as a routine part of medical care, and that gay and bisexual men and others at high risk get tested at least once a year. HIV testing is the only way to identify the nearly one in five Americans currently living with HIV who do not know they are infected and may be
This paper analyzes the main trend of the development of acquired immunodeficiency syndrome (AIDS) vaccines in recent years. Designing an HIV-1 vaccine that provides robust protection from HIV-1 infection remains a challenge despite many years of effort. Therefore, we describe the receptor binding domain of gp120 as a target for developing AIDS vaccines. And we recommend some measures that could induce efficiently and produce cross-reactive neutralizing antibodies with high binding affinity. Those measures may offer a new way of the research and development of the potent and broad AIDS vaccines.
Liu, Huan; Bi, Wenwen; Wang, Qian; Lu, Lu; Jiang, Shibo
The ultimate solution to the global HIV-1 epidemic will probably require the development of a safe and effective vaccine. Multiple vaccine platforms have been evaluated in preclinical and clinical trials, but given the disappointing results of clinical efficacy studies so far, novel vaccine approaches are needed. In this Opinion article, we discuss the scientific basis and clinical potential of novel adenovirus and cytomegalovirus vaccine vectors for HIV-1 as two contrasting but potentially complementary vector approaches. Both of these vector platforms have demonstrated partial protection against stringent simian immunodeficiency virus challenges in rhesus monkeys using different immunological mechanisms. PMID:25296195
Barouch, Dan H; Picker, Louis J
The ultimate solution to the global HIV-1 epidemic will probably require the development of a safe and effective vaccine. Multiple vaccine platforms have been evaluated in both preclinical and clinical trials, but, given the disappointing results of the clinical efficacy studies so far, novel vaccine approaches are needed. In this Opinion article, we discuss the scientific basis and clinical potential of novel adenovirus and cytomegalovirus vaccine vectors for HIV-1 as two contrasting, but potentially complementary, vector approaches. Both of these vector platforms have demonstrated partial protection against stringent simian immunodeficiency virus challenges in rhesus monkeys using different immunological mechanisms. PMID:25296195
Picker, Louis J.
HIV-1 Tat B-cell epitope vaccination was ineffectual in preventing viral rebound after ART cessation: HIV rebound with current ART appears to be due to infection with new endogenous founder virus and not to resurgence of pre-existing Tat-dependent viremia.
CD4 T cell activation, essential for productive HIV infection, is provided initially in acute HIV infection by innate immune system secretion of activating cytokines. This cytokine response wanes with time and long-term activation of CD4 cells is maintained by HIV Tat protein secreted by HIV infected cells. Structured treatment interruption (STI) in well-controlled antiretroviral-treated (ART) subjects was explored a decade ago with a consensus finding that, in most subjects, HIV levels rebounded within four weeks to pre-ART levels. Based on these observations we initiated a randomized placebo-controlled study of a universal anti-Tat epitope vaccine, TUTI-16, to determine if immunological blockade of Tat would prevent HIV rebound after ART cessation. TUTI-16 immunization was safe, with predominantly mild local and systemic injection-related adverse reactions. TUTI-16 was also immunogenic, with high levels of anti-Tat antibodies compared with levels previously shown to reduce HIV replication in vivo. Of 21 subjects analyzed, 13 (62%) had HIV rebounds vs. 8 (38%) that remained aviremia, but this distribution was not vaccine-related (p = 0.61 log-rank (Mantel-Cox) test), nullifying our hypothesis that anti-Tat antibodies would block rebound of Tat-dependent set-point HIV viremia after ART cessation. Our present findings are consistent with recent molecular findings that rebounding virus following STI is homogeneous and unrelated to previous circulating HIV, suggesting that rebounding HIV represents new founder virus, akin to the original acute HIV infection. We propose, therefore, that STI may have potential as a practical and economical approach to testing the safety and efficacy of candidate prophylactic HIV vaccines. PMID:23095869
Goldstein, Gideon; Damiano, Eve; Donikyan, Mardik; Pasha, Malika; Beckwith, Erik; Chicca, John
During the past two decades of the HIV/AIDS pandemic, several recruitment campaigns were designed to generate community involvement in preventive HIV vaccine clinical trials. These efforts utilized a blend of advertising and marketing strategies mixed with public relations and community education approaches to attract potential study participants to clinical trials (integrated marketing communications). Although more than 30,000 persons worldwide have participated in preventive HIV vaccine studies, no systematic analysis of recruitment campaigns exists. This content analysis study was conducted to examine several United States and Canadian recruitment campaigns for one of the largest-scale HIV vaccine trials to date (the “Step Study”). This study examined persuasive features consistent with the Elaboration Likelihood Model (ELM) including message content, personal relevance of HIV/AIDS and vaccine research, intended audiences, information sources, and other contextual features. The results indicated variation in messages and communication approaches with gay men more exclusively targeted in these regions. Racial/ethnic representations also differed by campaign. Most of the materials promote affective evaluation of the information through heuristic cueing. Implications for subsequent campaigns and research directions are discussed. PMID:19609373
Frew, Paula M.; Macias, Wendy; Chan, Kayshin; Harding, Ashley C.
This study examined HIV vaccine acceptability among immigrant Thai residents in Los Angeles, California. We combined a qualitative research method (focus groups) with an innovative market research method (conjoint analysis). Focus groups explored social issues, concerns, barriers and motivators associated with HIV vaccine acceptability. Conjoint analysis was used to assess preferences among eight hypothetical HIV vaccines with varying attribute profiles and the impact of various attributes on acceptability. Five main themes were identified in the focus groups regarding acceptance and utilization of preventive HIV vaccines: (1) vaccine characteristics, such as efficacy, physical side-effects and cost, (2) fear of a vaccine, (3) vaccine acceptability and optimism, (4) social and family responses and (5) behavioral disinhibition. Conjoint analysis revealed HIV vaccine acceptability ranging from 7.4 (SD = 19.4) to 85.2 (SD = 24.3) across eight hypothetical vaccines. The vaccine with the highest acceptability had the following attributes: 99% efficacy, no side-effects, 10 years of protection, protects against one sub-type, free, one dose and given by injection. Vaccine efficacy had the greatest impact on acceptability (51.4, p = .005), followed by side-effects (11.1, p = .005) and duration of protection (8.3, p = .005). Despite some apprehensions and concerns, Thai residents perceived an HIV vaccine as making an important contribution to society and to protecting oneself and one’s family from HIV infection. Nevertheless, acceptability of a partially efficacious vaccine may be low, suggesting the need for tailored social marketing interventions that might emphasize a collectivistic rather than an individualistic focus. Assessing HIV vaccine acceptability using a mixed-method approach is feasible with Thai residents and should lend itself to HIV vaccine research with other Asian Pacific Islander populations in the US. PMID:18608068
Lee, Sung-Jae; Brooks, Ronald A.; Newman, Peter A.; Seiden, Danielle; Sangthong, Rassamee; Duan, Naihua
Background Safety of vaccines remains a cornerstone of building public trust on the use of these cost-effective and life-saving public health interventions. In some settings, particularly Sub-Saharan Africa, there is a high prevalence of HIV infection and a high burden of vaccine-preventable diseases. There is evidence suggesting that the immunity induced by some commonly used vaccines is not durable in HIV-infected persons, and therefore, repeated vaccination may be considered to ensure optimal vaccine-induced immunity in this population. However, some vaccines, particularly the live vaccines, may be unsafe in HIV-infected persons. There is lack of evidence on the safety profile of commonly used vaccines among HIV-infected persons. We are therefore conducting a systematic review to assess the safety profile of routine vaccines administered to HIV-infected persons. Methods/Design We will select studies conducted in any setting where licensed and effective vaccines were administered to HIV-infected persons. We will search for eligible studies in PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, Africa-Wide, PDQ-Evidence and CINAHL as well as reference lists of relevant publications. We will screen search outputs, select studies and extract data in duplicate, resolving discrepancies by discussion and consensus. Discussion Globally, immunisation is a major public health strategy to mitigate morbidity and mortality caused by various infectious disease-causing agents. In general, there are efforts to increase vaccination coverage worldwide, and for these efforts to be successful, safety of the vaccines is paramount, even among people living with HIV, who in some situations may require repeated vaccination. Results from this systematic review will be discussed in the context of the safety of routine vaccines among HIV-infected persons. From the safety perspective, we will also discuss whether repeat vaccination strategies may be feasible among HIV-infected persons. Systematic review registration PROSPERO CRD42014009794. PMID:25212760
HIV epidemiology informs prevention trial design and program planning. Nine clinical research centers (CRC) in sub-Saharan Africa conducted HIV observational epidemiology studies in populations at risk for HIV infection as part of an HIV prevention and vaccine trial network. Annual HIV incidence ranged from below 2% to above 10% and varied by CRC and risk group, with rates above 5% observed in Zambian men in an HIV-discordant relationship, Ugandan men from Lake Victoria fishing communities, men who have sex with men, and several cohorts of women. HIV incidence tended to fall after the first three months in the study and over calendar time. Among suspected transmission pairs, 28% of HIV infections were not from the reported partner. Volunteers with high incidence were successfully identified and enrolled into large scale cohort studies. Over a quarter of new cases in couples acquired infection from persons other than the suspected transmitting partner. PMID:25602351
Kamali, Anatoli; Price, Matt A.; Lakhi, Shabir; Karita, Etienne; Inambao, Mubiana; Sanders, Eduard J.; Anzala, Omu; Latka, Mary H.; Bekker, Linda-Gail; Kaleebu, Pontiano; Asiki, Gershim; Ssetaala, Ali; Ruzagira, Eugene; Allen, Susan; Farmer, Paul; Hunter, Eric; Mutua, Gaudensia; Makkan, Heeran; Tichacek, Amanda; Brill, Ilene K.; Fast, Pat; Stevens, Gwynn; Chetty, Paramesh; Amornkul, Pauli N.; Gilmour, Jill
HIV epidemiology informs prevention trial design and program planning. Nine clinical research centers (CRC) in sub-Saharan Africa conducted HIV observational epidemiology studies in populations at risk for HIV infection as part of an HIV prevention and vaccine trial network. Annual HIV incidence ranged from below 2% to above 10% and varied by CRC and risk group, with rates above 5% observed in Zambian men in an HIV-discordant relationship, Ugandan men from Lake Victoria fishing communities, men who have sex with men, and several cohorts of women. HIV incidence tended to fall after the first three months in the study and over calendar time. Among suspected transmission pairs, 28% of HIV infections were not from the reported partner. Volunteers with high incidence were successfully identified and enrolled into large scale cohort studies. Over a quarter of new cases in couples acquired infection from persons other than the suspected transmitting partner. PMID:25602351
Kamali, Anatoli; Price, Matt A; Lakhi, Shabir; Karita, Etienne; Inambao, Mubiana; Sanders, Eduard J; Anzala, Omu; Latka, Mary H; Bekker, Linda-Gail; Kaleebu, Pontiano; Asiki, Gershim; Ssetaala, Ali; Ruzagira, Eugene; Allen, Susan; Farmer, Paul; Hunter, Eric; Mutua, Gaudensia; Makkan, Heeran; Tichacek, Amanda; Brill, Ilene K; Fast, Pat; Stevens, Gwynn; Chetty, Paramesh; Amornkul, Pauli N; Gilmour, Jill
While morbidity and mortality from vaccine preventable diseases have declined, some college students remain susceptible to measles, rubella, diptheria, tetanus, or polio. Colleges and universities have the opportunity to ensure protection of students, faculty, and employees by establishing and enforcing immunization requirements. (Author/DF)
Bart, Kenneth J.
Access to the article is free a year after publication, registration and sign-in are required: While the pursuit of basic laboratory research will continue to be important in the development of an HIV vaccine, the results of the Thai trial underscore the extraordinary importance of also performing focused human clinical trials of vaccine strategies.
Norman L. Letvin (Harvard Medical School;Department of Medicine)
The focus of most current HIV-1 vaccine development is on antibody-based approaches. This is because certain antibody responses correlated with protection from HIV-1 acquisition in the RV144 phase III trial, and because a series of potent and broad spectrum neutralizing antibodies have been isolated from infected individuals. Taken together, these two findings suggest ways forward to develop a neutralizing antibody-based vaccine. However, understanding of the correlates of protection from disease in HIV-1 and other infections strongly suggests that we should not ignore CTL-based research. Here we review recent progress in the field and highlight the challenges implicit in HIV-1 vaccine design and some potential solutions. PMID:23866844
Background It is important for public health and within the HIV vaccine development field to understand the potential population level impact of an HIV vaccine of partial efficacy—both in preventing infection and in reducing viral load in vaccinated individuals who become infected—in the context of a realistic future implementation scenario in resource limited settings. Methods An individual level model of HIV transmission, progression and the effect of antiretroviral therapy was used to predict the outcome to 2060 of introduction in 2025 of a partially effective vaccine with various combinations of efficacy characteristics, in the context of continued ART roll-out in southern Africa. Results In the context of our base case epidemic (in 2015 HIV prevalence 28% and incidence 1.7 per 100 person years), a vaccine with only 30% preventative efficacy could make a substantial difference in the rate with which HIV incidence declines; the impact on incidence in relative terms is projected to increase over time, with a projected 67% lower HIV incidence in 2060 compared with no vaccine introduction. The projected mean decline in the general adult population death rate 2040–2060 is 11%. A vaccine with no prevention efficacy but which reduces viral load by 1 log is predicted to result in a modest (14%) reduction in HIV incidence and an 8% reduction in death rate in the general adult population (mean 2040–2060). These effects were broadly similar in multivariable uncertainty analysis. Interpretation Introduction of a partially effective preventive HIV vaccine would make a substantial long-term impact on HIV epidemics in southern Africa, in addition to the effects of ART. Development of an HIV vaccine, even of relatively low apparent efficacy at the individual level, remains a critical global public health goal. PMID:25207973
Phillips, Andrew N.; Cambiano, Valentina; Nakagawa, Fumiyo; Ford, Deborah; Lundgren, Jens D.; Roset-Bahmanyar, Edith; Roman, François; Van Effelterre, Thierry
Dendritic cells have a central role in HIV infection. On one hand, they are essential to induce strong HIV-specific CD4+ helper T-cell responses that are crucial to achieve a sustained and effective HIV-specific CD8+ cytotoxic T-lymphocyte able to control HIV replication. On the other hand, DCs contribute to virus dissemination and HIV itself could avoid a correct antigen presentation. As the efficacy of immune therapy and therapeutic vaccines against HIV infection has been modest in the best of cases, it has been hypothesized that ex vivo generated DC therapeutic vaccines aimed to induce effective specific HIV immune responses might overcome some of these problems. In fact, DC-based vaccine clinical trials have yielded the best results in this field. However, despite these encouraging results, functional cure has not been reached with this strategy in any patient. In this Commentary, we discuss new approaches to improve the efficacy and feasibility of this type of therapeutic vaccine. PMID:23912672
García, Felipe; Plana, Montserrat; Climent, Nuria; León, Agathe; Gatell, Jose M; Gallart, Teresa
The use of human mucosal tissue models is an important tool advancing our understanding of the specific mechanisms of sexual HIV transmission. Despite 30 years of study, major gaps remain, including how HIV-1 transverses the epithelium and the identity of the early immune targets (gate keepers). Because defining HIV-1 transmission in vivo is difficult, mucosal tissue is being used ex vivo to identify key steps in HIV-1 entry and early dissemination. Elucidating early events of HIV-1 infection will help us develop more potent and specific HIV-1 preventatives such as microbicides and vaccines. Mucosal tissue has been incorporated into testing regimens for antiretroviral drugs and monoclonal antibodies. The use of mucosal tissue recapitulates the epithelium and immune cells that would be exposed in vivo to virus and drug. This review will discuss the use of mucosal tissue to better understand HIV-1 pathogenesis and prevention modalities. PMID:23224426
Dezzutti, Charlene S.; Hladik, Florian
Background. The number of new HIV infections among MSM of China is rapidly increasing in recent years and behavioral interventions have had limited effectiveness. To control the HIV pandemic may lie in an HIV vaccine. This study examined the factors associated with willingness to participate (WTP) in HIV vaccine clinical trials among China MSM. Methods. A cross-sectional survey was carried out among MSM from three cities in northeast China. Questionnaires pertaining to MSM risk behavior and WTP in HIV vaccine trials were administered through computer assisted self-interviewing (CASI). Results. A total of 626 MSM participated in this survey. 54.8% had occasional male partners and 52.2% always used condoms with male sex partners. HIV prevalence was 5.0%. 76.7% were WTP in a preventive HIV vaccine clinical trial. Results showed that HIV vaccination is a means of protection for spouses and family; family support to participate in vaccine trials and desire for economic incentives were significantly associated with WTP. Conclusions. There was a high proportion of WTP in HIV vaccine trials among Chinese MSM. The high HIV prevalence and high proportion of risky sexual behavior indicate that Liaoning MSM are potential candidates for HIV vaccine trials. PMID:24371825
Xu, Junjie; Reilly, Kathleen Heather; Lu, Chunming; Hu, Qinghai; Ma, Ning; Zhang, Min; Zhang, Jing; Jiang, Yongjun; Geng, Wenqing; Shang, Hong
Acquired immunodeficiency syndrome and tuberculosis (TB) are two of the world's most devastating diseases. The first vaccine the majority of infants born in Africa receive is Mycobacterium bovis bacillus Calmette-Guérin (BCG) as a prevention against TB. BCG protects against disseminated disease in the first 10 years of life, but provides a variable protection against pulmonary TB and enhancing boost delivered by recombinant modified vaccinia virus Ankara (rMVA) expressing antigen 85A (Ag85A) of M. tuberculosis is currently in phase IIb evaluation in African neonates. If the newborn's mother is positive for human immunodeficiency virus type 1 (HIV-1), the baby is at high risk of acquiring HIV-1 through breastfeeding. We suggested that a vaccination consisting of recombinant BCG expressing HIV-1 immunogen administered at birth followed by a boost with rMVA sharing the same immunogen could serve as a strategy for prevention of mother-to-child transmission of HIV-1 and rMVA expressing an African HIV-1-derived immunogen HIVA is currently in phase I trials in African neonates. Here, we aim to develop a dual neonate vaccine platform against HIV-1 and TB consisting of BCG.HIVA administered at birth followed by a boost with MVA.HIVA.85A. Thus, mMVA.HIVA.85A and sMVA.HIVA.85A vaccines were constructed, in which the transgene transcription is driven by either modified H5 or short synthetic promoters, respectively, and tested for immunogenicity alone and in combination with BCG.HIVA(222). mMVA.HIVA.85A was produced markerless and thus suitable for clinical manufacture. While sMVA.HIVA.85A expressed higher levels of the immunogens, it was less immunogenic than mMVA.HIVA.85A in BALB/c mice. A BCG.HIVA(222)-mMVA.HIVA.85A prime-boost regimen induced robust T cell responses to both HIV-1 and M. tuberculosis. Therefore, proof-of-principle for a dual anti-HIV-1/M. tuberculosis infant vaccine platform is established. Induction of immune responses against these pathogens soon after birth is highly desirable and may provide a basis for lifetime protection maintained by boosts later in life. PMID:21603645
Hopkins, Richard; Bridgeman, Anne; Joseph, Joan; Gilbert, Sarah C; McShane, Helen; Hanke, Tomáš
Using Cocaine or Heroin in the Last 7 Days,; Age Over 18 Years Old,; Competent to Sign Informed Consent for HIV/HBV/HCV Testing,; HIV/HBV Negatives Will be Randomized for HB Vaccine Study; HIV Infections
A safe, effective and accessible preventive vaccine is our best long-term hope for the control of the HIV\\/AIDS pandemic. Once the first generation of HIV vaccines are developed, many questions remain unanswered regarding their administration. For instance, which vaccines should be given to whom at what age and how many doses? We argue that pre- and early-adolescents will be one
C. J Clements; Q Abdool-Karim; M.-L Chang; B Nkowane; J Esparza
Microbicides represent a potential intervention strategy for preventing HIV transmission. Vaginal microbicides would meet the need for a discreet method that women could use to protect themselves against HIV. Although early-generation microbicides failed to demonstrate efficacy, newer candidates are based on more potent antiretroviral (ARV) products. Positive data from the CAPRISA 004 trial of tenofovir gel support use in women and represent a turning point for the field. This article reviews current progress in development of ARV-based microbicides. We discuss the consensus on selection criteria, the potential for drug resistance, rationale for drug combinations, and the use of pharmacokinetic (PK)/pharmacodynamic (PD) assessment in product development. The urgent need for continued progress in development of formulations for sustained delivery is emphasized. Finally, as the boundaries between different prevention technologies become increasingly blurred, consideration is given to the potential synergy of diverse approaches across the prevention landscape. PMID:22355798
Shattock, Robin J.; Rosenberg, Zeda
Background More and more HIV therapeutic vaccines will enter clinical trials; however, little is known about the willingness to participate (WTP) in HIV therapeutic vaccine trials among HIV-positive individuals. Objective To investigate the WTP in HIV therapeutic vaccine trials among Chinese HIV-infected patients. Methods We conducted a cross-sectional survey on HIV-positive inpatients and outpatients at Shanghai Public Health Center. A total of 447 participants were recruited into this study. Following an introduction with general information on HIV therapeutic vaccine and its potential effectiveness and side effects, each participant completed a questionnaire in a self-administered form. The questionnaires covered demographics, high-risk behaviors, clinical characteristics and willingness to participate in HIV therapeutic vaccine trial. Results The overall willingness to participate in HIV therapeutic vaccine trials was 91.5%. Interestingly, multivariate logistic regression analyses demonstrated that the willingness was higher for those sexually infected by HIV (odds ratio [OR]: 4.36; 95% confidence interval [CI]: 1.53–12.41), diagnosed as HIV-1 infection for greater than 5 years (OR: 7.12, 95% CI: 1.83–27.76), and with the presence of infectious complications (OR: 2.75; 95% CI: 1.02–7.45). The primary reason for participation was to delay or reduce antiretroviral treatment (ART) and to avoid ART side effects (76.6%), and then followed by delaying disease progression (74.9%), increasing immune response to suppress opportunistic infections (57.7%) and preventing the development of drug resistance (37.1%). Reasons for unwillingness to participate mainly included concern for safety (37.0%), lack of knowledge on therapeutic vaccine (33.3%), and satisfaction with ART effectiveness (22.2%). Conclusions The WTP in HIV therapeutic vaccine trials was high among HIV-infected Chinese patients. HIV+ subjects who acquired infection through sexual contact and who were diagnosed for more than 5 years may represent a good candidate population for enrollment in therapeutic vaccine trials. PMID:25372044
Dong, Yuan; Shen, Xiaoxing; Guo, Ruizhang; Liu, Baochi; Zhu, Lingyan; Wang, Jing; Zhang, Linxia; Sun, Jun; Zhang, Xiaoyan; Xu, Jianqing
... Navigation Bar Home Current Issue Past Issues HIV / AIDS HIV / AIDS: Symptoms , Diagnosis, Prevention and Treatment Past Issues / Summer ... and have resulted in a dramatic decrease in AIDS deaths in the U.S. NIH Research to Results ...
Compulsory vaccination is a frequently implemented policy option for ensuring comprehensive vaccine coverage. Ongoing controversies around human papillomavirus vaccine dissemination, and suboptimal coverage, suggest the value of assessing acceptability of compulsory vaccinations-particularly among likely target populations-in advance of their public availability to support evidence-informed interventions. With the first HIV vaccine to demonstrate partial efficacy in a large-scale clinical trial, we examined individual characteristics and attitudes associated with support for compulsory HIV vaccination policy among a diverse, representative sample of adults attending probable HIV vaccine dissemination venues in a large urban county. Participants were recruited using three-stage probability sampling from likely venues for future HIV vaccine dissemination. We used Audio-CASI to administer a 60-min structured questionnaire. Items included endorsement of compulsory HIV vaccination policy, sociodemographic characteristics, injecting drug use, vaccine attitudes and perceived HIV risk. Among 1,225 participants (mean age?=?36.8 years; 55.6 % males, 37.6 % non-English speaking Hispanic, 78.8 % heterosexual, 25.7 % injection drug users), almost half (48.2 %) endorsed a compulsory HIV vaccination policy. Non-English speaking Hispanics compared to whites, participants with less than high school education, higher positive vaccine attitude scores and higher perceived HIV risk were significantly more likely, and people who inject drugs significantly less likely to endorse compulsory HIV vaccination. Public health interventions to promote positive vaccine attitudes and accurate perceptions of HIV risk among vulnerable populations, and strategies tailored for people who inject drugs, may build support for compulsory HIV vaccination policy and promote broad HIV vaccine coverage. PMID:24464325
Newman, Peter A; Lee, Sung-Jae; Rudy, Ellen T; Diamant, Allison; Duan, Naihua; Nakazono, Terry; Nakazano, Terry; Cunningham, William E
Attempts to formulate a protective HIV-1 vaccine through classic vaccine design strategies have not been successful. Elicitation of HIV-1-specific broadly neutralizing antibodies (bnAbs) at high titers that are present before exposure might be required to achieve protection. Recently, the application of new technologies has facilitated the study of clonal lineages of HIV-1 envelope (Env) antibodies, which have provided insights into HIV-1 antibody development during infection and upon vaccination. Strategies are being developed for the analysis of infection and vaccine candidate-induced antibodies, their gene usage, and their maturation pathways such that this information can be used to attempt to guide rational vaccine design. PMID:22981828
Bonsignori, Mattia; Alam, S. Munir; Liao, Hua-Xin; Verkoczy, Laurent; Tomaras, Georgia D.; Haynes, Barton F.; Moody, M. Anthony
... recommended immunizations on time. Child and Preteen/Teen Vaccination Schedules For your convenience, print the easy-to- ... Teen Schedule Parents Guide to Childhood Immunizations State Vaccination Requirements Top of Page Images and logos on ...
With an estimated 2.6 million new HIV infections diagnosed annually, the world needs new prevention strategies to partner with condom use, harm reduction approaches for injection drug users, and male circumcision. Antiretrovirals can reduce the risk of mother-to-child HIV transmission and limit HIV acquisition after occupational exposure. Macaque models and clinical trials demonstrate efficacy of oral or topical antiretrovirals used prior to HIV exposure to prevent HIV transmission, ie pre-exposure prophylaxis (PrEP). Early initiation of effective HIV treatment in serodiscordant couples results in a 96% decrease in HIV transmission. HIV testing to determine serostatus and identify undiagnosed persons is foundational to these approaches. The relative efficacy of different approaches, adherence, cost and long-term safety will affect uptake and impact of these strategies. Ongoing research will help characterize the role for oral and topical formulations and help quantify potential benefits in sub-populations at risk for HIV acquisition. PMID:22351302
Flash, Charlene; Krakower, Douglas; Mayer, Kenneth H.
The rapidly changing media landscape and proliferation of new technologies creates vast new opportunities for HIV prevention. The fast growth of the relatively new eHealth field is a testament to the excitement and promise of these new technologies. eHealth interventions in HIV prevention tested to date include computer- and Internet-based interventions; chat room interventions; text messaging interventions; and social media. The current article provides a brief review of these types of interventions in HIV prevention, including their unique advantages and evidence of efficacy. Implications for future research in the eHealth HIV prevention field are discussed. PMID:22519523
Noar, Seth M; Willoughby, Jessica Fitts
The outcome of penile cancer is proportional to the stage at presentation. Strategies aimed at primary prevention would have a clear advantage, both for the individual and in terms of health economics. A number of preventative measures could be employed, including circumcision, smoking cessation, education on hygiene and human papillomavirus (HPV) prevention. There is a high prevalence of HPV infection associated with penile cancer worldwide. The recent development of HPV vaccines has facilitated interest in their use for the prevention of penile cancer. In this article we review the literature surrounding penile cancer prevention and HPV vaccination in men. PMID:23730331
Barod, Ravi; Hegarty, Paul K.; Minhas, Suks
Prevention of Human Immunodeficiency Virus (HIV) transmission is increasingly an international priority. Education of high-risk populations, such as incarcerated individuals, is particularly important in thwarting the spread of HIV. To address this concern, the attitudes, beliefs, and knowledge of inmates concerning HIV and AIDS related issues are…
Antonio, Michael E.; And Others
The consistent use of latex condoms continues to be advocated for primary prevention of HIV infection despite limited quantitative evidence regarding the effectiveness of condoms in blocking the sexual transmission of HIV. Although recent meta-analyses of condom effectiveness suggest that condoms are 60 to 70% effective when used for HIV prophylaxis, these studies do not isolate consistent condom use, and
Steven D. Pinkerton; Paul R. Abramson
Reducing the incidence of HIV infection continues to be a crucial public health priority in the United States, especially among populations at elevated risk such as men who have sex with men, transgender women, people who inject drugs, and racial and ethnic minority communities. Although most HIV prevention efforts to date have focused on changing risky behaviors, the past decade has yielded efficacious new biomedical technologies designed to prevent infection, such as the prophylactic use of antiretroviral drugs and the first indications of an efficacious vaccine. Access to prevention technologies will be a significant part of the next decade’s response to HIV, and advocates are mobilizing to achieve more widespread use of these interventions. These breakthroughs, however, arrive at a time of escalating healthcare costs; health insurance coverage therefore raises pressing new questions about priority-setting and the allocation of responsibility for public health. The goals of this Article are to identify legal challenges and potential solutions for expanding access to biomedical HIV prevention through health insurance coverage. This Article discusses the public policy implications of HIV prevention coverage decisions, assesses possible legal grounds on which insurers may initially deny coverage for these technologies, and evaluates the extent to which these denials may survive external and judicial review. Because several of these legal grounds may be persuasive, particularly denials on the basis of medical necessity, this Article also explores alternative strategies for financing biomedical HIV prevention efforts. PMID:23356098
654 Â· JID 2005:191 (1 March) Â· rgp120 HIV Vaccine Study Group M A J O R A R T I C L E Placebo-Controlled Phase 3 Trial of a Recombinant Glycoprotein 120 Vaccine to Prevent HIV-1 Infection The rgp120 HIV Vaccine Study Groupa (See the article by Gilbert et al., on pages 666Â77, and the editorial commentary
From data on HIV-1 characteristics measured on viruses isolated from vaccinated and unvaccinated persons infected while enrolled in preventive HIV-1 vaccine trials, interpretable inferences into strain variations of vaccine efficacy can be made with recently developed sieve analysis models. Four assumptions are needed for the parameters in these models to have meaningful interpretations in terms of vaccine-induced reductions in strain-specific per-contact transmission probabilities: (A1) vaccination impacts each strain-specific transmission probability homogeneously in vaccinated persons (leaky vaccine effect); (A2) for each strain biological susceptibility to infection given exposure is homogeneous among vaccinated trial participants and among unvaccinated trial participants; (A3) the distribution of exposure is equal in vaccinated and unvaccinated trial participants; (A4) the relative prevalence of circulating HIV-1 strains during the trial follow-up period is constant. Through theoretical considerations and simulations of an ongoing phase III HIV-1 vaccine efficacy trial in Bangkok, we evaluate the importance and necessity of these assumptions. We show that the models still provide estimates of biologically interpretable parameters when A1 is violated, but with bias the extent to which vaccine protection is heterogeneous. We also show that the models are highly robust to departures from A4, with implication that the time-independent models are adequate for applications. In addition, we suggest extensions of the sieve analysis models which incorporate random effects that account for unmeasured heterogeneity in infection risk. With these mixed models, usefully interpretable strain-specific vaccine efficacy parameters can be estimated without requiring A2. The conclusion is that A3, which is justified by randomization and blinding, is the essential assumption for the sieve models to provide reliable interpretable inferences into strain variations in vaccine efficacy. PMID:11169601
Gilbert, P B
Traditionally, vaccines have been evaluated in clinical trials that establish vaccine efficacy (VE) against etiology-confirmed disease outcomes, a measure important for licensure. Yet, VE does not reflect a vaccine's public health impact because it does not account for relative disease incidence. An additional measure that more directly establishes a vaccine's public health value is the vaccine preventable disease incidence (VPDI), which is the incidence of disease preventable by vaccine in a given context. We describe how VE and VPDI can vary, sometimes in inverse directions, across disease outcomes and vaccinated populations. We provide examples of how VPDI can be used to reveal the relative public health impact of vaccines in developing countries, which can be masked by focus on VE alone. We recommend that VPDI be incorporated along with VE into the analytic plans of vaccine trials, as well as decisions by funders, ministries of health, and regulatory authorities. PMID:24731817
Gessner, Bradford D; Feikin, Daniel R
The objective of this pilot study was to explore the knowledge of and preferences regarding effective biomedical interventions among high risk individuals attending a sexually transmitted diseases clinic, and to examine the effect of a brief information intervention on preference. Participants completed a baseline assessment, attended a presentation on human immunodeficiency virus (HIV) prevention methods, and completed a postintervention assessment. Outcome measures included: demographics and sexual risk factors, self-perceived HIV risk, and knowledge and attitudes regarding new biomedical methods of HIV prevention. After the baseline evaluation, participants were provided with information on new biomedical prevention strategies. Participants were given the option to review the information by reading a pamphlet or by viewing a brief video containing the same information. Participants (n=97) were female (n=51) and male (n=46). At baseline, only a small minority of participants were aware of the newer biomedical strategies to prevent HIV infection. Postintervention, 40% endorsed having heard about the use of HIV medications to prevent HIV infection; 72% had heard that male circumcision can decrease the risk of acquiring HIV infection in men; and 73% endorsed knowledge of the potential role of microbicides in decreasing the risk of acquiring HIV. Following the intervention, the most preferred prevention method was male condoms, followed by preexposure prophylaxis, and microbicides. The least preferred methods were male circumcision and female condoms. This study provides preliminary information on knowledge and attitudes regarding newer biomedical interventions to protect against HIV infection. PMID:25540597
Castro, Jose G; Jones, Deborah L; Weiss, Stephen M
The safety, stability, and ability for repeat homologous vaccination makes the DNA vaccine platform an excellent candidate for an effective HIV-1 vaccine. However, the immunogenicity of early DNA vaccines did not translate from small animal models into larger non-human primates and was markedly lower than viral vectors. In addition to improvements to the DNA vector itself, delivery with electroporation, the inclusion of molecular adjuvants, and heterologous prime-boost strategies have dramatically improved the immunogenicity of DNA vaccines for HIV and currently makes them a leading platform with many areas warranting further research and clinical development. PMID:22440782
Hutnick, Natalie A; Myles, Devin JF; Bian, Chaoran Billie; Muthumani, Karuppiah; Weiner, David B
Efficacy studies of investigational HIV vaccines require enrollment of individuals at 'high risk' for HIV. This paper examines participation in HIV vaccine trials among women at 'high risk' for HIV acquisition. In-depth interviews were conducted with 17 African-American women who use crack cocaine and/or exchange sex for money/drugs to elicit attitudes toward medical research and motivators and deterrents to HIV vaccine trial participation. Interviews were digitally recorded and transcribed; data were coded and compiled into themes. Most women expressed favorable attitudes toward medical research in general. Motivators for trial participation included compensation; personal benefits including information, social services, and the possibility that the trial vaccine could prevent HIV; and altruism. Deterrents included: dislike of needles; distrust; concern about future consequences of participating. In addition, contingencies, care-giving responsibilities, and convenience issues constituted barriers which could impede participation. Respondents described varied, complex perspectives, and individual cases illustrate how these themes played out as women contemplated trial participation. Understanding factors which influence vaccine research participation among women at 'high risk' can aid sites to tailor recruitment procedures to local contexts. Concerns about future reactions can be addressed through sustained community education. Convenience barriers can be ameliorated by providing rides to study visits when necessary, and/or conducting study visits in accessible neighborhood locations. Women in this sample thought carefully about enrolling in HIV vaccine trials given the structural constraints within which they lived. Further research is needed regarding structural factors which influence personal agency and individuals' thinking about research participation. PMID:21704110
Voytek, Chelsea D; Jones, Kevin T; Metzger, David S
Efficacy studies of investigational HIV vaccines require enrollment of individuals at ‘high risk’ for HIV. This paper examines participation in HIV vaccine trials among women at ‘high risk’ for HIV acquisition. In-depth interviews were conducted with 17 African-American women who use crack cocaine and/or exchange sex for money/drugs to elicit attitudes toward medical research and motivators and deterrents to HIV vaccine trial participation. Interviews were digitally recorded and transcribed; data were coded and compiled into themes. Most women expressed favorable attitudes toward medical research in general. Motivators for trial participation included compensation; personal benefits including information, social services, and the possibility that the trial vaccine could prevent HIV; and altruism. Deterrents included: dislike of needles; distrust; concern about future consequences of participating. In addition, contingencies, caregiving responsibilities, and convenience issues constituted barriers which could impede participation. Respondents described varied, complex perspectives, and individual cases illustrate how these themes played out as women contemplated trial participation. Understanding factors which influence vaccine research participation among women at ‘high risk’ can aid sites to tailor recruitment procedures to local contexts. Concerns about future reactions can be addressed through sustained community education. Convenience barriers can be ameliorated by providing rides to study visits when necessary, and/or conducting study visits in accessible neighborhood locations. Women in this sample thought carefully about enrolling in HIV vaccine trials given the structural constraints within which they lived. Further research is needed regarding structural factors which influence personal agency and individuals’ thinking about research participation. PMID:21704110
Voytek, Chelsea D.; Jones, Kevin T.; Metzger, David S.
Current guidelines recommend screening for HIV infected patients susceptible for vaccine preventable diseases and offering of immunization. However, data regarding the vaccination coverage among this group are largely missing. This study analyzed the serostatus for Measles, Mumps and Rubella of more than 700 HIV infected patients residing in Austria. These patients were representative for the Austrian HIV cohort regarding sex, age, transmission risk and HIV progression markers. 73.6% were on suppressive HAART, mean CD4 cell count was 603c/?l. Seronegativity was 8.4% for Measles, 33.4% for Mumps and 18.8% for Rubella. In total, out of the 713 HIV infected adults analyzed, almost half (47.8%) would require MMR vaccination. In a multivariate analysis migration was significantly associated with seronegativity for Measles (OR 0.5, CI 0.27-0.9) and Mumps (OR 0.57, CI 0.39-0.81). Importantly due to the well preserved immune status of nearly all participants vaccination would be feasible in the majority of the seronegative patients. Thus, a proactive approach would largely reduce the number of patients at risk for vaccine-preventable diseases. PMID:25203449
Grabmeier-Pfistershammer, K; Poeppl, W; Herkner, H; Touzeau-Roemer, V; Huschka, Emilia; Rieger, A; Burgmann, H
Introduction: Vaccination is the main preventive strategy against Yellow Fever (YF), which is a public health concern in Brazil. However, HIV-infected patients might have insufficient knowledge regarding YF, YF prevention, and vaccines in general. Methods: In this questionnaire-based study, data from 158 HIV-infected individuals were addressed in three distinct outpatient clinics in São Paulo. Information was collected on demographic and clinical characteristics, as well as patients' knowledge of vaccines, YF and YF preventive strategies. In addition, individual YF vaccine recommendations and vaccine status were investigated. Results: Although most participants adequately ascertain the vaccine as the main prevention strategy against YF, few participants were aware of the severity and lack of specific treatment for YF. Discrepancy in YF vaccine (patients who should have taken the vaccine, but did not) was observed in 18.8% of participants. Conclusion: YF is an important and preventable public health concern, and these results demonstrate that more information is necessary for the HIV-infected population. PMID:25229222
Avelino-Silva, Vivian Iida; Francelino, Hilario Sousa; Kallás, Esper Georges
Streptococcus pneumoniae is the leading bacterial opportunistic infection in HIV-infected individuals. Anti-retroviral treatment (ART) of HIV-infected individuals reduces their risk of invasive pneumococcal disease (IPD), however, it remains 20- to 40-fold greater compared with age-matched general population. This review summarizes the available published data on the immunogenicity, safety and efficacy of pneumococcal polysaccharide-protein conjugate vaccines (PCV) in HIV-infected children and adults. Several studies have demonstrated that PCV are safe in the HIV-infected persons. Although PCV are immunogenic in HIV-infected infants, the antibodies produced are functionally impaired, there is possibly a lack or loss of anamnestic responses and immunity declines in later life However, quantitative and qualitative antibody responses to PCV in HIV-infected infants are enhanced when vaccination occurs whilst on ART, as well as if vaccination occurs when the CD4+ cell percentage is ? 25% and if the nadir CD4+ is >15%. Although the efficacy of PCV was lower, the vaccine preventable burden of hospitalization for IPD and clinical pneumonia were 18-fold and 9-fold greater, respectively, in HIV-infected children compared with –uninfected children. In HIV-infected adults, PCV vaccination induces more durable and functional antibody responses in individuals on ART at the time of vaccination than in ART-naive adults, independently of baseline CD4+ cell count, although there does not appear to be much benefit from a second-dose of PCV. PCV has also been shown to reduce the risk of recurrent IPD by 74% in HIV-infected adults not on ART, albeit, also with subsequent decline in immunity and protection. PMID:22426374
Nunes, Marta C.; Madhi, Shabir A.
The Centers for Disease Control and Prevention (CDC) Sexually Transmitted Disease (STD) Treatment Guidelines were last updated in 2006. To update the “Clinical Guide to Prevention Services” section of the 2010 CDC STD Treatment Guidelines, we reviewed the recent science with reference to interventions designed to prevent acquisition of STDs, including human immunodeficiency virus (HIV) infection. Major interval developments include (1) licensure and uptake of immunization against genital human papillomavirus, (2) validation of male circumcision as a potent prevention tool against acquisition of HIV and some other sexually transmitted infections (STIs), (3) failure of a promising HIV vaccine candidate to afford protection against HIV acquisition, (4) encouragement about the use of antiretroviral agents as preexposure prophylaxis to reduce risk of HIV and herpes simplex virus acquisition, (5) enhanced emphasis on expedited partner management and rescreening for persons infected with Chlamydia trachomatis and Neisseria gonorrhoeae, (6) recognition that behavioral interventions will be needed to address a new trend of sexually transmitted hepatitis C among men who have sex with men, and (7) the availability of a modified female condom. A range of preventive interventions is needed to reduce the risks of acquiring STI, including HIV infection, among sexually active people, and a flexible approach targeted to specific populations should integrate combinations of biomedical, behavioral, and structural interventions. These would ideally involve an array of prevention contexts, including (1) communications and practices among sexual partners, (2) transactions between individual clients and their healthcare providers, and (3) comprehensive population-level strategies for prioritizing prevention research, ensuring accurate outcome assessment, and formulating health policy. PMID:22080271
Development of an effective HIV/AIDS vaccine remains a big challenge, largely due to the enormous HIV diversity which propels immune escape. Thus novel vaccine strategies are targeting multiple variants of conserved antibody and T cell epitopic regions which would incur a huge fitness cost to the virus in the event of mutational escape. Besides immunogen design, the delivery modality is critical for vaccine potency and efficacy, and should be carefully selected in order to not only maximize transgene expression, but to also enhance the immuno-stimulatory potential to activate innate and adaptive immune systems. To date, five HIV vaccine candidates have been evaluated for efficacy and protection from acquisition was only achieved in a small proportion of vaccinees in the RV144 study which used a canarypox vector for delivery. Conversely, in the STEP study (HVTN 502) where human adenovirus serotype 5 (Ad5) was used, strong immune responses were induced but vaccination was more associated with increased risk of HIV acquisition than protection in vaccinees with pre-existing Ad5 immunity. The possibility that pre-existing immunity to a highly promising delivery vector may alter the natural course of HIV to increase acquisition risk is quite worrisome and a huge setback for HIV vaccine development. Thus, HIV vaccine development efforts are now geared toward delivery platforms which attain superior immunogenicity while concurrently limiting potential catastrophic effects likely to arise from pre-existing immunity or vector-related immuno-modulation. However, it still remains unclear whether it is poor immunogenicity of HIV antigens or substandard immunological potency of the safer delivery vectors that has limited the success of HIV vaccines. This article discusses some of the promising delivery vectors to be harnessed for improved HIV vaccine efficacy. PMID:25202303
Ondondo, Beatrice O.
This study aimed to develop reliable scales of HIV vaccine attitudes. Gay men were recruited at the 2001 Sydney Gay and Lesbian Mardi Gras Fair Day, a large gay community gathering of thousands of people. A total of 776 participants completed a questionnaire containing 38 items about HIV vaccines. Factor analysis of the responses of 585 HIV-negative/untested men revealed four distinct factors (accounting cumulatively for 24.5% of the variance): I, Comfort with Participation in HIV Vaccine Trials, Cronbach alpha = 0.81; II, Confidence in HIV Vaccines/Vaccine Trials, Cronbach alpha = 0.71; III, Sexual Freedom, Cronbach alpha = 0.64; IV, Willingness to Participate in HIV Vaccine Trials, Cronbach alpha = 0.59. Of the HIV-negative/untested men, 162 (27.7%) were likely/very likely to volunteer for HIV vaccine trials, and 422 (72.3%) were unlikely/very unlikely to do so. As preliminary evidence of construct validity, the 162 men had a higher mean score on scale I (2.79), indicating greater comfort with trial participation than their 422 counterparts (2.47, p < 0.001). As preliminary evidence of concurrent validity, the 162 men had a higher mean score on scale IV (2.79), indicating greater willingness to participate than the rest (2.22, p < 0.001). Alongside HIV vaccine trials, these scales may be a useful adjunct to social research in gay communities; to monitor and be responsive to community concerns about HIV vaccine trials as well as their potential to undermine safe sex practices. PMID:12487804
Van De Ven, Paul; Bartholow, Bradford; Rawstorne, Patrick; Crawford, June; Kippax, Susan; Grulich, Andrew; Prestage, Garrett; Woodhouse, Michael; Murphy, Dean
Results from the first phase III efficacy trial of an HIV vaccine will be available within the next 2-3 years. Thus, it is imperative to start planning now to address how any effective vaccines should be used. In the absence of definitive information on the characteristics of the first generation of HIV vaccines, the following assumptions were made: the vaccine will (i) have only low to moderate efficacy (on the order of 50%); (ii) not be inexpensive (on the order of 10 to 30 US $ per dose); (iii) require multiple doses; and, (iv) at least initially, be available in limited quantities. A vaccine with that profile would not be suitable for general use in all countries, and it might have to be initially targeted to populations at higher risk of HIV infection. These populations will differ from region to region, according to the epidemiological situation. In most high and middle income countries potential target groups for an initial HIV immunization programme would include intravenous drug users, gay men, commercial sex workers, and high-risk heterosexuals, as well as healthcare workers exposed to blood. In sub-Saharan Africa, future HIV immunization programmes might include larger segments of the population. In order to plan future vaccination programmes it is important to estimate the need (size of target population) and the demand (uptake in target populations) for future HIV vaccines. In addition to the public sector demand for an HIV vaccine (to be used in public health programmes), there will also be a private sector demand driven by the willingness and ability of individuals and employers to pay for the vaccine. HIV vaccines would need to be delivered as part of comprehensive HIV prevention packages, including behavioral and health promotion interventions. This would be especially important with vaccines of moderate efficacy, in order to prevent increased risk behavior among vaccine recipients. To avoid false expectations, the vaccine message would need to be recast as part of the total prevention strategy, rather than the "magic bullet" that people have come to expect. Initial deployment of HIV vaccines could proceed through targeted vaccination campaigns, drawing from experience with other vaccines. These campaigns would be complex and expensive, and would require full participation and collaboration from all levels of the community, as well as considerable strengthening of the infrastructures required for vaccine delivery. Current candidate vaccines in phase III trials may not be appropriate for much of Africa and South Asia, two areas most in need of an HIV vaccine. Credible international efforts (''push and pull" mechanisms) are needed to create incentives for the industry to develop vaccines for these regions. Feasible financing mechanisms may have to be established to cover the cost of production and delivery of vaccines, in order to ensure equitable access to HIV vaccines around the world. In parallel to the deployment of the initial vaccine, additional bridging studies and effectiveness trials may be needed to expand vaccine use. Research should also continue at an increased pace to develop new generations of more effective vaccines, especially vaccines appropriate to Africa. Achieving these goals will require real political commitment from government and international organizations, to be materialized in specific actions and budget allocations. The daunting challenge of making future effective vaccines accessible to all populations in need will require a sustained collaborative effort on the part of all parties involved. PMID:11399975
Vaccine 21 (2003) 4486Â4504 Mapping cross-clade HIV-1 vaccine epitopes using a bioinformatics T cell (CTL) epitopes were identified by screening protein sequences in the Los Alamos National). Putative HIV-1 CTL epitopes were selected from this list using the epitope prediction tool Epi
BACKGROUND: Patients with HIV infection are at risk of co-infection with HBV, as the routes of transmission are shared and thus immunization with HBV vaccine could be protective in them. The aim of the present study was to assess the efficacy of recombinant vaccine in treatment-naive HIV positive patients and healthy controls, and to dissect out differences if any, in
Neelam Pasricha; Usha Datta; Yogesh Chawla; Surjit Singh; Sunil K Arora; Archana Sud; Ranjana W Minz; Biman Saikia; Haqeeqat Singh; Isaac James; Shobha Sehgal
Cervical cancer can be prevented with HPV vaccines. NCI-supported researchers helped establish HPV as a cause of cervical cancer. They also helped create the first HPV vaccines, were involved in the vaccine trials, and contribute to ongoing studies.
A major challenge for the development of a highly effective AIDS vaccine is the identification of mechanisms of protective immunity. To address this question, we used a nonhuman primate challenge model with simian immunodeficiency virus (SIV). We show that antibodies to the SIV envelope are necessary and sufficient to prevent infection. Moreover, sequencing of viruses from breakthrough infections revealed selective pressure against neutralization-sensitive viruses; we identified a two-amino-acid signature that alters antigenicity and confers neutralization resistance. A similar signature confers resistance of human immunodeficiency virus (HIV)-1 to neutralization by monoclonal antibodies against variable regions 1 and 2 (V1V2), suggesting that SIV and HIV share a fundamental mechanism of immune escape from vaccine-elicited or naturally elicited antibodies. These analyses provide insight into the limited efficacy seen in HIV vaccine trials. PMID:24352234
Roederer, Mario; Keele, Brandon F; Schmidt, Stephen D; Mason, Rosemarie D; Welles, Hugh C; Fischer, Will; Labranche, Celia; Foulds, Kathryn E; Louder, Mark K; Yang, Zhi-Yong; Todd, John-Paul M; Buzby, Adam P; Mach, Linh V; Shen, Ling; Seaton, Kelly E; Ward, Brandy M; Bailer, Robert T; Gottardo, Raphael; Gu, Wenjuan; Ferrari, Guido; Alam, S Munir; Denny, Thomas N; Montefiori, David C; Tomaras, Georgia D; Korber, Bette T; Nason, Martha C; Seder, Robert A; Koup, Richard A; Letvin, Norman L; Rao, Srinivas S; Nabel, Gary J; Mascola, John R
Summary A major challenge for the development of a highly effective AIDS vaccine is the identification of mechanisms of protective immunity. To address this question, we used a non-human primate challenge model with simian immunodeficiency virus (SIV). We show that antibodies to the SIV Envelope are necessary and sufficient to prevent infection. Moreover, sequencing of viruses from breakthrough infections revealed selective pressure against neutralization-sensitive viruses; we identified a two amino acid signature that alters antigenicity and confers neutralization resistance. A similar signature confers resistance of HIV-1 to neutralization by monoclonal antibodies against variable regions 1 and 2 (V1V2), suggesting that SIV and HIV share a fundamental mechanism of immune escape from vaccine- or naturally-elicited antibodies. These analyses provide insight into the limited efficacy seen in HIV vaccine trials. PMID:24352234
Roederer, Mario; Keele, Brandon F.; Schmidt, Stephen D.; Mason, Rosemarie D.; Welles, Hugh C.; Fischer, Will; Labranche, Celia; Foulds, Kathryn E.; Louder, Mark K.; Yang, Zhi-Yong; Todd, John-Paul M.; Buzby, Adam P.; Mach, Linh V.; Shen, Ling; Seaton, Kelly E.; Ward, Brandy M.; Bailer, Robert T.; Gottardo, Raphael; Gu, Wenjuan; Ferrari, Guido; Alam, S. Munir; Denny, Thomas N.; Montefiori, David C.; Tomaras, Georgia D.; Korber, Bette T.; Nason, Martha C.; Seder, Robert A.; Koup, Richard A.; Letvin, Norman L.; Rao, Srinivas S.; Nabel, Gary J.; Mascola, John R.
In the past 25 years, the field of HIV prevention research has been transformed repeatedly. Today, effective HIV prevention requires a combination of behavioral, biomedical, and structural intervention strategies. Risk of transmitting or acquiring HIV is reduced by consistent male and female-condom use, reductions in concurrent and/or sequential sexual and needle-sharing partners, male circumcision, and treatment with antiretroviral medications. At least 144 behavioral prevention programs have been found effective in reducing HIV transmission acts; however, scale up of these programs has not occurred outside of the United States. A series of recent failures of HIV-prevention efficacy trials for biomedical innovations such as HIV vaccines, treating herpes simplex 2 and other sexually transmitted infections, and diaphragm and microbicide barriers highlights the need for behavioral strategies to accompany biomedical strategies. This challenges prevention researchers to reconceptualize how cost-effective, useful, realistic, and sustainable prevention programs will be designed, delivered, tested, and diffused. The next generation of HIV prevention science must draw from the successes of existing evidence-based interventions and the expertise of the market sector to integrate preventive innovations and behaviors into everyday routines. PMID:19327028
Rotheram-Borus, Mary Jane; Swendeman, Dallas; Chovnick, Gary
There is growing interest in the role of anti-HIV antibody-dependent cellular cytotoxicity (ADCC) antibodies in the prevention and control of HIV infection. Passive transfer studies in macaques support a role for the Fc region of antibodies in assisting in the prevention of simian-human immunodeficiency virus (SHIV) infection. The Thai RV144 HIV-1 vaccine trial induced anti-HIV ADCC antibodies that may have played a role in the partial protection observed. Several observational studies support a role for ADCC antibodies in slowing HIV disease progression. However, HIV evolves to escape ADCC antibodies and chronic HIV infections causes dysfunction of effector cells such as natural killer (NK) cells that mediate the ADCC functions. Further, four recent studies show that the HIV-1 Vpu protein, by promoting release of virions, reduces the capacity of ADCC antibodies to recognize HIV-infected cells. The review dissects some of the recent research on HIV-specific ADCC antibodies and discusses mechanisms to further harness ADCC antibodies in the prevention and control of HIV infection. PMID:25396265
Kramski, Marit; Stratov, Ivan; Kent, Stephen J
The virus-like particle(VLPs) vaccine is an ideal HIV-1 vaccine, which can simultaneously induce a neutralizing antibody reaction and cell-mediated immunity effectively. In this study, two kinds of plasmids have been used, one can express the HIV-1 main structure proteins, Gagpol and Env, and the other contains an antibiotic gene. The two kinds of plasmids have been cotransfected into 293 cells.
Dong-hai ZHAO; Xi-zhen ZHANG; Xiang-hui YU; Wei KONG
Long-term safety is critical for the development and later use of a vaccine to prevent HIV/AIDS. Likewise, the persistence of vaccine-induced antibodies and their impact on HIV testing must be established. IAVI has sponsored several Phase I and IIA HIV vaccine trials enrolling healthy, HIV-seronegative African volunteers. Plasmid DNA and viral vector based vaccines were tested. No vaccine-related serious adverse events were reported. After completion of vaccine trials conducted between 2001-2007, both vaccine and placebo recipients were offered enrolment into an observational long-term follow-up study (LTFU) to monitor potential late health effects and persistence of immune responses. At scheduled 6-monthly clinic visits, a health questionnaire was administered; clinical events were recorded and graded for severity. Blood was drawn for HIV testing and cellular immune assays. 287 volunteers were enrolled; total follow-up after last vaccination was 1463 person years (median: 5.2 years). Ninety-three (93)% of volunteers reported good health at their last LTFU visit. Infectious diseases and injuries accounted for almost 50% of the 175 reported clinical events, of which over 95% were mild or moderate in severity. There were 30 six pregnancies, six incident HIV infections and 14 volunteers reported cases of social harm. Persistence of immune responses was rare. No safety signal was identified. No potentially vaccine-related medical condition, no immune mediated disease, or malignancy was reported. HIV vaccines studied in these trials had a low potential of induction of persisting HIV antibodies. PMID:24374365
Schmidt, Claudia; Jaoko, Walter; Omosa-Manyonyi, Gloria; Kaleebu, Pontiano; Mpendo, Juliet; Nanvubya, Annet; Karita, Etienne; Bayingana, Roger; Bekker, Linda-Gail; Chomba, Elwyn; Kilembe, William; Nchabeleng, Maphoshane; Nyombayire, Julien; Stevens, Gwynn; Chetty, Paramesh; Lehrman, Jennifer; Cox, Josephine; Allen, Susan; Dally, Len; Smith, Carol; Fast, Patricia E
Being able to recruit high-risk volunteers who are also willing to consider future participation in vaccine trials are critical features of vaccine preparedness studies. We described data from two cohorts of injection- and non-injection drug users in Barcelona, Spain [Red Cross centre] and in San Francisco, USA, [UFO-VAX study] at high risk of HIV/HCV infection to assess behaviour risk exposure and willingness to participate in future preventive HIV vaccine trials. We successfully identified drug-using populations that would be eligible for future HIV vaccine efficacy trials, based on reported levels of risk during screening and high levels of willingness to participate. In both groups, Red Cross and UFO-VAX respectively, HCV infection was highly prevalent at baseline (41% and 34%), HIV baseline seroprevalence was 4.2% and 1.5%, and high levels of willingness were seen (83% and 78%). PMID:21241735
Etcheverry, M Florencia; Lum, Paula J; Evans, Jennifer L; Sanchez, Emilia; de Lazzari, Elisa; Mendez-Arancibia, Eva; Sierra, Ernesto; Gatell, José M; Page, Kimberly; Joseph, Joan
... immunodeficiency virus (HIV) prevention (or prophylaxis ) includes both safe sex practices and medications. Preventing the Spread of HIV HIV can be spread through blood, semen, vaginal fluid, or breast milk. It is most often spread through sexual contact. Therefore, an important part of HIV prevention ...
Background.?South Africa introduced 7-valent pneumococcal conjugate vaccine (PCV7) in April 2009 using a 2 + 1 schedule (6 and 14 weeks and 9 months). We estimated the effectiveness of ?2 PCV7 doses against invasive pneumococcal disease (IPD) in human immunodeficiency virus (HIV)–infected and -uninfected children. Methods.?IPD (pneumococcus identified from a normally sterile site) cases were identified through national laboratory-based surveillance. Specimens were serotyped by Quellung or polymerase chain reaction. Four controls, matched for age, HIV status, and hospital were sought for each case. Using conditional logistic regression, we calculated vaccine effectiveness (VE) as 1 minus the adjusted odds ratio for vaccination. Results.?From March 2010 through November 2012, we enrolled 187 HIV-uninfected (48 [26%] vaccine serotype) and 109 HIV-infected (43 [39%] vaccine serotype) cases and 752 HIV-uninfected and 347 HIV-infected controls aged ?16 weeks. Effectiveness of ?2 PCV7 doses against vaccine-serotype IPD was 74% (95% confidence interval [CI], 25%–91%) among HIV-uninfected and ?12% (95% CI, ?449% to 77%) among HIV-infected children. Effectiveness of ?3 doses against vaccine-serotype IPD was 90% (95% CI, 14%–99%) among HIV-uninfected and 57% (95% CI, ?371% to 96%) among HIV-infected children. Among HIV-exposed but -uninfected children, effectiveness of ?2 doses was 92% (95% CI, 47%–99%) against vaccine-serotype IPD. Effectiveness of ?2 doses against all-serotype multidrug-resistant IPD was 96% (95% CI, 62%–100%) among HIV-uninfected children. Conclusions.?A 2 + 1 PCV7 schedule was effective in preventing vaccine-serotype IPD in HIV-uninfected and HIV-exposed, uninfected children. This finding supports the World Health Organization recommendation for this schedule as an alternative to a 3-dose primary series among HIV-uninfected individuals. PMID:24917657
Cohen, Cheryl; von Mollendorf, Claire; de Gouveia, Linda; Naidoo, Nireshni; Meiring, Susan; Quan, Vanessa; Nokeri, Vusi; Fortuin-de Smit, Melony; Malope-Kgokong, Babatyi; Moore, David; Reubenson, Gary; Moshe, Mamokgethi; Madhi, Shabir A.; Eley, Brian; Hallbauer, Ute; Kularatne, Ranmini; Conklin, Laura; O'Brien, Katherine L.; Zell, Elizabeth R.; Klugman, Keith; Whitney, Cynthia G.; von Gottberg, Anne; Moore, David; Verwey, Charl; Varughese, Sheeba; Archary, Moherndran; Naby, Fathima; Dawood, Khathija; Naidoo, Ramola; Elliott, Gene; Hallbauer, Ute; Eley, Brian; Nuttall, James; Cooke, Louise; Finlayson, Heather; Rabie, Helena; Whitelaw, Andrew; Perez, Dania; Jooste, Pieter; Naidoo, Dhamiran; Kularatne, Ranmini; Reubenson, Gary; Cohen, Cheryl; de Gouveia, Linda; du Plessis, Mignon; Govender, Nevashan; Meiring, Susan; Quan, Vanessa; von Mollendorf, Claire; Fortuin-de Smidt, Melony; Naidoo, Nireshni; Malope-Kgokong, Babatyi; Nokeri, Vusi; Ncha, Relebohile; Lindani, Sonwabo; von Gottberg, Anne; Spies, Barry; Sono, Lino; Maredi, Phasweni; Hamese, Ken; Moshe, Mamokgethi; Nchabeleng, Maphosane; Ngcobo, Ntombenhle; van den Heever, Johann; Madhi, Shabir; Conklin, Laura; Verani, Jennifer; Whitney, Cynthia; Zell, Elizabeth; Loo, Jennifer; Nelson, George; Klugman, Keith; O'Brien, Katherine
This site describes recently launched clinical tests of a new vaccine directed at the three most globally important HIV subtypes, as developed by scientists at the Dale and Betty Bumpers Vaccine Research Center of the National Institute of Allergy and infectious Diseases.
Infants born to HIV-infected mothers are at high risk of becoming infected during gestation or the breastfeeding period. A search is thus warranted for vaccine formulations that will prevent mother-to-child HIV transmission. The LAMP\\/gag DNA chimeric vaccine encodes the HIV-1 p55gag fused to the lysosome-associated membrane protein-1 (LAMP-1) and has been shown to enhance anti-Gag antibody (Ab) and cellular immune
Paula Ordonhez Rigato; Milton Maciel; Adriana Letícia Goldoni; Orlando Guerra Piubelli; Noemia Mie Orii; Ernesto Torres Marques; Joseph Thomas August; Alberto José da Silva Duarte; Maria Notomi Sato
Human immunodeficiency virus (HIV), causative agent of acquired immunodeficiency syndrome (AIDS), is a global health concern. To control its transmission, safe sex has been proposed as one of the strategies. Microbicides- intravaginal/intrarectal topical formulations of anti-HIV agents have also been proposed to prevent HIV transmission. Microbicides would provide protection by directly inactivating HIV or preventing the attachment, entry or replication of HIV in susceptible target cells as well as their dissemination from target cells present in semen or the host cells lining the vaginal/rectal wall to other migratory cells. Microbicides must be safe, effective following vaginal or rectal administration, and should cause minimal or no genital symptoms or inflammations following long-term repeated usage. However, a safe and efficacious anti-HIV microbicide is not yet available despite the fact that more than 60 candidate agents have been identified to have in vitro activity against HIV, several of which have advanced to clinical testing. Nonetheless, proof-of-concept of microbicides has been established based on the results of recent CAPRISA 004 clinical trials. In this article, the trends and challenges in the development of effective and safe microbicides to combat HIV transmission are reviewed. PMID:22310826
Nutan; Gupta, Satish K.
Background Gene-based vaccine delivery is an important strategy in the development of a preventive vaccine for acquired immunodeficiency syndrome (AIDS). Vaccine Research Center (VRC) 004 is the first phase 1 dose-escalation study of a multiclade HIV-1 DNA vaccine. Methods VRC-HIVDNA009?00-VP is a 4-plasmid mixture encoding subtype B Gag-Pol-Nef fusion protein and modified envelope (Env) constructs from subtypes A, B, and C. Fifty healthy, uninfected adults were randomized to receive either placebo (n = 10) or study vaccine at 2 mg (n = 5), 4 mg (n = 20), or 8 mg (n = 15) by needle-free intramuscular injection. Humoral responses (measured by enzyme-linked immunosorbant assay, Western blotting, and neutralization assay) and T cell responses (measured by enzyme-linked immunospot assay and intracellular cytokine staining after stimulation with antigen-specific peptide pools) were measured. Results The vaccine was well tolerated and induced cellular and humoral responses. The maximal CD4+ and CD8+ T cell responses occurred after 3 injections and were in response to Env peptide pools. The pattern of cytokine expression by vaccine-induced HIV-specific T cells evolved over time, with a diminished frequency of interferon-?–producing T cells and an increased frequency of interleukin-2–producing T cells at 1 year. Conclusions DNA vaccination induced antibody to and T cell responses against 3 major HIV-1 subtypes and will be further evaluated as a potential component of a preventive AIDS vaccine regimen. PMID:17109336
Graham, Barney S.; Koup, Richard A.; Roederer, Mario; Bailer, Robert T.; Enama, Mary E.; Moodie, Zoe; Martin, Julie E.; McCluskey, Margaret M.; Chakrabarti, Bimal K.; Lamoreaux, Laurie; Andrews, Charla A.; Gomez, Phillip L.; Mascola, John R.; Nabel, Gary J.
A safe, effective and accessible preventive vaccine is our best long-term hope for the control of the HIV/AIDS pandemic. Once the first generation of HIV vaccines are developed, many questions remain unanswered regarding their administration. For instance, which vaccines should be given to whom at what age and how many doses? We argue that pre- and early-adolescents will be one of the main target groups for future HIV vaccines, that is, before the age of exposure to the virus. Historically, immunization has mainly focused on infants. Indeed, vaccines have only occasionally been systematically targeted at adolescents, even in industrialized countries. Delivering vaccines to pre-adolescents and adolescents in developing countries would, to a great extent, be a new challenge. But it is not just HIV/AIDS vaccines that are coming down the pipeline. Herpes simplex type2 (HSV-2) and human papillomavirus (HPV) vaccines are also among the exciting candidate vaccines that may be the agents of change needed to encourage even the poorest countries to develop strategies for reaching adolescents with vaccines and other health services in the coming decade. Together, they may also provide the impetus for changing the paradigm for how vaccines are administered. Not only will more antigens be included in national immunization schedules, but the age of target groups will range much more widely than at present, encompassing older children, adolescents and young adults. While presenting major difficulties for delivery, these new ingredients also offer stimulating opportunities to completely rethink how vaccines are presented, administered and delivered. We predict that even the poorest countries will be looking to developing integrated, sustainable strategies for reaching pre-adolescents and adolescents with vaccines in the coming decade. PMID:15246617
Clements, C J; Abdool-Karim, Q; Chang, M-L; Nkowane, B; Esparza, J
HIV vaccines offer the best long-term hope of controlling the AIDS pandemic; yet, the advent of HIV vaccines will not ensure their acceptability. We conducted a cross-sectional survey (n=143), incorporating conjoint analysis, to assess HIV vaccine acceptability among participants recruited using multi-site (n=9), venue-based sampling in Los Angeles. We used a fractional factorial experimental design to construct eight hypothetical HIV vaccines, each with seven dichotomous attributes. The acceptability of each vaccine was assessed individually and then averaged across participants. Next, the impact of each attribute on vaccine acceptability was estimated for each participant using ANOVA and then analyzed across participants. Acceptability of the eight hypothetical HIV vaccines ranged from 33.2 (S.D. 34.9) to 82.2 (S.D. 31.3) on a 0-100 scale; mean=60.0 (S.D. 21.9). Efficacy had the greatest impact on acceptability (22.7; CI: 18.5-27.1; p<0.0001), followed by cross-clade protection (12.5; CI: 8.7-16.3, p<0.0001), side effects (11.5; CI: 7.4-15.5; p<0.0001), and duration of protection (6.1; CI: 3.2-9.0; p<.0001). Route of administration, number of doses and cost were not significant. Low acceptability of "partial efficacy" vaccines may present obstacles to future HIV vaccine dissemination. Educational and social marketing interventions may be necessary to ensure broad HIV vaccine uptake. PMID:16332402
Newman, Peter A; Duan, Naihua; Lee, Sung-Jae; Rudy, Ellen T; Seiden, Danielle S; Kakinami, Lisa; Cunningham, William E
Background Phambili, the Merck (MRK)-Adenovirus Type 5 (Ad5) HIV-1 gag/pol/nef subtype B vaccine study, conducted in South Africa, suspended enrollment and vaccination when companion study, Step, was found non-efficacious. Although the vaccine did not prevent HIV-1 infection or lower viral-load setpoint, immune responses recognized clades B and C HIV-1 subtypes. We investigated predictors of the vaccine-induced antigen-specific immune responses. Methods Vaccine-induced immunogenicity was ascertained by interferon-? ELISpot assays on the first 186 enrolled participants receiving two vaccinations. Analyses, stratified by study arm/sex, were performed on baseline demographics [sex, age, Body Mass Index (BMI), site, Adenovirus Type-5 (Ad5) titer, Herpes Simplex Virus Type-2 (HSV2) status, heavy drinking]. Multivariate logistic regression determined predictors. Results Of the 186 participants, 53.7% (n?=?100) were female, median BMI was 22.5 [IQR: 20.4–27.0], 85.5% (n?=?159) were Ad5 seropositive, and 18.8% (n?=?35) drank heavily. All vaccine recipients responded to both clade B (n?=?87; 47%) and/or C (n?=?74; 40%), p?=?0.17. In multivariate analysis, female sex [Adjusted Odds Ratio (AOR): 6.478; p?=?0.0159], overweight/obese BMI (AOR: 0.186; p?=?0.0452), and heavy drinking (AOR: 0.270; p?=?0.048) significantly predicted immune response to clade C for any antigens. A marginally significant predictor of clade C-pol antigen was female sex (AOR: 3.182; p?=?0.0500). Conclusions Sex, BMI, and heavy drinking affected vaccine-induced HIV-1 specific immune responses to clade C antigens. The role of female sex and overweight/obese BMI boosting and suppressing vaccine-induced HIV-1 specific immune responses, respectively, requires elucidation, including any effect on HIV vaccine efficacy, especially in the era of colliding epidemics (HIV and obesity). PMID:25090110
Hopkins, Kathryn L.; Laher, Fatima; Otwombe, Kennedy; Churchyard, Gavin; Bekker, Linda-Gail; DeRosa, Stephen; Nchabeleng, Maphoshane; Mlisana, Koleka; Kublin, James; Gray, Glenda
With the continuing march of the AIDS epidemic and little hope for an effective vaccine in the near future, work to develop a topical strategy to prevent HIV infection is increasingly important. This stated, the track record of large scale "microbicide" trials has been disappointing with nonspecific inhibitors either failing to protect women from infection or even increasing HIV acquisition. Newer strategies that target directly the elements needed for viral entry into cells have shown promise in non-human primate models of HIV transmission and as these agents have not yet been broadly introduced in regions of highest HIV prevalence, they are particularly attractive for prophylaxis. We review here the agents that can block HIV cellular entry and that show promise as topical strategies or "virustats" to prevent mucosal transmission of HIV infection PMID:19094217
Lederman, Michael M; Jump, Robin; Pilch-Cooper, Heather A; Root, Michael; Sieg, Scott F
From early in the HIV epidemic it was appreciated that many inflammatory markers such as neopterin and TNF-? were elevated in patients with AIDS. With the advent of modern technology able to measure a broad array of cytokines, we now know that from the earliest points of infection HIV induces a cytokine storm. This review will focus on how cytokines are disturbed in HIV infection and will explore potential therapeutic uses of cytokines. These factors can be used directly as therapy during HIV infection, either to suppress viral replication or prevent deleterious immune effects of infection, such as CD4+ T cell depletion. Cytokines also show great promise as adjuvants in the development of HIV vaccines, which would be critical for the eventual control of the epidemic. PMID:22743035
Keating, Sheila M.; Jacobs, Evan S.; Norris, Philip J.
The Influenza virus A, B and C causes disease in humans, birds and animals. The Influenza type A causes moderate to severe illness in all age groups in humans while the illness caused by type B is of milder and it is primarily affects children. Among many subtypes of influenza A viruses, currently influenza A(H1N1) and A(H3N2) subtypes are circulating among humans. Influenza is a serious public health problem that causes severe illnesses and deaths for higher risk populations. Influenza virus is characterized by frequent mutations - antigenic drifts (minor antigenic change, both A and B) and antigenic shifts (major antigenic change, only A). The current human pandemic A/H1N1 is an example of antigenic shift. It slowly established circulation globally; subsequently endemic/seasonal viruses in both hemi-spheres are H3N2 and H1N1. The novel Influenza A (H1N1) 2009 virus was first identified by United State Centers for Disease Control and Prevention (US CDC) on 17th April, 2009 in samples from two Californian children. As of August 2010, 18,000 people had died globally due to the pandemic flu. The illness rates were highest in children and young adults (20-40% of the population), the hospitalization rates highest in children below the age of one. The case fatality rates varied tremendously and were estimated to be between 0.0004- 1.5% (0.05% in US, 0.025% in UK, lowest in children). The most effective way to prevent the disease or severe outcomes from the illness is vaccination. The Trivalent Inactivated vaccines (TIV) are of three types: whole virus, split-product, subunit surface-antigen formulations and they are grown in embryonated hen's eggs. Whole-virus vaccines, because of adverse reactions, especially in children, are not currently used. Most influenza vaccines are split-product vaccines, produced from detergent treated, highly purified influenza virus, or surface-antigen vaccines containing purified hemagglutinin and neuraminidase. PMID:22634439
Verma, Ramesh; Khanna, Pardeep; Chawla, Suraj
Can Influenza Epidemics Be Prevented by Voluntary Vaccination? Raffaele Vardavas, Romulus Breban the vaccination coverage level necessary for preventing influenza epidemics, but have not shown whether, whether the critical coverage for influenza can be achieved by voluntary vaccination. We construct a novel
October 9, 2000) The utility of live attenuated vaccines for controlling HIV epidemics is being debated HIV vaccine (LAHV) (3Â6); however, the debate about the potential utility of developing LAHVs has beenLive attenuated HIV vaccines: Predicting the tradeoff between efficacy and safety S. M. Blower* , K
... Share Compartir Occupational HIV Transmission and Prevention Among Health Care Workers Fast Facts Occupational transmission of HIV to ... every hour counts. Building Better Prevention Programs for Health Care Workers Continued diligence in the following areas is ...
The massive growth in global health research in past decades has posed many challenges for its effective ethical oversight, not least of which is how best to provide effective protection of research participants. The extent of the HIV epidemic in sub-Saharan Africa in particular makes research into prevention technologies for HIV, including HIV vaccine research, a global priority. However, the need for vaccine research must be considered in conjunction with the individual's right to informed consent, which is based on the principle of respect for autonomy. One of the primary human rights violations likely to occur in the context of HIV vaccine research is that potential research participants may not fully understand what participation in research studies entails. People who elect to enrol in HIV vaccine trials are required to understand both the potential negative effects of participation (eg, discrimination) as well as complex scientific concepts such as randomisation and prophylaxis in order to be ethically enrolled. In this study, two vignettes are presented to illustrate two core issues in conducting phase III HIV vaccine trials in low-income countries-namely, (1) from the perspective of participants, the extent to which understanding is a prerequisite for consenting to participate in a trial, and (2) from the perspective of trial investigators, whether it is appropriate to persuade eligible people to enrol in a trial, even though their initial reaction is to decline to participate. These vignettes are used to analyse these issues through the prisms of research ethics and human rights in order to identify helpful synergies. It is argued that the human rights perspective provides a helpful lens on ethical issues. PMID:22147744
London, Leslie; Kagee, Ashraf; Moodley, Keymanthri; Swartz, Leslie
- 1 - Closer to HIV vaccine goal with new insight into viral factors February 14, 2012 New insight into viral factors that facilitate HIV transmission Understanding viral factors that facilitate transmission of HIV infection is critical to developing vaccines The HIV-1 pandemic afflicts more than 34 million
Background Hepatitis B virus (HBV) vaccine responsiveness is associated with reduced risk of AIDS or death in HIV-infected individuals. Although HIV controllers (HIC) typically have favorable immunologic and clinical characteristics compared to non-controllers, vaccine responsiveness has not been studied. Methods and Findings In the U.S. Military HIV Natural History Study, HBV vaccine response was defined as antibody to hepatitis B surface antigen (anti-HBs) ?10 IU/L after last vaccination. For determination of vaccine responsiveness, HIC (n?=?44) and treatment-naïve non-controllers (n?=?476) were not on highly active antiretroviral therapy (HAART) when vaccinated while treated non-controllers (n?=?284) received all HBV vaccine doses during viral load (VL)-suppressive HAART. Progression to AIDS or death was also compared for all HIC (n?=?143) and non-controllers (n?=?1566) with documented anti-HBs regardless of the timing of HBV vaccination. Positive vaccine responses were more common in HIC (65.9%) compared to HAART-naïve non-controllers (36.6%; P<0.001), but similar to non-controllers on HAART (59.9%; P?=?0.549). Factors associated with vaccine response for HIC compared to HAART-naïve non-controllers include HIC status (OR 2.65, 95% CI 1.23–5.89; P?=?0.014), CD4 count at last vaccination (OR 1.28, 1.15–1.45 for every 100 cells/uL; P<0.001), and number of vaccine doses administered (OR 0.56, 0.35–0.88; P?=?0.011). When HIC were compared to non-controllers on HAART, only CD4 count at last vaccination was significant (OR 1.23, 1.1–1.38 for every 100 cells/uL; P<0.001). The rate of AIDS or death per 100 person/years for HIC compared to non-controllers was 0.14 (95% CI 0–0.76) versus 0.98 (95% CI 0.74–1.28) for vaccine responders and 0 (95% CI 0–2.22) versus 4.11 (95% CI 3.38–4.96) for non-responders, respectively. Conclusions HIC have improved HBV vaccine responsiveness compared to treatment-naïve non-controllers, but similar to those on VL-suppressive HAART. Progression to AIDS or death can be predicted by HBV vaccine responder status for non-controllers, however these events are rarely observed in HIC. PMID:25144773
Okulicz, Jason F.; Mesner, Octavio; Ganesan, Anuradha; O’Bryan, Thomas A.; Deiss, Robert G.; Agan, Brian K.
This publication was designed to provide teachers with guidance in offering instruction in Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) prevention education to students in the public and non-public schools of Virginia. This publication provides information that will help educators meet the needs of students in grades…
Virginia State Dept. of Education, Richmond.
Effective infection control in dentistry is unfeasible without an adequate immunization program for dental health care providers (DHCPs). Such an assumption is demonstrated for some vaccine preventable infectious diseases (VPIDs), such as Hepatitis B, Influenza and Varicella. However, excluding Hepatitis B vaccine, immunization programs for DHCPs are few and often unclear about which vaccinations are recommended, thus leading to generally low awareness and consequent low vaccination rates. This survey investigated dentists' awareness toward VPIDs. At the moment of registration to a dental congress, a questionnaire regarding the immunization status toward VPIDs was anonymously filled in by 379 Italian dentists (86% of the contacted dentists), with at least fifteen years of activity. DHCP specific awareness was considered high if dentists reported to have controlled the serum level of anti-HBs during the last ten years and have received seasonal influenza vaccine annually. Awareness toward VPIDs was classified high if dentists reported to be immune against six or seven of the following VIPDs, Hepatitis B, Influenza, Varicella, Measles, Mumps, Rubella and Tetanus. DHCP specific awareness resulted high for 32.5% of subjects and low for 31.1%. None of the subjects reported high awareness toward VPIDs, while for 60% of them, such awareness was low (immunization status reported for none or one of the seven VPIDs). Low dentists' awareness stresses the need for a transparent immunization program which is effective in controlling VPID transmission in the dental health care settings and focuses on those VPIDs which pose a true risk of infection for DHCPs and patients. PMID:21856363
Petti, Stefano; Messano, Giuseppe A; Polimeni, Antonella
Vaccination against hepatitis A is an important intervention to prevent disease in HIV-patients. There are insufficient data on the association of the response to hepatitis A vaccine with immunological parameters, including subpopulations of T-cells. We studied HIV-infected adults with CD4 T-cells>200 cells/mm(3) who received two doses of hepatitis A vaccine (Havrix or Vaqta). The counts of CD3, CD4, CD8, CD4+T-cells, NK, NK CD8+, NK CD8 - cells, and HIV RNA were measured at the time of first dose administration and one month after the end of the vaccination period. The geometric mean titer of antibodies to hepatitis A virus (anti-HAV) and factors affecting response were evaluated. 113 patients (50 antiretroviral treatment-naïve and 63 treatment-experienced) were enrolled in the study. There was no change in the immunological parameters and in the HIV-RNA post-vaccination, except for a decrease in CD8 and in double positive CD4+CD8+t-cell count. The immune response and geometric mean titer of anti-HAV were similar among treated and naïve patients (78% vs. 76% and 237?mIU/mL vs. 158?mIU/mL). Vaccine response was achieved in 71% of patients with CD4=200-499 cells/mm(3) compared with 80% of participants with CD4 ?500 cells/mm(3) (p>0.05). Logistic regression revealed that immunological cells tested do not affect response differently in treatment-naïve vs. experienced patients. The only factor affecting response is the CD4 T-cell count at vaccination (OR 1.320; 95% CI 1.052-1.656; p=0.016). Patients with CD4 T-cell count ?500 cells/mm(3) were 4.3 times more likely to respond to the vaccine than patients with CD4 T-cell count 200-499 cells/mm(3) (p=0.005). In conclusion, successful vaccination is associated with CD4 T-cells. The count of other immune cells or the administration of antiretroviral therapy does not predict response to hepatitis A vaccine in HIV patient with baseline CD4 T-cell>200 cells/mm(3). PMID:24044625
Kourkounti, Sofia; Papaizos, Vassilios; Leuow, Kirsten; Kordosis, Theodoros; Antoniou, Christina
An Outdated Notion of Antibody Specificity is One of the Major Detrimental Assumptions of the Structure-Based Reverse Vaccinology Paradigm, Which Prevented It from Helping to Develop an Effective HIV-1 Vaccine
The importance of paradigms for guiding scientific research is explained with reference to the seminal work of Karl Popper and Thomas Kuhn. A prevalent paradigm, followed for more than a decade in HIV-1 vaccine research, which gave rise to the strategy known as structure-based reverse vaccinology is described in detail. Several reasons why this paradigm did not allow the development of an effective HIV-1 vaccine are analyzed. A major reason is the belief shared by many vaccinologists that antibodies possess a narrow specificity for a single epitope and are not polyspecific for a diverse group of potential epitopes. When this belief is abandoned, it becomes obvious that the one particular epitope structure observed during the crystallographic analysis of a neutralizing antibody–antigen complex does not necessarily reveal, which immunogenic structure should be used to elicit the same type of neutralizing antibody. In the physical sciences, scientific explanations are usually presented as logical deductions derived from a relevant law of nature together with certain initial conditions. In immunology, causal explanations in terms of a single cause acting according to a law of nature are not possible because numerous factors always play a role in bringing about an effect. The implications of this state of affairs for the rational design of HIV vaccines are outlined. An alternative approach to obtain useful scientific understanding consists in intervening empirically in the immune system and it is suggested that manipulating the system experimentally is needed to learn to control it and achieve protective immunity by vaccination. PMID:25477882
Van Regenmortel, Marc H. V.
The consistent use of latex condoms continues to be advocated for primary prevention of HIV infection despite limited quantitative evidence regarding the effectiveness of condoms in blocking the sexual transmission of HIV. Although recent meta-analyses of condom effectiveness suggest that condoms are 60 to 70% effective when used for HIV prophylaxis, these studies do not isolate consistent condom use, and therefore provide only a lower bound on the true effectiveness of correct and consistent condom use. A reexamination of HIV seroconversion studies suggests that condoms are 90 to 95% effective when used consistently, i.e. consistent condom users are 10 to 20 times less likely to become infected when exposed to the virus than are inconsistent or non-users. Similar results are obtained utilizing model-based estimation techniques, which indicate that condoms decrease the per-contact probability of male-to-female transmission of HIV by about 95%. Though imperfect, condoms provide substantial protection against HIV infection. Condom promotion therefore remains an important international priority in the fight against AIDS. PMID:9141163
Pinkerton, S D; Abramson, P R
Although some success was achieved in recent years in HIV prevention, an effective vaccine remains the means with the most potential of curtailing HIV-1 infections worldwide. Despite multiple failed attempts, a recent HIV vaccine regimen demonstrated modest protection from infection. Although the protective efficacy in this trial was not sufficient to warrant licensure, it spurred renewed optimism in the field and has provided valuable insights for improving future vaccine designs. This review summarizes the pertinent details of vaccine development and discusses ways the field is moving forward to develop a vaccine to prevent HIV infection and disease progression. PMID:25287587
Goepfert, Paul; Bansal, Anju
Objective(s) Few HIV prevention interventions have been evaluated in randomized controlled trials (RCTs). We examined design, implementation, and contextual considerations that may limit detection of a positive or adverse effect in HIV prevention trials. Design A systematic review of late phase RCTs for prevention of sexual transmission of HIV that 1) randomly allocated intervention and comparison groups; 2) evaluated interventions to prevent sexual transmission in non-pregnant populations; and 3) reported HIV incidence as the primary or secondary outcome. Methods PubMed/MEDLINE, other electronic databases, and electronic conference proceedings of recent HIV/AIDS-related conferences were searched to identify published or unpublished trials meeting the inclusion criteria. Descriptive, methodological, and contextual factors were abstracted from each trial. Results The review included 36 HIV prevention RCTs reporting on 38 unique interventions. Only six RCTs, all evaluating biomedical interventions, demonstrated definitive effects on HIV incidence. Five of the six RCTs significantly reduced HIV infection: all three male circumcision trials, one trial of STI treatment and care, and one vaccine trial. One microbicide trial of nonoxynol-9 gel produced adverse results. Lack of statistical power, poor adherence, and diluted versions of the intervention in comparison groups may have been important issues for the other trials that demonstrated “flat” results. Conclusions Almost 90% of HIV prevention trials had “flat” results, which may be attributable to trial design and/or implementation. The HIV prevention community must not only examine evidence from significant RCTs, but must also examine flat trials, and address design and implementation issues that limit detection of an effect. PMID:20179575
PADIAN, Nancy S.; McLOY, Sandra I.; BALKUS, Jennifer E.; WASSERHEIT, Judith N.
In contrast to other countries in Southeast Asia, the HIV/ AIDS epidemic is in the initial stages in Viet Nam, although the rates have increased notably since 1997. This study examined attitudes towards the use of an HIV vaccine (when one becomes available) as a means for preventing the disease. Since injecting drug users are the great majority of…
A recent $168 million 5-year cooperative agreement funded by the US Agency for International Development combines elements of its earlier AIDSTECH and AIDSCOM projects under the AIDS Control and Prevention Project (AIDSCAP). Instead of working to effect broad-scale behavior change toward the prevention of HIV transmission, AIDSCAP strategically targets locations for condom distribution, behavior change messages, and the treatment of sexually transmitted diseases. In Lagos and the states of Cross River and Jigawa where the AIDS epidemic is firmly established, for example, AIDSCAP is intervening to increase condom demand and accessibility; alter sexual behaviors which carry a high risk for HIV transmission; and reduce the prevalence of STDs which enhance the transmission of HIV. The project began in fall of 1991 and has expanded to include Ethiopia, Kenya, Malawi, Nigeria, Rwanda, Senegal, Brazil, Haiti, Jamaica, India, and Thailand; limited assistance is also provided to 7 other African countries, 4 Latin America countries, and 1 in Asia. 4 more countries are in the final stages of negotiations to be included in the project. The USAID mission in the host country and the government must invite AIDSCAP involvement in order for the country to attain priority status. Countries are selected based on the HIV prevalence rate, population size and distribution, level of commitment to HIV prevention/control, capacity to respond to the AIDSCAP plan of action, level of other donor support, the USAID Mission's development priorities, and the Mission's commitment of substantial funds from its own budget. Once involved, AIDSCAP is mandated to implement interventions through in-country agencies. PMID:12344871
Finger, W R
Despite substantial attention in the past decade to the co-morbidity of mental health problems among people living with HIV/AIDS (PLWHA), these problems remain a significant barrier to maintaining health and secondary prevention. To address these issues, program staff from the Center for Mental Health Research on AIDS at the NIMH convened a meeting on 19th and 20th July 2007 to discuss the intersection of mental health and HIV. The conveners brought together leaders in the fields of mental illness and HIV to discuss current gaps in the research related to the prevention, diagnosis, and treatment of mental disorders among PLWHA, and how attention to mental health can affect a variety of health outcomes. Attendees were asked to discuss key questions that, if addressed through empirical investigation, could move the field toward the aim of reducing or alleviating the burden of mental illness for those living with HIV disease. The purpose of this brief report is to summarize this meeting's proceedings, overview key points of discussion, and outline areas that may be useful to consider for clinical researchers in the field. PMID:19057989
Grossman, Cynthia I; Gordon, Christopher M
A Phase 1, double-blind, placebo controlled trial was conducted in Longchuan County, China, to evaluate the safety and immunogenicity of a prototype HIV-1 synthetic peptide vaccine in a target population at risk for HIV infection, and to establish the infrastructure for future large-scale HIV vaccine efficacy trials. Subjects were randomly assigned to receive 100 microg or 500 microg of vaccine or alum placebo, and were given three injections at an accelerated 0, 1, and 2 month schedule. The vaccine was well tolerated with no significant local or systemic reactions observed in any subjects. Fifty-five percent (100 microg dose) and 64% (500 microg dose) of subjects who received the vaccine produced binding antibody to the immunogen as determined by ELISA. However, HIV-1 (MN) neutralizing antibody was detected in only 23% (3/13) of subjects with detectable HIV-1 specific binding antibody. It was concluded that this prototype HIV-1 synthetic peptide vaccine was well tolerated, safe and immunogenic, and that a 0, 1, 2 month schedule was not as effective in stimulating HIV-1 specific neutralizing antibodies compared with previous trials utilizing a 0, 1, 6 month schedule. Finally, this trial demonstrated that well-designed HIV vaccine trials can be performed at this clinical trials site in Yunnan, China, and that this site should be considered for conducting larger safety, immunogenicity and efficacy trials of candidate HIV vaccines. PMID:9346275
Li, D; Forrest, B D; Li, Z; Xue, P; Hanson, C V; Duan, S; Cheng, H; Li, M; Wang, C Y; Koff, W C
Animal and human data from various viral infections and vaccine studies suggest that nonneutralizing antibodies (nNAb) without neutralizing activity in vitro may play an important role in protection against viral infection in vivo. This was illustrated by the recent human immunodeficiency virus (HIV) RV144 vaccine efficacy trial, which demonstrated that HIV-specific IgG-mediated nNAb directed against the V2 loop of HIV type 1 envelope (Env) were inversely correlated with risk for HIV acquisition, while Env-specific plasma IgA-mediated antibodies were directly correlated with risk. However, tier 1 NAb in the subset of responders with a low level of plasma Env-specific IgA correlated with decreased risk. Nonhuman primate simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV) challenge studies suggest that Env-mediated antibodies are essential and sufficient for protection. A comparison of immune responses generated in human efficacy trials reveals subtle differences in the fine specificities of the antibody responses, in particular in HIV-specific IgG subclasses. The underlying mechanisms that may have contributed to protection against HIV acquisition in humans, although not fully understood, are possibly mediated by antibody-dependent cell-mediated cytotoxicity (ADCC) and/or other nonneutralizing humoral effector functions, such as antibody-mediated phagocytosis. The presence of such functional nNAb in mucosal tissues and cervico-vaginal and rectal secretions challenges the paradigm that NAb are the predominant immune response conferring protection, although this does not negate the desirability of evoking neutralizing antibodies through vaccination. Instead, NAb and nNAb should be looked upon as complementary or synergistic humoral effector functions. Several HIV vaccine clinical trials to study these antibody responses in various prime-boost modalities in the systemic and mucosal compartments are ongoing. The induction of high-frequency HIV-specific functional nNAb at high titers may represent an attractive hypothesis-testing strategy in future HIV vaccine efficacy trials. PMID:24920599
Ake, Julie; Robb, Merlin L.; Kim, Jerome H.; Plotkin, Stanley A.
Abstract Influenza vaccination is recommended for HAART-treated HIV patients to prevent influenza illness and complications. Due to the known ability of T cells to mediate a broadly cross-reactive response, vaccination effectiveness in cell-mediated immune (CMI) response induction is a main objective in new influenza vaccination strategies. Nevertheless, data on CMI responses after pandemic vaccination in HIV subjects are still missing. In the present study, the ability of a single dose of adjuvanted pandemic influenza vaccine to induce humoral and CMI responses was compared in HAART-treated HIV patients and in healthcare workers. Healthcare workers (HCW, n=65) and HAART-treated HIV patients (HIV, n=67) receiving pandemic vaccination were enrolled and analyzed before (t0) and after (t1) vaccination. The analysis of strain-specific humoral response was performed by HAI assay; CMI against pandemic (A/H1N1/Cal/09) and seasonal (A/H1N1/Brisb/07 and A/H3N2/Brisb/07) strains was analyzed by ELISpot and intracellular staining followed by flow cytometry. Pandemic vaccination was effective in inducing both humoral and cell-mediated responses in HAART-treated HIV patients as well as in HCWs. A large fraction of both HCWs and HIV-infected patients showed a T cell response to the pandemic strain before vaccination, suggesting possible previous exposure to A/H1N1/pdm/09 and/or cross-reactive T cells. Notably, pandemic vaccine was also able to boost cross-reactive immune responses to seasonal strains. Finally, a weaker boost of both strain-specific and cross-reactive T cell immunity was found in individuals showing a higher baseline response. These data show the effectiveness of adjuvanted pandemic vaccine to induce both humoral and cellular (strain-specific and cross-reactive) immune responses in HIV patients similar to HCWs. PMID:22439734
Gioia, Cristiana; Castilletti, Concetta; Lapa, Daniele; Berno, Giulia; Puro, Vincenzo; Carletti, Fabrizio; Cimini, Eleonora; Nisii, Carla; Castellino, Flora; Martini, Federico; Capobianchi, Maria R.
Influenza vaccination is recommended for HAART-treated HIV patients to prevent influenza illness and complications. Due to the known ability of T cells to mediate a broadly cross-reactive response, vaccination effectiveness in cell-mediated immune (CMI) response induction is a main objective in new influenza vaccination strategies. Nevertheless, data on CMI responses after pandemic vaccination in HIV subjects are still missing. In the present study, the ability of a single dose of adjuvanted pandemic influenza vaccine to induce humoral and CMI responses was compared in HAART-treated HIV patients and in healthcare workers. Healthcare workers (HCW, n=65) and HAART-treated HIV patients (HIV, n=67) receiving pandemic vaccination were enrolled and analyzed before (t0) and after (t1) vaccination. The analysis of strain-specific humoral response was performed by HAI assay; CMI against pandemic (A/H1N1/Cal/09) and seasonal (A/H1N1/Brisb/07 and A/H3N2/Brisb/07) strains was analyzed by ELISpot and intracellular staining followed by flow cytometry. Pandemic vaccination was effective in inducing both humoral and cell-mediated responses in HAART-treated HIV patients as well as in HCWs. A large fraction of both HCWs and HIV-infected patients showed a T cell response to the pandemic strain before vaccination, suggesting possible previous exposure to A/H1N1/pdm/09 and/or cross-reactive T cells. Notably, pandemic vaccine was also able to boost cross-reactive immune responses to seasonal strains. Finally, a weaker boost of both strain-specific and cross-reactive T cell immunity was found in individuals showing a higher baseline response. These data show the effectiveness of adjuvanted pandemic vaccine to induce both humoral and cellular (strain-specific and cross-reactive) immune responses in HIV patients similar to HCWs. PMID:22439734
Agrati, Chiara; Gioia, Cristiana; Castilletti, Concetta; Lapa, Daniele; Berno, Giulia; Puro, Vincenzo; Carletti, Fabrizio; Cimini, Eleonora; Nisii, Carla; Castellino, Flora; Martini, Federico; Capobianchi, Maria R
Multipurpose prevention technologies (MPTs) that aim to simultaneously prevent unintended pregnancy, HIV-1 infection and other sexually transmitted infections are among the most innovative and complex products currently in development within women's sexual and reproductive health care. In this review article, MPTs are placed within the wider context of combination products, combination drug products and multi-indication products. The current MPT product landscape is mapped and assessed with reference to existing products for the corresponding single indications, before identifying the gaps in the current MPT product pipeline and highlighting priority products and challenges moving forward. PMID:25335842
Malcolm, R K; Boyd, P; McCoy, C F; Murphy, D J
In HIV vaccine trials, the collection and analysis of participant behavior data associated with risk of acquiring HIV-infection is important for a number of reasons. Although the rationale for behavioral risk assessment in HIV vaccine clinical trials is clear, consistent collection of behavioral data over time and across protocols has been challenging for the HIV Vaccine Trials Network (HVTN). Integrating biomedical and behavioral research within the same preventive vaccine clinical trial has proven difficult. The HVTN conducted an internal landscape analysis to: (1) evaluate the challenges of behavioral risk assessment in HIV vaccine trials and observational studies; (2) explore the impact of the Step Study on behavioral risk assessment measures; and (3) identify strategies to overcome existing challenges and improve the quality of data resulting from behavioral risk analysis. These analyses of behavioral risk within the HVTN revealed several challenges and recommendations for improved behavioral risk data collection in future protocols. The recommendations for improvement include: (1) establishment of protocol-specific behavioral risk working groups that include social and behavioral experts; (2) provision of behavioral rationale and objectives to the development team; (3) creation of a template for geographic- and population-specific assessment of low and high risk behaviors; and (4) pilot testing of behavioral risk assessments. Results also underscored the need for routinely conducted analyses of behavioral data. PMID:23859840
Andrasik, Michele Peake; Karuna, Shelly T; Nebergall, Michelle; Koblin, Beryl A; Kublin, Jim G
Abstract The HIV cure agenda has rekindled interest in the development of a therapeutic HIV vaccine. An iterative clinical trial strategy that proved successful for the development of effective cancer chemotherapies in the 1960s may be applicable to the development of a CD8 T lymphocyte-based therapeutic HIV vaccine. However, while cancer chemotherapy development could begin with iterative clinical trials to improve the use of active drugs, the first step in therapeutic HIV vaccine design should be discovery of immunogen constructs with potential for activity and their optimization to meet the challenges of HIV-1 sequence diversity and human polymorphism in T cell antigen presentation. A strategy for doing this is discussed in this article. The proposed strategy relies on a major commitment by funding organizations to fund organized and coordinated manufacture and clinical testing of a series of first- and second-generation constructs to test basic concepts in product design. This is presented as an alternative to funding a more traditional competition among private manufacturers and product champions of individual, already designed products. PMID:25286142
Shapiro, Stuart Z
The prevalence rate of HIV infection in jails and prisons is approximately 5 times the rate in the U.S. general population. The authors surveyed state prison officials to assess HIV testing and HIV prevention policies--specifically voluntary testing, group HIV prevention counseling, and peer education--in the 50 states and to determine whether those policies are associated with the characteristics of the state and its prison population. PMID:24532813
Lyons, Thomas; Osunkoya, Emmanuel; Anguh, Ivonne; Adefuye, Adedeji; Balogun, Joseph
The field of HIV prevention has indeed progressed in leaps and bounds, but with major limitations of the current prevention and treatment options, the world remains desperate for an HIV vaccine. Sadly, this continues to be elusive, because more than 30?years since its discovery there is no licensed HIV vaccine. Research aiming to define immunological biomarkers to accurately predict vaccine efficacy have focused mainly on systemic immune responses, and as such, studies defining correlates of protection in the genitorectal mucosa, the primary target site for HIV entry and seeding are sparse. Clearly, difficulties in sampling and analysis of mucosal specimens, as well as their limited size have been a major deterrent in characterizing the type (mucosal antibodies, cytokines, chemokines, or CTL), threshold (magnitude, depth, and breadth) and viral inhibitory capacity of HIV-1-specific immune responses in the genitorectal mucosa, where they are needed to immediately block HIV acquisition and arrest subsequent virus dissemination. Nevertheless, a few studies document the existence of HIV-specific immune responses in the genitorectal mucosa of HIV-infected aviremic and viremic controllers, as well as in highly exposed persistently seronegative (HEPS) individuals with natural resistance to HIV-1. Some of these responses strongly correlate with protection from HIV acquisition and/or disease progression, thus providing significant clues of the ideal components of an efficacious HIV vaccine. In this study, we provide an overview of the key features of protective immune responses found in HEPS, elite and viremic controllers, and discuss how these can be achieved through mucosal immunization. Inevitably, HIV vaccine development research will have to consider strategies that elicit potent antibody and cellular immune responses within the genitorectal mucosa or induction of systemic immune cells with an inherent potential to home and persist at mucosal sites of HIV entry. PMID:24847327
Chanzu, Nadia; Ondondo, Beatrice
Millions of people worldwide are currently infected with human papillomavirus (HPV), herpes simplex virus (HSV) or human immunodeficiency virus (HIV). For this enormous contingent of people, the search for preventive and therapeutic immunological approaches represents a hope for the eradication of latent infection and/or virus-associated cancer. To date, attempts to develop vaccines against these viruses have been mainly based on a monovalent concept, in which one or more antigens of a virus are incorporated into a vaccine formulation. In the present report, we designed and tested an immunization strategy based on DNA vaccines that simultaneously encode antigens for HIV, HSV and HPV. With this purpose in mind, we tested two bicistronic DNA vaccines (pIRES I and pIRES II) that encode the HPV-16 oncoprotein E7 and the HIV protein p24 both genetically fused to the HSV-1 gD envelope protein. Mice i.m. immunized with the DNA vaccines mounted antigen-specific CD8+ T cell responses, including in vivo cytotoxic responses, against the three antigens. Under experimental conditions, the vaccines conferred protective immunity against challenges with a vaccinia virus expressing the HIV-derived protein Gag, an HSV-1 virus strain and implantation of tumor cells expressing the HPV-16 oncoproteins. Altogether, our results show that the concept of a trivalent HIV, HSV, and HPV vaccine capable to induce CD8+ T cell-dependent responses is feasible and may aid in the development of preventive and/or therapeutic approaches for the control of diseases associated with these viruses. PMID:23951135
Santana, Vinicius C.; Diniz, Mariana O.; Cariri, Francisco A. M. O.; Ventura, Armando M.; Cunha-Neto, Edécio; Almeida, Rafael R.; Campos, Marco A.; Lima, Graciela K.; Ferreira, Luís C. S.
Millions of people worldwide are currently infected with human papillomavirus (HPV), herpes simplex virus (HSV) or human immunodeficiency virus (HIV). For this enormous contingent of people, the search for preventive and therapeutic immunological approaches represents a hope for the eradication of latent infection and/or virus-associated cancer. To date, attempts to develop vaccines against these viruses have been mainly based on a monovalent concept, in which one or more antigens of a virus are incorporated into a vaccine formulation. In the present report, we designed and tested an immunization strategy based on DNA vaccines that simultaneously encode antigens for HIV, HSV and HPV. With this purpose in mind, we tested two bicistronic DNA vaccines (pIRES I and pIRES II) that encode the HPV-16 oncoprotein E7 and the HIV protein p24 both genetically fused to the HSV-1 gD envelope protein. Mice i.m. immunized with the DNA vaccines mounted antigen-specific CD8? T cell responses, including in vivo cytotoxic responses, against the three antigens. Under experimental conditions, the vaccines conferred protective immunity against challenges with a vaccinia virus expressing the HIV-derived protein Gag, an HSV-1 virus strain and implantation of tumor cells expressing the HPV-16 oncoproteins. Altogether, our results show that the concept of a trivalent HIV, HSV, and HPV vaccine capable to induce CD8? T cell-dependent responses is feasible and may aid in the development of preventive and/or therapeutic approaches for the control of diseases associated with these viruses. PMID:23951135
Santana, Vinicius C; Diniz, Mariana O; Cariri, Francisco A M O; Ventura, Armando M; Cunha-Neto, Edécio; Almeida, Rafael R; Campos, Marco A; Lima, Graciela K; Ferreira, Luís C S
Public health agencies have recommended incorporating HIV prevention counseling into the medical care of persons living with HIV\\/AIDS. Injection drug users (IDUs) especially need HIV risk-reduction counseling because of their high risk for HIV transmission through both sexual and injection behaviors. The objective of this study was to assess the prevalence of, and patient factors associated with, the delivery of
James D. Wilkinson; Wei Zhao; Scott Santibanez; Julia Arnsten; Amy Knowlton; Cynthia A. Gómez; Lisa R. Metsch
This paper describes a 16-month health education pilot program based on diffusion of innovation and social network theories. The program was implemented by volunteer community liaisons for the purposes of increasing awareness of and support for HIV vaccine research in minority populations. This theoretically driven pilot program allowed the liaisons to integrate delivery of the HIV vaccine research messages created for the program into their existing activities and routines. Through training in participatory engagement, volunteers were able to tailor and adapt an HIV prevention message for their communities. Process evaluation data showed that the acceptance of participatory engagement and HIV vaccine message dissemination far exceeded expectations. The anticipated number of community members to receive the message was estimated at 500 with 10 volunteer liaisons or 50 per person. However, the actual number of people reached was 644, with only 7 volunteer liaisons, or an average of 92 persons per liaison, almost double the original number. Further research is recommended to analyze the specific behavioral changes that can come from the use of social networks in HIV vaccine research awareness within minority populations. PMID:22327809
Kelley, R T; Hannans, A; Kreps, G L; Johnson, K
Viral vector-based vaccines that induce protective CD8+ T cell immunity can prevent or control pathogenic SIV infections, but issues of preexisting immunity and safety have impeded their implementation in HIV-1. Here, we report the development of what we believe to be a novel antigen-targeting DNA vaccine strategy that exploits the binding of programmed death-1 (PD1) to its ligands expressed on dendritic cells (DCs) by fusing soluble PD1 with HIV-1 GAG p24 antigen. As compared with non-DC-targeting vaccines, intramuscular immunization via electroporation (EP) of the fusion DNA in mice elicited consistently high frequencies of GAG-specific, broadly reactive, polyfunctional, long-lived, and cytotoxic CD8+ T cells and robust anti-GAG antibody titers. Vaccination conferred remarkable protection against mucosal challenge with vaccinia GAG viruses. Soluble PD1-based vaccination potentiated CD8+ T cell responses by enhancing antigen binding and uptake in DCs and activation in the draining lymph node. It also increased IL-12-producing DCs and engaged antigen cross-presentation when compared with anti-DEC205 antibody-mediated DC targeting. The high frequency of durable and protective GAG-specific CD8+ T cell immunity induced by soluble PD1-based vaccination suggests that PD1-based DNA vaccines could potentially be used against HIV-1 and other pathogens. PMID:23635778
Zhou, Jingying; Cheung, Allen K L; Tan, Zhiwu; Wang, Haibo; Yu, Wenbo; Du, Yanhua; Kang, Yuanxi; Lu, Xiaofan; Liu, Li; Yuen, Kwok-Yung; Chen, Zhiwei
HIV's rapid global spread and the human suffering it has left in its wake have made AIDS a global heath priority for the 25 years since its discovery. Yet its capacity to rapidly evolve has made combating this virus a tremendous challenge. The obstacles to creating an effective HIV vaccine are formidable, but there are advances in the field on many fronts, in terms of novel vectors, adjuvants, and antigen design strategies. SIV live attenuated vaccine models are able to confer protection against heterologous challenge, and this continues to provide opportunities to explore the biological underpinnings of a protective effect (9). More indirect, but equally important, is new understanding regarding the biology of acute infection (43), the role of immune response in long-term non-progression (6,62, 81), and defining characteristics of broadly neutralizing antibodies (4). In this review we will focus on summarizing strategies directed towards a single issue, that of contending with HIV variation in terms of designing aT-cell vaccine. The strategies that prove most effective in this area can ultimately be combined with the best strategies under development in other areas, with the hope of ultimately converging on a viable vaccine candidate. Only two large HIV vaccine efficacy trials have been completed and both have failed to prevent infection or confer a benefit to infected individual (23,34), but there is ample reason to continue our efforts. A historic breakthrough came in 1996, when it was realized that although the virus could escape from a single antiretroviral (ARV) therapy, it could be thwarted by a combination of medications that simultaneously targeted different parts of the virus (HAART) (38). This revelation came after 15 years of research, thought, and clinical testing; to enable that vital progress the research and clinical communities had to first define and understand, then develop a strategy to counter, the remarkable evolutionary potential of the virus. HAART, for the first time, provided an effective treatment to help those with living with HIV stay healthy. Nonetheless, the treatment has limitations. People with HIV face a lifetime of expensive daily multi-drug regimens, often with side effects; drug resistance at the individual and population level are issues (56); and universal access, despite substantial progress, is a dream not yet realized for many of the millions of the world's poor who are living with HIV (68). These issues, combined with the growing numbers of people infected globally and impact of HIV on society, make the development of an HIV vaccine or a prophylactic prevention strategy a crucial if elusive goal. In some ways, the history of HIV vaccine deVelopment has paralleled the early stages of designing effective therapy. We had to test the simple strategies first, but meanwhile the story of the impact of diversity from an immunological perspective is still unfolding, and novel ideas countermeasures are being explored.
Korber, Bette [Los Alamos National Laboratory
We propose a set of common factors in evidence-based interventions (EBI) for HIV prevention, which cut across theoretical models of behavior change. Three existing literatures support this agenda: (1) Common factors in psychotherapy; (2) core elements from the Centers for Disease Control and Prevention EBIs; and (3) component analyses of EBI. To stimulate discussion among prevention researchers, we propose a set of common factors at the highest level of abstraction that describe what all effective programs do: (1) establish a framework to understand behavior change; (2) convey issue-specific and population-specific information necessary for healthy actions; (3) build cognitive, affective, and behavioral self-management skills; (4) address environmental barriers to implementing health behaviors; and (5) provide tools to develop ongoing social and community support for healthy actions. A focus on common factors will enhance research on new HIV prevention interventions, encourage collaboration among researchers, provide guidelines for adapting EBI, and simplify and speed the adoption of EBI for providers. PMID:18830813
Swendeman, Dallas; Flannery, Diane; Rice, Eric; Adamson, David M.; Ingram, Barbara
Rhesus macaques are an important animal model for the study of human disease and the development of vaccines against HIV and AIDS. HIV vaccines have been benchmarked in rhesus macaque preclinical challenge studies using chimeric viruses made up of parts of HIV and simian immunodeficency viruses. However, the lack of efficacy in a recent clinical trial calls for a re-evaluation of the scientific assumptions regarding the predictive value of using data generated from rhesus macaques as a ‘gatekeeper’ for the advancement of candidate vaccines into the clinic. In this context, there is significant consensus among HIV vaccinologists that next-generation HIV vaccines must generate ‘better’ immunity in rhesus macaques than clinically unsuccessful vaccines generated using validated assays. Defining better immunity is the core challenge of HIV vaccine development in this system and is the focus of this Review. PMID:19859066
Shedlock, Devon J.; Silvestri, Guido; Weiner, David B.
Background.?In studies from high-income countries, human immunodeficiency virus type 1 (HIV-1)–infected persons have diminished responses to hepatitis B virus (HBV) vaccination, compared with HIV-1–uninfected persons, but data from other settings are limited. Methods.?We compared the immune response to HBV vaccination among HIV-1–infected and HIV-1–uninfected Kenyan adults and assessed the response of HIV-1–infected initial nonresponders to revaccination with a standard HBV vaccine series. Results.?Of 603 participants, 310 (51.4%) were HIV-1–infected, for whom the median CD4+ T-cell count was 557 cells/?L (interquartile range, 428–725 cells/?L); none were receiving antiretroviral therapy. Nonresponse to HBV vaccine was higher among HIV-1–infected participants, compared with HIV-1–uninfected participants (35.8% vs 14.3%; odds ratio, 3.33; P < .001). Of 102 HIV-1–infected initial nonresponders, 88 (86.3%) responded to revaccination, for an overall response, including to revaccination, of 94.9%. Among HIV-1–infected individuals, lower CD4+ T-cell counts and male sex were independent predictors of nonresponse to initial vaccination, and lower body mass index, higher plasma HIV-1 RNA levels, and longer time to revaccination predicted nonresponse to revaccination. Conclusions.?Kenyan adults had similar HBV vaccination responses as persons from high-income countries. Timely revaccination of HIV-1–infected nonresponders increased response to the vaccine to 95%. PMID:23175769
Irungu, Elizabeth; Mugo, Nelly; Ngure, Kenneth; Njuguna, Robert; Celum, Connie; Farquhar, Carey; Dhanireddy, Shireesha; Baeten, Jared M.
The success of the HPTN 052 trial has led to revisions in HIV-1 treatment guidelines. Antiretroviral therapy (ART) may reduce the risk of HIV-1 transmissions at the population-level. The design of successful Treatment as Prevention interventions will be predicated on a comprehensive understanding of the spatial, temporal, and biological dynamics of heterosexual (HET), men having sex with men (MSM), and intravenous drug user (IDU) epidemics. Viral phylogenetics can capture the underlying structure of transmission networks based on the genetic interrelatedness of viral sequences and cluster networks that could not be otherwise identified. This article describes the phylogenetic expansion of the Montreal MSM epidemic over the last decade. High rates of co-clustering of primary infections are associated with one infection leading to 13 onward transmissions. Phylogeny substantiates the role of primary and recent stage infection in transmission dynamics, underlying the importance of timely diagnosis and immediate ART initiation to avert transmission cascades. PMID:23764643
Brenner, Bluma G.; Wainberg, Mark A.
Although HIV prevention researchers have conducted numerous controlled outcome studies to evaluate the effectiveness of theory-based interventions aimed at reducing HIV risk behaviors, many HIV risk reduction interventions are conducted not by researchers but by staff in local health departments or community-based organizations (CBOs). Despite…
Eke, Agatha N.; Mezoff, Jane S.; Duncan, Ted; Sogolow, Ellen D.
BACKGROUND: A large proportion of the 2.5 million new adult HIV infections that occurred worldwide in 2007 were in stable couples. Feasible and acceptable strategies to improve HIV prevention in a conjugal context are scarce. In the preparatory phase of the ANRS 12127 Prenahtest multi-site HIV prevention trial, we assessed the acceptability of couple-oriented post-test HIV counseling (COC) and men's
Joanna Orne-Gliemann; Patrice T Tchendjou; Marija Miric; Mukta Gadgil; Maia Butsashvili; Fred Eboko; Eddy Perez-Then; Shrinivas Darak; Sanjeevani Kulkarni; George Kamkamidze; Eric Balestre; Annabel du Loû; Francois Dabis
Background As HIV infection continues to devastate low-income countries, efforts to search for an effective HIV vaccine are crucial. Therefore, participation in HIV vaccine trials will be useful for the development of a preventive vaccine that will work and thus reduce the global HIV epidemic. Objective The objective of this study was to analyse the willingness to volunteer (WTV) in a Phase I/II HIV vaccine trial among police officers in Dar es Salaam, Tanzania. Design We included a convenience sample of 329 participants (79% males) from sensitisation workshops that were held once at each of the 32 police stations. Participants were recruited from 23 stations which were included according to availability. Data about personal characteristics, general HIV and AIDS knowledge and sexual behaviour, attitudes towards vaccines and willingness to participate in the HIV vaccine trial were obtained through an interview-administered questionnaire with both closed and open-ended questions. Results Overall, 61% of the participants expressed WTV in HIV vaccine trials. WTV was significantly associated with: positive attitude towards use of effective vaccine, Odds ratio (OR), 36.48 (95% CI: 15.07–88.28); the intention to tell others about one's decision to participate in the trial, OR, 6.61 (95% CI: 3.89–11.24); Tanzania becoming a partner in developing the vaccine, OR, 4.28 (95% CI: 2.28–8.03); having an extra sexual partner, OR, 3.05 (95% CI: 1.63–5.69); perceived higher risk of getting HIV infection, OR, 2.11 (95% CI: 1.34–3.33); and high knowledge about HIV and AIDS, OR, 1.92 (95% CI: 1.22–3.01). Conclusion The results indicated that a majority of police officers in this study were willing to participate in HIV vaccine trials. However, there is a need to provide the respondents with precise information about the purpose of a Phase I/II HIV vaccine trial and the fact that it does not protect against HIV infection, in order to avoid increasing risky behaviour. PMID:20027266
Tarimo, Edith A.M.; Thorson, Anna; Bakari, Muhammad; Mwami, Joachim; Sandström, Eric; Kulane, Asli
Background Recruitment, enrollment and retention of volunteers in an HIV vaccine trial is important in the efforts to ultimately develop a vaccine that can prevent new HIV infections. Following recruitment, some randomized individuals decline to be enrolled in an HIV vaccine trial. The reasons for such a decision are not well known. This article describes why individuals who were randomized in a phase I and II HIV vaccine trial in Dar es Salaam, Tanzania declined to be enrolled. Methods Face-to-face interviews were conducted with 14 individuals (7 men and 7 women). Repeated readings of the 14 interview transcripts to look for reasons for declining to enroll in the trial were performed. Data was analyzed using the content analysis approach. Results Informants expressed fear of the outcome of an experimental HIV vaccine in their lives. Unlike women, some men were concerned over the effect of the vaccine on their reproduction intentions. Women were concerned about the unknown effects of the vaccine in their bodies. Also, to a large extent, informants faced resistance from significant others such as fiancées, parents, relatives, and friends. Women were influenced by their potential intimate sexual partners; men were forbidden by their parents, and mothers had the most influential opinion. Conclusions Fear of the negative outcome of an experimental vaccine and resistance from significant others are the main reasons for declining to enroll in the HIV vaccine trial among eligible volunteers after randomization. The resistance from the significant others provides valuable guidance for designing future trials in Tanzania; for example, expanding the HIV vaccine trial education to the general population from the onset of the trial design. PMID:21358826
Tarimo, Edith A. M.; Thorson, Anna; Kohi, Thecla W.; Bakari, Muhammad; Mhalu, Fred; Kulane, Asli
Background: Women and adolescent girls bear a significant burden of the global HIV pandemic. Both behavioral and biomedical prevention approaches have been shown to be effective. In order to foster the most effective combination HIV-prevention approaches for women and girls, it is imperative to understand the unique biological, social, and structural considerations that increase vulnerability to acquiring HIV within this population. Primary Study Objective: The purpose of this article is to propose novel ideas for personalized biobehavioral HIV prevention for women and adolescent girls. The central argument is that we must transcend unilevel solutions for HIV prevention toward comprehensive, multilevel combination HIV prevention packages to actualize personalized biobehavioral HIV prevention. Our hope is to foster transnational dialogue among researchers, practitioners, educators, and policy makers toward the actualization of the proposed recommendations. Methods: We present a commentary organized to review biological, social, and structural factors that increase vulnerability to HIV acquisition among women and adolescent girls. The overview is followed by recommendations to curb HIV rates in the target population in a sustainable manner. Results: The physiology of the lower female reproductive system biologically increases HIV risk among women and girls. Social (eg, intimate partner violence) and structural (eg, gender inequality) factors exacerbate this risk by increasing the likelihood of viral exposure. Our recommendations for personalized biobehavioral HIV prevention are to (1) create innovative mechanisms for personalized HIV risk—reduction assessments; (2) develop mathematical models of local epidemics; (3) prepare personalized, evidence-based combination HIV risk—reduction packages; (4) structure gender equity into society; and (5) eliminate violence (both physical and structural) against women and girls. Conclusions: Generalized programs and interventions may not have universal, transnational, and crosscultural implications. Personalized biobehavioral strategies are needed to comprehensively address vulnerabilities at biological, social, and structural levels. PMID:24416702
Teitelman, Anne M.; Bevilacqua, Amanda W.; Jemmott, Loretta Sweet
Japan is well known as a country with a strong health record. However its incidence rates of vaccine preventable diseases (VPD) such as hepatitis B, measles, mumps, rubella, and varicella remain higher than other developed countries. This article reviews the factors that contribute to the high rates of VPD in Japan. These include historical and political factors that delayed the introduction of several important vaccines until recently. Access has also been affected by vaccines being divided into government-funded "routine" (eg, polio, pertussis) and self-pay "voluntary" groups (eg, hepatitis A and B). Routine vaccines have higher rates of administration than voluntary vaccines. Administration factors include differences in well child care schedules, the approach to simultaneous vaccination, vaccination contraindication due to fever, and vaccination spacing. Parental factors include low intention to fully vaccinate their children and misperceptions about side effects and efficacy. There are also provider knowledge gaps regarding indications, adverse effects, interval, and simultaneous vaccination. These multifactorial issues combine to produce lower population immunization rates and a higher incidence of VPD than other developed countries. This article will provide insight into the current situation of Japanese vaccinations, the issues to be addressed and suggestions for public health promotion. PMID:25628969
Kuwabara, Norimitsu; Ching, Michael Sl
Japan is well known as a country with a strong health record. However its incidence rates of vaccine preventable diseases (VPD) such as hepatitis B, measles, mumps, rubella, and varicella remain higher than other developed countries. This article reviews the factors that contribute to the high rates of VPD in Japan. These include historical and political factors that delayed the introduction of several important vaccines until recently. Access has also been affected by vaccines being divided into government-funded “routine” (eg, polio, pertussis) and self-pay “voluntary” groups (eg, hepatitis A and B). Routine vaccines have higher rates of administration than voluntary vaccines. Administration factors include differences in well child care schedules, the approach to simultaneous vaccination, vaccination contraindication due to fever, and vaccination spacing. Parental factors include low intention to fully vaccinate their children and misperceptions about side effects and efficacy. There are also provider knowledge gaps regarding indications, adverse effects, interval, and simultaneous vaccination. These multifactorial issues combine to produce lower population immunization rates and a higher incidence of VPD than other developed countries. This article will provide insight into the current situation of Japanese vaccinations, the issues to be addressed and suggestions for public health promotion.
Ching, Michael SL
The recent availability of "big data" from social media and mobile technologies provides promise for development of new tools and methods to address the HIV epidemic. This manuscript presents recent work in this growing area of bioinformatics, digital epidemiology, and disease modeling, describes how it can be applied to address HIV prevention, and presents issues that need to be addressed prior to implementing a mobile technology big-data approach to HIV prevention. PMID:25449693
Young, Sean D
Evidence-based programs for substance use and HIV prevention (SUHIP) were adapted for high-risk juveniles detained at 24-hour secure correctional facilities. In this pilot study, comparisons were made between adolescents who received the SUHIP intervention and a control group on changes in: (1) knowledge of HIV prevention behaviors, (2) attitudes…
Mouttapa, Michele; Watson, Donnie W.; McCuller, William J.; Reiber, Chris; Tsai, Winnie
This article first presents the political, personal, and epidemiological context of Hortensia Amaro's 1988 publication in "Psychology of Women Quarterly" ("PWQ"), "Considerations for Prevention of HIV Infection Among Hispanic Women" (Amaro, 1988). Second, it provides a brief summary of progress in HIV prevention with Latinas. The third section…
Amaro, Hortensia; Raj, Anita; Reed, Elizabeth; Ulibarri, Monica
This issue in the "Literacy Matters" looks at the relationship between literacy and HIV prevention education. It is the result of the UNESCO Institute for Lifelong Learning's work on examining the contribution of non-formal education (NFE) to HIV prevention, carried out in collaboration with the Association for the Development of Education in…
Medel-Anonuevo, Carolyn; Cheick, Diarra Mahamadou
In the United States, the number and proportion of HIV/AIDS cases among black/African Americans continue to highlight the need for new biomedical prevention interventions, including an HIV vaccine, microbicide, or new antiretroviral (ARV) prevention strategies such as pre-exposure prophylaxis (PrEP) to complement existing condom usage, harm reduction methods, and behavioral change strategies to stem the HIV epidemic. Although black/African Americans are disproportionately impacted by HIV/AIDS, their participation in HIV clinical research continues to have unique challenges. We theorize that interaction among multilevel factors creates ideal alignment for minority participation in HIV clinical studies. Thus, we initially set out to test an extended model of reasoned action with 362 participants to understand the interplay of sociopsychological and network-level considerations influencing minority participation in HIV prevention research efforts. In this study, we linked the intrapersonal dimensions of attitudes, beliefs, and normative concerns to community-level components, appraisal of involvement with the clinical research organization, an entity which operates within a networked structure of community partner agencies, and identification with coalition advocacy aims. Various participatory outcomes were explored including involvement in future HIV vaccine community functions, participation in community promotion of HIV vaccine research, and community mobilization. Three-stage least squares estimates indicated similar findings across three models. Significant effects demonstrate the importance of positive attitudes toward HIV vaccine research, favorable health research beliefs, perceived social support for participation, HIV/AIDS issue engagement, and perceived relevance of the clinical research site's mission and values. Identification of these nuanced pathway effects provides implications for tailored community program development. PMID:20012200
Frew, Paula M; Archibald, Matthew; Diallo, Dazon Dixon; Hou, Su-I; Horton, Takeia; Chan, Kayshin; Mulligan, Mark J; del Rio, Carlos
Background The immunogenicity of pneumococcal conjugate vaccine (PCV) has not been evaluated in HIV-infected infants following the first and second PCV-doses. We studied antibody kinetics of serotypes included in 7-valent PCV in HIV-infected and HIV-uninfected infants prior to and following each of three PCV-doses. Methods HIV-uninfected infants born to HIV-uninfected (HUU) and HIV-infected mothers (HEU); and perinatal HIV-infected children with CD4+ < 25% randomized to initiate antiretroviral treatment (ART) when clinically and/or immunologically indicated (ART?) or immediately (ART+) were enrolled. Vaccination occurred at approximately 7.4, 11.5 and 15.5 weeks of age. Serotype-specific antibody was measured by ELISA following each PCV-dose and opsonophagocytic activity (OPA) to three serotypes following the second and third doses. Results Pre-vaccination, antibody geometric mean concentrations (GMCs) were higher in HUU compared to HIV-exposed groups for most serotypes. GMCs and proportion of infants with antibody ?0.35 ?g/ml were similar in HUU compared to other groups following the second PCV-dose. In all groups, GMCs were greater following the third compared to post-second dose; and a higher proportion within each group had antibody ?0.35 ?g/ml to 6B and 23F. OPA GMTs increased after the third compared to post-second dose for studied-serotypes; as did the proportion with OPA ?8 to 23F. Conclusion A two-dose primary-series of PCV probably confers similar protection against invasive pneumococcal disease in HIV-infected compared to HUU children. The inferior response to serotypes 6B and 23F, and lower GMCs and OPA GMTs, following two compared to after three PCV-doses may have implications in the prevention of pneumococcal disease in high-burden countries. PMID:23228814
Madhi, Shabir A.; Izu, Alane; Violari, Avye; Cotton, Mark F.; Panchia, Ravindre; Dobbels, Els; Sewraj, Poonam; van Niekerk, Nadia; Jean-Philippe, Patrick; Adrian, Peter V.
Recombinant protein subunit AIDS vaccines have been based predominantly on the virus envelope protein. Such vaccines elicit neutralizing antibody responses that can provide type-specific sterilizing immunity, but in most cases do not confer protection against divergent viruses. In this report we demonstrate that a multiantigen subunit protein vaccine was able to prevent the development of disease induced in rhesus monkeys by a partially heterologous AIDS virus. The vaccine was composed of recombinant human immunodeficiency virus type 1 (HIV-1) gp120, NefTat fusion protein, and simian immunodeficiency virus (SIV) Nef formulated in the clinically tested adjuvant AS02A. Upon challenge of genetically unselected rhesus monkeys with the highly pathogenic and partially heterologous SIV/HIV strain SHIV89.6p the vaccine was able to reduce virus load and protect the animals from a decline in CD4-positive cells. Furthermore, vaccination prevented the development of AIDS for more than 2.5 years. The combination of the regulatory proteins Nef and Tat together with the structural protein gp120 was required for vaccine efficacy. PMID:12502820
Voss, Gerald; Manson, Kelledy; Montefiori, David; Watkins, David I.; Heeney, Jonathan; Wyand, Michael; Cohen, Joe; Bruck, Claudine
Rabies vaccines have evolved from the first crude nerve tissue vaccines developed by Louis Pasteur and his colleagues in 1885. Currently, safe and efficacious rabies vaccines for humans and animals are produced in several cell culture systems with 10 vaccine regimens recommended by WHO and/or ACIP for pre-exposure and post-exposure prophylaxis in humans. Rabies vaccines are a critical component in the strategy to reduce the dog rabies, the cause of 98% of all global human rabies deaths. However, eliminating rabies in the reservoir animal species is not possible without an intersectoral approach including collaboration between animal and human health experts. There is an urgent need to establish national risk assessment systems in regions where surveillance is limited to non-existent. PMID:22503445
Briggs, Deborah J
Introduction: During the war in Bosnia and Herzegovina, which lasted from 1992-1995, the functioning of all sectors was disturbed, including the health sector. The priority of the heath sector was treatment and less attention was paid to prevention, and this applies also to the Program of implementation of obligatory immunization, as one of the most important prevention measures. This program was conducted with difficulty and sometimes was completely interrupted because of the lack of necessary vaccines and the inability of adequate maintenance of the cold chain. It was difficult and sometimes completely impossible to bring children to vaccination. Because of these problems, a great number of children stayed unvaccinated so they suffered from vaccine-preventable diseases several years after the war. Materials and methods: This is a retrospective epidemiological study. We analyzed data from January 1994 to July 2014 in Canton Sarajevo, and data about measles outbreak in 2014. Results: In the period from January 1994 to July 2014, 3897 vaccine-preventable diseases were registered in Canton Sarajevo. Among them measles, rubella and mumps were the most frequent. In March 2014, measles outbreak was registered. Almost all cases are unvaccinated (99%) and 43% of all cases are connected with failure of vaccination during the war. Conclusion: During the war, routine immunization program was disrupted in Bosnia and Herzegovina (also in Canton Sarajevo). The consequences are presented as vaccine preventable diseases cases.
Obradovic, Zarema; Balta, Snjezana; Obradovic, Amina; Mesic, Salih
Background Over the last few decades, biomedical HIV prevention research had engaged multiple African stakeholders. There have however been few platforms to enable regional stakeholders to engage with one another. In partnership with the World AIDS Campaign International, the Institute of Public Health of Obafemi Awolowo University, and the National Agency for the Control of AIDS in Nigeria, the New HIV Vaccine and Microbicide Advocacy Society hosted a forum on biomedical HIV prevention research in Africa. Stakeholders’ present explored evidences related to biomedical HIV prevention research and development in Africa, and made recommendations to inform policy, guidelines and future research agenda. Discussion The BHPF hosted 342 participants. Topics discussed included the use of antiretrovirals for HIV prevention, considerations for biomedical HIV prevention among key populations; HIV vaccine development; HIV cure; community and civil society engagement; and ethical considerations in implementation of biomedical HIV prevention research. Participants identified challenges for implementation of proven efficacious interventions and discovery of other new prevention options for Africa. Concerns raised included limited funding by African governments, lack of cohesive advocacy and policy agenda for biomedical HIV prevention research and development by Africa, varied ethical practices, and limited support to communities’ capacity to actively engaged with clinical trial conducts. Participants recommended that the African Government implement the Abuja +12 declaration; the civil society build stronger partnerships with diverse stakeholders, and develop a coherent advocacy agenda that also enhances community research literacy; and researchers and sponsors of trials on the African continent establish a process for determining appropriate standards for trial conduct on the continent. Conclusion By highlighting key considerations for biomedical HIV prevention research and development in Africa, the forum has helped identify key advocacy issues that Civil Society can expend efforts on so as to strengthen support for future biomedical HIV prevention research on the continent.
Efficacy trials of adenovirus 5-vectored candidate HIV vaccines [recombinant Ad5 (rAd5)-HIV] were halted for futility due to lack of vaccine efficacy and unexpected excess HIV infections in the vaccine recipients. The potential immunologic basis for these observations is unclear. We comparatively evaluated the HIV susceptibility and phenotypes of human CD4 T cells specific to Ad5 and CMV, two viruses that have been used as HIV vaccine vectors. We show that Ad5-specific CD4 T cells, either induced by natural Ad5 exposure or expanded by rAd5 vaccination, are highly susceptible to HIV in vitro and are preferentially lost in HIV-infected individuals compared with CMV-specific CD4 T cells. Further investigation demonstrated that Ad5-specific CD4 T cells selectively display a proinflammatory Th17-like phenotype and express macrophage inflammatory protein 3? and ?4?7 integrin, suggestive of gut mucosa homing potential of these cells. Analysis of HIV p24 and cytokine coexpression using flow cytometry revealed preferential infection of IL-17- and IL-2-producing, Ad5-specific CD4 T cells by HIV in vitro. Our data suggest a potential mechanism explaining the excess HIV infections in vaccine recipients after rAd5-HIV vaccination and highlight the importance of testing the HIV susceptibility of vaccine-generated, vector and insert-specific CD4 T cells in future HIV vaccine studies. PMID:25197078
Hu, Haitao; Eller, Michael A; Zafar, Shah; Zhou, Yu; Gu, Mengnan; Wei, Zhi; Currier, Jeffrey R; Marovich, Mary A; Kibuuka, Hannah N; Bailer, Robert T; Koup, Richard A; Robb, Merlin L; Michael, Nelson L; Kim, Jerome H; Ratto-Kim, Silvia
A current debate in the HIV-1 vaccine field concerns the ability of an immunodeficiency virus to elicit a protective response. One argument is that HIV-1 superinfections are frequent in healthy individuals, because virus evades conventional immune surveillance, a serious obstacle to vaccine design. The opposing argument is that protection from superinfection is significant, reflecting a robust immune response that might be harnessed by vaccination to prevent disease. In an experiment designed to address the debate, two macaques received an I.V. inoculation with SHIV KU-1-d (a derivative of SHIV KU-1) and were rested for ?10 months. Infection elicited diverse neutralizing antibody activities in both animals. Animals were then exposed to SHIV 89.6P (I.V.), a virus carrying a heterologous envelope protein relative to the vaccine strain. Infection was monitored by viral load and CD4+ T-cell measurements. All control animals were infected and most succumbed to disease. In contrast, protection from superinfection was statistically significant in test monkeys; one animal showed no evidence of superinfection at any time point and the second showed evidence of virus at only one time point over a 6-month observation period. Neither animal showed signs of disease. Perhaps this protective state may serve as a ‘gold-standard’ for HIV-1 vaccine development, as a similar degree of protection against immunodeficiency virus infections in humans would be much desired. PMID:19925400
Sealy, Robert; Zhan, Xiaoyan; Lockey, Timothy D.; Martin, Louis; Blanchard, James; Traina-Dorge, Vicki; Hurwitz, Julia L.
HIV disproportionately affects people of color, suggesting a need for innovative prevention programs and collaborations as\\u000a part of prevention efforts. African Americans have close ties to the church and faith-based organizations. African American\\u000a faith communities were slow to address HIV prevention, but in recent years, they have become more involved in such activities.\\u000a This study reviews the empirical literature on
Shelley A. Francis; Joan Liverpool
We examined whether engagement in prevention advocacy among HIV clients is associated with their own condom use and HIV care adherence. Longitudinal data merged from three studies in Uganda produced a sample of 1,882 participants who were administered assessments at baseline and months 6 and 12. The measure of prevention advocacy was the mean of two Likert scale items assessing encouragement of others to (1) use condoms, and (2) get HIV tested. In regression analyses controlling for demographics and known correlates of the dependent variables, increased prevention advocacy from baseline to month 12 was significantly associated with increased consistent condom use and marginally associated with increased antiretroviral adherence and clinic attendance. These results suggest that empowering HIV clients to engage in prevention advocacy with others may benefit their own HIV protective behaviors and should be promoted as a component to interventions targeting positive living among people living with HIV. PMID:25433651
Wagner, Glenn J; Ghosh-Dastidar, Bonnie; Slaughter, Mary Ellen
Background Despite evidence that HIV positive women may suffer higher rates of heart disease, diabetes, human papillomavirus infection, and some types of cancer, the provision of preventive health services to HIV positive women is unknown. Preventive health services recommended for such women include breast, colorectal and cervical cancer screening, sexually transmitted infection (STI) testing, vaccinations, and patient counseling on a number of issues including sexual behaviors. Methods This retrospective cohort study utilized medical record reviews of 192 HIV positive women who were patients at the University of Utah Infectious Diseases Clinic in 2009. Medical records were reviewed for all encounters during 2009 using a standardized data collection form; data were collected on patient demographics and a variety of preventive health services. Chi squared tests were used to assess receipt of preventive health services by demographic factors, and multivariable logistic regression was used to determine predictors of receiving select services. Results The most commonly recorded preventive services included blood pressure screening, screening for Hepatitis A and B, Tetanus-Diphtheria-Pertussis vaccination, Pneumococcal pneumonia vaccination, substance abuse screening, and mental health screening. STI testing and safe sex counseling were documented in the medical records of only 37% and 33.9% of women, respectively. Documentation of cancer screening was also low, with cervical cancer screening documented for 56.8% of women, mammography for 65% (N?=?26/40) of women, and colorectal cancer screening for 10% (N?=?4/40) of women, where indicated. In multivariable models, women with private health insurance were less likely to have documented STI testing (OR 0.20; 95% CI 0.08 - 0.52), and, Hispanic women were less likely to have documented safe-sex counseling (OR 0.26; 95% CI 0.07 - 0.94). Conclusions HIV/AIDS providers should focus on the needs of all women for preventive care services, including those with fewer socio-demographic risk factors (i.e., insured, stable housing etc.). In addition, failure to provide STI testing, cancer screening, or safe sex counseling to all patients represents a missed opportunity for provision of services that are important from both a clinical and public health perspective. PMID:24592813
Introduction Community mobilizing strategies are essential to health promotion and uptake of HIV prevention. However, there has been little conceptual work conducted to establish the core components of community mobilization, which are needed to guide HIV prevention programming and evaluation. Objectives We aimed to identify the key domains of community mobilization (CM) essential to change health outcomes or behaviors, and to determine whether these hypothesized CM domains were relevant to a rural South African setting. Method We studied social movements and community capacity, empowerment and development literatures, assessing common elements needed to operationalize HIV programs at a community level. After synthesizing these elements into six essential CM domains, we explored the salience of these CM domains qualitatively, through analysis of 10 key informant in-depth-interviews and seven focus groups in three villages in Bushbuckridge. Results CM domains include: 1) shared concerns, 2) critical consciousness, 3) organizational structures/networks, 4) leadership (individual and/or institutional), 5) collective activities/actions, and 6) social cohesion. Qualitative data indicated that the proposed domains tapped into theoretically consistent constructs comprising aspects of CM processes. Some domains, extracted from largely Western theory, required little adaptation for the South African context; others translated less effortlessly. For example, critical consciousness to collectively question and resolve community challenges functioned as expected. However, organizations/networks, while essential, operated differently than originally hypothesized - not through formal organizations, but through diffuse family networks. Conclusions To date, few community mobilizing efforts in HIV prevention have clearly defined the meaning and domains of CM prior to intervention design. We distilled six CM domains from the literature; all were pertinent to mobilization in rural South Africa. While some adaptation of specific domains is required, they provide an extremely valuable organizational tool to guide CM programming and evaluation of critically needed mobilizing initiatives in Southern Africa. PMID:24147121
Lippman, Sheri A.; Maman, Suzanne; MacPhail, Catherine; Twine, Rhian; Peacock, Dean; Kahn, Kathleen; Pettifor, Audrey
This study examines the relationship between masculine ideology, adherence to norms, and HIV prevention among young Black heterosexual and gay men on the campus of a historically Black college/university. The data from four focus groups and nine individual interviews (N = 35) were aggregated and two recurring themes emerged: sexual communication, and mate availability. Additional themes related to HIV prevention were stigma, protection, and testing. The importance of investigating masculinity with young men is highlighted and implications for professionals working with college students to prevent the transmission of HIV are included.
Hall, Naomi M.; Applewhite, Sheldon
Young Latino immigrant men who have sex with men (MSM) are at risk for HIV and for delayed diagnosis. A need exists to raise awareness about HIV prevention in this population, including the benefits of timely HIV testing. This project was developed through collaboration between University of WA researchers and Entre Hermanos, a community-based organization serving Latinos. Building from a community-based participatory research approach, the researchers developed a campaign that was executed by Activate Brands, based in Denver, Colorado. The authors (a) describe the development of HIV prevention messages through the integration of previously collected formative data; (b) describe the process of translating these messages into PSAs, including the application of a marketing strategy; (c) describe testing the PSAs within the Latino MSM community; and (c) determine a set of important factors to consider when developing HIV prevention messages for young Latino MSM who do not identify as gay. PMID:24864201
Solorio, Rosa; Forehand, Mark; Aguirre, Joel
Renewed enthusiasm for biomedical HIV prevention strategies has followed the recent publication of several high-profile HIV antiretroviral therapy-based HIV prevention trials. In a recent article, Roberts & Matthews (2012) accurately note some of the shortcomings of these individually targeted approaches to HIV prevention and advocate for increased emphasis on structural interventions that have more fundamental effects on the population distribution of HIV. However, they make some implicit assumptions about the extent to which structural interventions are user-independent and more sustainable than biomedical or behavioral interventions. In this article, I elaborate a simple typology of structural interventions along these two axes and suggest that they may be neither user-independent nor sustainable and therefore subject to the same sustainability concerns, costs, and potential unintended consequences as biomedical and behavioral interventions. PMID:22877933
Tsai, Alexander C.
Background Most HIV-1 transmission in Africa occurs among HIV-1-discordant couples (one partner HIV-1 infected and one uninfected) who are unaware of their discordant HIV-1 serostatus. Given the high HIV-1 incidence among HIV-1 discordant couples and to assess efficacy of interventions for reducing HIV-1 transmission, HIV-1 discordant couples represent a critical target population for HIV-1 prevention interventions and prevention trials. Substantial regional differences exist in HIV-1 prevalence in Africa, but regional differences in HIV-1 discordance among African couples, has not previously been reported. Methodology/Principal Findings The Partners in Prevention HSV-2/HIV-1 Transmission Trial (“Partners HSV-2 Study”), the first large HIV-1 prevention trial in Africa involving HIV-1 discordant couples, completed enrollment in May 2007. Partners HSV-2 Study recruitment data from 12 sites from East and Southern Africa were used to assess HIV-1 discordance among couples accessing couples HIV-1 counseling and testing, and to correlate with enrollment of HIV-1 discordant couples. HIV-1 discordance at Partners HSV-2 Study sites ranged from 8–31% of couples tested from the community. Across all study sites and, among all couples with one HIV-1 infected partner, almost half (49%) of couples were HIV-1 discordant. Site-specific monthly enrollment of HIV-1 discordant couples into the clinical trial was not directly associated with prevalence of HIV-1 discordance, but was modestly correlated with national HIV-1 counseling and testing rates and access to palliative care/basic health care (r?=?0.74, p?=?0.09). Conclusions/Significance HIV-1 discordant couples are a critical target for HIV-1 prevention in Africa. In addition to community prevalence of HIV-1 discordance, national infrastructure for HIV-1 testing and healthcare delivery and effective community outreach strategies impact recruitment of HIV-1 discordant couples into HIV-1 prevention trials. PMID:18183292
Lingappa, Jairam R.; Lambdin, Barrot; Bukusi, Elizabeth Ann; Ngure, Kenneth; Kavuma, Linda; Inambao, Mubiana; Kanweka, William; Allen, Susan; Kiarie, James N.; Makhema, Joseph; Were, Edwin; Manongi, Rachel; Coetzee, David; de Bruyn, Guy; Delany-Moretlwe, Sinead; Magaret, Amalia; Mugo, Nelly; Mujugira, Andrew; Ndase, Patrick; Celum, Connie
Pneumococcal infections, including pneumonia and invasive disease, are major sources of morbidity and mortality worldwide. Prevention of the first acquisition of Streptococcus pneumoniae through the use of vaccines represents an effective method to reduce the burden of the disease in both children and adults. Two vaccines are currently available in adults: a pneumococcal polysaccharide vaccine (PPV23) that includes 23 purified capsular polysaccharide antigens and a pneumococcal protein-conjugate vaccine (PCV13) that includes capsular polysaccharide antigens covalently linked to a non-toxic protein. The PPV23 induces a humoral immune response and since it has been licensed has been the subject of debates and controversies. Numerous studies and meta-analyses have shown that PPV23 protects against invasive pneumococcal disease, although there are conflicting data regarding its efficacy for the prevention of pneumonia. Vaccination with PCV13 stimulates good antibody responses as well as mucosal immunity and suppresses colonization. A conjugate vaccine can be expected to have benefits over a polysaccharide vaccine because of the characteristics of a T-cell-dependent response in terms of affinity, maturation of antibodies with repeated exposure, induction of immunological memory and long-lasting immunity. PCV13 has demonstrated all of these characteristics in children and fundamental differences in adults are not expected. The efficacy in adults is currently being investigated and results will be available soon. PMID:24410778
Aliberti, S; Mantero, M; Mirsaeidi, M; Blasi, F
Prevention of hepatitis C virus (HCV) infection by vaccination has been a priority since discovery of the virus and the need has not diminished over the past 25 years. Infection rates are increasing in developed countries because of intravenous drug use. Reducing transmission will be difficult without a vaccine to prevent persistence of primary infections, and also secondary infections that may occur after cure of chronic hepatitis C with increasingly effective direct-acting antiviral (DAA) regimens. Vaccine need is also acute in resource poor countries where most new infections occur and DAAs may be unaffordable. Spontaneous resolution of HCV infection confers durable protection, but mechanisms of immunity remain obscure and contested in the context of vaccine design. A vaccine must elicit a CD4+ helper T cell response that does not fail during acute infection. The need for neutralizing antibodies versus cytotoxic CD8+ T cells is unsettled and reflected in the design of two very different vaccines evaluated in humans for safety and immunogenicity. Here we review the status of vaccine development and the scientific and practical challenges that must be met if the burden of liver disease caused by HCV is to be reduced or eliminated. PMID:24782261
Honegger, Jonathan R.; Zhou, Yan; Walker, Christopher M.
Worldwide, transgender women who engage in sex work have a disproportionate risk for HIV compared with natal male and female sex workers. We reviewed recent epidemiological research on HIV in transgender women and show that transgender women sex workers (TSW) face unique structural, interpersonal, and individual vulnerabilities that contribute to risk for HIV. Only six studies of evidence-based prevention interventions were identified, none of which focused exclusively on TSW. We developed a deterministic model based on findings related to HIV risks and interventions. The model examines HIV prevention approaches in TSW in two settings (Lima, Peru and San Francisco, CA, USA) to identify which interventions would probably achieve the UN goal of 50% reduction in HIV incidence in 10 years. A combination of interventions that achieves small changes in behaviour and low coverage of biomedical interventions was promising in both settings, suggesting that the expansion of prevention services in TSW would be highly effective. However, this expansion needs appropriate sustainable interventions to tackle the upstream drivers of HIV risk and successfully reach this population. Case studies of six countries show context-specific issues that should inform development and implementation of key interventions across heterogeneous settings. We summarise the evidence and knowledge gaps that affect the HIV epidemic in TSW, and propose a research agenda to improve HIV services and policies for this population. PMID:25059941
Poteat, Tonia; Wirtz, Andrea L; Radix, Anita; Borquez, Annick; Silva-Santisteban, Alfonso; Deutsch, Madeline B; Khan, Sharful Islam; Winter, Sam; Operario, Don
In this paper, we explore the benefits of storytelling in health communication and, in particular, immunization education. During the mid-20th century polio epidemic, both personal stories and scientific information abounded in the media. However, as rates of vaccine-preventable diseases declined, narratives about the dangers of such diseases faded as did the public fear of them. Meanwhile, anti-vaccine advocates flooded the media and Internet with stories of injured children and tied those injuries, such as autism, to vaccines. Medical experts often counter anti-vaccine concerns with scientific information which can fail to persuade parents. Furthermore, evidence suggests that many people misunderstand quantitative information resulting in a misinterpretation of risk. Compared to scientific information, stories relate life lessons and values. They are effective because they are memorable and relatable. Evidence also suggests that storytelling can effectively improve health knowledge and behaviors. Inspired by In Harm's Way--True Stories of Uninsured Texas Children by the Children's Defense Fund and Faces of Influenza by the American Lung Association, we published Vaccine-Preventable Disease: The Forgotten Story, a collection of photographs and personal stories of families affected by vaccine-preventable diseases. We have found that the stories included in our booklet capture all the benefits of storytelling. Given the many benefits of storytelling, providers should strive to include stories along with medical facts in their daily practice. PMID:23444587
Cunningham, Rachel M; Boom, Julie A
We aim to describe the epidemiology of selected vaccine-preventable diseases in New South Wales (NSW) for 2012. Data from the NSW Notifiable Conditions Information Management System were analysed by: local health district of residence, age, Aboriginality, vaccination status and organism, where available. Risk factor and vaccination status data were collected by public health units for cases following notification under the NSW Public Health Act 2010. The largest outbreak of measles since 1998 was reported in 2012. Pacific Islander and Aboriginal people were at higher risk as were infants less than 12 months of age. Notifications of invasive pneumococcal disease (IPD) in children less than five years declined; however, the overall number of notifications for IPD increased. Mumps case notifications were also elevated. There were no Haemophilus influenzae type b case notifications in children less than five years of age for the first time since the vaccine was introduced. Invasive meningococcal disease case notifications were at their lowest rates since case notification began in 1991. Case notification rates for other selected vaccine-preventable diseases remained stable. Vaccine-preventable disease control is continually strengthening in NSW with notable successes in invasive bacterial infections. However, strengthening measles immunization in Pacific Islander and Aboriginal communities remains essential to maintain measles elimination. PMID:25077033
Spokes, Paula; Gilmour, Robin
Some of the central challenges for developing effective vaccines against HIV and hepatitis C virus (HCV) are similar. Both infections are caused by small, highly mutable, rapidly replicating RNA viruses with the ability to establish long-term chronic pathogenic infection in human hosts. HIV has caused 60 million infections globally and HCV 180 million and both viruses may co-exist among certain populations by virtue of common blood-borne, sexual, or vertical transmission. Persistence of both pathogens is achieved by evasion of intrinsic, innate, and adaptive immune defenses but with some distinct mechanisms reflecting their differences in evolutionary history, replication characteristics, cell tropism, and visibility to mucosal versus systemic and hepatic immune responses. A potent and durable antibody and T cell response is a likely requirement of future HIV and HCV vaccines. Perhaps the single biggest difference between the two vaccine design challenges is that in HCV, a natural model of protective immunity can be found in those who resolve acute infection spontaneously. Such spontaneous resolvers exhibit durable and functional CD4+ and CD8+ T cell responses (Diepolder et al., 1995; Cooper et al., 1999; Thimme et al., 2001; Grakoui et al., 2003; Lauer et al., 2004; Schulze Zur Wiesch et al., 2012). However, frequent re-infection suggests partial or lack of protective immunity against heterologous HCV strains, possibly indicative of the degree of genetic diversity of circulating HCV genotypes and subtypes. There is no natural model of protective immunity in HIV, however, studies of “elite controllers,” or individuals who have durably suppressed levels of plasma HIV RNA without antiretroviral therapy, has provided the strongest evidence for CD8+ T cell responses in controlling viremia and limiting reservoir burden in established infection. Here we compare and contrast the specific mechanisms of immune evasion used by HIV and HCV, which subvert adaptive human leukocyte antigen (HLA)-restricted T cell immunity in natural infection, and the challenges these pose for designing effective preventative or therapeutic vaccines. PMID:25352836
John, Mina; Gaudieri, Silvana
This manual was written to help school-based professionals implement school health education programs to prevent the spread of the human immunodeficiency virus (HIV). The manual provides a framework and plan to promote an interdisciplinary approach to HIV education in schools. The manual begins with a review of basic facts about acquired immune…
Kerr, Dianne L.; And Others
Background Since human immunodeficiency virus (HIV)-infected individuals are at increased risk of severe disease from pandemic influenza A (H1N1pdm09), vaccination was recommended as a prevention strategy. The aim of the present study was to evaluate the safety, immunogenicity and persistence of the immune response after vaccination against pandemic influenza A (H1N1pdm09) with an adjuvanted vaccine in human immunodeficiency virus (HIV)-infected adults using two single and two double doses. Methodology/Principal Findings Open label, randomized trial to evaluate the immune response following H1N1pdm09 vaccination in HIV-infected participants compared to HIV-negative controls (NCT01155037). HIV-infected participants were randomized to receive 2 single (3.75 µg hemagglutinin) or 2 double (7.5 µg hemagglutinin) doses of the vaccine, 21 days apart. Controls received one dose of the vaccine. The primary endpoint was seroconversion as measured by hemagglutination inhibition assay. Two hundred fifty six HIV-infected participants (129 and 127 randomized to single and double doses, respectively) and 71 HIV-negative controls were enrolled. Among HIV-infected participants, seroconversion increased from 46.7% and 51.7% after the first dose to 77.2% and 83.8% after the second dose of the vaccine using single and double doses, respectively. Participants aged >40 years showed higher seroconversion compared to younger participants. Seroconversion among HIV-infected women and those with nadir CD4<200 cells/mm3 was significantly higher with double doses. Persistence of protective antibodies six months after vaccination was achieved by 80% and 89.9% of the HIV-infected participants who received single and double doses, respectively. Conclusions/Significance Our results support the recommendation of two double doses of adjuvanted H1N1pdm09 vaccine for HIV-infected individuals, particularly women, and those aged >40 years or with nadir CD4<200 cells/mm3, to achieve antibody levels that are both higher and more sustained. Trial Registration ClinicalTrials.gov NCT01155037 PMID:22761759
Santini-Oliveira, Marilia; Camacho, Luiz A. B.; Souza, Thiago M. L.; Luz, Paula M.; Vasconcellos, Mauricio T. L.; Giacoia-Gripp, Carmem B. W.; Morgado, Mariza G.; Nunes, Estevão P.; Lemos, Alberto S.; Ferreira, Ana C. G.; Moreira, Ronaldo I.; Veloso, Valdiléa G.; Siqueira, Marilda M.; Grinsztejn, Beatriz
Around 2.5 million people become infected with HIV each year. This extraordinary toll on human life and public health worldwide will only be reversed with effective prevention. What’s more, in the next few years, it is likely at least, that no single prevention strategy will be sufficient to contain the spread of the disease. There is a need for combination prevention as there is for combination treatment, including biomedical, behavioral, and structural interventions. Expanded HIV prevention must be grounded in a systematic analysis of the epidemic’s dynamics in local contexts. Although 85% of HIV is transmitted sexually, effective combinations of prevention have been shown for people who inject drugs. Combination prevention should be based on scientifically derived evidence, with input and engagement from local communities that fosters the successful integration of care and treatment. PMID:22908192
Bekker, Linda-Gail; Beyrer, Chris; Quinn, Thomas C.
Objective Building a successful combination prevention program requires understanding the community’s local epidemiological profile, the social community norms that shape vulnerability to HIV and access to care, and the available community resources. We carried out a situational analysis in order to shape a comprehensive HIV prevention program that address local barriers to care at multiple contextual levels in the North West Province of South Africa. Method The situational analysis was conducted in two sub-districts in 2012 and guided by an adaptation of WHO’s Strategic Approach, a predominantly qualitative method, including observation of service delivery points and in-depth interviews and focus groups with local leaders, providers, and community members, in order to recommend context-specific HIV prevention strategies. Analysis began during fieldwork with nightly discussions of findings and continued with coding original textual data from the fieldwork notebooks and a select number of recorded interviews. Results We conducted over 200 individual and group interviews and gleaned four principal social barriers to HIV prevention and care, including: HIV fatalism, traditional gender norms, HIV-related stigma, and challenges with communication around HIV, all of which fuel the HIV epidemic. At the different levels of response needed to stem the epidemic, we found evidence of national policies and programs that are mitigating the social risk factors but little community-based responses that address social risk factors to HIV. Conclusions Understanding social and structural barriers to care helped shape our comprehensive HIV prevention program, which address the four ‘themes’ identified into each component of the program. Activities are underway to engage communities, offer community-based testing in high transmission areas, community stigma reduction, and a positive health, dignity and prevention program for stigma reduction and improve communication skills. The situational analysis process successfully shaped key programmatic decisions and cultivated a deeper collaboration with local stakeholders to support program implementation. PMID:25028976
Lippman, Sheri A.; Treves-Kagan, Sarah; Gilvydis, Jennifer M.; Naidoo, Evasen; Khumalo-Sakutukwa, Gertrude; Darbes, Lynae; Raphela, Elsie; Ntswane, Lebogang; Barnhart, Scott
Although vaccination against hepatitis A virus (HAV) is essential for human immunodeficiency virus (HIV)-infected patients, the uptake of HAV vaccine is reported to be very low. From 2007 to 2012, 912 HIV-infected men in Athens, Greece were screened for exposure to HAV. Two doses of an HAV vaccine were recommended to 569 eligible patients. Reminder cards with scheduled vaccination visits were given to each patient. Among eligible patients, 62.2% (354/569) received both doses. Patients who were fully vaccinated compared with non-adherent patients were natives, older, had undetectable HIV viral load, higher CD4 T cell counts and lower nadir CD4 T cell counts. Multivariate logistic regression revealed that the patient's country of origin (p?=?0.024; OR?=?2.712; 95% CI, 1.139-6.457), CD4 T cell count (p?0.001) and nadir CD4 T cell count (p?0.001) were factors directly associated to adherence. In conclusion, adherence to HAV vaccination was better than in previously published data. Because many of the factors related to vaccination compliance are parameters of HIV infection, it appears that physician interest in HIV care and vaccination planning is crucial to enhancing vaccine uptake. PMID:25411352
Kourkounti, Sofia; Paparizos, Vassilios; Leuow, Kirsten; Paparizou, Eleni; Antoniou, Christina
Objectives. We examined HIV-infected parents’ conversations about HIV prevention with their uninfected children, including what facilitated or hindered communication. Methods. Parents with HIV/AIDS (n?=?90) who had children aged 10 to 18 years were recruited for a mixed method study from 2009 to 2010. Interviews assessed facilitators and barriers to discussing HIV prevention. A questionnaire identified the frequency and content of conversations, parental confidence level, and perceived importance of discussing preventive topics. Results. Eighty-one percent of parents reported “sometimes” or “often” communicating about HIV prevention. A subset of parents found these conversations difficult; 44% indicated their desire for support. Facilitators to communication included utilizing support, focusing on the benefits of talking, and having a previous relationship with one’s child. Barriers to discussions included fear of negative consequences, living in denial, and lacking a parental role model who discussed safer sex. Parents varied as to how they believed their HIV status affected communication. Those who did not disclose their HIV status to their children reported less frequent communication; self-efficacy partially mediated this relationship. Conclusions. Findings highlighted the need for communication skills training that support HIV-infected parents in their efforts to discuss HIV-related information with adolescents. PMID:23763390
Reis, Janet S.; Weber, Kathleen M.
Because sexual transmission of HIV occurs across mucosal membranes, understanding the immune responses of the genital mucosa to vaccines may contribute knowledge to finding an effective candidate HIV vaccine. We describe the uptake of rectal secretion, cervical secretion and seminal mucosal secretion sampling amongst volunteers in a Phase 1b HIV vaccine trial. Age at screening, gender, study site and the designation of the person conducting the informed consent procedure were collected for volunteers who screened for the HVTN 097 study. A total of 211 volunteers (54% female) were screened at three sites in South Africa: Soweto (n?=?70, 33%), Cape Town (n?=?68, 32%) and Klerksdorp (n?=?73, 35%). Overall uptake of optional mucosal sampling amongst trial volunteers was 71% (n?=?149). Compared to Cape Town, volunteers from Soweto and Klerksdorp were less likely to consent to sampling (Soweto OR 0.08 CI: 0.03–0.25 p<0.001 and Klerksdorp OR 0.13 CI: 0.04–0.41 p?=?0.001). In contrast, volunteers over 25 years of age were 2.39 times more likely to consent than younger volunteers (CI: 1.13–5.08, p?=?0.02). Further studies are required to better understand the cultural, demographic and sociobehavioral factors which influence willingness to participate in mucosal sampling in HIV prevention studies. Trial Registration ClinicalTrials.gov: NCT02109354 PMID:25401780
Lazarus, Erica Maxine; Otwombe, Kennedy; Adonis, Tania; Sebastian, Elaine; Gray, Glenda; Grunenberg, Nicole; Roux, Surita; Churchyard, Gavin; Innes, Craig; Laher, Fatima
The immunodominant epitopes expressed by the HIV-1 envelope protein gp120 are hypermutable, defeating attempts to develop an effective HIV vaccine. Targeting the structurally conserved gp120 determinant that binds host CD4 receptors (CD4BD) and initiates infection is a more promising route to vaccination, but this has proved difficult because of the conformational flexibility of gp120 and immune evasion mechanisms used by the virus. Mimicking the outer CD4BD conformational epitopes is difficult because of their discontinuous nature. The CD4BD region composed of residues 421–433 (CD4BDcore) is a linear epitope, but this region possesses B cell superantigenic character. While superantigen epitopes are vulnerable to a small subset of spontaneously produced neutralizing antibodies present in humans without infection (innate antibodies), their non-covalent binding to B cell receptors (BCRs) does not stimulate an effective adaptive response from B cells. Covalent binding at naturally occurring nucleophilic sites of the BCRs by an electrophilic gp120 (E-gp120) analog is a promising solution. E-gp120 induces the synthesis of neutralizing antibodies the CD4BDcore. The highly energetic covalent reaction is hypothesized to convert the abortive superantigens–BCR interaction into a stimulatory signal, and the binding of a spatially distinct epitope at the traditional combining site of the BCRs may furnish a second stimulatory signal. Flexible synthetic peptides can detect pre-existing CD4BDcore-specific neutralizing antibodies. However, induced-fit conformational transitions of the peptides dictated by the antibody combining site structure may induce the synthesis of non-neutralizing antibodies. Successful vaccine targeting of the CD4BD will require a sufficiently rigid immunogen that mimics the native epitope conformation and bypasses B cell checkpoints restricting synthesis of the neutralizing antibodies. PMID:23251137
Nishiyama, Yasuhiro; Planque, Stephanie; Hanson, Carl V.; Massey, Richard J.; Paul, Sudhir
Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Exposed and HIV-Infected to the care of HIV-infected infants, children, adolescents, and pregnant women whose work and advocacy saved for the Prevention and Treatment of Opportunistic Infections in HIV-Exposed and HIV-Infected Children: Panel
Bandettini, Peter A.
The incidence of HIV infection has increased to alarming proportions among minority youth, in particular among young men who\\u000a have sex with men and among teenage girls. The unique socioeconomic, behavioral, and emotional vulnerability of adolescents\\u000a for sexually transmitted diseases, including HIV, requires early identification of HIV infection for linkage to care. Differences\\u000a in the clinical and psychosocial presentations of
Hans M. L. Spiegel; Donna C. Futterman
The degree and depth to which primary care physicians counsel patients at risk for human immunodeficiency virus (HIV) infection is a major concern. To determine which factors influence whether physicians counsel patients at risk for HIV, primary care physicians's clinical experience, knowledge, attitudes, and preventive counseling advice in hypothetical case scenarios were assessed. Ninety-nine adult primary care physicians in the Washington, D.C., metropolitan area were interviewed by telephone from May through November 1987. Ninety-one physicians had tested or referred patients for HIV antibody tests. However, 58% could not name the ELISA or Western blot as the tests. The most frequent HIV prevention recommendations were using condoms (67.7%), abstaining from sexual activity (36.4%), getting tested for HIV (30.3%), and safe sex (23.2%). Naming the HIV antibody tests was the most significant predictor of preventive counseling advice; other significant predictors included physicians' personal comfort with counseling homosexual patients and various physician practice and demographic characteristics. Previous studies showed that homophobia was the main inhibitor of effective AIDS counseling. These results suggest that physicians' lack of knowledge and general discomfort in counseling patients about sexual risk factors, rather than homophobia alone, are important barriers to preventive counseling about HIV infection. PMID:2765288
Fredman, L; Rabin, D L; Bowman, M; Bandemer, C; Sardeson, K; Taggart, V S; English, D K
Community engagement is crucial to ongoing development and testing of sorely needed new biomedical HIV prevention technologies. Yet, negative trial results raise significant challenges for community engagement in HIV prevention trials, including the early termination of the Cellulose Sulfate microbicide trial and two Phase IIb HIV vaccine trials (STEP and Phambili). The present study aimed to explore the perspectives and experiences of civil society organization (CSO) representatives regarding negative HIV prevention trial results and perceived implications for future trials. We conducted in-depth interviews with 14 respondents from a broad range of South African and international CSOs, and analyzed data using thematic analysis. CSO representatives reported disappointment in response to negative trial results, but acknowledged such outcomes as inherent to clinical research. Respondents indicated that in theory negative trial results seem likely to impact on willingness to participate in future trials, but that in practice people in South Africa have continued to volunteer. Negative trial results were described as having contributed to improving ethical standards, and to a re-evaluation of the scientific agenda. Such negative results were identified as potentially impacting on funding for trials and engagement activities. Our findings indicate that trial closures may be used constructively to support opportunities for reflection and renewed vigilance in strategies for stakeholder engagement, communicating trial outcomes, and building research literacy among communities; however, these strategies require sustained resources for community engagement and capacity-building. PMID:22360605
Essack, Zaynab; Koen, Jennifer; Slack, Catherine; Lindegger, Graham; Newman, Peter A
Early achievements in biomedical approaches for HIV prevention included physical barriers (condoms), clean injection equipment (both for medical use and for injection drug users), blood and blood product safety, and prevention of mother to child transmission. In recent years, antiretroviral drugs to reduce risk of transmission (when the infected person takes the medicines; treatment as prevention or TasP) or reduce risk of acquisition (when the seronegative person takes them; pre-exposure prophylaxis or PrEP) have proven efficacious. Circumcision of men has also been a major tool relevant for higher prevalence regions such as sub-Saharan Africa. Well-established prevention strategies in the control of sexually transmitted diseases and tuberculosis are highly relevant for HIV (i.e., screening, linkage to care, early treatment, and contact tracing). Unfortunately, only slow progress is being made in some available HIV prevention strategies such as family planning for HIV-infected women who do not want more children and prevention mother-to-child HIV transmission. Current studies seek to integrate strategies into approaches that combine biomedical, behavioral, and structural methods to achieve prevention synergies. This review identifies the major biomedical approaches demonstrated to be efficacious that are now available. We also highlight the need for behavioral risk reduction and adherence as essential components of any biomedical approach. PMID:23673881
Vermund, Sten H.; Tique, José A.; Cassell, Holly M.; Johnson, Megan E.; Ciampa, Philip J.; Audet, Carolyn M.
The preventative effects of antiretroviral therapy for people with HIV have been debated since they were first raised. Models commenced studying the preventive effects of treatment in the 1990s, prior to initial public reports. However, the outcomes of the preventive effects of antiretroviral use were not consistent. Some outcomes of dynamic models were based on unfeasible assumptions, such as no consideration of drug resistance, behavior disinhibition, or economic inputs in poor countries, and unrealistic input variables, for example, overstated initiation time, adherence, coverage, and efficacy of treatment. This paper reviewed dynamic mathematical models to ascertain the complex effects of ART on HIV transmission. This review discusses more conservative inputs and outcomes relative to antiretroviral use in HIV infections in dynamic mathematical models. ART alone cannot eliminate HIV transmission. PMID:25580461
Norris, Jessie L.; Jia, Yujiang; Wang, Ning
The development of HIV vaccines has been hampered by the lack of an animal model that can accurately predict vaccine efficacy. Chimpanzees can be infected with HIV-1 but are not practical for research. However, several species of macaques are susceptible to the Simian Immunodeficiency Viruses (SIV) that causes a disease in macaques that closely mimics HIV in humans. Thus, macaque-SIV models of HIV infection have become a critical foundation for AIDS vaccine development. Here, we examine the multiple variables and considerations that must be taken into account to use this NHP model effectively. These include the species and subspecies of macaques, virus strain, dose and route of administration and macaque genetics including Major Histocompatibility Complex molecules that affect immune responses and other virus restriction factors. We illustrate how these NHP models can be used to carry out studies of immune responses in mucosal and other tissues than could not easily be performed on human volunteers. Futhermore macaques are an ideal model system to optimize adjuvants, test vaccine platforms, and identify correlates of protection that can advance the HIV vaccine field. We also illustrate techniques used to identify different macaque lymphocyte populations and review some poxvirus vaccine candidates that are in various stages of clinical trials. Understanding how to effectively use this valuable model will greatly increase the likelihood of finding a successful vaccine for HIV. PMID:24510515
Sui, Yongjun; Gordon, Shari; Franchini, Genoveffa; Berzofsky, Jay A.
Racial/ethnic minorities in the Southeastern USA are disproportionately affected by HIV, and would benefit from a preventive vaccine. We conducted a cross-sectional survey of 220 community college students in Atlanta to evaluate racial/ethnic differences in knowledge and willingness to participate in HIV vaccine trials. Willingness to participate did not differ by race/ethnicity, age, or gender, and was not associated with knowledge. African-Americans and Asians were more likely than Whites to: believe that an HIV vaccine exists, but is being withheld from the public; believe that AIDS was caused by a government conspiracy; feel that having other participants and investigators of their ethnic background in the trial was important. Misconceptions regarding HIV vaccines are common and differ by race/ethnicity. However, willingness to participate was not associated with knowledge or race/ethnicity. Efforts to increase participation should address the ethnic diversity of the trial personnel, and education to eliminate misconceptions about HIV vaccines and trials. PMID:16464270
Priddy, F H; Cheng, A C; Salazar, L F; Frew, P M
BACKGROUND: In South Africa, HIV prevalence among youth aged 15-24 is among the world's highest. Given the urgent need to identify effective HIV prevention approaches, this review assesses the evidence base for youth HIV prevention in South Africa. METHODS: Systematic, analytical review of HIV prevention interventions targeting youth in South Africa since 2000. Critical assessment of interventions in 4 domains:
Abigail Harrison; Marie-Louise Newell; John Imrie; Graeme Hoddinott
This is a PowerPoint presentation outlining HIV and AIDS background, as well as specifically showing the progress and future goals of vaccination attempts. The level of specificity goes to cell biology.
PhD Nancy L Haigwood (Seattle Biomedical Research Institute University of Washington)
Objective This study examines whether men-who-have-sex-with-men (MSM) and transgender (TG) persons’ attitudes, beliefs, and risk perceptions toward human immunodeficiency virus (HIV) vaccine research have been altered as a result of the negative findings from a phase 2B HIV vaccine study. Design We conducted a cross-sectional survey among MSM and TG persons (N = 176) recruited from community settings in Atlanta from 2007 to 2008. The first group was recruited during an active phase 2B HIV vaccine trial in which a candidate vaccine was being evaluated (the “Step Study”), and the second group was recruited after product futility was widely reported in the media. Methods Descriptive statistics, t tests, and chi-square tests were conducted to ascertain differences between the groups, and ordinal logistic regressions examined the influences of the above-mentioned factors on a critical outcome, future HIV vaccine study participation. The ordinal regression outcomes evaluated the influences on disinclination, neutrality, and inclination to study participation. Results Behavioral outcomes such as future recruitment, event attendance, study promotion, and community mobilization did not reveal any differences in participants’ intentions between the groups. However, we observed greater interest in HIV vaccine study screening (t = 1.07, P < 0.05) and enrollment (t = 1.15, P < 0.05) following negative vaccine findings. Means on perceptions, attitudes, and beliefs did not differ between the groups. Before this development, only beliefs exhibited a strong relationship on the enrollment intention (? = 2.166, P = 0.002). However, the effect disappeared following negative trial results, with the positive assessment of the study-site perceptions being the only significant contributing factor on enrollment intentions (? = 1.369, P = 0.011). Conclusion Findings show greater enrollment intention among this population in the wake of negative efficacy findings from the Step Study. The resolve of this community to find an HIV vaccine is evident. Moreover, any exposure to information disseminated in the public arena did not appear to negatively influence the potential for future participation in HIV vaccine studies among this population. The results suggest that subsequent studies testing candidate vaccines could be conducted in this population. PMID:21152413
Frew, Paula M; Mulligan, Mark J; Hou, Su-I; Chan, Kayshin; del Rio, Carlos
The inclusion of adolescents in HIV prevention clinical research has the potential to improve the current understanding of the safety and efficacy of biomedical prevention technologies in younger populations that are at increasing risk of HIV infection. However, there are significant individual, operational, and community-level barriers to engaging adolescents in clinical prevention trials. This paper identifies and addresses individual, operational, and community-level barriers to adolescents' participation in HIV biomedical prevention research. Barriers identified and addressed in the paper include: (1) insufficient understanding of clinic prevention research, (2) self-presentation bias, (3) issues surrounding parental consent, (4) access to clinical trials, (5) mistrust of research, and (6) stigma associated with participation in clinical trials. Examples of programs where adolescents have been successfully engaged in prevention research are highlighted and the lessons learned from these programs indicate that establishing collaborations with key stakeholders in the community are essential for conducting biomedical research with vulnerable populations, including adolescents. Given the importance of understanding young peoples' reactions to, acceptability, and utilization of new biomedical prevention technologies it is imperative that researchers acknowledge and address these barriers to enhance adolescents' participation and retention in HIV biomedical prevention research. PMID:20571418
DiClemente, Ralph J.; Sales, Jessica McDermott; Borek, Nicolette
Any therapeutic vaccination approach against HIV-1 must induce CTL and Th1 cells. But, therapeutic vaccination is more than that. For extensive application of a therapeutic vaccine several questions need to be solved in advance to achieve a global impact. In this commentary some of them are addressed. We analyze the epidemiology, sociology, economy and immunopathology related to the HIV/AIDS disease. Also, important technical issues and real possibilities to overcome at least some of the major limitation of the antiretroviral treatments in the pursuit of an effective vaccine are considered. From the integration of previous analyses some conclusions are drawn. Because it is just a commentary some arguments are not unveiled into their full extension. At the end, we discuss some issues in relation to the development of the vaccine candidate TERAVAC-HIV-1 as a case study. PMID:23571171
Background Eventual control of HIV/AIDS is believed to be ultimately dependent on a safe, effective and affordable vaccine. Participation of sub-Saharan Africa in the conduct of HIV trials is crucial as this region still experiences high HIV incidences. We describe the experience of recruiting and retaining volunteers in the first HIV vaccine trial (HIVIS03) in Tanzania. Methods In this trial enrolled volunteers from amongst Police Officers (POs) in Dar es Salaam were primed with HIV-1 DNA vaccine at months 0, 1 and 3; and boosted with HIV-1 MVA vaccine at months 9 and 21. A stepwise education provision/sensitization approach was employed to eventual recruitment. Having identified a “core” group of POs keen on HIV prevention activities, those interested to participate in the vaccine trial were invited for a first screening session that comprised of provision of detailed study information and medical evaluation. In the second screening session results of the initial assessment were provided and those eligible were assessed for willingness to participate (WTP). Those willing were consented and eventually randomized into the trial having met the eligibility criteria. Voluntary participation was emphasized throughout. Results Out of 408 POs who formed the core group, 364 (89.0%) attended the educational sessions. 263 out of 364 (72.2%) indicated willingness to participate in the HIV vaccine trial. 98% of those indicating WTP attended the pre-screening workshops. 220 (85.0%) indicated willingness to undergo first screening and 177 POs attended for initial screenings, of whom 162 (91.5%) underwent both clinical and laboratory screenings. 119 volunteers (73.5%) were eligible for the study. 79 were randomized into the trial, while 19 did not turn up, the major reason being partner/family advice. 60 volunteers including 15 females were recruited during a one-year period. All participated in the planned progress updates workshops. Retention into the schedule was: 98% for the 3 DNA/placebo vaccinations, while it was 83% and 73% for the first and second MVA/placebo vaccinations respectively. Conclusion In this first HIV vaccine trial in Tanzania, we successfully recruited the volunteers and there was no significant loss to follow up. Close contact and updates on study progress facilitated the observed retention rates. Trial registration numbers ISRCTN90053831 ISRNCT01132976 and ATMR2009040001075080 PMID:24321091
The discovery of the human immunodeficiency virus type 1 (HIV-1) in 1982 soon led to the identification and development of antiviral compounds to be used in treatment strategies for infected patients. Early in the epidemic, drug monotherapies frequently led to treatment failures because the virus quickly developed resistance to the single drug. Following the advent of highly active antiretroviral therapy (HAART) in 1995, dramatic improvements in HIV-1-infected patient health and survival were realized as more refined combination therapies resulted in reductions in viral loads and increases in CD4+ T-cell counts. In the absence of an effective vaccine, prevention of HIV-1 infection has also gained traction as an approach to curbing the pandemic. The development of compounds as safe and effective microbicides has intensified and has focused on blocking the transmission of HIV-1 during all forms of sexual intercourse. Initial preclinical investigations and clinical trials of microbicides focused on single compounds effective against HIV-1. However, the remarkable successes achieved using combination therapy to treat systemic HIV-1 infection have subsequently stimulated the study and development of combination microbicides that will simultaneously inhibit multiple aspects of the HIV-1 transmission process by targeting incoming viral particles, virus-infected cells, and cells susceptible to HIV-1 infection. This review focuses on existing and developing combination therapies, covering preclinical development, in vitro and in vivo efficacy studies, and subsequent clinical trials. The shift in focus within the microbicide development field from single compounds to combination approaches is also explored. PMID:21343462
Pirrone, Vanessa; Thakkar, Nina; Jacobson, Jeffrey M.; Wigdahl, Brian; Krebs, Fred C.
This study explored HIV vaccine acceptability and strategies for culturally appropriate dissemination among sexually diverse Aboriginal peoples in Canada, among those at highest HIV risk. We conducted four focus groups (n=23) with Aboriginal male (1) and female (1) service users, peer educators (1) and service providers (1) in Ontario, Canada. Transcripts were analysed with narrative thematic techniques from grounded theory, using NVivo. Participants' mean age was 37 years; about half (52%) were female, half (48%) Two-spirit or lesbian, gay or bisexual (LGB)-identified, 48% had a high-school education or less and 57% were unemployed. Vaccine uptake was motivated by community survival; however, negative HIV vaccine perceptions, historically based mistrust of government and healthcare institutions, perceived conflict between western and traditional medicine, sexual prejudice and AIDS stigma within and outside of Aboriginal communities, and vaccine cost may present formidable obstacles to HIV vaccine acceptability. Culturally appropriate processes of engagement emerged on individual levels (i.e., respect for self-determination, explanations in Native languages, use of modelling and traditional healing concepts) and community levels (i.e., leadership by Aboriginal HIV advocates and political representatives, identification of gatekeepers, and procuring Elders' endorsements). Building on cultural strengths and acknowledging the history and context of mistrust and social exclusion are fundamental to effective HIV vaccine dissemination. PMID:21390966
Newman, P A; Woodford, M R; Logie, C
This study assessed the preparedness of school health personnel to develop and deliver HIV/AIDS prevention education programmes for young people in China. A survey of 653 personnel working in secondary schools in 14 cities was conducted. More than 90% had basic knowledge of ways in which HIV can be transmitted, but knowledge of ways in which the virus is not transmitted needs improvement. Substantial numbers of teachers were not sure whether there was an effective preventive vaccine (42%) or did not know whether AIDS was a curable illness or not (32%). The great majority approved of AIDS prevention programmes in universities (98%) and secondary schools (91%), although fewer (58%) agreed that the topic was appropriate for primary schools. Currently, most classroom activities focuses on teaching facts about HIV/AIDS transmission, while less than half are taught about HIV/AIDS related discrimination and life skills to reduce peer pressure. Personnel with some prior training on HIV/ AIDS education (53%) had better factual knowledge, more tolerant attitudes and more confidence in teaching about HIV/AIDS than those without training. The majority of teachers indicated a need for more resource books, audiovisual products, expert guidance, school principal support and dissemination of national AIDS prevention education guidelines to schools. PMID:18839862
Chen, J Q; Dunne, M P; Zhao, D C
Objective To review the current state of knowledge on the prevention of sexual transmission of HIV in adolescents and to highlight existing gaps and priority areas for future research. Background A disproportionate burden of HIV infections falls on adolescents, a developmental stage marked by unique neural, biological, and social transition. Successful interventions are critical to prevent the spread of HIV in this vulnerable population. Methods We summarized the current state of research on HIV prevention in adolescents by providing examples of successful interventions and best practices, and highlighting current research gaps. Results Adolescent interventions fall into three main categories: biomedical, behavioral, and structural. The majority of current research has focused on individual behavior change, while promising biomedical and structural interventions have been largely understudied in adolescents. Combination prevention interventions may be particularly valuable to this group. Conclusions Adolescents have unique needs with respect to HIV prevention and, thus, interventions should be designed to most effectively reach this population with information and services that will be relevant to them. PMID:23764629
Pettifor, Audrey; Bekker, Linda-Gail; Hosek, Sybil; DiClemente, Ralph; Rosenberg, Molly; Bull, Sheana; Allison, Susannah; Delany-Moretlwe, Sinead; Kapogiannis, Bill G.; Cowan, Frances
Each interpersonally delivered, evidence-based (EB) program for HIV prevention shares common features that aim to shift HIV\\u000a risk behaviors. We used qualitative research methods to examine manuals from five EB programs for adolescents and identified\\u000a 10 core principles embedded in each program’s activities. Principles reflect the stated goals and anticipated lessons in an activity. The principles were: Believe in your
Mary Jane Rotheram-Borus; Barbara L. Ingram; Dallas Swendeman; Diane Flannery
The HIV Prevention Trials Network (HPTN) 052 study, which showed the effectiveness of antiretroviral treatment in reducing HIV transmission, has been hailed as a “game changer” in the fight against HIV, prompting calls for scaling up treatment as prevention (TasP). However, it is unclear how TasP can be financed, given flat-lining support for global HIV programs. We assess whether TasP is indeed a game changer or if comparable benefits are obtainable at similar or lower cost by increasing coverage of medical male circumcision (MMC) and antiretroviral treatment (ART) at CD4 <350/?L. We develop a new mathematical model and apply it to South Africa, finding that high ART coverage combined with high MMC coverage provides approximately the same HIV incidence reduction as TasP, for $5 billion less over 2009–2020. MMC outperforms ART significantly in cost per infection averted ($1,096 vs. $6,790) and performs comparably in cost per death averted ($5,198 vs. $5,604). TasP is substantially less cost effective at $8,375 per infection and $7,739 per death averted. The prevention benefits of HIV treatment are largely reaped with high ART coverage. The most cost-effective HIV prevention strategy is to expand MMC coverage and then scale up ART, but the most cost-effective HIV-mortality reduction strategy is to scale up MMC and ART jointly. TasP is cost effective by commonly used absolute benchmarks but it is far less cost effective than MMC and ART. Given South Africa’s current annual ART spending, the $5 billion in savings offered by MMC and ART over TasP in the next decade, for similar health benefits, challenges the widely hailed status of TasP as a game changer. PMID:23223563
Bärnighausen, Till; Bloom, David E.; Humair, Salal
to rethink the cur- rent approach to developing an HIV vaccine. Better communication and cooperation of understanding of the immune system. Specifi- cally, the `rules' for making a successful vaccine are currently, as much as possible, the immune recognition events that happen during a natural infec- tion with the same
South African townships have high HIV prevalence and a strong need for collective action to change normative sexual risk behaviors. This study investigated the relationship between perceptions of individuals about collective efficacy in the community’s ability to prevent HIV and their personal HIV risk behaviors. Men (n=1581) and women (n=718) completed anonymous surveys within four Black African Townships in Cape Town, South Africa from June 2008 to December 2010. Measures included demographics, alcohol use, attitudinal and behavioral norms, sexual health communications, and sexual risk behaviors. In multivariate logistic regressions, men were more likely to endorse collective efficacy if they were married, drank less often in alcohol serving establishments, believed that fewer men approve of HIV risk behaviors, talk more with others about HIV/AIDS, and had more sex partners in the past month. Women were more likely to endorse collective efficacy if they drank alcohol less often, talked more with others about HIV/AIDS, had more sex partners in the past month, but reported fewer unprotected sex acts in the past month. Community level interventions that strengthen collective efficacy beliefs will have to consider both protective and risk behaviors associated with believing that the community is ready and capable of preventing HIV. PMID:23660646
Cain, Demetria; Pitpitan, Eileen V.; Eaton, Lisa; Carey, Kate B.; Carey, Michael P.; Mehlomakulu, Vuyelwa; Harel, Ofer; Simbayi, Leickness C.; Mwaba, Kelvin; Kalichman, Seth C.
A scientist with the National Centre in HIV Epidemiology and Clinical Research at the University of New South Wales in Sydney, Australia, addresses the fact that Australians working in the area of HIV infection have been very successful in prevention, treatment, and care. In the early 1980s, a bipartisan political decision was made to foster an effective partnership between HIV-infected communities, health care providers, and governments. HIV-infected communities included sex workers, prisoners, Aboriginal people, and high profile gay community activists. These three different groups succeeded in forming such a partnership, as reflected in the fact that the annual number of new HIV cases is down to 500 from a peak of 3000 in 1984. A key method used to contain HIV infection was needle-and-syringe exchange programs and continuing access to needles to prevent HIV transmission in the injecting drug community. Even though Australia has all this experience and success, it had a backseat role in ushering in the UNAIDS program because Australia did not contribute a significant share of the agency's relatively small budget (US$100 million/year). If Australia were to give just 10%, it would acquire a front row seat along with the Netherlands, Sweden, Belgium, France, and the UK. These nations have the greatest say as to where UNAIDS funds go. The Australian international aid organization has recently received an increase in funds, $110 million for 4 years to spend on four areas, one of which is HIV/AIDS. Australia has just allocated $25 million for a 5-year program for HIV/STD (sexually transmitted disease) prevention in Indonesia. This money would have been able to buy Australia a leading role in UNAIDS. Australians need to reassess their priorities. Australians can help their neighbors in the Asia-Pacific region move away from their denial of HIV to HIV prevention and care. They can conduct clinical trials of shorter and more user-friendly regimens of antiviral drugs that may lead to reduced perinatal transmission and research on microbicides. They can prevent tuberculosis and introduce manageable methods of securing safe blood supplies and mass screening. PMID:8616207
Cooper, D A
This paper describes the development, content, and capabilities of the online Global HIV Archive (GHA). With the goal of facilitating widespread adaptation and appropriate use of efficacious HIV prevention programs throughout the globe, GHA has: first, expanded and updated the search for HIV prevention programs originating in low-resource countries; second, identified those meritorious HIV prevention programs meeting established efficacy criteria of technical merit, replicability, and positive outcomes; third, prepared both implementation and evaluation materials from the efficacious programs for public use; fourth, developed interactive wizards or capacity-building tools to facilitate appropriate program selection, implementation, and adaptation; and, fifth, made the efficacious programs and accompanying wizards available to health practitioners throughout the globe in both printed and online formats. PMID:24563820
Card, Josefina J.; Newman, Emily N.; Golden, Rachel E.; Kuhn, Tamara; Lomonaco, Carmela
We describe murine monoclonal antibodies (mAbs) raised by immunization with an electrophilic gp120 analog (E-gp120) expressing the rare ability to neutralize genetically heterologous human immunodeficiency virus (HIV) strains. Unlike gp120, E-gp120 formed covalent oligomers. The reactivity of gp120 and E-gp120 with mAbs to reference neutralizing epitopes was markedly different, indicating their divergent structures. Epitope mapping with synthetic peptides and electrophilic peptide analogs indicated binary recognition of two distinct gp120 regions by anti-E-gp120 mAbs, the 421-433 and 288-306 peptide regions. Univalent Fab and single chain Fv fragments expressed the ability to recognize both peptides. X-ray crystallography of an anti-E-gp120 Fab fragment revealed two neighboring cavities, the typical antigen-binding cavity formed by the complementarity determining regions (CDRs) and another cavity dominated by antibody heavy chain variable (VH) domain framework (FR) residues. Substitution of the FR cavity VH Lys-19 residue by an Ala residue resulted in attenuated binding of the 421-433 region peptide probe. The CDRs and VH FR replacement/silent mutation ratios exceeded the ratio for a random mutation process, suggesting adaptive development of both putative binding sites. All mAbs studied were derived from VH1 family genes, suggesting biased recruitment of the V gene germ line repertoire by E-gp120. The conserved 421-433 region of gp120 is essential for HIV binding to host CD4 receptors. This region is recognized weakly by the FR of antibodies produced without exposure to HIV, but it usually fails to induce adaptive synthesis of neutralizing antibodies. We present models accounting for improved CD4-binding site recognition and broad HIV neutralizing activity of the mAbs, long sought goals in HIV vaccine development.
Nishiyama, Yasuhiro; Planque, Stephanie; Mitsuda, Yukie; Nitti, Giovanni; Taguchi, Hiroaki; Jin, Lei; Symersky, Jindrich; Boivin, Stephane; Sienczyk, Marcin; Salas, Maria; Hanson, Carl V.; Paul, Sudhir; (Texas-MED); (Viral Rickettsial)
The growing evidence base for biomedical HIV prevention interventions – such as oral pre-exposure prophylaxis, microbicides, male circumcision, treatment as prevention, and eventually prevention vaccines – has given rise to concerns about the ways in which users of these biomedical products may adjust their HIV risk behaviors based on the perception that they are prevented from infection. Known as risk compensation, this behavioral adjustment draws on the theory of “risk homeostasis,” which has previously been applied to phenomena as diverse as Lyme disease vaccination, insurance mandates, and automobile safety. Little rigorous evidence exists to answer risk compensation concerns in the biomedical HIV prevention literature, in part because the field has not systematically evaluated the study designs available for testing these behaviors. The goals of this Commentary are to explain the origins of risk compensation behavior in risk homeostasis theory, to reframe risk compensation as a testable response to the perception of reduced risk, and to assess the methodological rigor and ethical justification of study designs aiming to isolate risk compensation responses. Although the most rigorous methodological designs for assessing risk compensation behavior may be unavailable due to ethical flaws, several strategies can help investigators identify potential risk compensation behavior during Phase II, Phase III, and Phase IV testing of new technologies. Where concerns arise regarding risk compensation behavior, empirical evidence about the incidence, types, and extent of these behavioral changes can illuminate opportunities to better support the users of new HIV prevention strategies. This Commentary concludes by suggesting a new way to conceptualize risk compensation behavior in the HIV prevention context. PMID:23597916
Objective?To conduct a critical review of all HIV prevention intervention studies conducted with adolescents in juvenile justice settings to inform future intervention development.?Method?PubMed and PsycInfo database searches were conducted for peer-reviewed, published HIV prevention intervention studies with juvenile offenders.?Results?Sixteen studies were identified (N = 3,700 adolescents). Half of the projects utilized rigorous methodologies to determine intervention effect on behavior change, such as conducting a randomized controlled trial (n = 8). Nine studies reported behaviors at least 3 months post-intervention and five out of nine showed decreases in sexual risk behavior.?Conclusions?Several HIV prevention programs with juvenile offenders have led to sexual risk reduction, although effect sizes are modest. Most existing programs have neglected to address the impact of family, mental health, and substance use on HIV risk. More work is needed to develop evidence-based interventions that include HIV prevention strategies relevant and appropriate for the juvenile justice setting. PMID:19741021
Stewart, Angela; Fasciano, John; Brown, Larry K.
Biomedical research is critical to identifying effective and safe interventions, such as vaccines, microbicides, male circumcision and antiretrovirals, for prevention. Funding for clinical prevention trials is highly competitive and the benchmarks of success ultimately reduce to quickly enrolling a select group of people at risk, keeping them enrolled, and inducing them to be compliant with trial requirements - all at the lowest cost possible. Juxtaposed with this reality is the fact that HIV is situated with poverty, exploitation, assaults on human dignity, and human rights abuses. The result is a complex web of ethical challenges that are socially constructed along lines of wealth and power. While social science research methods are commonly employed to examine such topics, they have played a marginal role in biomedical HIV prevention research. Why? To answer this question, a core set of persistent interlocking social, behavioural and ethical challenges to biomedical HIV prevention research are described. A critique is offered on how the social has been framed relative to the behavioural, ethical and biomedical components. Examples of how this framing has devalued social knowledge are provided, including the conflation of qualitative research with anecdotal reporting, a bias toward brevity and accuracy over external validity, and difficulties in distinguishing between a moral understanding of social norms and achieving a moral outcome when confronted with ethical challenges in research. Lastly, opportunities are identified for enhancing the success of biomedical HIV prevention research through development of a coherent programme of social science research. Recommendations are offered for reframing the social as a valid domain of scientific inquiry in this highly applied and interdisciplinary context. PMID:21968079
Objective To reconstruct the local HIV-1 transmission network from 1996 to 2011 and use network data to evaluate and guide efforts to interrupt transmission. Design HIV-1 pol sequence data were analyzed to infer the local transmission network. Methods We analyzed HIV-1 pol sequence data to infer a partial local transmission network among 478 recently HIV-1 infected persons and 170 of their sexual and social contacts in San Diego, California. A transmission network score (TNS) was developed to estimate the risk of HIV transmission from a newly diagnosed individual to a new partner and target prevention interventions. Results HIV-1 pol sequences from 339 individuals (52.3%) were highly similar to sequences from at least one other participant (i.e., clustered). A high TNS (top 25%) was significantly correlated with baseline risk behaviors (number of unique sexual partners and insertive unprotected anal intercourse (p?=?0.014 and p?=?0.0455, respectively) and predicted risk of transmission (p<0.0001). Retrospective analysis of antiretroviral therapy (ART) use, and simulations of ART targeted to individuals with the highest TNS, showed significantly reduced network level HIV transmission (p<0.05). Conclusions Sequence data from an HIV-1 screening program focused on recently infected persons and their social and sexual contacts enabled the characterization of a highly connected transmission network. The network-based risk score (TNS) was highly correlated with transmission risk behaviors and outcomes, and can be used identify and target effective prevention interventions, like ART, to those at a greater risk for HIV-1 transmission. PMID:24901437
Little, Susan J.; Kosakovsky Pond, Sergei L.; Anderson, Christy M.; Young, Jason A.; Wertheim, Joel O.; Mehta, Sanjay R.; May, Susanne; Smith, Davey M.
Background Characterization of viruses in HIV-1 transmission pairs will help identify biological determinants of infectiousness and evaluate candidate interventions to reduce transmission. Although HIV-1 sequencing is frequently used to substantiate linkage between newly HIV-1 infected individuals and their sexual partners in epidemiologic and forensic studies, viral sequencing is seldom applied in HIV-1 prevention trials. The Partners in Prevention HSV/HIV Transmission Study (ClinicalTrials.gov #NCT00194519) was a prospective randomized placebo-controlled trial that enrolled serodiscordant heterosexual couples to determine the efficacy of genital herpes suppression in reducing HIV-1 transmission; as part of the study analysis, HIV-1 sequences were examined for genetic linkage between seroconverters and their enrolled partners. Methodology/Principal Findings We obtained partial consensus HIV-1 env and gag sequences from blood plasma for 151 transmission pairs and performed deep sequencing of env in some cases. We analyzed sequences with phylogenetic techniques and developed a Bayesian algorithm to evaluate the probability of linkage. For linkage, we required monophyletic clustering between enrolled partners' sequences and a Bayesian posterior probability of ?50%. Adjudicators classified each seroconversion, finding 108 (71.5%) linked, 40 (26.5%) unlinked, and 3 (2.0%) indeterminate transmissions, with linkage determined by consensus env sequencing in 91 (84%). Male seroconverters had a higher frequency of unlinked transmissions than female seroconverters. The likelihood of transmission from the enrolled partner was related to time on study, with increasing numbers of unlinked transmissions occurring after longer observation periods. Finally, baseline viral load was found to be significantly higher among linked transmitters. Conclusions/Significance In this first use of HIV-1 sequencing to establish endpoints in a large clinical trial, more than one-fourth of transmissions were unlinked to the enrolled partner, illustrating the relevance of these methods in the design of future HIV-1 prevention trials in serodiscordant couples. A hierarchy of sequencing techniques, analysis methods, and expert adjudication contributed to the linkage determination process. PMID:21399681
Campbell, Mary S.; Mullins, James I.; Hughes, James P.; Celum, Connie; Wong, Kim G.; Raugi, Dana N.; Sorensen, Stefanie; Stoddard, Julia N.; Zhao, Hong; Deng, Wenjie; Kahle, Erin; Panteleeff, Dana; Baeten, Jared M.; McCutchan, Francine E.; Albert, Jan; Leitner, Thomas; Wald, Anna; Corey, Lawrence; Lingappa, Jairam R.
Background We conducted a double-blind, randomized, placebo-controlled Phase I study of a recombinant replication-defective adenovirus type 5 (rAd5) vector expressing HIV-1 Gag and Pol from subtype B and Env from subtypes A, B and C, given alone or as boost following a DNA plasmid vaccine expressing the same HIV-1 proteins plus Nef, in 114 healthy HIV-uninfected African adults. Methodology/Principal Findings Volunteers were randomized to 4 groups receiving the rAd5 vaccine intramuscularly at dosage levels of 1×1010 or 1×1011 particle units (PU) either alone or as boost following 3 injections of the DNA vaccine given at 4 mg/dose intramuscularly by needle-free injection using Biojector® 2000. Safety and immunogenicity were evaluated for 12 months. Both vaccines were well-tolerated. Overall, 62% and 86% of vaccine recipients in the rAd5 alone and DNA prime - rAd5 boost groups, respectively, responded to the HIV-1 proteins by an interferon-gamma (IFN-?) ELISPOT. The frequency of immune responses was independent of rAd5 dosage levels. The highest frequency of responses after rAd5 alone was detected at 6 weeks; after DNA prime - rAd5 boost, at 6 months (end of study). At baseline, neutralizing antibodies against Ad5 were present in 81% of volunteers; the distribution was similar across the 4 groups. Pre-existing immunity to Ad5 did not appear to have a significant impact on reactogenicity or immune response rates to HIV antigens by IFN-? ELISPOT. Binding antibodies against Env were detected in up to 100% recipients of DNA prime - rAd5 boost. One volunteer acquired HIV infection after the study ended, two years after receipt of rAd5 alone. Conclusions/Significance The HIV-1 rAd5 vaccine, either alone or as a boost following HIV-1 DNA vaccine, was well-tolerated and immunogenic in African adults. DNA priming increased the frequency and magnitude of cellular and humoral immune responses, but there was no effect of rAd5 dosage on immunogenicity endpoints. Trial Registration ClinicalTrials.gov NCT00124007 PMID:20877623
Allen, Susan; Than, Soe; Adams, Elizabeth M.; Graham, Barney S.; Koup, Richard A.; Bailer, Robert T.; Smith, Carol; Dally, Len; Tarragona-Fiol, Tony; Bergin, Philip J.; Hayes, Peter; Ho, Martin; Loughran, Kelley; Komaroff, Wendy; Stevens, Gwynneth; Thomson, Helen; Boaz, Mark J.; Cox, Josephine H.; Schmidt, Claudia; Gilmour, Jill; Nabel, Gary J.; Fast, Patricia
Virus diversity and escape from immune responses are the biggest challenges to the development of an effective vaccine against HIV-1. We hypothesized that T-cell vaccines targeting the most conserved regions of the HIV-1 proteome, which are common to most variants and bear fitness costs when mutated, will generate effectors that efficiently recognize and kill virus-infected cells early enough after transmission to potentially impact on HIV-1 replication and will do so more efficiently than whole protein-based T-cell vaccines. Here, we describe the first-ever administration of conserved immunogen vaccines vectored using prime-boost regimens of DNA, simian adenovirus and modified vaccinia virus Ankara to uninfected UK volunteers. The vaccine induced high levels of effector T cells that recognized virus-infected autologous CD4(+) cells and inhibited HIV-1 replication by up to 5.79 log10. The virus inhibition was mediated by both Gag- and Pol- specific effector CD8(+) T cells targeting epitopes that are typically subdominant in natural infection. These results provide proof of concept for using a vaccine to target T cells at conserved epitopes, showing that these T cells can control HIV-1 replication in vitro. PMID:24166483
Borthwick, Nicola; Ahmed, Tina; Ondondo, Beatrice; Hayes, Peter; Rose, Annie; Ebrahimsa, Umar; Hayton, Emma-Jo; Black, Antony; Bridgeman, Anne; Rosario, Maximillian; Hill, Adrian V S; Berrie, Eleanor; Moyle, Sarah; Frahm, Nicole; Cox, Josephine; Colloca, Stefano; Nicosia, Alfredo; Gilmour, Jill; McMichael, Andrew J; Dorrell, Lucy; Hanke, Tomáš
The aim of this study was to systematically review published studies that evaluated the efficiency of inactivated influenza vaccination in preventing seasonal influenza in children. The vaccine evaluated was the influenza-inactivated vaccine in 10 studies and the virosomal inactivated vaccine in 3 studies. The results show that yearly vaccination of children with the inactivated influenza vaccine saves money from the societal and family perspectives but not from the public or private provider perspective. When vaccination does not save money, the cost-effectiveness ratios were very acceptable. It can be concluded, that inactivated influenza vaccination of children is a very efficient intervention. PMID:23295894
Salleras, Luis; Navas, Encarna; Torner, Nuria; Prat, Andreu A.; Garrido, Patricio; Soldevila, Núria; Domínguez, Angela
It has been argued that women's economic vulnerability and dependence on men increases their vulnerability to HIV by constraining their ability to negotiate the conditions, including sexual abstinence, condom use and multiple partnerships, which shape their risk of infection. In the face of escalating infection rates among women, and particularly young women, many have pointed to the potential importance of economic empowerment strategies for HIV prevention responses. Global evidence suggests that the relationship between poverty and HIV risk is complex, and that poverty on its own cannot be viewed simplistically as a driver of the HIV epidemic. Rather, its role appears to be multidimensional and to interact with a range of other factors, including mobility, social and economic inequalities and social capital, which converge in a particularly potent way for young women living in southern Africa. To date, there have been few interventions that have explicitly attempted to combine economic empowerment with the goal of HIV prevention, and even fewer that have been rigorously evaluated. This paper explores how programmes such as microfinance, livelihood training and efforts to safeguard women's food security and access to property have begun to incorporate an HIV prevention focus. Although such circumscribed interventions, by themselves, are unlikely to lead to significant impacts on a national or regional scale, they are useful for testing cross-sectoral partnership models, generating practical lessons and providing a metaphor for what might be possible in promoting women's economic empowerment more broadly. Despite numerous calls to 'mainstream AIDS' in economic development, cross-sectoral responses have not been widely taken up by government or other stakeholders. We suggest potential reasons for limited progress to date and conclude by presenting programme and policy recommendations for further exploring and harnessing linkages between economic empowerment and HIV prevention in Southern Africa. PMID:19033756
Kim, Julia; Pronyk, Paul; Barnett, Tony; Watts, Charlotte
The extraordinary variability of HIV-1 poses a major obstacle to vaccine development. The effectiveness of a vaccine is likely to vary dramatically in different populations infected with different HIV-1 subtypes, unless innovative vaccine immunogens are developed to protect against the range of HIV-1 diversity. Immunogen design for stimulating neutralizing antibody responses focuses on “breadth” – the targeting of a handful of highly conserved neutralizing determinants on the HIV-1 Envelope protein that can recognize the majority of viruses across all HIV-1 subtypes. An effective vaccine will likely require the generation of both broadly cross-neutralizing antibodies and non-neutralizing antibodies, as well as broadly cross-reactive T cells. Several approaches have been taken to design such broadly-reactive and cross-protective T cell immunogens. Artificial sequences have been designed that reduce the genetic distance between a vaccine strain and contemporary circulating viruses; “mosaic” immunogens extend this concept to contain multiple potential T cell epitope (PTE) variants; and further efforts attempt to focus T cell immunity on highly conserved regions of the HIV-1 genome. Thus far, a number of pre-clinical and early clinical studies have been performed assessing these new immunogens. In this review, the potential use of these new immunogens is explored. PMID:25341662
Tongo, Marcel; Burgers, Wendy A.
Managing the dynamics of vaccine supply and demand represents a significant challenge with very high stakes. Insufficient vaccine supplies can necessitate rationing, lead to preventable adverse health outcomes, delay the achievements of elimination or eradication goals, and/or pose reputation risks for public health authorities and/or manufacturers. This article explores the dynamics of global vaccine supply and demand to consider the opportunities to develop and maintain optimal global vaccine stockpiles for universal vaccines, characterized by large global demand (for which we use measles vaccines as an example), and nonuniversal (including new and niche) vaccines (for which we use oral cholera vaccine as an example). We contrast our approach with other vaccine stockpile optimization frameworks previously developed for the United States pediatric vaccine stockpile to address disruptions in supply and global emergency response vaccine stockpiles to provide on-demand vaccines for use in outbreaks. For measles vaccine, we explore the complexity that arises due to different formulations and presentations of vaccines, consideration of rubella, and the context of regional elimination goals. We conclude that global health policy leaders and stakeholders should procure and maintain appropriate global vaccine rotating stocks for measles and rubella vaccine now to support current regional elimination goals, and should probably also do so for other vaccines to help prevent and control endemic or epidemic diseases. This work suggests the need to better model global vaccine supplies to improve efficiency in the vaccine supply chain, ensure adequate supplies to support elimination and eradication initiatives, and support progress toward the goals of the Global Vaccine Action Plan. PMID:25109229
Thompson, Kimberly M; Duintjer Tebbens, Radboud J
We designed synthetic, epitope-focused immunogens that preferentially display individual neutralization epitopes targeted by cross-subtype anti-HIV V3 loop neutralizing monoclonal antibodies (mAbs). Vaccination of rabbits with these immunogens resulted in the elicitation of distinct polyclonal serum Abs that exhibit cross-subtype neutralization specificities mimicking the mAbs that guided the design. Our results prove the principle that a predictable range of epitope-specific polyclonal cross-subtype HIV-1 neutralizing Abs can be intentionally elicited in mammals by vaccination. The precise boundaries of the epitopes and conformational flexibility in the presentation of the epitopes in the immunogen appeared to be important for successful elicitation. This work may serve as a starting point for translating the activities of human broadly neutralizing anti-HIV-1 monoclonal antibodies (bNAbs) into matched immunogens that can contribute to an efficacious HIV-1 vaccine. PMID:25045827
Cardozo, Timothy; Wang, Shixia; Jiang, Xunqing; Kong, Xiang-Peng; Hioe, Catarina; Krachmarov, Chavdar
ABSTRACT The RV144 HIV-1 vaccine trial demonstrated partial efficacy of 31% against HIV-1 infection. Studies into possible correlates of protection found that antibodies specific to the V1 and V2 (V1/V2) region of envelope correlated inversely with infection risk and that viruses isolated from trial participants contained genetic signatures of vaccine-induced pressure in the V1/V2 region. We explored the hypothesis that the genetic signatures in V1 and V2 could be partly attributed to selection by vaccine-primed T cells. We performed a T-cell-based sieve analysis of breakthrough viruses in the RV144 trial and found evidence of predicted HLA binding escape that was greater in vaccine versus placebo recipients. The predicted escape depended on class I HLA A*02- and A*11-restricted epitopes in the MN strain rgp120 vaccine immunogen. Though we hypothesized that this was indicative of postacquisition selection pressure, we also found that vaccine efficacy (VE) was greater in A*02-positive (A*02+) participants than in A*02? participants (VE = 54% versus 3%, P = 0.05). Vaccine efficacy against viruses with a lysine residue at site 169, important to antibody binding and implicated in vaccine-induced immune pressure, was also greater in A*02+ participants (VE = 74% versus 15%, P = 0.02). Additionally, a reanalysis of vaccine-induced immune responses that focused on those that were shown to correlate with infection risk suggested that the humoral responses may have differed in A*02+ participants. These exploratory and hypothesis-generating analyses indicate there may be an association between a class I HLA allele and vaccine efficacy, highlighting the importance of considering HLA alleles and host immune genetics in HIV vaccine trials. IMPORTANCE The RV144 trial was the first to show efficacy against HIV-1 infection. Subsequently, much effort has been directed toward understanding the mechanisms of protection. Here, we conducted a T-cell-based sieve analysis, which compared the genetic sequences of viruses isolated from infected vaccine and placebo recipients. Though we hypothesized that the observed sieve effect indicated postacquisition T-cell selection, we also found that vaccine efficacy was greater for participants who expressed HLA A*02, an allele implicated in the sieve analysis. Though HLA alleles have been associated with disease progression and viral load in HIV-1 infection, these data are the first to suggest the association of a class I HLA allele and vaccine efficacy. While these statistical analyses do not provide mechanistic evidence of protection in RV144, they generate testable hypotheses for the HIV vaccine community and they highlight the importance of assessing the impact of host immune genetics in vaccine-induced immunity and protection. (This study has been registered at ClinicalTrials.gov under registration no. NCT00223080.) PMID:24829343
Gartland, Andrew J.; Li, Sue; McNevin, John; Tomaras, Georgia D.; Gottardo, Raphael; Janes, Holly; Fong, Youyi; Morris, Daryl; Geraghty, Daniel E.; Kijak, Gustavo H.; Edlefsen, Paul T.; Frahm, Nicole; Larsen, Brendan B.; Tovanabutra, Sodsai; Sanders-Buell, Eric; deCamp, Allan C.; Magaret, Craig A.; Ahmed, Hasan; Goodridge, Jodie P.; Chen, Lennie; Konopa, Philip; Nariya, Snehal; Stoddard, Julia N.; Wong, Kim; Zhao, Hong; Deng, Wenjie; Maust, Brandon S.; Bose, Meera; Howell, Shana; Bates, Adam; Lazzaro, Michelle; O'Sullivan, Annemarie; Lei, Esther; Bradfield, Andrea; Ibitamuno, Grace; Assawadarachai, Vatcharain; O'Connell, Robert J.; deSouza, Mark S.; Nitayaphan, Sorachai; Rerks-Ngarm, Supachai; Robb, Merlin L.; Sidney, John; Sette, Alessandro; Zolla-Pazner, Susan; Montefiori, David; McElrath, M. Juliana; Mullins, James I.; Kim, Jerome H.; Gilbert, Peter B.
...Hispanic Communities and Among Black and Hispanic Researchers To Conduct HIV/AIDS Epidemiologic and Prevention Research, Funding...Hispanic Researchers to Conduct HIV/AIDS Epidemiologic and Prevention Research, FOA...
The HIV epidemic continues unabated, with no highly effective vaccine and no cure. Each new infection has significant economic, social and human costs and prevention efforts are now as great a priority as global antiretroviral therapy (ART) scale up. Reverse transcriptase inhibitors, the first licensed class of ART, have been at the forefront of treatment and prevention of mother to child transmission over the past two decades. Now, their use in adult prevention is being extensively investigated. We describe two approaches: treatment as prevention (TasP) - the use of combination ART (2NRTI and 1NNRTI) following HIV diagnosis to limit transmission and pre-exposure prophylaxis (PrEP) –the use of single or dual oral agents prior to sexual exposure. Prevention of mother-to-child transmission using NRTI has been highly successful, though does not involve sustained use of NRTI to limit transmission. Despite theoretical and preliminary support for TasP and PrEP, data thus far indicate that adherence, retention in care and late diagnosis are the major barriers to their successful, sustained implementation. Future advances in drug technologies will be needed to overcome the issue of drug adherence, through development of drugs that involve both less frequent dosing as well as reduced toxicity, possibly through specific targeting of infected cells. PMID:23902855
This guide is intended to help parents of adolescents and adults with mental retardation to teach their sons and daughters about HIV (Human Immunodeficiency Virus) and AIDS (Acquired Immune Deficiency Syndrome). An official resolution on AIDS adopted by The Arc, an organization for citizens with mental retardation, begins the guide. This…
This study was a pilot investigation of the feasibility, acceptability, and effects of TRAIN (Transit to Russia AIDS Intervention with Newcomers) a three-session HIV preventive intervention for Tajik male labor migrants performed in transit. Sixty adult Tajik male labor migrants on the 5-day train ride from Dushanbe to Moscow were randomly assigned to either the intervention or a control condition. Each initially completed an in-person survey then another 3 days later (immediately postintervention), and participated in a cell phone survey three months later. All participants came to all intervention sessions, were satisfied with the program, and completed all postassessments. In comparison with the controls, the TRAIN group reported significant increases in condom use with sex workers and non-sex workers, condom knowledge, worry about HIV/AIDS, talking with persons about HIV/AIDS, talking with wife about HIV/AIDS, community activities, and religious activities. HIV/AIDS prevention performed in transit is feasible, accceptable, and potentially efficacious in diminishing HIV risk behaviors in labor migrants. PMID:21696244
Bahromov, Mahbat; Weine, Stevan
This paper examines the ways in which HIV prevention is understood including “biomedical”, “behavioural”, “structural”, and “combination” prevention. In it I argue that effective prevention entails developing community capacity and requires that public health addresses people not only as individuals but also as connected members of groups, networks and collectives who interact (talk, negotiate, have sex, use drugs, etc.) together. I also examine the evaluation of prevention programmes or interventions and argue that the distinction between efficacy and effectiveness is often glossed and that, while efficacy can be evaluated by randomized controlled trials, the evaluation of effectiveness requires long-term descriptive strategies and/or modelling. Using examples from a number of countries, including a detailed account of the Australian HIV prevention response, effectiveness is shown to be dependent not only on the efficacy of the prevention technology or tool but also on the responses of people – individuals, communities and governments – to those technologies. Whether a particular HIV prevention technology is adopted and its use sustained depends on a range of social, cultural and political factors. The paper concludes by calling on biomedical and social scientists to work together and describes a “social public health”. PMID:22713254
Antiretroviral drugs that inhibit viral replication were expected to reduce transmission of HIV by lowering the concentration of HIV in the genital tract. In 11 of 13 observational studies, antiretroviral therapy (ART) provided to an HIV-infected index case led to greatly reduced transmission of HIV to a sexual partner. In the HPTN 052 randomised controlled trial, ART used in combination with condoms and counselling reduced HIV transmission by 96·4%. Evidence is growing that wider, earlier initiation of ART could reduce population-level incidence of HIV. However, the full benefits of this strategy will probably need universal access to very early ART and excellent adherence to treatment. Challenges to this approach are substantial. First, not all HIV-infected individuals can be located, especially people with acute and early infection who are most contagious. Second, the ability of ART to prevent HIV transmission in men who have sex with men (MSM) and people who use intravenous drugs has not been shown. Indeed, the stable or increased incidence of HIV in MSM in some communities where widespread use of ART has been established emphasises the concern that not enough is known about treatment as prevention for this crucial population. Third, although US guidelines call for immediate use of ART, such guidelines have not been embraced worldwide. Some experts do not believe that immediate or early ART is justified by present evidence, or that health-care infrastructure for this approach is sufficient. These concerns are very difficult to resolve. Ongoing community-based prospective trials of early ART are likely to help to establish the population-level benefit of ART, and—if successful—to galvanise treatment as prevention. PMID:24152938
Cohen, Myron S; Smith, M Kumi; Muessig, Kathryn E; Hallett, Timothy B; Powers, Kimberly A; Kashuba, Angela D
Australia has not seen a Human Immunodeficiency Virus (HIV) epidemic among young people. However, early research in the Australian context had indicated that the degree of unprotected sexual activity, partner change, and STI infection in this cohort would fuel a young people's epidemic if HIV ever reached a tipping point in the country. The difficulty of reaching young people outside school for HIV prevention has been no more successfully addressed in Australia than elsewhere. Therefore, the investment of Australian HIV prevention funds for youth has had an emphasis on school-based programs. This emphasis on formal schooling has led to a history of engagement with the ad hoc and unreliable nature of sexuality education in Australian schools. It has particularly been the catalyst for a struggle to construct young people as sexually active and as possessing a right to appropriate education, against tides of both secular and religiously-motivated resistance. The eight state and territory education sectors, along with the independent sectors, have had differing and sometimes troubled histories with HIV prevention. This paper discusses the differing HIV education policies and programs that have emerged in Australian schooling historically, and in some cases been abandoned altogether, amid strong public debates. It also considers current approaches, the new national curriculum, and future challenges. Additionally, the particular case of same sex attracted young men, who have a heightened level of vulnerability to HIV, is explored. Australian schools have struggled to address both the imperative for relevant sexuality education for same-sex-attracted young people and the broader issue of combating homophobia, which research has linked directly to this vulnerability. PMID:24846485
Jones, Tiffany; Mitchell, Anne
A combination of prevention and treatment modalities will be needed to successfully control the global spread of HIV. Microbicides, drug products topically applied to mucosal surfaces to prevent HIV infection, are one of these biomedical interventions that hold great promise. In order to be efficacious, microbicides must overcome several challenges imposed by the mucosal microenvironment they intend to protect and the mischievous human immunodeficiency virus with its enormous capacity to adapt. Recent data, however, supports the establishment of the primo-infection by only a small number of founder viruses, which are highly vulnerable to microbicidal intervention at the initial stages of mucosal invasion. The biological foundation of these challenges and opportunities in microbicide development is explored in this review. This article forms part of a special supplement on presentations covering HIV transmission and microbicides, based on the symposium "Trends in Microbicide Formulations", held on 25 and 26 January 2010, Arlington, VA. PMID:21109065
Hladik, Florian; Doncel, Gustavo F.
Background After more than 25 years, public health programs have not been able to sufficiently reduce the number of new HIV infections. Over 7,000 people become infected with HIV every day. Lack of convincing evidence of cost-effectiveness (CE) may be one of the reasons why implementation of effective programs is not occurring at sufficient scale. This paper identifies, summarizes and critiques the CE literature related to HIV-prevention interventions in low- and middle-income countries during 2005-2008. Methods Systematic identification of publications was conducted through several methods: electronic databases, internet search of international organizations and major funding/implementing agencies, and journal browsing. Inclusion criteria included: HIV prevention intervention, year for publication (2005-2008), setting (low- and middle-income countries), and CE estimation (empirical or modeling) using outcomes in terms of cost per HIV infection averted and/or cost per disability-adjusted life year (DALY) or quality-adjusted life year (QALY). Results We found 21 distinct studies analyzing the CE of HIV-prevention interventions published in the past four years (2005-2008). Seventeen CE studies analyzed biomedical interventions; only a few dealt with behavioral and environmental/structural interventions. Sixteen studies focused on sub-Saharan Africa, and only a handful on Asia, Latin America and Eastern Europe. Many HIV-prevention interventions are very cost effective in absolute terms (using costs per DALY averted), and also in country-specific relative terms (in cost per DALY measured as percentage of GDP per capita). Conclusion There are several types of interventions for which CE studies are still not available or insufficient, including surveillance, abstinence, school-based education, universal precautions, prevention for positives and most structural interventions. The sparse CE evidence available is not easily comparable; thus, not very useful for decision making. More than 25 years into the AIDS epidemic and billions of dollars of spending later, there is still much work to be done both on costs and effectiveness to adequately inform HIV prevention planning. PMID:19922689
The promising results obtained with the HIV-1 Tat-based vaccines in mice, monkeys and humans, a better understanding of Tat immuno- modulatory functions, as well as evidence that vaccination with trimeric V2 loop-deleted HIV-1 Env induces cross-clade neutralizing anti- bodies led to the rational design of a novel vaccine based on the combination of Tat and V2-deleted Env. © 2005 Elsevier
Barbara Ensoli; Aurelio Cafaro; Antonella Caputo; Valeria Fiorelli; Fabrizio Ensoli; Riccardo Gavioli; Flavia Ferrantelli; Andrea Cara; Fausto Titti; Mauro Magnani
This study compared two groups of adolescents seeking help at HIV prevention drop-in agencies. The first group attended agencies in low-income Hispanic neighborhoods which recruited within the locale. The second group of youth attended agencies that recruited based upon a specific population--they targeted homeless and LGBQ youth. We explored the…
Hohman, Melinda; Shillington, Audrey M.; Min, Jong Won; Clapp, John D.; Mueller, Kristin; Hovell, Melbourne
The transtheoretical model of health behavior change is described and supporting empirical work is presented that reviews the central constructs of the model: the stages of change, processes of change, decisional balance, confidence, and temptation. Model-based applications to a broad range of problem behaviors are summarized. Applications to human immunodeficiency virus (HIV) prevention behavior changes are highlighted for each variable.
James O. Prochaska; Colleen A. Redding; Lisa L. Harlow; Joseph S. Rossi; Wayne F. Velicer
Purpose To explore the feasibility of engaging community businesses in HIV prevention. Design Randomly selected business owners/managers were asked to display discreetly wrapped condoms and brochures provided free-of-charge for 3 months. Assessments were conducted at baseline, mid-, and post-program. Customer feedback was obtained through an online survey. Setting San Diego, California neighborhood with a high rate of AIDS. Subjects Fifty-one business owners/managers representing 10 retail categories, and 52 customers. Measures Participation rates, descriptive characteristics, number of condoms and brochures distributed, customer feedback, business owners'/managers' program satisfaction and willingness to provide future support for HIV prevention. Analysis Kruskal-Wallis, Mann-Whitney U, Fisher's exact, and McNemar's tests were used to analyze data. Results The 20 business owners/managers (39%) who agreed to distribute condoms and brochures reported fewer years in business and more employees than those who agreed only to distribute brochures (20%) or refused to participate (41%), p <.05. Bars were the easiest of ten retail categories to recruit. Businesses with more employees and customers distributed more condoms and brochures, p < .05. More than 90% of customers supported distributing condoms and brochures in businesses and 96% of business owners/managers described their program experience as “positive.” Conclusion Businesses are willing to distribute condoms and brochures to prevent HIV. Policies to increase business participation in HIV prevention should be developed and tested. PMID:20465150
Rovniak, Liza S.; Hovell, Melbourne F.; Hofstetter, C. Richard; Blumberg, Elaine J.; Sipan, Carol L.; Batista, Marcia F.; Martinez-Donate, Ana P.; Mulvihill, Mary M.; Ayala, Guadalupe X.
This study evaluates the first year of a novel HIV and substance use prevention program for inner city youth (Offering New Youth eXperiences--ONYX). Baseline and follow-up measures of knowledge, attitudes, and risk behaviors were administered seven months apart to 441 youth participating in the ONYX program. Youth (n=71) who provided data at both…
Goggin, K.; Metcalf, K.; Wise, D.; Kennedy, S.; Murray, T.; Burgess, D.; Reese-Smith, J.; Terhune, N.; Broadus, K.; Downes, A.; Buckendahl, H.
Objective To determine factors associated with HIV status unawareness and assess HIV prevention knowledge and condom use among people living with HIV/AIDS (PLHIV) in Mozambique. Design Cross-sectional household-based nationally representative AIDS Indicator Survey. Methods Analyses focused on HIV-infected adults and were weighted for the complex sampling design. We identified PLHIV who had never been tested for HIV or received their test results prior to this survey. Logistic regression was used to assess factors associated with HIV status unawareness. Results Of persons with positive HIV test results (N?=?1182), 61% (95% confidence interval [CI] 57–65%) were unaware of their serostatus. Men had twice the odds of being unaware of their serostatus compared with women [adjusted odds ratio (aOR) 2.05, CI 1.40–2.98]. PLHIV in the poorest wealth quintile were most likely to be unaware of their serostatus (aOR 3.15, CI 1.09–9.12) compared to those in the middle wealth quintile. Most PLHIV (83%, CI 79–87%) reported not using a condom during their last sexual intercourse, and PLHIV who reported not using a condom during their last sexual intercourse were more likely to be unaware of their serostatus (aOR 2.32, CI 1.57–3.43) than those who used a condom. Conclusions Knowledge of HIV-positive status is associated with more frequent condom use in Mozambique. However, most HIV-infected persons are unaware of their serostatus, with men and persons in the poorest wealth quintile being more likely to be unaware. These findings support calls for expanded HIV testing, especially among groups less likely to be aware of their HIV status and key populations at higher risk for infection. PMID:25222010
Dokubo, E. Kainne; Shiraishi, Ray W.; Young, Peter W.; Neal, Joyce J.; Aberle-Grasse, John; Honwana, Nely; Mbofana, Francisco
Human immunodeficiency virus (HIV) vaccines have the potential to improve antiretroviral drug treatment by inducing cytotoxic killing of HIV-infected cells. Prophylactic vaccines utilize new antigens to initiate immunity; however, in HIV-infected individuals the load of viral antigen is not the limiting factor for the restoration of immune responses. Here we describe a novel immunization strategy with DermaVir that improves viral antigen presentation using dendritic cells (DC). DermaVir contains a distinctive plasmid DNA expressing all HIV proteins except integrase to induce immune responses with broad specificity. The DNA is formulated to a mannosilated particle to target antigen-presenting cells and to protect the DNA from intracellular degradation. After topical application, DermaVir-transduced cells migrate from the skin to the draining lymph node and interdigitate as DermaVir-expressing, antigen-presenting DC. We compared the immunogenicity of topical and ex vivo DC-based DermaVir vaccinations in naive rhesus macaques. Both vaccinations induced simian immunodeficiency virus-specific CD4 helper and CD8 memory T cells detected by an in vivo skin test and an in vitro intracellular cytokine-based assay. Topical DermaVir vaccination represents an improvement upon existing ex vivo DC-based immunization technologies and may provide a new therapeutic option for HIV-infected patients. PMID:15654970
Lisziewicz, Julianna; Trocio, Jeffrey; Whitman, Lucia; Varga, Georg; Xu, Jianqing; Bakare, Nyasha; Erbacher, Patrick; Fox, Cecil; Woodward, Ruth; Markham, Phil; Arya, Suresh; Behr, Jean-Paul; Lori, Franco
An effective AIDS vaccine must control highly diverse circulating strains of HIV-1. Among HIV -I gene products, the envelope (Env) protein contains variable as well as conserved regions. In this report, an informatic approach to the design of T-cell vaccines directed to HIV -I Env M group global sequences was tested. Synthetic Env antigens were designed to express mosaics that maximize the inclusion of common potential Tcell epitope (PTE) 9-mers and minimize the inclusion of rare epitopes likely to elicit strain-specific responses. DNA vaccines were evaluated using intracellular cytokine staining (ICS) in inbred mice with a standardized panel of highly conserved 15-mer PTE peptides. I, 2 and 3 mosaic sets were developed that increased theoretical epitope coverage. The breadth and magnitude ofT-cell immunity stimulated by these vaccines were compared to natural strain Env's; additional comparisons were performed on mutant Env's, including gpl60 or gpl45 with or without V regions and gp41 deletions. Among them, the 2 or 3 mosaic Env sets elicited the optimal CD4 and CD8 responses. These responses were most evident in CD8 T cells; the 3 mosaic set elicited responses to an average of 8 peptide pools compared to 2 pools for a set of3 natural Env's. Synthetic mosaic HIV -I antigens can therefore induce T-cell responses with expanded breadth and may facilitate the development of effective T -cell-based HIV -1 vaccines.
Korber, Bette [Los Alamos National Laboratory; Fischer, William [Los Alamos National Laboratory; Wallstrom, Timothy [Los Alamos National Laboratory
A current debate in the HIV-1 vaccine field concerns the ability of an immunodeficiency virus to elicit a protective response. One argument is that HIV-1 superinfections are frequent in healthy individuals, because virus evades conventional immune surveillance, a serious obstacle to vaccine design. The opposing argument is that protection from superinfection is significant, reflecting a robust immune response that might
Robert Sealy; Xiaoyan Zhan; Timothy D. Lockey; Louis Martin; James Blanchard; Vicki Traina-Dorge; Julia L. Hurwitz
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
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.
Traditional vaccine strategies that induce antibody responses have failed to protect against HIV infection in clinical trials, and thus cell-mediated immunity is now an additional criterion. Recent clinical trials that aimed to induce strong T cell responses failed to do so. Therefore, to enhance induction of protective T cell responses, it is crucial that the optimum antigen combination is chosen. Limited research has been performed into the number of antigens selected for an HIV vaccine. This study aimed to compare DNA vaccines encoding either a single HIV antigen or a combination of two antigens, using intradermal vaccination of C57BL/6 mice. Immune assays were performed on splenocytes, and in vivo protection was examined by challenge with a chimeric virus, EcoHIV, able to infect mouse but not human leukocytes, at 10 days (short term) and 60 days (long term) post final vaccination. At 60 days there was significantly lower frequency of induced antigen-specific CD8(+) T cells in the spleens of pCMVgag-pol-vaccinated mice compared with mice which received pCMVgag only. Most importantly, short term viral control of EcoHIV was similar for pCMVgag and pCMVgag-pol-vaccinated mice at day 10, but only the pCMVgag-vaccinated significantly controlled EcoHIV at day 60 compared with pCMV-vaccinated mice, showing that control was reduced with the inclusion of the HIV pol gene. PMID:25152448
Garrod, Tamsin J; Gargett, Tessa; Yu, Wenbo; Major, Lee; Burrell, Christopher J; Wesselingh, Steven; Suhrbier, Andreas; Grubor-Bauk, Branka; Gowans, Eric J
Introduction Cash payments to vulnerable households and/or individuals have increasingly garnered attention as a means to reduce poverty, improve health and achieve other development-related outcomes. Recent evidence from Malawi and Tanzania suggests that cash transfers can impact HIV-related behaviours and outcomes and, therefore, could serve as an important addition to HIV prevention efforts. Discussion This article reviews the current evidence on cash transfers for HIV prevention and suggests unresolved questions for further research. Gaps include (1) understanding more about the mechanisms and pathways through which cash transfers affect HIV-related outcomes; (2) addressing key operational questions, including the potential feasibility and the costs and benefits of different models of transfers and conditionality; and (3) evaluating and enhancing the wider impacts of cash transfers on health and development. Conclusions Ongoing and future studies should build on current findings to unpack unresolved questions and to collect additional evidence on the multiple impacts of transfers in different settings. Furthermore, in order to address questions on sustainability, cash transfer programmes need to be integrated with other sectors and programmes that address structural factors such as education and programming to promote gender equality and address HIV. PMID:23972159
Heise, Lori; Lutz, Brian; Ranganathan, Meghna; Watts, Charlotte
HIV infection is the greatest health crisis in human history. It continues to spread unchecked among the poor in the developing world because we have failed to design simple preventative methods that are available and affordable to those living on under $2 a day. Five new methods are discussed. (i) A natural microbicide. Intravaginal lime or lemon juice has been used for centuries as a traditional contraceptive. The juice can also kill HIV in the laboratory, but clinical trials are needed to see if vaginal application is acceptable, safe and effective. (ii) Intravaginal oestrogen. Monkeys can be protected from Simian immunodeficiency virus (SIV) infection by keratinizing the vagina with topical oestrogen. If women take the oral contraceptive pill vaginally it retains its contraceptive efficacy, and the oestrogen it contains should thicken the vagina and protect against HIV infection. Clinical trials are needed. (iii) Male circumcision. Removal of the inner foreskin removes the main site of HIV entry into the penis, resulting in a sevenfold reduction in susceptibility to infection. The practice needs to be promoted. (iv) Post-coital penile hygiene. Wiping the penis immediately after intercourse with lime or lemon juice or vinegar should kill the virus before it has had a chance to infect. A clinical trial of efficacy is needed. (v) PhotoVoice. Asking schoolchildren in developing countries to photograph their impressions of HIV/AIDS is a powerful way of getting them to discuss the subject openly, and develop their own preventative strategies. PMID:16627296
The aim of this review is to summarise the evidence on the population-level effect of antiretroviral therapy (ART) in preventing HIV infections, and to discuss potential implications in the European context of recommending starting ART when the CD4 count is above 350 cells/mm3. The ability of ART to reduce the risk of HIV transmission has been reported in observational studies and in a randomised controlled trial (HPTN 052), in which ART initiation reduced HIV transmission by 96% within serodiscordant couples. As yet, there is no direct evidence for such an effect among men having sex with men or people who inject drugs. HPTN 052 led international organisations to develop recommendations with a higher CD4 threshold for ART initiation. However, there remains a lack of strong evidence of clinical benefit for HIV-positive individuals starting ART with CD4 count above 350 cells/mm3. The main goal of ART provision should be to increase ART coverage for all those in need, based on the current guidelines, and the offer of ART to those who wish to reduce infectivity; increased HIV testing is therefore a key requirement. Other proven prevention means such as condom use and harm reduction for people who inject drugs remain critical. PMID:24308982
Cambiano, V; O'Connor, J; Phillips, A N; Rodger, A; Lodwick, R; Pharris, A; Lampe, F; Nakagawa, F; Smith, C; van de Laar, M J
Background.?The licensing of herpes zoster vaccine has demonstrated that therapeutic vaccination can help control chronic viral infection. Unfortunately, human trials of immunodeficiency virus (HIV) vaccine have shown only marginal efficacy. Methods.?In this double-blind study, 17 HIV-infected individuals with viral loads of <50 copies/mL and CD4+ T-cell counts of >350 cells/µL were randomly assigned to the vaccine or placebo arm. Vaccine recipients received 3 intramuscular injections of HIV DNA (4 mg) coding for clade B Gag, Pol, and Nef and clade A, B, and C Env, followed by a replication-deficient adenovirus type 5 boost (1010 particle units) encoding all DNA vaccine antigens except Nef. Humoral, total T-cell, and CD8+ cytotoxic T-lymphocyte (CTL) responses were studied before and after vaccination. Single-copy viral loads and frequencies of latently infected CD4+ T cells were determined. Results.?Vaccination was safe and well tolerated. Significantly stronger HIV-specific T-cell responses against Gag, Pol, and Env, with increased polyfunctionality and a broadened epitope-specific CTL repertoire, were observed after vaccination. No changes in single-copy viral load or the frequency of latent infection were observed. Conclusions.?Vaccination of individuals with existing HIV-specific immunity improved the magnitude, breadth, and polyfunctionality of HIV-specific memory T-cell responses but did not impact markers of viral control. Clinical Trials Registration.?NCT00270465 PMID:23482645
Casazza, Joseph P.; Bowman, Kathryn A.; Adzaku, Selorm; Smith, Emily C.; Enama, Mary E.; Bailer, Robert T.; Price, David A.; Gostick, Emma; Gordon, Ingelise J.; Ambrozak, David R.; Nason, Martha C.; Roederer, Mario; Andrews, Charla A.; Maldarelli, Frank M.; Wiegand, Ann; Kearney, Mary F.; Persaud, Deborah; Ziemniak, Carrie; Gottardo, Raphael; Ledgerwood, Julie E.; Graham, Barney S.; Koup, Richard A.
In the United States, women are a significant proportion of the correctional population. Women also account for an increasing proportion of newly diagnosed human immunodeficiency virus (HIV) cases. When compared with white women, black women have higher incarceration rates and represent more of the newly diagnosed HIV cases. Correctional facilities offer an opportunity to provide women with HIV testing and prevention services so that they will know their status and receive HIV/sexually transmitted disease (STD) risk-reduction counseling and other preventive services. In this report, we describe incarcerated population statistics and HIV surveillance epidemiology for women. We also describe HIV prevention activities undertaken by the Centers for Disease Control and Prevention's National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention. Additional research, program development, and implementation are needed to improve HIV prevention efforts for high-risk women. PMID:24116966
Fleming, Eleanor B; LeBlanc, Tanya Telfair; Reid, Laurie C
Enteroviruses and humans have long co-existed. Although recognized in ancient times, poliomyelitis and type 1 diabetes (T1D) were exceptionally rare and not epidemic, due in large part to poor sanitation and personal hygiene which resulted in repeated exposure to fecal-oral transmitted viruses and other infectious agents and viruses and the generation of a broad protective immunity. As a function of a growing acceptance of the benefits of hygienic practices and microbiologically clean(er) water supplies, the likelihood of exposure to diverse infectious agents and viruses declined. The effort to vaccinate against poliomyelitis demonstrated that enteroviral diseases are preventable by vaccination and led to understanding how to successfully attenuate enteroviruses. Type 1 diabetes onset has been convincingly linked to infection by numerous enteroviruses including the group B coxsackieviruses (CVB), while studies of CVB infections in NOD mice have demonstrated not only a clear link between disease onset but an ability to reduce the incidence of T1D as well: CVB infections can suppress naturally occurring autoimmune T1D. We propose here that if we can harness and develop the capacity to use attenuated enteroviral strains to induce regulatory T cell populations in the host through vaccination, then a vaccine could be considered that should function to protect against both autoimmune as well as virus-triggered T1D. Such a vaccine would not only specifically protect from certain enterovirus types but more importantly, also reset the organism's regulatory rheostat making the further development of pathogenic autoimmunity less likely. Copyright © 2014 John Wiley & Sons, Ltd. PMID:25430610
Drescher, Kristen M; von Herrath, Matthias; Tracy, Steven
Background Recruitment of low- and middle-income country volunteers from most-at-risk populations in HIV vaccine trials is essential to vaccine development. In India, men who have sex with men (MSM) are at disproportionately high risk for HIV infection and an important population for trial recruitment. Investigations of willingness to participate (WTP) in HIV vaccine trials have focused predominantly on individual-level determinants. We explored multi-level factors associated with WTP among MSM in India. Methods We conducted 12 focus groups (n?=?68) with low socioeconomic MSM in Chennai and Mumbai, and 14 key informant interviews with MSM community leaders and service providers. Focus groups/interviews were recorded, transcribed and translated into English. Two bilingual investigators conducted thematic analysis using line-by-line coding and a constant comparative method, with member-checking by community representatives. Results Factors associated with WTP were evidenced across the social ecology of MSM–social-structural: poverty, HIV-, sexual- and gender non-conformity stigma, institutionalized discrimination and government sponsorship of trials; community-level: endorsement by MSM community leaders and organizations, and fear of within-group discrimination; interpersonal: anticipated family discord, partner rejection, having financially-dependent family members and disclosure of same-sex sexuality; and individual-level: HIV vaccine trial knowledge and misconceptions, safety concerns, altruism and preventive misconception. Conclusion Pervasive familial, community and social-structural factors characteristic of the Indian sociocultural context may complicate individual-focused approaches to WTP and thereby constrain the effectiveness of interventions to support recruitment and retention in HIV vaccine trials. Interventions to reduce stigma and discrimination against MSM and people living with HIV, capacity-building of MSM community organizations and transparent communications tailored to the knowledge and educational level of local communities may support meaningful engagement of MSM in HIV vaccine trials. Vigilance in providing fair but not excessive compensation and healthcare benefits and in mitigating preventive misconception are warranted to support ethical conduct of trials among MSM in India. PMID:23226560
Chakrapani, Venkatesan; Newman, Peter A.; Singhal, Neeti; Jerajani, Jhalak; Shunmugam, Murali
HIV-1 neutralization requires Ab accessibility to the functional envelope glycoprotein (Env) spike. We recently reported the isolation of previously unidentified vaccine-elicited, CD4 binding site (CD4bs)-directed mAbs from rhesus macaques immunized with soluble Env trimers, indicating that this region is immunogenic in the context of subunit vaccination. To elucidate the interaction of the trimer-elicited mAbs with gp120 and their insufficient interaction with the HIV-1 primary isolate spike, we crystallized the Fab fragments of two mAbs, GE136 and GE148. Alanine scanning of their complementarity-determining regions, coupled with epitope scanning of their epitopes on gp120, revealed putative contact residues at the Ab/gp120 interface. Docking of the GE136 and GE148 Fabs to gp120, coupled with EM reconstructions of these nonbroadly neutralizing mAbs (non-bNAbs) binding to gp120 monomers and EM modeling to well-ordered trimers, suggested Ab approach to the CD4bs by a vertical angle of access relative to the more lateral mode of interaction used by the CD4bs-directed bNAbs VRC01 and PGV04. Fitting the structures into the available cryo-EM native spike density indicated clashes between these two vaccine-elicited mAbs and the topside variable region spike cap, whereas the bNAbs duck under this quaternary shield to access the CD4bs effectively on primary HIV isolates. These results provide a structural basis for the limited neutralizing breadth observed by current vaccine-induced, CD4bs-directed Abs and highlight the need for better ordered trimer immunogens. The analysis presented here therefore provides valuable information to guide HIV-1 vaccine immunogen redesign. PMID:24550318
Tran, Karen; Poulsen, Christian; Guenaga, Javier; de Val, Natalia; Wilson, Richard; Sundling, Christopher; Li, Yuxing; Stanfield, Robyn L.; Wilson, Ian A.; Ward, Andrew B.; Karlsson Hedestam, Gunilla B.; Wyatt, Richard T.
...HRSA Advisory Committee on HIV, Viral Hepatitis and STD Prevention and Treatment...HRSA Advisory Committee on HIV, Viral Hepatitis and STD Prevention and Treatment...services to persons living with HIV/AIDS, and education of health...
...HRSA Advisory Committee on HIV, Viral Hepatitis and STD Prevention and Treatment...activities related to prevention and control of HIV/AIDS, Viral Hepatitis and...services to persons living with HIV/AIDS, and education of health...
The burden of disease associated with Streptococcus pneumoniae infection in adults can be considerable but is largely preventable through routine vaccination. Although substantial progress has been made with the recent licensure of the new vaccines for prevention of pneumonia in adults, vaccine uptake rates need to be improved significantly to tackle adult pneumococcal disease effectively. Increased education regarding pneumococcal disease and improved vaccine availability may contribute to a reduction in pneumococcal disease through increased vaccination rates. The increase in the elderly population in Singapore as well as globally makes intervention in reducing pneumococcal disease an important priority. Globally, all adult vaccines remain underused and family physicians give little priority to pneumococcal vaccination for adults in daily practice. Family physicians are specialists in preventive care and can be leaders in ensuring that adult patients get the full benefit of protection against vaccine-preventable diseases. They can play a key role in the immunization delivery of new and routine vaccines by educating the public on the risks and benefits associated with vaccines. Local recommendations by advisory groups on vaccination in adults will also help to tackle vaccine preventable diseases in adults. PMID:24729726
Eng, Philip; Lim, Lean Huat; Loo, Chian Min; Low, James Alvin; Tan, Carol; Tan, Eng Kiat; Wong, Sin Yew; Setia, Sajita
The Centers for Disease Control and Prevention (CDC) estimates that approximately 1.1 million persons are living with HIV in the United States. 1 This number is expected to continue to increase over time, as antiretroviral treatments prolong the lives of those who are infected and more people become infected with HIV than die from the disease each year. As the number of people living with HIV — or HIV prevalence — grows, so does the opportunity for HIV transmission to others. Therefore, it is critical to have not only a clear understanding of the number of new infections that occur annually — or HIV incidence — it is also important to know the rate of HIV transmission in order to accurately gauge the impact of HIV prevention efforts on the U.S. epidemic. Innovative Measure of HIV Prevention Shows Success Although CDC recently reported that annual HIV incidence has remained stable in the United States in recent years, 2 these estimates do not provide a full picture of the effect that HIV prevention efforts are having across the country. While stability in new infections is one sign of progress, these incidence data alone cannot quantify the amount of transmission that occurs in relation to the growing population infected with HIV.
A successful HIV vaccine will likely induce both humoral and cell-mediated immunity, however, the enormous diversity of HIV has hampered the development of a vaccine that effectively elicits both arms of the adaptive immune response. To tackle the problem of viral diversity, T cell-based vaccine approaches have focused on two main strategies (i) increasing the breadth of vaccine-induced responses or (ii) increasing vaccine-induced responses targeting only conserved regions of the virus. The relative extent to which set-point viremia is impacted by epitope-conservation of CD8+ T cell responses elicited during early HIV-infection is unknown but has important implications for vaccine design. To address this question, we comprehensively mapped HIV-1 CD8+ T cell epitope-specificities in 23 ART-naïve individuals during early infection and computed their conservation score (CS) by three different methods (prevalence, entropy and conseq) on clade-B and group-M sequence alignments. The majority of CD8+ T cell responses were directed against variable epitopes (p<0.01). Interestingly, increasing breadth of CD8+ T cell responses specifically recognizing conserved epitopes was associated with lower set-point viremia (r?=?- 0.65, p?=?0.009). Moreover, subjects possessing CD8+ T cells recognizing at least one conserved epitope had 1.4 log10 lower set-point viremia compared to those recognizing only variable epitopes (p?=?0.021). The association between viral control and the breadth of conserved CD8+ T cell responses may be influenced by the method of CS definition and sequences used to determine conservation levels. Strikingly, targeting variable versus conserved epitopes was independent of HLA type (p?=?0.215). The associations with viral control were independent of functional avidity of CD8+ T cell responses elicited during early infection. Taken together, these data suggest that the next-generation of T-cell based HIV-1 vaccines should focus on strategies that can elicit CD8+ T cell responses to multiple conserved epitopes of HIV-1. PMID:23741326
Kunwar, Pratima; Hawkins, Natalie; Dinges, Warren L.; Liu, Yi; Gabriel, Erin E.; Swan, David A.; Stevens, Claire E.; Maenza, Janine; Collier, Ann C.; Mullins, James I.; Hertz, Tomer; Yu, Xuesong; Horton, Helen
Human papillomavirus (HPV) infection is highly prevalent and can lead to cancer; the development of safe and efficacious vaccines for HPV is a major public health concern. The two licensed HPV vaccines contain recombinant virus-like particles of HPV 16 and 18; one of such vaccines also protects against HPV types 6 and 11 which cause genital warts. We determined safety and immunogenicity of quadrivalent HPV vaccine in HIV-infected and HIV-negative adolescents and young adults, aged 13-27 years. The seroconversion rate, assessed by antibody titers, 1 month after the administration of the third vaccine dose was 0.85 (95% CI 0.75-0.95) in the HIV-infected group and 0.91 (0.83-0.99) in the HIV-negative subjects (p=0.52). The vaccine was generally safe and well tolerated; the most common side effect was local pain and the most frequent systemic side effect was headache. This is the first report on response to HPV vaccination in both female and male HIV-infected adolescents and young adults and highlights that this population may benefit from HPV immunoprophylaxis. Further studies are needed to examine the long term efficacy of this vaccine in HIV-infected individuals. PMID:25149430
Giacomet, Vania; Penagini, Francesca; Trabattoni, Daria; Viganò, Alessandra; Rainone, Veronica; Bernazzani, Giada; Bonardi, Claudia Maria; Clerici, Mario; Bedogni, Giorgio; Zuccotti, Gian Vincenzo
Purpose of the review Recent breakthroughs in HIV-prevention science led us to evaluate the current state of combination HIV-prevention for injection drug users (IDUs). We review the recent literature focusing on possible reasons why coverage of prevention interventions for HIV, HCV and tuberculosis among IDUs remains dismal. We make recommendations for future HIV research and policy. Recent findings IDUs disproportionately under-utilize VCT, primary care and ART, especially in countries that have the largest burden of HIV among IDUs. IDUs present later in the course of HIV infection and experience greater morbidity and mortality. Why are IDUs under-represented in HIV-prevention research, access to treatment for both HIV and addiction, and access to HIV combination prevention? Possible explanations include addictophobia, apathy, and inattention, which we describe in the context of recent literature and events. Summary This commentary discusses the current state of HIV-prevention interventions for IDUs including, VCT, NSP, OST, ART and PrEP, and discusses ways to work towards true combination HIV-prevention for IDU populations. Communities need to overcome tacit assumptions that IDUs can navigate through systems that are maintained as separate silos, and take a rights-based approach to HIV-prevention to ensure that IDUs have equitable access to life-saving prevention and treatments. PMID:22498479
Strathdee, Steffanie A.; Shoptaw, Steven; Dyer, Typhanye Penniman; Quan, Vu Minh; Aramrattana, Apinun
Background Following universal access to antiretroviral therapy in Thailand, evidence from National AIDS Spending Assessment indicates a decreasing proportion of expenditure on prevention interventions. To prompt policymakers to revitalize HIV prevention, this study identifies a comprehensive list of HIV/AIDs preventive interventions that are likely to be effective and cost-effective in Thailand. Methods A systematic review of the national and international literature on HIV prevention strategies from 1997 to 2008 was undertaken. The outcomes used to consider the effectiveness of HIV prevention interventions were changes in HIV risk behaviour and HIV incidence. Economic evaluations that presented their results in terms of cost per HIV infection averted or cost per quality-adjusted life year (QALY) gained were also included. All studies were assessed against quality criteria. Results The findings demonstrated that school based-sex education plus life-skill programs, voluntary and routine HIV counselling and testing, male condoms, street outreach programs, needle and syringe programs, programs for the prevention of mother-to-child HIV transmission, male circumcision, screening blood products and donated organs for HIV, and increased alcohol tax were all effective in reducing HIV infection among target populations in a cost-effective manner. Conclusion We found very limited local evidence regarding the effectiveness of HIV interventions amongst specific high risk populations. This underlines the urgent need to prioritise health research resources to assess the effectiveness and cost-effectiveness of HIV interventions aimed at reducing HIV infection among high risk groups in Thailand. PMID:20604975
An efficacious HIV vaccine is urgently needed to curb the AIDS pandemic. The modest protection elicited in the phase III clinical vaccine trial in Thailand provided hope that this goal might be achieved. However, new approaches are necessary for further advances. As HIV is transmitted primarily across mucosal surfaces, development of immunity at these sites is critical, but few clinical vaccine trials have targeted these sites or assessed vaccine-elicited mucosal immune responses. Pre-clinical studies in non-human primate models have facilitated progress in mucosal vaccine development by evaluating candidate vaccine approaches, developing methodologies for collecting and assessing mucosal samples, and providing clues to immune correlates of protective immunity for further investigation. In this review we have focused on non-human primate studies which have provided important information for future design of vaccine strategies, targeting of mucosal inductive sites, and assessment of mucosal immunity. Knowledge gained in these studies will inform mucosal vaccine design and evaluation in human clinical trials. PMID:25196380
Tuero, Iskra; Robert-Guroff, Marjorie
Injecting drug use is the main route of HIV transmission in many parts of Indonesia. Efforts to prevent HIV-transmission through injecting drug use mostly focus on subjects who actively inject. In scientific publications, the term 'injecting drug users' tends to be used without a clear definition and without specifying the pattern of drug use as current or former drug use, frequency, duration, type of injected drug(s) or context (e.g. imprisonment). Actually, injecting drug users (IDUs) have different drug use patterns, risk behavior, somatic co-morbidity, psychiatric co-morbidity, and psychosocial problems. In fact, these patients are suffering from addiction as a chronic brain disease in co-occurrence with somatic and psychiatric disorder and many social problems. Failing in addressing the problems comprehensively will lead to the failure of drug treatment. This is why addiction can be best studied and treated from a biopsychosocial perspective. Accordingly, treatment goals can be differentiated in crisis intervention, cure or recovery (detoxification, relapse prevention), and care or partial remission (stabilization and harm reduction). In summary, injecting drug use in Indonesia is not a single entity and patient oriented prevention and care for IDUs, especially focusing on their addiction, should be addressed to prevent the transmission of HIV/AIDS. PMID:19920297
Iskandar, Shelly; van Crevel, Reinout; Siregar, I M P; Achmad, T H; van der Ven, A J A M; de Jong, C A J
Europrise is a Network of Excellence supported by the European Commission within the 6th Framework programme from 2007 to 2012. The Network has involved over 50 institutions from 13 European countries together with 3 industrial partners and 6 African countries. The Network encompasses an integrated program of research, training, dissemination and advocacy within the field of HIV vaccines and microbicides. A central and timely theme of the Network is the development of the unique concept of co-usage of vaccines and microbicides. Training of PhD students has been a major task, and some of these post-graduate students have here summarized novel ideas emanating from presentations at the last annual Europrise meeting in Prague. The latest data and ideas concerning HIV vaccine and microbicide studies are included in this review; these studies are so recent that the majority have yet to be published. Data were presented and discussed concerning novel immunisation strategies; microbicides and PrEP (alone and in combination with vaccines); mucosal transmission of HIV/SIV; mucosal vaccination; novel adjuvants; neutralizing antibodies; innate immune responses; HIV/SIV pathogenesis and disease progression; new methods and reagents. These – necessarily overlapping topics - are comprehensively summarised by the Europrise students in the context of other recent exciting data. PMID:22784600
HIV vaccine clinical research occurs within a context where biomedical science and social issues are interlinked. Previous HIV vaccine research has considered behavioral and social issues, but often treated them as independent of clinical research processes. Systematic attention to the intersection of behavioral and social issues within a defined clinical research framework is needed to address gaps, such as those related to participation in trials, completion of trials, and the overall research experience. Rigorous attention to these issues at project inception can inform trial design and conduct by matching research approaches to the context in which trials are to be conducted. Conducting behavioral and social sciences research concurrent with vaccine clinical research is important because it can help identify potential barriers to trial implementation, as well as ultimate acceptance and dissemination of trial results. We therefore propose a conceptual framework for behavioral and social science in HIV vaccine clinical research and use examples from the behavioral and social science literature to demonstrate how the model can facilitate identification of significant areas meriting additional exploration. Standardized use of the conceptual framework could improve HIV vaccine clinical research efficiency and relevance. PMID:21821083
Lau, Chuen-Yen; Swann, Edith M.; Singh, Sagri; Kafaar, Zuhayr; Meissner, Helen I.; Stansbury, James P.
The rare, broadly neutralizing antibodies, 4E10 and 2F5, that target the HIV-1 membrane proximal external region also associate with HIV-1 membrane lipids as part of a required first-step in HIV-1 neutralization. HIV-1 virions have high concentration of cholesterol and sphingomyelin, which are able to organize into liquid-ordered domains (i.e., lipid rafts), and could influence the interaction of neutralizing antibodies with epitopes proximal to the membrane. The objective of this research is to understand how these lipid domains contribute to 2F5/4E10 membrane interactions and to antigen presentation in liposomal form of HIV-1 vaccines. To this end we have engineered biomimetic supported lipid bilayers and are able to use atomic force microscopy to visualize membrane domains, antigen clustering, and antibody-membrane interactions. Our results demonstrate that 2F5/4E10 do not interact with highly ordered gel and liquid-ordered domains and exclusively bind to a liquid-disordered lipid phase. This suggests that vaccine liposomes that contain key viral membrane components, such as high cholesterol content, may not be advantageous for 2F5/4E10 vaccine strategies. Rather, vaccine liposomes that primarily contain a liquid-disordered phase may be more likely to elicit production of lipid reactive, 2F5- and 4E10-like antibodies. PMID:25019685
Hardy, Gregory J; Wong, Gene C; Nayak, Rahul; Anasti, Kara; Hirtz, Michael; Shapter, Joseph G; Alam, S Munir; Zauscher, Stefan
In 2002 MTV launched a global multicomponent HIV prevention campaign, "Staying Alive," reaching over 166 countries worldwide. An evaluation of this campaign focused on three diverse sites: Kathmandu, Nepal; Sao Paulo, Brazil; and Dakar, Senegal. Data were collected before and after campaign implementation through population-based household…
Geary, Cynthia Waszak; Burke; Holly McClain; Castelnau, Laure; Neupane; Shailes; Sall, Yacine Ba; Wong, Emily; Tucker, Heidi Toms
The Centers for Disease Control and Prevention have recommended that HIV care clinics incorporate prevention into clinical practice. This report summarizes HIV care providers' attitudes and counseling practices before and after they received training to deliver a counseling intervention to patients. Providers at seven HIV clinics received training…
Thrun, Mark; Cook, Paul F.; Bradley-Springer, Lucy A.; Gardner, Lytt; Marks, Gary; Wright, Julie; Wilson, Tracey E.; Quinlivan, E. Byrd; O'Daniels, Christine; Raffanti, Stephen; Thompson, Melanie; Golin, Carol
HIV-prevention intervention effectiveness depends on understanding whether clients with highest need for HIV-prevention counseling accept it. With this objective, a field study with a high-risk community sample from the southeastern United States (N = 350) investigated whether initial knowledge about HIV, motivation to use condoms,…
Earl, Allison; Albarracin, Dolores; Durantini, Marta R.; Gunnoe, Joann B.; Leeper, Josh; Levitt, Justin H.
...CDC/HRSA Advisory Committee on HIV and STD Prevention and Treatment In...related to prevention and control of HIV/AIDS and other STDs, the support of health care services to persons living with HIV/AIDS, and education of health...
...CDC/HRSA Advisory Committee on HIV and STD Prevention and Treatment In...related to prevention and control of HIV/AIDS and other STDs, the support of health care services to persons living with HIV/AIDS, and education of health...
...CDC/HRSA Advisory Committee on HIV and STD Prevention and Treatment In...related to prevention and control of HIV/AIDS and other STDs, the support of health care services to persons living with HIV/AIDS, and education of health...
Women account for half of new infections with HIV annually. Heterosexual transmission is the most common route of infection in resource limited settings (RLS). An effective microbicide would help decrease transmission of HIV and potentially enable women to have more control in sexual relationships. Research into microbicides is done predominantly in RLS. In addition, there will be different issues and challenges to consider with respect to rectal microbicide use in men. There exist several ethical issues around microbicide development and clinical research which we explore in this review. Respect for persons, including autonomy and protection of vulnerable populations, beneficence, and justice are explored as they relate to microbicide research. Improving standards of care in RLS, trial design, and informed consent are discussed in more detail. Special populations including pregnant women, adolescents, and men who have sex with men are considered in more detail. A multipronged approach to HIV prevention will be necessary to have an impact on HIV prevention. A continued discussion around ethical issues in regard to study design, interpretation of results and implementation of compounds brought to market will remain critically important. PMID:22264052
Gangestad, Angelina K; Salata, Robert A
Abstract In the past few years, the transdisciplinary field of HIV prevention has reached several milestones. Topically applied tenofovir gel provided significant protection from sexual transmission of HIV in a large-scale clinical trial and oral Truvada (emtricitabine/tenofovir disoproxil fumarate) was recently approved for preexposure prophylaxis (PrEP) following two successful clinical trials in men and women. These achievements are tempered by the disappointing results of other clinical trials, which highlight the complexities of prevention research. In this perspective, we discuss scientific and developmental gaps for topical chemoprophylaxis of the sexual transmission of HIV, which depends on the complex interactions between the pharmacokinetics and pharmacodynamics of drugs, formulation and delivery systems, anatomic site of transmission, and host mucosal immune defenses. Despite the considerable time and resources devoted to unraveling the initial steps in sexual transmission of HIV, current knowledge is based on animal models and human explanted tissue, which may not fully recapitulate what happens clinically. Understanding these events, including the role that sex hormones, semen, and mucosal secretions play in transmission, and the interplay between innate immunity, the mucosal environment, and drug efficacy is paramount. This drives some of the most pressing questions in the field. PMID:22966871
Mesquita, Pedro M.M.; Herold, Betsy C.
Since its discovery and characterization in the early 1980s as a virus that attacks the immune system, there has been some success for the treatment of human immunodeficiency virus-1 (HIV-1) infection. However, due to the overwhelming public health impact of this virus, a vaccine is needed urgently. Despite the tireless efforts of scientist and clinicians, there is still no safe and effective vaccine that provides sterilizing immunity. A vaccine that provides sterilizing immunity against HIV infection remains elusive in part due to the following reasons: 1) degree of diversity of the virus, 2) ability of the virus to evade the hosts' immunity, and 3) lack of appropriate animal models in which to test vaccine candidates. There have been several attempts to stimulate the immune system to provide protection against HIV-infection. Here, we will discuss attempts that have been made to induce sterilizing immunity, including traditional vaccination attempts, induction of broadly neutralizing antibody production, DNA vaccines, and use of viral vectors. Some of these attempts show promise pending continued research efforts. PMID:21267356
Gamble, Lena J; Matthews, Qiana L
Objective Randomized clinical trials of HIV prevention in high-risk populations of women often assume that all participants have similar exposure to HIV. However, a substantial fraction of women enrolled in the trial may have no or low exposure to HIV. Our objective was to estimate the proportion of women exposed to HIV throughout a hypothetical high-risk study population. Methods A stochastic individual-based model was developed to simulate the sexual behavior and the risk of HIV acquisition for a cohort of sexually active HIV-uninfected women in high HIV prevalence settings. Key behavior and epidemic assumptions in the model were based on published studies on HIV transmission in South Africa. The prevalence of exposure, defined as the proportion of women who have sex with HIV-infected partner, and HIV incidence were evaluated. Results Our model projects that in communities with HIV incidence rate of 1 per 100 person years, only 5-6% of women are exposed to HIV annually while in communities with an HIV incidence of 5 per 100 person years 20-25% of women are exposed to HIV. Approximately 70% of the new infections are acquired from partners with asymptomatic HIV. Conclusions Mathematical models suggest that a high proportion of women enrolled in HIV prevention trials may be unexposed to HIV even when incidence rates are high. The relationship between HIV exposure and other risk factors should be carefully analyzed when future clinical trials are planned. PMID:25569838
Dimitrov, Dobromir; Donnell, Deborah; Brown, Elizabeth R.
Efficacy of Vaccination against HPV Infections to Prevent Cervical Cancer in France: Present Assessment and Pathways to Improve Vaccination Policies Laureen Ribassin-Majed1 *, Rachid Lounes1 , Stephan and 1,067 deaths from cervical cancer occurred in 2005. Two vaccines against HPV infections
Paris-Sud XI, UniversitÃ© de
Background With the persistent challenges towards controlling the HIV epidemic, there is an ongoing need for research into HIV vaccines and drugs. Sub-Saharan African countries - worst affected by the HIV pandemic - have participated in the conduct of clinical trials for HIV vaccines. In Kenya, the Kenya AIDS Vaccine Initiative (KAVI) at the University of Nairobi has conducted HIV vaccine clinical trials since 2001. Methodology Participants were recruited after an extensive informed consent process followed by screening to determine eligibility. Screening included an assessment of risk behavior, medical history and physical examination, and if clinically healthy, laboratory testing. In the absence of locally derived laboratory reference ranges, the ranges used in these trials were derived from populations in the West. Principal findings Two hundred eighty-one participants were screened between 2003 and 2006 for two clinical trials. Of these, 167 (59.4%) met the inclusion/exclusion criteria. Overall, laboratory abnormalities based on the non-indigenous laboratory references used were the most frequent reasons (61.4%) for ineligibility. Medical abnormalities contributed 30.7% of the total reasons for ineligibility. Based on the laboratory reference intervals now developed from East and Southern Africa, those ineligible due to laboratory abnormalities would have been 46.3%. Of the eligible participants, 18.6% declined enrolment. Conclusions Participant recruitment for HIV vaccine clinical trials is a rigorous and time-consuming exercise. Over 61% of the screening exclusions in clinically healthy people were due to laboratory abnormalities. It is essential that laboratory reference ranges generated from local populations for laboratory values be used in the conduct of clinical trials to avoid unnecessary exclusion of willing participants and to avoid over-reporting of adverse events for enrolled participants. Trial registration Protocol IAVI VRC V001 . ClinicalTrials.gov NCT00124007 Protocol IAVI 010  (registration with ClincalTrials.gov is in progress) Protocols IAVI 002 and IAVI 004 are Phase 1 trials only mentioned in introductory paragraphs; details will not be reported. Registration was not required when they were conducted. PMID:21283743
Omosa-Manyonyi, Gloria S.; Jaoko, Walter; Anzala, Omu; Ogutu, Hilda; Wakasiaka, Sabina; Malogo, Roselyn; Nyange, Jacqueline; Njuguna, Pamela; Ndinya-Achola, Jeckoniah; Bhatt, Kirana; Farah, Bashir; Oyaro, Micah; Schmidt, Claudia; Priddy, Frances; Fast, Patricia
Despite a long-lasting global effort, the Holy Grail quest for a protective vaccine, able to confer prevention to HIV infection, did not reach the hoped for results, nor seems able to do so in the near future. Since mucosal surfaces of the host serve as the main entry point for HIV, it seems now logical to switch from a systemic to a localized view of events, in order to reveal critical steps useful in designing new and different vaccination strategies. In this context, the recent description of the very early phases of infection, from the eclipse to the viremia peak phase, seems to define a point-of-no-return threshold after which the main HIV infection steps, i.e. the massive destruction of the CD4+CCR5+ cell pool, the destruction of the mucosal physical barrier, and the establishment of reservoir sanctuaries, have already been accomplished. Nevertheless, the underlying mechanisms, the timing, and the consequences of evasion mechanisms exploited by HIV are still under scrutiny. Innate immunity, as part of a rapid lymphoid stress surveillance system, is known to play a central role in host responses to many infectious agents. In particular, V?9V?2 T-cells are able to quickly respond to danger signals without the need for classical major histocompatibility complex presentation, and may act as a bridge between innate and acquired arms of immune response, being able to kill infected/transformed cells, release antimicrobial soluble factors, and increase the deployment of other innate and acquired responses. Many experimental evidences suggest a direct role of circulating V?9V?2 T-cells during HIV disease. They may exert a direct anti-HIV role by secreting chemokines competing for HIV entry coreceptors as well as other soluble antiviral factors, and by killing infected cells by cytotoxic natural killer-like mechanisms. Moreover, they were found progressively depleted and anergic in advanced stages of HIV disease, this effect being directly linked to uncontrolled HIV replication. Scarce evidences are available on the involvement of mucosal gamma/delta T-cells during the early phases of HIV infection. In particular, the relative cause/effect links between HIV infection, destruction of the mucosal physical barrier, nonspecific activation of the immune system, and mucosal innate cell activation and effector functions, are still not completely defined. In order to attain an effective manipulation of innate immune cells, aiming at the induction of an effective adaptive immunity against HIV, any information on the role of mucosal antiviral factors and innate immune cells will be very important. The aim of this review is to summarize the information on the role of gamma/delta T-cells during HIV infection, from the general circulating population to mucosal sites, in order to better describe areas deserving increased attention. In particular, strategies enhancing gamma/delta T-cell functions may open the possibility to formulate new immunotherapeutic regimens, which could impact the improvement of immune control of HIV disease. PMID:21412385
Agrati, Chiara; D'Offizi, Gianpiero; Gougeon, Marie-Lise; Malkovsky, Miroslav; Sacchi, Alessandra; Casetti, Rita; Bordoni, Veronica; Cimini, Eleonora; Martini, Federico
Despite increasing rates of HIV infection among young men who have sex with men (YMSM), only a minority participate in formal HIV prevention efforts. Semi-structured mixed-methods interviews were conducted with a diverse sample of YMSM (N = 100, M(age) = 25.0 years) in Los Angeles, California, to identify facilitators and barriers to participation in HIV prevention programs. Summative content analyses were used to evaluate transcribed field notes from these interviews. Results showed that 28.0 % of all participants had previously attended an HIV prevention program, and that 21.3 % of those who were also asked if they had ever participated in any research pertaining to HIV prevention had done so. A significantly higher percentage of those who had participated in HIV prevention programs had been tested for HIV in the past 6 months compared to those who had not (p < .05). The most frequently mentioned barriers to participation in such a program were being too busy to attend (12.0 %), not perceiving themselves to be at risk for HIV infection (14.0 %), and believing that they already knew everything they needed to know about HIV transmission (23.0 %). YMSM suggested that future interventions should use technology (e.g., the Internet, mobile devices), engage their social networks, and highlight HIV prevention as a means for community connection. Collectively, these results provide some explanations for why YMSM account for a minority of HIV prevention program participants and offer possible directions for future HIV prevention efforts that target YMSM. PMID:23132515
Holloway, Ian W; Cederbaum, Julie A; Ajayi, Antonette; Shoptaw, Steven
The phase III RV144 HIV-1 vaccine trial estimated vaccine efficacy (VE) to be 31.2%. This trial demonstrated that the presence of HIV-1-specific IgG-binding Abs to envelope (Env) V1V2 inversely correlated with infection risk, while the presence of Env-specific plasma IgA Abs directly correlated with risk of HIV-1 infection. Moreover, Ab-dependent cellular cytotoxicity responses inversely correlated with risk of infection in vaccine recipients with low IgA; therefore, we hypothesized that vaccine-induced Fc receptor-mediated (FcR-mediated) Ab function is indicative of vaccine protection. We sequenced exons and surrounding areas of FcR-encoding genes and found one FCGR2C tag SNP (rs114945036) that associated with VE against HIV-1 subtype CRF01_AE, with lysine at position 169 (169K) in the V2 loop (CRF01_AE 169K). Individuals carrying CC in this SNP had an estimated VE of 15%, while individuals carrying CT or TT exhibited a VE of 91%. Furthermore, the rs114945036 SNP was highly associated with 3 other FCGR2C SNPs (rs138747765, rs78603008, and rs373013207). Env-specific IgG and IgG3 Abs, IgG avidity, and neutralizing Abs inversely correlated with CRF01_AE 169K HIV-1 infection risk in the CT- or TT-carrying vaccine recipients only. These data suggest a potent role of Fc-? receptors and Fc-mediated Ab function in conferring protection from transmission risk in the RV144 VE trial. PMID:25105367
Li, Shuying S; Gilbert, Peter B; Tomaras, Georgia D; Kijak, Gustavo; Ferrari, Guido; Thomas, Rasmi; Pyo, Chul-Woo; Zolla-Pazner, Susan; Montefiori, David; Liao, Hua-Xin; Nabel, Gary; Pinter, Abraham; Evans, David T; Gottardo, Raphael; Dai, James Y; Janes, Holly; Morris, Daryl; Fong, Youyi; Edlefsen, Paul T; Li, Fusheng; Frahm, Nicole; Alpert, Michael D; Prentice, Heather; Rerks-Ngarm, Supachai; Pitisuttithum, Punnee; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Robb, Merlin L; O'Connell, Robert J; Haynes, Barton F; Michael, Nelson L; Kim, Jerome H; McElrath, M Juliana; Geraghty, Daniel E
The use of advanced imaging techniques has allowed researchers to visualize how a key part of the human immunodeficiency virus (HIV) changes shape after binding to immune system cells or to infection-fighting antibodies. Although scientists had been able to visualize individual components of this part of the virus, called the HIV spike, the new research characterizes, for the first time, the structure of the intact spike on virus particles, which is a crucial piece of knowledge that may aid the design of new vaccines or drugs to fight HIV infection.
The PEDVAC study is the first trial designed to analyze safety and immunogenicity of a therapeutic vaccination with a multiclade multigene HIV DNA vaccine (HIVIS) in infected children. Twenty HIV-1 vertically infected children (6-16 years of age), on stable antiretroviral treatment for at least 6 months with HIV-1 RNA<50 copies/ml and stable CD4 counts (> 400 cells/mm³ or 25%) over 12 months of follow-up, were recruited into the study. Enrolled patients have been randomized into two arms: a control group of 10 children who continued previous antiretroviral treatment (HAART) (arm A) and a group of 10 children immunized intramuscularly with the HIVIS DNA vaccine in addition to previous HAART (arm B). Immunizations took place at week 0, 4, 12 and the boosting dose is planned at week 36. The 10 children in the vaccine group have received the first 3 priming doses of the HIVIS vaccine. Safety data showed good tolerance to the vaccination schedule. Mild cutaneous self-limeted reactions consisted of local irritation, usually itching or erythema +/- swelling at the injection site, were reported. No severe systemic adverse events have been observed. No vaccinated children had a decrease of CD4 T-cell counts from baseline. None experienced virological failure. Analysis of cellular immune responses was scheduled at week 0, 4, 12, 16, 20, 40, 60, 72 and 96 by standard lymphoproliferation assay, intracellular cytokine staining and cell-ELISA, a miniaturized assay to measure antigen-induced IFN? secretion. Evaluation of these results is in progress and will provide key information on the status and changes of antigen specific immunity during HIV DNA immunization. PMID:21216310
Palma, Paolo; Romiti, Maria Luisa; Li Pira, Giuseppina; Montesano, Carla; Mora, Nadia; Aquilani, Angela; Santilli, Veronica; Tchidjou, Hyppolite K; Ivaldi, Federico; Giovannelli, Luigi; Pontrelli, Giuseppe; Borra, Giada; Blomberg, Pontus; Gudmundsdotter, Lindvi; Bråve, Andreas; Montano, Marco; Bernardi, Stefania; Manca, Fabrizio; Wahren, Britta; Rossi, Paolo
DNA vaccines are an important vaccine approach for many infectious diseases including human immunodeficiency virus (HIV). Recently, there have been exciting results reported for plasmid vaccination in pathogenic SHIV model systems. In these studies, plasmid vaccines supplemented by IL-2 Ig cytokine gene adjuvants or boosted by recombinant MVA vectors expressing relevant SIV and HIV antigens prevented CD4+ T-cell loss and
Karuppiah Muthumani; Mark Bagarazzi; Dan Conway; Daniel S. Hwang; Kelledy Manson; Richard Ciccarelli; Zimmra Israel; David C. Montefiori; Kenneth Ugen; Nancy Miller; Jong Kim; Jean Boyer; David B. Weiner
This guidebook is for school administrators, teachers, health care workers, parents, and students who want to help their schools prevent HIV, sexually transmitted diseases, and unwanted pregnancy among young people. The experience in more than 120 high schools in New York City has been the basis for the guide, which was developed with the help of…
Freudenberg, Nicholas; Radosh, Alice
The development of an HIV vaccine will require a more precise understanding of the immunological and virological underpinnings of HIV infection. Magnetofection, the process of magnetizing HIV by coupling it to ferrous nanoparticles and coordinating infection using a magnetic field, synchronizes the viral replication cycle at attachment while recapitulating the events of natural infection. Although spinoculation also concentrates virus onto target cells to increase infection, it does not synchronize infection. The synchronization of HIV infection in vitro facilitates the study of events in the viral replication cycle and the antiviral immune response on timelines previously impossible. Furthermore, by infecting a high percentage of cells in a short time frame, magnetofection increases the throughput of in vitro assays. Once a virus stock is generated, magnetofection of target cells is rapid, requiring only 1-2 h. Here we present a detailed protocol for this assay and review its applications for studying the immune response to HIV. PMID:20134424
Sacha, Jonah B; Watkins, David I
Secondary HIV prevention, or “positive prevention,” is concerned with reducing HIV transmission risk behavior and optimizing\\u000a the health and quality of life of people living with HIV\\/AIDS (PLWHA). The association between mental health and HIV transmission\\u000a risk (i.e., sexual risk and poor medication adherence) is well established, although most of this evidence is observational.\\u000a Further, a number of efficacious mental
Kathleen J. Sikkema; Melissa H. Watt; Anya S. Drabkin; Christina S. Meade; Nathan B. Hansen; Brian W. Pence
Abstract The Thai Phase III clinical trial (RV144) showed modest efficacy in preventing HIV-1 acquisition. Plasma collected from HIV-1-uninfected trial participants completing all injections with ALVAC-HIV (vCP1521) prime and AIDSVAX B/E boost were tested for antibody responses against HIV-1 gp120 envelope (Env). Peptide microarray analysis from six HIV-1 subtypes and group M consensus showed that vaccination induced antibody responses to the second variable (V2) loop of gp120 of multiple subtypes. We further evaluated V2 responses by ELISA and surface plasmon resonance using cyclic (Cyc) and linear V2 loop peptides. Thirty-one of 32 vaccine recipients tested (97%) had antibody responses against Cyc V2 at 2 weeks postimmunization with a reciprocal geometric mean titer (GMT) of 1100 (range: 200–3200). The frequency of detecting plasma V2 antibodies declined to 19% at 28 weeks post-last injection (GMT: 110, range: 100–200). Antibody responses targeted the mid-region of the V2 loop that contains conserved epitopes and has the amino acid sequence KQKVHALFYKLDIVPI (HXB2 Numbering sequence 169–184). Valine at position 172 was critical for antibody binding. The frequency of V3 responses at 2 weeks postimmunization was modest (18/32, 56%) with a GMT of 185 (range: 100–800). In contrast, naturally infected HIV-1 individuals had a lower frequency of antibody responses to V2 (10/20, 50%; p=0.003) and a higher frequency of responses to V3 (19/20, 95%), with GMTs of 400 (range: 100–3200) and 3570 (range: 200–12,800), respectively. RV144 vaccination induced antibodies that targeted a region of the V2 loop that contains conserved epitopes. Early HIV-1 transmission events involve V2 loop interactions, raising the possibility that anti-V2 antibodies in RV144 may have contributed to viral inhibition. PMID:23035746
Billings, Erik; Rao, Mangala; Williams, Constance; Zolla-Pazner, Susan; Bailer, Robert T.; Koup, Richard A.; Madnote, Sirinan; Arworn, Duangnapa; Shen, Xiaoying; Tomaras, Georgia D.; Currier, Jeffrey R.; Jiang, Mike; Magaret, Craig; Andrews, Charla; Gottardo, Raphael; Gilbert, Peter; Cardozo, Timothy J.; Rerks-Ngarm, Supachai; Nitayaphan, Sorachai; Pitisuttithum, Punnee; Kaewkungwal, Jaranit; Paris, Robert; Greene, Kelli; Gao, Hongmei; Gurunathan, Sanjay; Tartaglia, Jim; Sinangil, Faruk; Korber, Bette T.; Montefiori, David C.; Mascola, John R.; Robb, Merlin L.; Haynes, Barton F.; Ngauy, Viseth; Michael, Nelson L.; Kim, Jerome H.; de Souza, Mark S.
BackgroundThe immunogenicity of 2009 pandemic influenza A(H1N1) (pH1N1) vaccines and the effect of previous influenza vaccination is a matter of current interest and debate. We measured the immune response to pH1N1 vaccine in HIV-infected patients and in healthy controls. In addition we tested whether recent vaccination with seasonal trivalent inactivated vaccine (TIV) induced cross-reactive antibodies to pH1N1. (clinicaltrials.gov Identifier:NCT01066169)Methods and
Darius Soonawala; Guus F. Rimmelzwaan; Luc B. S. Gelinck; Leo G. Visser; Frank P. Kroon; Douglas Nixon
Presents two recent cases that can be used in the classroom to illustrate the application of scientific methods in biological research: (1) the use of a complementary RNA or DNA molecule to block the production or translation of an mRNA molecule; and (2) the development of HIV trial vaccines. Contains 20 references. (WRM)
Abstract To assess qualities and outcomes of women participating in a large, community-based HIV vaccine trial, the present study was conducted among female participants of the RV 144 prime-boost trial in Thailand from 2003 to 2009. Qualities of participation refer to complete vaccination, retention, and status change. Outcomes of participation refer to incident rate, adverse event, and participation impact event. A total of 6,334 (38.6%) women participated in the trial, of whom about 50% were classified as low risk and 11% as high risk. About 85% of participants completed four vaccinations and 76% were included in the per-protocol analysis of the on-time vaccination schedule. More women (88%) completed 42 months follow-up compared with men (85%). Women aged 21 and above had more adverse events compared to younger age groups. More women (5%) compared with men (3%) reported participation impact events (PIEs). High-risk women had more PIEs and a higher infection rate compared to the low-risk group. Complete vaccination and retention on last follow-up were more common in married women aged above 21, and being a housewife. Female volunteers showed the same qualities and outcomes of participation as males in the HIV vaccine trial. There was no statistically significant difference in vaccine efficacy between men and women, especially among the high-risk and married women. The study highlighted the important behavioral, social, and cultural issues that could be considered for future HIV vaccine trial designs. PMID:23343395
Kaewkungwal, Jaranit; Rerks-ngarm, Supachai; Nitayaphan, Sorachai; Khamboonruang, Chirasak; Kunasol, Prayura; Suntharasamai, Pravan; Pungpak, Swangjai; Vanijanonta, Sirivan; Bussaratid, Valai; Maek-a-nantawat, Wirach; Dhitavat, Jittima; Thongcharoen, Prasert; Pawarana, Rungrawee; Sabmee, Yupa; Benenson, Mike W.; Morgan, Patricia; O’Connell, Robert J.; Kim, Jerome
Here we describe a prime-boost regimen of vaccination in Macaca fascicularis that combines priming with novel anionic microspheres designed to deliver the biologically active HIV-1 Tat protein and boosting with Tat in Alum. This regimen of immunization modulated the IgG subclass profile and elicited a balanced Th1-Th2 type of humoral and cellular responses. Remarkably, following intravenous challenge with SHIV89.6Pcy243, vaccinees significantly blunted acute viremia, as compared to control monkeys, and this control was associated with significantly lower CD4+ T cell depletion rate during the acute phase of infection and higher ability to resume the CD4+ T cell counts in the post-acute and chronic phases of infection. The long lasting control of viremia was associated with the persistence of high titers anti-Tat antibodies whose profile clearly distinguished vaccinees in controllers and viremics. Controllers, as opposed to vaccinated and viremic cynos, exhibited significantly higher pre-challenge antibody responses to peptides spanning the glutamine-rich and the RGD-integrin-binding regions of Tat. Finally, among vaccinees, titers of anti-Tat IgG1, IgG3 and IgG4 subclasses had a significant association with control of viremia in the acute and post-acute phases of infection. Altogether these findings indicate that the Tat/H1D/Alum regimen of immunization holds promise for next generation vaccines with Tat protein or other proteins for which maintenance of the native conformation and activity are critical for optimal immunogenicity. Our results also provide novel information on the role of anti-Tat responses in the prevention of HIV pathogenesis and for the design of new vaccine candidates. PMID:25356594
Titti, Fausto; Maggiorella, Maria T.; Ferrantelli, Flavia; Sernicola, Leonardo; Bellino, Stefania; Collacchi, Barbara; Belasio, Emanuele Fanales; Moretti, Sonia; Pavone Cossut, Maria Rosaria; Belli, Roberto; Olivieri, Erika; Farcomeni, Stefania; Compagnoni, Daniela; Michelini, Zuleika; Sabbatucci, Michela; Sparnacci, Katia; Tondelli, Luisa; Laus, Michele; Cafaro, Aurelio; Caputo, Antonella; Ensoli, Barbara
The public sector supports most HIV/AIDS prevention and care activities in developing countries, with significant funding provided by the US Agency for International Development, the Overseas Development Authority, the European Community, and international banking institutions such as the World Bank. Local nongovernmental organizations (NGOs) and international private voluntary organizations (PVOs) implement many of the grassroots prevention and care efforts in developing countries, but often require support from donor agencies. While the private commercial sector has played a minor role in supporting HIV/AIDS prevention and care efforts, a number of local and multinational companies are beginning to recognize the importance of protecting their workers from HIV infection. These companies are motivated by a sense of moral obligation and/or view HIV/AIDS prevention as a cost-effective investment. Mainly affecting the most economically productive age groups, the HIV/AIDS epidemic will have a significant impact upon private industry. Workplace-based prevention programs and policies, private sector resources for HIV/AIDS prevention and care, how HIV/AIDS programs can benefit from the private sector's experience in commercial service delivery, research and development, and corporate direct cash and in-kind contributions to government and NGO HIV/AIDS prevention activities are discussed. The AIDS Control and Prevention (AIDSCAP) Project's Businesses Managing AIDS Project helps owners and managers understand the potential impact of HIV/AIDS upon their businesses and the benefits of HIV/AIDS prevention. PMID:12347592
Recombinant modified vaccinia virus Ankara (MVA) expressing SIV or SHIV Gag-Pol and Env, alone or in conjunction with a related DNA vaccine, effectively controls immunodeficiency virus infections in nonhuman primates. Here we describe the construction, characterization, and immunogenicity of MVA/HIV 48, a candidate HIV-1 clade B Gag-Pol-Env vaccine. A novel transfer vector was designed to allow the incorporation of HIV genes regulated by vaccinia virus promoters together with a reporter gene into a single site in the MVA genome and to automatically delete the reporter after the initial isolation of the recombinant MVA. MVA/HIV 48 contains chimeric HIV-1 HXB-2/BH10 gag-pol sequences, a deletion of integrase, inactivating point mutations in reverse transcriptase, and HIV-1 ADA env sequences with a truncation of most of the cytoplasmic domain to enhance expression on the plasma membrane. Cells infected with MVA/HIV 48 expressed HIV proteins, which were processed to the expected size. The Env was inserted into the plasma membrane and was functional in a CCR5 coreceptor-dependent cell fusion assay. Moreover, virus-like particles were released into the medium and budding particles containing Env were visualized by immunoelectron microscopy. Rodents that were immunized with MVA/HIV 48 produced antibodies, which neutralized a heterologous HIV-MN strain, and Gag-specific CD8 T cells. In the accompanying paper, we show that MVA/HIV 48 provided efficient boosting of an HIV DNA vaccine. PMID:15242542
Wyatt, Linda S; Earl, Patricia L; Liu, Jin Yan; Smith, James M; Montefiori, David C; Robinson, Harriet L; Moss, Bernard
African American women continue to be disproportionately affected by the HIV/AIDS epidemic, yet there are few effective HIV prevention interventions that are exclusively tailored to their lives and that address their risk factors. Using an ecological framework, we offer a comprehensive overview of the risk factors that are driving the HIV/AIDS epidemic among African American women and explicate the consequences of ignoring these factors in HIV prevention strategies. We also recommend ways to improve HIV prevention programs by taking into consideration the unique life experiences of adult African American women. PMID:19372518
Caldeira, Nathilee A.; Ruglass, Lesia M.; Gilbert, Louisa
With accumulating evidence indicating the importance of cytotoxic T lymphocytes (CTLs) in containing human immunodeficiency virus-1 (HIV-1) replication in infected individuals, strategies are being pursued to elicit virus-specific CTLs with prototype HIV-1 vaccines. Here, we report the protective efficacy of vaccine-elicited immune responses against a pathogenic SHIV-89.6P challenge in rhesus monkeys. Immune responses were elicited by DNA vaccines expressing SIVmac239
Dan H. Barouch; Sampa Santra; Jörn E. Schmitz; Marcelo J. Kuroda; Tong-Ming Fu; Wendeline Wagner; Miroslawa Bilska; Abie Craiu; Xin Xiao Zheng; Georgia R. Krivulka; Kristin Beaudry; Michelle A. Lifton; Christine E. Nickerson; Wendy L. Trigona; Kara Punt; Dan C. Freed; Liming Guan; Sheri Dubey; Danilo Casimiro; Adam Simon; Mary-Ellen Davies; Michael Chastain; Terry B. Strom; Rebecca S. Gelman; David C. Montefiori; Mark G. Lewis; Emilio A. Emini; John W. Shiver; Norman L. Letvin
The use of antiretroviral medications in HIV-negative individuals as pre-exposure prophylaxis (PrEP) is a promising approach to prevent HIV infection. Tenofovir disoproxil fumarate (TDF) and emtricitabine exhibit desirable properties for PrEP including: favourable pharmacokinetics that support infrequent dosing; few major drug-drug or drug-food interactions; an excellent clinical safety record; and pre-clinical evidence for efficacy. Several large, randomized, controlled clinical trials are evaluating the safety and efficacy of TDF and emtricitabine for this new indication. A thorough understanding of variability in drug response will help determine future investigations in the field and/or implementation into clinical care. Because tenofovir and emtricitabine are nucleos(t)ide analogues, the HIV prevention and toxicity effects depend on the triphosphate analogue formed intracellularly. This review identifies important cellular pharmacology considerations for tenofovir and emtricitabine, which include drug penetration into relevant tissues and cell types, race/ethnicity/pharmacogenetics, gender, cellular activation state and appropriate episodic or alternative dosing strategies based on pharmacokinetic principles. The current state of knowledge in these areas is summarized and the future utility of intracellular pharmacokinetics/pharmacodynamics for the PrEP field is discussed. PMID:21118913
Anderson, Peter L; Kiser, Jennifer J; Gardner, Edward M; Rower, Joseph E; Meditz, Amie; Grant, Robert M
Challenge studies following passive immunization with neutralizing antibodies suggest that an HIV vaccine could be efficacious were it able to elicit broadly neutralizing antibodies (bNAbs4). To better understand the requirements for activation of B cells producing bNAbs, we generated cell lines expressing bNAbs or their germline-reverted versions (gl-bNAbs) as BCRs. We then tested the abilities of the bNAb-expressing cells to recognize HIV pseudovirions and vaccine candidate proteins by binding and activation assays. The results suggest that HIV Env antigen-expressing, infection-competent virions are poorly recognized by high affinity bNAb-expressing cells, as measured by the inability of antigens to induce rapid increases in intracellular calcium levels. Other antigen forms appear to be highly stimulatory: in particular, soluble gp140 trimers and a multimerized, scaffolded epitope protein. Virions failed to efficiently activate bNAb-expressing B cells owing to delayed or inefficient BCR recognition, most likely caused by the low density of Env spikes. Importantly, B cells carrying gl-bNAb BCRs were not stimulated by any of the tested vaccine candidates. These data provide insight into why many HIV immunogens, and natural HIV infections, fail to rapidly stimulate bNAb responses and suggest that bNAb-expressing cell lines might be useful tools in evaluation of vaccine antigens for infectious diseases. As soluble Env trimers or multimerized scaffolded epitopes are best at activating B cell expressing bNAbs, these antigenic forms should be considered as preferred vaccine components, though they should be modified to better target naïve gl-bNAb B cells. PMID:23066156
Ota, Takayuki; Doyle-Cooper, Colleen; Cooper, Anthony B.; Huber, Michael; Falkowska, Emilia; Doores, Katherine J.; Hangartner, Lars; Le, Khoa; Sok, Devin; Jardine, Joseph; Lifson, Jeffrey; Wu, Xueling; Mascola, John R.; Poignard, Pascal; Binley, James M.; Chakrabarti, Bimal K.; Schief, William R.; Wyatt, Richard T.; Burton, Dennis R.; Nemazee, David
The effort to prevent further HIV infection for high risk populations has been largely limited, in practice, to health education efforts. Prevention policy must utilize techniques which, in combination with health education efforts, works to decrease behaviors which are implicated in HIV transmission. It is argued taht this approach to prevention will work best if it is designed with an
Intradermal vaccination against influenza represents a new method of protection against the heavy incidence disease. For its very good immunity response, intradermal injections are frequently used for many types of vaccines. Results of clinical studies are presented and the system of intradermal microinjections for vaccine administration is introduced. Sensitive vaccination can increase the prevalence of vaccinated persons and thus decrease morbidity and mortality of influenza. PMID:19642311
... child transmission of HIV even in women who did not take HIV medicine during pregnancy? Zidovudine is ... child transmission of HIV even in women who did not take HIV medicines during pregnancy. When should ...
The RV144 clinical trial showed the partial efficacy of a vaccine regimen with an estimated vaccine efficacy (VE) of 31% for protecting low-risk Thai volunteers against acquisition of HIV-1. The impact of vaccine-induced immune responses can be investigated through sieve analysis of HIV-1 breakthrough infections (infected vaccine and placebo recipients). A V1/V2-targeted comparison of the genomes of HIV-1 breakthrough viruses identified two V2 amino acid sites that differed between the vaccine and placebo groups. Here we extended the V1/V2 analysis to the entire HIV-1 genome using an array of methods based on individual sites, k-mers and genes/proteins. We identified 56 amino acid sites or “signatures” and 119 k-mers that differed between the vaccine and placebo groups. Of those, 19 sites and 38 k-mers were located in the regions comprising the RV144 vaccine (Env-gp120, Gag, and Pro). The nine signature sites in Env-gp120 were significantly enriched for known antibody-associated sites (p = 0.0021). In particular, site 317 in the third variable loop (V3) overlapped with a hotspot of antibody recognition, and sites 369 and 424 were linked to CD4 binding site neutralization. The identified signature sites significantly covaried with other sites across the genome (mean = 32.1) more than did non-signature sites (mean = 0.9) (p < 0.0001), suggesting functional and/or structural relevance of the signature sites. Since signature sites were not preferentially restricted to the vaccine immunogens and because most of the associations were insignificant following correction for multiple testing, we predict that few of the genetic differences are strongly linked to the RV144 vaccine-induced immune pressure. In addition to presenting results of the first complete-genome analysis of the breakthrough infections in the RV144 trial, this work describes a set of statistical methods and tools applicable to analysis of breakthrough infection genomes in general vaccine efficacy trials for diverse pathogens. PMID:25646817
Edlefsen, Paul T.; Rolland, Morgane; Hertz, Tomer; Tovanabutra, Sodsai; Gartland, Andrew J.; deCamp, Allan C.; Magaret, Craig A.; Ahmed, Hasan; Gottardo, Raphael; Juraska, Michal; McCoy, Connor; Larsen, Brendan B.; Sanders-Buell, Eric; Carrico, Chris; Menis, Sergey; Bose, Meera; Arroyo, Miguel A.; O’Connell, Robert J.; Nitayaphan, Sorachai; Pitisuttithum, Punnee; Kaewkungwal, Jaranit; Rerks-Ngarm, Supachai; Robb, Merlin L.; Kirys, Tatsiana; Georgiev, Ivelin S.; Kwong, Peter D.; Scheffler, Konrad; Pond, Sergei L. Kosakovsky; Carlson, Jonathan M.; Michael, Nelson L.; Schief, William R.; Mullins, James I.; Kim, Jerome H.; Gilbert, Peter B.
The RV144 clinical trial showed the partial efficacy of a vaccine regimen with an estimated vaccine efficacy (VE) of 31% for protecting low-risk Thai volunteers against acquisition of HIV-1. The impact of vaccine-induced immune responses can be investigated through sieve analysis of HIV-1 breakthrough infections (infected vaccine and placebo recipients). A V1/V2-targeted comparison of the genomes of HIV-1 breakthrough viruses identified two V2 amino acid sites that differed between the vaccine and placebo groups. Here we extended the V1/V2 analysis to the entire HIV-1 genome using an array of methods based on individual sites, k-mers and genes/proteins. We identified 56 amino acid sites or "signatures" and 119 k-mers that differed between the vaccine and placebo groups. Of those, 19 sites and 38 k-mers were located in the regions comprising the RV144 vaccine (Env-gp120, Gag, and Pro). The nine signature sites in Env-gp120 were significantly enriched for known antibody-associated sites (p = 0.0021). In particular, site 317 in the third variable loop (V3) overlapped with a hotspot of antibody recognition, and sites 369 and 424 were linked to CD4 binding site neutralization. The identified signature sites significantly covaried with other sites across the genome (mean = 32.1) more than did non-signature sites (mean = 0.9) (p < 0.0001), suggesting functional and/or structural relevance of the signature sites. Since signature sites were not preferentially restricted to the vaccine immunogens and because most of the associations were insignificant following correction for multiple testing, we predict that few of the genetic differences are strongly linked to the RV144 vaccine-induced immune pressure. In addition to presenting results of the first complete-genome analysis of the breakthrough infections in the RV144 trial, this work describes a set of statistical methods and tools applicable to analysis of breakthrough infection genomes in general vaccine efficacy trials for diverse pathogens. PMID:25646817
Edlefsen, Paul T; Rolland, Morgane; Hertz, Tomer; Tovanabutra, Sodsai; Gartland, Andrew J; deCamp, Allan C; Magaret, Craig A; Ahmed, Hasan; Gottardo, Raphael; Juraska, Michal; McCoy, Connor; Larsen, Brendan B; Sanders-Buell, Eric; Carrico, Chris; Menis, Sergey; Bose, Meera; Arroyo, Miguel A; O'Connell, Robert J; Nitayaphan, Sorachai; Pitisuttithum, Punnee; Kaewkungwal, Jaranit; Rerks-Ngarm, Supachai; Robb, Merlin L; Kirys, Tatsiana; Georgiev, Ivelin S; Kwong, Peter D; Scheffler, Konrad; Pond, Sergei L Kosakovsky; Carlson, Jonathan M; Michael, Nelson L; Schief, William R; Mullins, James I; Kim, Jerome H; Gilbert, Peter B
Most children in Africa receive their vaccine against tuberculosis at birth. Those infants born to human immunodeficiency virus type 1 (HIV-1)-positive mothers are at high risk of acquiring HIV-1 infection through breastfeeding in the first weeks of their lives. Thus, the development of a vaccine which would protect newborns against both of these major global killers is a logical yet highly scientifically, ethically, and practically challenging aim. Here, a recombinant lysine auxotroph of Mycobacterium bovis bacillus Calmette-Guérin (BCG), a BCG strain that is safer than those currently used and expresses an African HIV-1 clade-derived immunogen, was generated and shown to be stable and to induce durable, high-quality HIV-1-specific CD4(+)- and CD8(+)-T-cell responses. Furthermore, when the recombinant BCG vaccine was used in a priming-boosting regimen with heterologous components, the HIV-1-specific responses provided protection against surrogate virus challenge, and the recombinant BCG vaccine alone protected against aerosol challenge with M. tuberculosis. Thus, inserting an HIV-1-derived immunogen into the scheduled BCG vaccine delivered at or soon after birth may prime HIV-1-specific responses, which can be boosted by natural exposure to HIV-1 in the breast milk and/or by a heterologous vaccine such as recombinant modified vaccinia virus Ankara delivering the same immunogen, and decrease mother-to-child transmission of HIV-1 during breastfeeding. PMID:17596303
Im, Eung-Jun; Saubi, Narcís; Virgili, Goretti; Sander, Clare; Teoh, Denise; Gatell, Jose M; McShane, Helen; Joseph, Joan; Hanke, Tomás
Each interpersonally delivered, evidence-based (EB) program for HIV prevention shares common features that aim to shift HIV risk behaviors. We used qualitative research methods to examine manuals from five EB programs for adolescents and identified 10 core principles embedded in each program’s activities. Principles reflect the stated goals and anticipated lessons in an activity. The principles were: Believe in your own worth and your right to a happy future; Commit to change; Distinguish fact from myth; Plan ahead and be prepared; Practice self-control; Know pleasurable alternatives to high risk activities; Negotiate verbally, not nonverbally; Evaluate options and consequences; Show concern for others; Choose to limit your own freedom; and Act to help others protect themselves. Focusing on common features rather than the unique properties of each EB program may allow community providers to have more flexibility and ownership in adapting EB programs, and may also facilitate development of new EB program. PMID:19224358
Rotheram-Borus, Mary Jane; Ingram, Barbara L.; Swendeman, Dallas; Flannery, Diane
Since the first reports of plasmid vaccines, there have been substantial changes made to the design of plasmid backbones, as well as to the antibiotic resistance markers chosen for clinical vectors compared with first generation vectors. These changes aid manufacturing, production and scale up and at the same time aid conceptual safety by limiting the ability of the vaccines to
Karuppiah Muthumani; Sagar Kudchodkar; Donghui Zhang; M. L Bagarazzi; Joseph J Kim; J. D Boyer; Velpandi Ayyavoo; George N Pavlakis; David B Weiner
Pre-exposure prophylaxis (PrEP), in which HIV-uninfected persons with ongoing HIV risk use antiretroviral medications to reduce their risk of acquiring HIV infection, is an efficacious and promising new HIV prevention strategy. The past two years have seen significant new advances in knowledge regarding PrEP, including definitive demonstration that PrEP reduces the risk of HIV acquisition, regulatory approval of combination oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) as the first PrEP agent with a label indication for sexual HIV prevention, and the development of normative guidance for clinical prescribing of PrEP. In PrEP clinical trials, HIV protection was strongly correlated with PrEP adherence; therefore understanding and supporting adherence to PrEP are key to maximizing its public health impact. As would be expected for any new HIV prevention approach, questions remain, including how to motivate uptake of and sustain adherence to PrEP for HIV prevention in high-risk populations, how much use is sufficient to achieve HIV protection, and the potential of “next-generation” PrEP agents to improve this effective prevention strategy. At this important transition point – from demonstration of efficacy in clinical trials to thinking about implementation and effectiveness – this review addresses where we have been and where we are going with PrEP for HIV prevention. PMID:23764623
Baeten, Jared M.; Haberer, Jessica E.; Liu, Albert Y.; Sista, Nirupama
Background & objectives: Systematic data on existing coverage and willingness for HIV prevention strategies among truckers are not readily available in India. The present study aimed to further the understanding on contact of truckers with existing HIV prevention services and to assess willingness for new HIV prevention strategies. Methods: A total of 1,800 truck drivers and helpers aged 16-65 yr passing through Hyderabad were approached to assess contact made with HIV prevention programmes, history of previous HIV testing and their acceptance for circumcision, oral HIV testing, new medications to control HIV (PrEP) and telephonic counselling. Dried blood samples were collected on filter paper and tested for HIV. Multiple logistic regression was performed for analysis of association between contact with HIV prevention programme and socio-demographic, sexual risk behaviour variables and work characteristics. Results: A total of 1,602 (89%) truckers gave interview and provided blood sample. Forty five truckers tested positive for HIV resulting in HIV prevalence of 2.8 per cent (95% CI 2.0-3.6%). Only 126 truckers (7.9%; 95% CI 6.5-9.2%) reported ever being contacted by staff providing HIV prevention interventions. Previous HIV testing was reported by19 per cent (95% CI 17.3-21.2%). Those reporting contact with HIV prevention programmes ever were more likely to have undergone HIV testing (odds ratio 3.6, 95% CI 2.4-5.4). The acceptance for pre-exposure prophylaxis (PrEP) was 87 per cent, oral HIV testing 98 per cent, and telephonic counselling 82 per cent, but was only 9 per cent for circumcision. Truckers who reported having sex with a man and those who halted regularly at dhabas were significantly more willing to undergo circumcision for HIV prevention (odds ratios 2.7, 95% CI 1.4-5.4 and 2.1, 95% CI 1.3-3.2, respectively). Interpretation & conclusions: Our findings showed that truckers had low contact with HIV prevention programmes, suggesting a need for urgent measures to reach this population more effectively. The willingness for new HIV interventions was high except for circumcision. These findings could be used for further planning of HIV prevention programmes for truckers in India. PMID:23852287
Prem Kumar, S.G.; Kumar, G. Anil; Poluru, Ramesh; Schneider, John A.; Dandona, Lalit; Vemu, Lakshmi; Sudha, T.; Mayer, Kenneth H.; Dandona, Rakhi
??This ethnographic dissertation research project examines HIV prevention programs in Warsaw, Poland to explore the concurrent processes of democratization and privatization as Poland begins European… (more)
Owczarzak, Jill Teresa
Background The burden of invasive pneumococcal disease in young children decreased dramatically following introduction of the 7-valent pneumococcal conjugate vaccine (PCV7). The epidemiology of S. pneumoniae now reflects infections caused by serotypes not included in PCV7. Recently introduced higher valency pneumococcal vaccines target the residual burden of invasive and non-invasive infections, including those caused by serotypes not included in PCV7. This review is based on presentations made at the European Society of Pediatric Infectious Diseases in June 2011. Discussion Surveillance data show increased circulation of the non-PCV7 vaccine serotypes 1, 3, 6A, 6C, 7?F and 19A in countries with routine vaccination. Preliminary evidence suggests that broadened serotype coverage offered by higher valency vaccines may be having an effect on invasive disease caused by some of those serotypes, including 19A, 7?F and 6C. Aetiology of community acquired pneumonia remains a difficult clinical diagnosis. However, recent reports indicate that pneumococcal vaccination has reduced hospitalisations of children for vaccine serotype pneumonia. Variations in serotype circulation and occurrence of complicated and non-complicated pneumonia caused by non-PCV7 serotypes highlight the potential of higher valency vaccines to decrease the remaining burden. PCVs reduce nasopharyngeal carriage and acute otitis media (AOM) caused by vaccine serotypes. Recent investigations of the interaction between S. pneumoniae and non-typeable H. influenzae suggest that considerable reduction in severe, complicated AOM infections may be achieved by prevention of early pneumococcal carriage and AOM infections. Extension of the vaccine serotype spectrum beyond PCV7 may provide additional benefit in preventing the evolution of AOM. The direct and indirect costs associated with pneumococcal disease are high, thus herd protection and infections caused by non-vaccine serotypes both have strong effects on the cost effectiveness of pneumococcal vaccination. Recent evaluations highlight the public health significance of indirect benefits, prevention of pneumonia and AOM and coverage of non-PCV7 serotypes by higher valency vaccines. Summary Routine vaccination has greatly reduced the burden of pneumococcal diseases in children. The pneumococcal serotypes present in the 7-valent vaccine have greatly diminished among disease isolates. The prevalence of some non-vaccine serotypes (e.g. 1, 7?F and 19A) has increased. Pneumococcal vaccines with broadened serotype coverage are likely to continue decreasing the burden of invasive disease, and community acquired pneumonia in children. Further reductions in pneumococcal carriage and increased prevention of early AOM infections may prevent the evolution of severe, complicated AOM. Evaluation of the public health benefits of pneumococcal conjugate vaccines should include consideration of non-invasive pneumococcal infections, indirect effects of vaccination and broadened serotype coverage. PMID:22954038
ABSTRACT Mucosal epithelial cell surface galactosylceramide (Galcer) has been postulated to be a receptor for HIV-1 envelope (Env) interactions with mucosal epithelial cells. Disruption of the HIV-1 Env interaction with such alternate receptors could be one strategy to prevent HIV-1 entry through the mucosal barrier. To study antibody modulation of HIV-1 Env-Galcer interactions, we used Galcer-containing liposomes to assess whether natural- and vaccine-induced monoclonal antibodies can block HIV-1 Env binding to Galcer. HIV-1 Env gp140 proteins bound to Galcer liposomes with Kds (dissociation constants) in the nanomolar range. Several HIV-1 ALVAC/AIDSVAX vaccinee-derived monoclonal antibodies (MAbs) specific for the gp120 first constant (C1) region blocked Galcer binding of a transmitted/founder HIV-1 Env gp140. Among the C1-specific MAbs that showed Galcer blocking, the antibody-dependent cellular cytotoxicity-mediating CH38 IgG and its natural IgA isotype were the most potent blocking antibodies. C1-specific IgG monoclonal antibodies that blocked Env binding to Galcer induced upregulation of the gp120 CD4-inducible (CD4i) epitope bound by MAb 17B, demonstrating that a conformational change in gp120 may be required for Galcer blocking. However, the MAb 17B itself did not block Env-Galcer binding, suggesting that the C1 antibody-induced gp120 conformational changes resulted in alteration in a Galcer binding site distant from the CD4i 17B MAb binding site. IMPORTANCE Galactosyl ceramide, a glycosphingolipid, has been postulated to be a receptor for the HIV-1 envelope glycoprotein (Env) interaction with mucosal epithelial cells. Here, we have mimicked this interaction by using an artificial membrane containing synthetic Galcer and recombinant HIV-1 Env proteins to identify antibodies that would block the HIV-1 Env-Galcer interaction. Our study revealed that a class of vaccine-induced human antibodies potently blocks HIV-1 Env-Galcer binding by perturbing the HIV-1 Env conformation. PMID:24920809
Dennison, S. Moses; Anasti, Kara M.; Jaeger, Frederick H.; Stewart, Shelley M.; Pollara, Justin; Liu, Pinghuang; Kunz, Erika L.; Zhang, Ruijun; Vandergrift, Nathan; Permar, Sallie; Ferrari, Guido; Tomaras, Georgia D.; Bonsignori, Mattia; Michael, Nelson L.; Kim, Jerome H.; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Pitisuttithum, Punnee; Rerks-Ngarm, Supachai; Liao, Hua-Xin
Background Human immunodeficiency virus type 1 (HIV-1) has infected more than 40 million people worldwide, mainly in sub-Saharan Africa. The high prevalence of HIV-1 subtype C in southern Africa necessitates the development of cheap, effective vaccines. One means of production is the use of plants, for which a number of different techniques have been successfully developed. HIV-1 Pr55Gag is a promising HIV-1 vaccine candidate: we compared the expression of this and a truncated Gag (p17/p24) and the p24 capsid subunit in Nicotiana spp. using transgenic plants and transient expression via Agrobacterium tumefaciens and recombinant tobamovirus vectors. We also investigated the influence of subcellular localisation of recombinant protein to the chloroplast and the endoplasmic reticulum (ER) on protein yield. We partially purified a selected vaccine candidate and tested its stimulation of a humoral and cellular immune response in mice. Results Both transient and transgenic expression of the HIV antigens were successful, although expression of Pr55Gag was low in all systems; however, the Agrobacterium-mediated transient expression of p24 and p17/p24 yielded best, to more than 1 mg p24/kg fresh weight. Chloroplast targeted protein levels were highest in transient and transgenic expression of p24 and p17/p24. The transiently-expressed p17/p24 was not immunogenic in mice as a homologous vaccine, but it significantly boosted a humoral and T cell immune response primed by a gag DNA vaccine, pTHGagC. Conclusion Transient agroinfiltration was best for expression of all of the recombinant proteins tested, and p24 and p17/p24 were expressed at much higher levels than Pr55Gag. Our results highlight the usefulness of plastid signal peptides in enhancing the production of recombinant proteins meant for use as vaccines. The p17/p24 protein effectively boosted T cell and humoral responses in mice primed by the DNA vaccine pTHGagC, showing that this plant-produced protein has potential for use as a vaccine. PMID:18573204
Meyers, Ann; Chakauya, Ereck; Shephard, Enid; Tanzer, Fiona L; Maclean, James; Lynch, Alisson; Williamson, Anna-Lise; Rybicki, Edward P
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-?, IL-6, IL-12, IL-15, IL-8, MCP-1, MIP-1?, MIP-1?, RANTES, IP-10, MIG, and IFN-?). 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-?, IL-2, TNF-?, MIP-1?, MIP-1?, 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
Climent, Núria; Guerra, Susana; García, Felipe; Rovira, Cristina; Miralles, Laia; Gómez, Carmen Elena; Piqué, Núria; Gil, Cristina; Gatell, José María; Esteban, Mariano; Gallart, Teresa
Biodistribution of DNA Plasmid Vaccines against HIV-1, Ebola, Severe Acute Respiratory Syndrome, or West Nile Virus Is Similar, without Integration, despite Differing Plasmid Backbones or Gene Inserts
The Vaccine Research Center has developed a number of vaccine candidates for different diseases/infectious agents (HIV-1, Severe Acute Respiratory Syndrome virus, West Nile virus, and Ebola virus, plus a plasmid cytokine adjuvant—IL-2/Ig) based on a DNA plasmid vaccine platform. To support the clinical development of each of these vaccine candidates, preclinical studies have been performed in mice or rabbits to determine where in the body these plasmid vaccines would biodistribute and how rapidly they would clear. In the course of these studies, it has been observed that regardless of the gene insert (expressing the vaccine immunogen or cytokine adjuvant) and regardless of the promoter used to drive expression of the gene insert in the plasmid backbone, the plasmid vaccines do not biodistribute widely and remain essentially in the site of injection, in the muscle and overlying subcutis. Even though ? 1014 molecules are inoculated in the studies in rabbits, by day 8 or 9(? 1 week postinoculation), already all but on the order of 104?106 molecules per microgram of DNA extracted from tissue have been cleared at the injection site. Over the course of 2 months, the plasmid clears from the site of injection with only a small percentage of animals (generally 10?20%) retaining a small number of copies (generally around 100 copies) in the muscle at the injection site. This pattern of biodistribution (confined to the injection site) and clearance (within 2 months) is consistent regardless of differences in the promoter in the plasmid backbone or differences in the gene insert being expressed by the plasmid vaccine. In addition, integration has not been observed with plasmid vaccine candidates inoculated i.m. by Biojector 2000 or by needle and syringe. These data build on the repeated-dose toxicology studies performed (see companion article, Sheets et al., 2006) to demonstrate the safety and suitability for investigational human use of DNA plasmid vaccine candidates for a variety of infectious disease prevention indications. PMID:16569729
Sheets, Rebecca L.; Stein, Judith; Manetz, T. Scott; Duffy, Chris; Nason, Martha; Andrews, Charla; Kong, Wing-Pui; Nabel, Gary J.; Gomez, Phillip L.
Background In the Step Study, the MRKAd5 HIV-1 gag/pol/nef vaccine did not lower post-infection plasma viremia, and HIV-1 incidence was higher in vaccine-treated than placebo-treated males with pre-existing adenovirus serotype 5 (Ad5) immunity. We evaluated vaccine-induced immunity and its potential contributions to infection risk. Methods To assess immunogenicity, HIV-specific T-cells were characterized ex vivo using validated IFN-? ELISpot and intracellular cytokine staining (ICS) assays, employing a case-cohort design. To determine effects of vaccine and pre-existing Ad5 immunity on infection risk, flow cytometric studies measured Ad5-specific T-cells and circulating activated (Ki67+/Bcl- 2lo) CD4+ T-cells expressing CCR5. Findings IFN-?-secreting HIV-specific T-cells (range, 163–686/106 PBMC) were detected ex vivo by ELISpot in 77% (258/354) of vaccinees; the majority recognized 2–3 HIV proteins. HIV- specific CD4+ T-cells were identified by ICS in 41%; ~85% expressed IL-2, and two-thirds of these co-expressed IFN-? and/or TNF-?. HIV-specific CD8+ T-cells (range, 0.4–1.0%) were observed in 73%, expressing predominantly either IFN-? alone or with TNF-?. No major differences were found in vaccine-induced HIV-specific immunity, including response rate, magnitude, and cytokine profile comparing vaccinated male cases (pre-infection) with non-cases. Interestingly, Ad5-specific T-cells were lower in cases than non-cases in several subgroup analyses. The percent circulating Ki67+Bcl-2lo/CCR5+ CD4+ T-cells did not differ between cases and non-cases. Interpretation Consistent with previous trials, the MrkAd5/HIV-1 gag/pol/nef vaccine was highly immunogenic for inducing HIV-specific CD8+ T-cells. Comparative analyses did not reveal differences in HIV-specific immunologic responses between cases and non-cases that explain the lack of vaccine efficacy and potential infection enhancement. If T-cell immunity is critical in vaccine-induced HIV protection, our findings suggest that future candidate vaccines must elicit responses that either exceed in magnitude or differ in breadth and/or function from those observed in this trial. Funding National Institute of Allergy and Infectious Diseases, U.S. National Institute of Health; Merck Research Laboratories PMID:19012957
McElrath, M. Juliana; De Rosa, Stephen C.; Moodie, Zoe; Dubey, Sheri; Kierstead, Lisa; Janes, Holly; Defawe, Olivier D.; Carter, Donald K.; Hural, John; Akondy, Rama; Buchbinder, Susan P.; Robertson, Michael N.; Mehrotra, Devan V.; Self, Steven G.; Corey, Lawrence; Shiver, John W.; Casimiro, Danilo R.
Nigeria is second in the world for the number of people with HIV and has a high rate of mother-to-child transmission (MTCT). Over 60% of births in Nigeria occur outside of health care facilities, and because of this, Traditional Birth Attendants (TBAs) play a significant role in maternal and child health. It is important that TBAs be knowledgeable about HIV prevention. The purpose of this study was to determine the impact of HIV testing and counseling (HTC) knowledge on the HIV prevention practices among TBAs in Nigeria. Five hundred TBAs were surveyed. Chi-square and logistic regression were used to assess differences in HIV prevention practices between TBAs with and without HTC knowledge. TBAs with HTC knowledge are significantly more likely to engage in HIV prevention practices than TBAs without HTC. Prevention practices included: wearing gloves during delivery (p < 0.01), sterilization of delivery equipment (p < 0.01), participation in blood safety training (p < 0.01), and disposal of sharps (p < 0.01). As long as a high percent of births occur outside health care facilities in Nigeria, there will be a need for TBAs. Providing TBAs with HTC training increases HIV prevention practices and can be a key to improve maternal and child health. PMID:25674783
Osuji, Alice; Pharr, Jennifer R; Nwokoro, Uche; Ike, Anulika; Ali, Christiana; Ejiro, Ogheneaga; Osuyali, John; Obiefune, Michael; Fiscella, Kevin; Ezeanolue, Echezona E
The National Institutes of Health (NIH/NIMH), the Centers for Disease Control and Prevention (CDC), and the HIV/AIDS Bureau of the Health Resources and Services Administration (HRSA) support the CDC's Serostatus Approach to Fighting the HIV Epidemic (SAFE; Janssen et al., 2001). One aim of the strategy is to help individuals living with HIV (and…
Gordon, Christopher M.; Forsyth, Andrew D.; Stall, Ron; Cheever, Laura W.
As of April 2003, 64,801 HIV cases have been documented in Vietnam (Policy Project 2003), 53.9% of which are among individuals 20-29 years of age. Although HIV education efforts have increased, there remains a need for proven effective programs. We present findings from a randomized-controlled effectiveness trial of an HIV prevention program for…
Kaljee, Linda M.; Genberg, Becky; Riel, Rosemary; Cole, Matthew; Tho, Le Huu; Thoa, Le Thi Kim; Stanton, Bonita; Li, Xiaoming; Minh, Tuong Tan
This article presents preliminary findings of a randomized HIV prevention study in Trinidad and Tobago in the Caribbean. The study centers on a family HIV workshop aimed at strengthening parenting skills that are empirically linked to reducing adolescent HIV exposure and other sexual risks. These skills include parental monitoring; educating youth…
Baptiste, Donna R.; Kapungu, Chisina; Miller, Steve; Crown, Laurel; Henry, David; Da Costa Martinez, Dona; Jo-Bennett, Karen
The estimated number of HIV cases in Asia now exceeds the "worst case" scenario envisioned by the World Bank in 1993. While prevention efforts have failed to contain the epidemic in other parts of the world, Asia's private sector has the resources to contain the epidemic if it acts quickly. In parts of Asia, work place-based medical and health services already exist, but, to date, efforts to gain the cooperation of business and industry in HIV prevention programs have led to disappointment. Businesses in Thailand, on the other hand, have begun a vigorous prevention campaign led by the Thailand Business Coalition on AIDS. The countries where the epidemic has not yet made a big impact (Japan, Korea, Hong Kong, Indonesia, Viet Nam, and the Philippines) are those where intervention could be most effective. Unfortunately, little corporate cooperation is occurring in these areas. Asian companies seem to fear contamination from the disease if they engage in prevention activities. Businesses in Asia have not faced the reality of the costs of AIDS which will rob companies of highly skilled workers who are expensive to replace, drive away foreign capital, and shrink the home market as people dedicate their resources to health care. While the impact of AIDS on businesses follows a tiered approach, all enterprises will eventually be affected adversely. The interrelated nature of Asia economies will also mean that even nations which are not experiencing the epidemic will feel its economic impact (for example, Japan will see its gross national product decrease because of trade losses caused by the epidemic in Thailand). Prevention efforts by businesses must be supported and encouraged by governments with financial and other incentives. Multinational corporations can have an effect on national companies as well as organize programs for their own employees. Because they depend upon longterm strategic thinking, Asian financial institutions are beginning to understand the role that businesses can play and the severity of the economic impact of AIDS. The private sector in Asia must act quickly, however, in order to be able to take advantage of the opportunity to contribute to the prevention of HIV infections. PMID:8642964
Kimball, A M; Thant, M
We used the simian immunodeficiency virus mac251 (SIVmac251) macaque model to study the effect of the dose of mucosal exposure on vaccine efficacy. We immunized macaques with a DNA prime followed by SIV gp120 protein immunization with ALVAC-SIV and gp120 in alum, and we challenged them with SIVmac251 at either a single high dose or at two repeated low-dose exposures to a 10-fold-lower dose. Infection was neither prevented nor modified following a single high-dose challenge of the immunized macaques. However, two exposures to a 10-fold-lower dose resulted in protection from SIVmac251 acquisition in 3 out of 12 macaques. The remaining animals that were infected had a modulated pathogenesis, significant downregulation of interferon responsive genes, and upregulation of genes involved in B- and T-cell responses. Thus, the choice of the experimental model greatly influences the vaccine efficacy of vaccines for human immunodeficiency virus (HIV). PMID:23325681
Vaccari, Monica; Keele, Brandon F.; Bosinger, Steven E.; Doster, Melvin N.; Ma, Zhong-Min; Pollara, Justin; Hryniewicz, Anna; Ferrari, Guido; Guan, Yongjun; Forthal, Donald N.; Venzon, David; Fenizia, Claudio; Morgan, Tia; Montefiori, David; Lifson, Jeffrey D.; Miller, Chris J.; Silvestri, Guido; Rosati, Margherita; Felber, Barbara K.; Pavlakis, George N.; Tartaglia, James
We used the simian immunodeficiency virus mac251 (SIV(mac251)) macaque model to study the effect of the dose of mucosal exposure on vaccine efficacy. We immunized macaques with a DNA prime followed by SIV gp120 protein immunization with ALVAC-SIV and gp120 in alum, and we challenged them with SIV(mac251) at either a single high dose or at two repeated low-dose exposures to a 10-fold-lower dose. Infection was neither prevented nor modified following a single high-dose challenge of the immunized macaques. However, two exposures to a 10-fold-lower dose resulted in protection from SIV(mac251) acquisition in 3 out of 12 macaques. The remaining animals that were infected had a modulated pathogenesis, significant downregulation of interferon responsive genes, and upregulation of genes involved in B- and T-cell responses. Thus, the choice of the experimental model greatly influences the vaccine efficacy of vaccines for human immunodeficiency virus (HIV). PMID:23325681
Vaccari, Monica; Keele, Brandon F; Bosinger, Steven E; Doster, Melvin N; Ma, Zhong-Min; Pollara, Justin; Hryniewicz, Anna; Ferrari, Guido; Guan, Yongjun; Forthal, Donald N; Venzon, David; Fenizia, Claudio; Morgan, Tia; Montefiori, David; Lifson, Jeffrey D; Miller, Chris J; Silvestri, Guido; Rosati, Margherita; Felber, Barbara K; Pavlakis, George N; Tartaglia, James; Franchini, Genoveffa
Background In 2011 an Investment Framework was proposed that described how the scale-up of key HIV interventions could dramatically reduce new HIV infections and deaths in low and middle income countries by 2015. This framework included ambitious coverage goals for prevention and treatment services resulting in a reduction of new HIV infections by more than half. However, it also estimated a leveling in the number of new infections at about 1 million annually after 2015. Methods We modeled how the response to AIDS can be further expanded by scaling up antiretroviral treatment (ART) within the framework provided by the 2013 WHO treatment guidelines. We further explored the potential contributions of new prevention technologies: ‘Test and Treat’, pre-exposure prophylaxis and an HIV vaccine. Findings Immediate aggressive scale up of existing approaches including the 2013 WHO guidelines could reduce new infections by 80%. A ‘Test and Treat’ approach could further reduce new infections. This could be further enhanced by a future highly effective pre-exposure prophylaxis and an HIV vaccine, so that a combination of all four approaches could reduce new infections to as low as 80,000 per year by 2050 and annual AIDS deaths to 260,000. Interpretation In a set of ambitious scenarios, we find that immediate implementation of the 2013 WHO antiretroviral therapy guidelines could reduce new HIV infections by 80%. Further reductions may be achieved by moving to a ‘Test and Treat’ approach, and eventually by adding a highly effective pre-exposure prophylaxis and an HIV vaccine, if they become available. PMID:25372770
Stover, John; Hallett, Timothy B.; Wu, Zunyou; Warren, Mitchell; Gopalappa, Chaitra; Pretorius, Carel; Ghys, Peter D.; Montaner, Julio; Schwartländer, Bernhard
The prevalence of HIV/AIDS infection among prisoners is 3 to 4 times higher than in the U.S. population. Given that one in seven HIV-positive Americans pass through a correctional facility every year, the criminal justice system is in an ideal position to aggressively implement effective HIV education, treatment, and prevention. This study examines barriers to the effective delivery of these services and evaluates differences in risk perception among nearly 600 female and male inmates. The results underscore gender differences in Perceived Risk of Seroconversion and Exposure to HIV Education, suggesting that jails should implement gender-specific HIV prevention programming. PMID:24659758
Alarid, Leanne Fiftal; Hahl, Jeannie M
Despite the growing body of research on faith-based human immunodeficiency virus (HIV) initiatives, there are few studies exploring the perspective of faith leaders involved in HIV prevention efforts. This exploratory study examined how 29 faith leaders conceptualized key aspects of HIV prevention. Sexual health beliefs, perspectives on condom distribution, and facilitating factors and barriers to implementing an HIV program were explored. Seventy-six percent of participants agreed with the statement "they would be willing to make condoms available to adolescents." These findings highlight the importance of reconciling any differences between religious doctrine, leadership role, and beliefs of faith leaders in addressing HIV in churches. PMID:23718961
Pichon, Latrice C; Williams, Terrinieka T; Campbell, Bettina
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
Kang, Ezer; Chin, John J.; Behar, Elana
IntroductionStable heterosexual HIV-1 serodiscordant couples in Africa have high HIV-1 transmission rates and are a critical population for evaluation of new HIV-1 prevention strategies. The Partners PrEP Study is a randomized, double-blind, placebo-controlled trial of tenofovir and emtricitabine-tenofovir pre-exposure prophylaxis to decrease HIV-1 acquisition within heterosexual HIV-1 serodiscordant couples. We describe the trial design and characteristics of the study cohort.MethodsHIV-1
Andrew Mujugira; Jared M. Baeten; Deborah Donnell; Patrick Ndase; Nelly R. Mugo; Linda Barnes; James D. Campbell; Jonathan Wangisi; Jordan W. Tappero; Elizabeth Bukusi; Craig R. Cohen; Elly Katabira; Allan Ronald; Elioda Tumwesigye; Edwin Were; Kenneth H. Fife; James Kiarie; Carey Farquhar; Grace John-Stewart; Lara Kidoguchi; Dana Panteleeff; Meighan Krows; Heena Shah; Jennifer Revall; Susan Morrison; Lisa Ondrejcek; Charlotte Ingram; Robert W. Coombs; Jairam R. Lingappa; Connie Celum; Claire Thorne
Early use of highly active antiretroviral treatment (ART) in people living with HIV for HIV prevention has gained legitimacy but remains controversial. Nineteen French HIV experts with diverse specializations (over half of whom were clinicians) were qualitatively interviewed on their views about ART irrespective of CD4 count of more than 500 cells/mm3 for purposes of HIV prevention, which is not systematically recommended in France. Content analysis identified 2 broad categories: individual considerations (subcategories: patient health and well-being; patient preparedness and choice) and collective considerations (subcategories:HIV transmission risk; impact on the epidemic; cost). Uncertainty surrounded many experts' considerations, and unity was lacking on key issues (eg, candidacy for early preventive treatment, expected clinical- and population-level effects). An umbrella theme labeled "Weighing the merits of early ART in the face of uncertainties was identified. Our analyses raise doubts about the current acceptability of widespread implementation of early ART for HIV prevention in France. PMID:23761218
Lebouché, Bertrand; Engler, Kim; Lévy, Joseph J; Gilmore, Norbert; Spire, Bruno; Rozenbaum, Willy; Lacene, Tinhinane; Routy, Jean-Pierre
In the continuing effort to develop effective HIV prevention methods for women, a vaginal ring containing the non-nucleoside reverse transcriptase inhibitor dapivirine is currently being tested in two safety and efficacy trials. This paper reviews dapivirine ring's pipeline development process, including efforts to determine safe and effective dosing levels as well as identify delivery platforms with the greatest likelihood of success for correct and consistent use. Dapivirine gel and other formulations were developed and tested in preclinical and clinical studies. Multiple vaginal ring prototypes were also tested, resulting in the current ring design as well as additional designs under consideration for future testing. Efficacy results from clinical trials are expected in 2015. Through ongoing consultations with national regulatory authorities, licensure requirements for dapivirine vaginal ring approval have been defined. This article is based on a presentation at the "Product Development Workshop 2013: HIV and Multipurpose Prevention Technologies," held in Arlington, Virginia on February 21-22, 2013. It forms part of a special supplement to Antiviral Research. PMID:24188702
Devlin, Bríd; Nuttall, Jeremy; Wilder, Susan; Woodsong, Cynthia; Rosenberg, Zeda
This study is a step towards a behavioral intervention to prevent HIV transmission among Chinese internal migrants. To explore important and changeable determinants of condom use and inspect effective and feasible methods to increase condom use for the target population, we conducted a three-round web-based Delphi study among a panel of 62 experts between October 2012 and March 2013. The panelists were purposely selected using a stepwise procedure to represent topic-related areas of expertise. The response rate per round ranges from 21% to 81%. The panelists identified 19 possible determinants of condom use and reported 16 intervention methods they considered successful. They agreed that attitude towards condom use was the most important and changeable determinant, while applying behavioral theory, increasing sexual education and condom access, performing worksite health promotion, detecting risk factors, and working closely with relevant organizations and the government were effective and feasible methods to increase condom use among internal migrants in China. In conclusion, results of this study highlight the importance of attitude in changing condom use and underscore the need to apply behavior theory and integrate multiple educational approaches for developing behavioral HIV prevention interventions targeting internal migrants in China. PMID:25610903
Erasmus, Vicki; Sun, Xinying; Shi, Yuhui; Richardus, Jan Hendrik
Summary Vaccines are among the greatest successes in the history of public health. However, past strategies for vaccine development are unlikely to succeed in the future against major global diseases such as AIDS, TB, and malaria. For such diseases, the correlates of protection are poorly defined and the pathogens evade immune detection and/or exhibit extensive genetic variability. Recent advances have heralded in a new era of vaccine discovery. However, translation of these advances into vaccines remains impeded by lack of understanding of key vaccinology principles in humans. We review these advances towards vaccine discovery and suggest that for accelerating successful vaccine development, new human immunology-based clinical research initiatives be implemented with the goal of elucidating and more effectively inducing vaccine-induced protective immune responses. PMID:23723240
Koff, Wayne C; Burton, Dennis R.; R.Johnson, Philip; Walker, Bruce D.; King, Charles R.; Nabel, Gary J.; Ahmed, Rafi; Bhan, Maharaj Kishan; Plotkin, Stanley A.
Successes in preventing HIV transmission among substance using populations have focused primarily among injection drug users, which have produced measurable reductions in HIV incidence and prevalence. By contrast, the majority of substances used worldwide are administered by non-injectable means, and there is a dearth of HIV prevention interventions that target non-injecting substance users. Increased surveillance of trends in substance use, especially cocaine (including crack) and methamphetamine in addition to new and emerging substances (e.g., synthetic cannabinoids, cathinones and other amphetamine analogs) are needed to develop and scale-up effective and robust interventions for populations at risk for HIV-transmission via sexual behaviors related to non-injection substance use. Strategies are needed that address unique challenges to HIV prevention for substance users who are HIV-infected and those who are HIV- uninfected and at high risk. We propose a research agenda that prioritizes: (1) ) combination HIV prevention strategies in substance users; (2) behavioral HIV prevention programs that reduce sexual transmission behaviors in non-treatment seeking individuals; (3) medical and/or behavioral treatments for substance abuse that reduce/eliminate substance-related sexual transmission behaviors; and (4) structural interventions to reduce HIV incidence. PMID:23764632
Shoptaw, Steve; Montgomery, Brooke; Williams, Chyvette T.; El-Bassel, Nabila; Aramrattana, Apinun; Metzger, David S.; Kuo, Irene; Bastos, Francisco I.; Strathdee, Steffanie A.
Background Patients with Tuberculosis (TB) are a vulnerable group for acquiring HIV infection. Therefore, countries with a concentrated HIV epidemic and high prevalence of TB should provide adequate information about HIV prevention to TB patients. Methods We conducted a cross-sectional study to evaluate the level of knowledge on HIV prevention and transmission among newly diagnosed TB patients in Lima, Peru. The survey evaluated knowledge about HIV infection and prevention and was administered before HIV counseling and blood sampling for HIV testing were performed. Results A total of 171 TB patients were enrolled; mean age was 31.1 years, 101 (59%) were male. The overall mean level of knowledge of HIV was 59%; but the specific mean level of knowledge on HIV transmission and prevention was only 33.3% and 41.5%, respectively. Age and level of education correlated with overall level of knowledge in the multivariate model (P-value: 0.02 and <0.001 respectively). Conclusions The study shows inadequate levels of knowledge about HIV transmission and prevention among newly-diagnosed TB patients in this setting, and underscores the need for implementing educational interventions in this population. PMID:24373517
This book explores the power of educators to serve as HIV and AIDS prevention agents. The definitive text represents the work of a distinguished panel of teacher educators and health scientists who identify core information and skills effective educators of HIV and AIDS prevention should learn as they prepare to attend to the academic and human…
Paradigm Publishers, 2006
We adapted a U.S. HIV prevention program to address knowledge gaps and cultural pressures that increase the risk of infection in adolescent Ghanaian girls. The theory-based nine-module HIV prevention program combines didactics and games, an interactive computer program about sugar daddies, and tie-and-dye training to demonstrate an economic…
Fiscian, Vivian Sarpomaa; Obeng, E. Kwame; Goldstein, Karen; Shea, Judy A.; Turner, Barbara J.
A peer-led HIV prevention initiative, based on a diffusion of innovation model, was developed for gay men attending gyms in central London. Peer educators were recruited from people who used the gym regularly according to standard selection criteria. After initial training, peer educators agreed to talk to gay men at their gym about HIV prevention, focusing on sexual risk and
J. Elford; L. Sherr; G. Bolding; F. Serle; M. Maguire
Since 1999, the Centers for Disease Control and Prevention have trained over 10,000 service providers from more than 5,000 agencies to implement evidence-based HIV prevention interventions through its Diffusion of Effective Behavioral Interventions DEBI) program. Based on in-depth, semistructured interviews with a convenience sample of 22 HIV…
Owczarzak, Jill; Dickson-Gomez, Julia
Purpose – This study seeks to explore the perspectives of young women in Uganda with the aim of better informing re HIV prevention. Design\\/methodology\\/approach – Group discussions and interviews were used to explore issues relating to HIV prevention. An inductive content analysis identified emerging themes and patterns in the participants' conversations. Findings – The study revealed that, although young women
Background With the failure of the latest vaccine trial, HVTN-505, HIV prevention efforts remain critical. Social and structural factors contributing to HIV and STI transmission include stigma regarding sexual violence, HIV infection and sexual orientation. For instance, HIV prevention and overall sexual health programs in Peru have been implemented yet key populations of youth (sex workers, male and transgender youth) continue to be overrepresented in new cases of HIV and STI. This suggests that interventions must take new directions and highlights the need for additional research. Discussion While interdisciplinary, international research collaborations often are indicated as best practice in developing new knowledge in global health and an important component of the leadership in health systems, this does not mean they are free of challenges. In this debate we document our reflections on some of the challenges in developing an interdisciplinary and international research team to understand HIV and STI prevention priorities among youth in two culturally diverse cities in Peru: Lima, the capital city, and Ayacucho, in the Andean region. Summary Rather than offering solutions we aim to contribute to the debate about the object and purpose of global health research in the context of developing international research partnerships that genuinely promote a reciprocal and bidirectional flow of knowledge between the Global South and the Global North, and researchers at intersections of these locations. PMID:24886493
HIV prevention trials have demonstrated the effectiveness of a number of behavioral and biomedical interventions. HIV prevention packages are combinations of interventions and offer potential to significantly increase the effectiveness of any single intervention. Estimates of the effectiveness of prevention packages are important for guiding the development of prevention strategies and for characterizing effect sizes before embarking on large scale trials. Unfortunately, most research to date has focused on testing single interventions rather than HIV prevention packages. Here we report the results from agent-based modeling of the effectiveness of HIV prevention packages for men who have sex with men (MSM) in South Africa. We consider packages consisting of four components: antiretroviral therapy for HIV infected persons with CD4 count <350; PrEP for high risk uninfected persons; behavioral interventions to reduce rates of unprotected anal intercourse (UAI); and campaigns to increase HIV testing. We considered 163 HIV prevention packages corresponding to different intensity levels of the four components. We performed 2252 simulation runs of our agent-based model to evaluate those packages. We found that a four component package consisting of a 15% reduction in the rate of UAI, 50% PrEP coverage of high risk uninfected persons, 50% reduction in persons who never test for HIV, and 50% ART coverage over and above persons already receiving ART at baseline, could prevent 33.9% of infections over 5 years (95% confidence interval, 31.5, 36.3). The package components with the largest incremental prevention effects were UAI reduction and PrEP coverage. The impact of increased HIV testing was magnified in the presence of PrEP. We find that HIV prevention packages that include both behavioral and biomedical components can in combination prevent significant numbers of infections with levels of coverage, acceptance and adherence that are potentially achievable among MSM in South Africa. PMID:25398143
Brookmeyer, Ron; Boren, David; Baral, Stefan D.; Bekker, Linda- Gail; Phaswana-Mafuya, Nancy; Beyrer, Chris; Sullivan, Patrick S.
Despite advances in HIV prevention and care, African American and Latino Americans remain at much higher risk of acquiring HIV, are more likely to be unaware of their HIV-positive status, are less likely to be linked to and retained in care, or to have suppressed viral load than are Whites. The first National HIV/AIDS Strategy (NHAS) has reducing these disparities as one of its three goals by encouraging the implementation of combination high impact HIV intervention strategies. Federal agencies have expanded their collaborations in order to decrease HIV-related disparities by: better implementation of data-driven decision-making; integration and consolidation of the continuum of HIV care; and the reorganization of relationships among public health agencies, researchers, community-based organizations (CBO), and HIV advocates. Combination Prevention, the integration of evidence-based and impactful behavioral, biomedical, and structural intervention strategies to reduce HIV incidence, provides the tools to address the HIV epidemic. Unfortunately, health disparities exist at every step along the HIV testing-to-care continuum. This provides an opportunity and a challenge to everyone involved in HIV prevention and care to understand and address health disparities as integral to ending the HIV epidemic in the U.S. To further reduce health disparities, successful implementation of NHAS and combination prevention strategies will require multi-disciplinary teams, including psychologists with diverse cultural backgrounds and experiences, to successfully engage groups at highest risk for HIV and those already HIV-infected. In order to utilize the comprehensive care continuum, psychologists and behavioral scientists have a role to play in re-conceptualizing the continuum of care, conducting research to address health disparities, and creating community mobilization strategies. PMID:23688091
Grossman, Cynthia I.; Purcell, David W.; Rotheram-Borus, Mary Jane; Veniegas, Rose
Human immunodeficiency virus type 1 (HIV-1) vaccines that elicit protective antibody responses at mucosal sites would be highly desirable. Here, we report that intramuscular immunization of candidate HIV-1 vaccine vectors and purified Env proteins elicited potent and durable humoral immune responses in colorectal mucosa in rhesus monkeys. The kinetics, isotypes, functionality, and epitope specificity of these mucosal antibody responses were similar to those of peripheral responses in serum. These data suggest a close immunological relationship between mucosal and systemic antibody responses following vaccination in primates. PMID:25210178
Li, Hualin; Stephenson, Kathryn E.; Kang, Zi Han; Lavine, Christy L.; Seaman, Michael S.
The term "expatriates" refers to professionals and their families who live abroad for several months or years. Owing to potential prolonged exposure, and living conditions that may be closer to those of the local population, they are at higher risk of acquiring infectious diseases that are endemic in their new place of residence. They often have reduced access to medical services, putting them at higher risk of complications and more severe outcomes. Vaccination is probably one of the most effective means of preventing expatriates from acquiring endemic or epidemic diseases. Incapacitation or sickness in the field may cause serious disruption to project activities and impose an extra workload on the local team. It may also result in repatriation, with further extra direct and indirect costs for the organization. Predeparture advice and preparation, to promote risk reduction behavior, coupled with adequate support in the field are key ingredients to ensure effective and successful activities of collaborators. Institutions and organizations sending expatriates to developing countries have a clear responsibility, and it is in their own interests to promote the health of their employees working abroad. PMID:16225806
Dijkstra, Jan A; Chappuis, François; Loutan, Louis
The immune-correlate analysis of the RV144 clinical trial revealed that human plasma IgA immune responses elicited by the RV144 vaccine correlated positively with a risk for HIV acquisition. This result once again emphasized that HIV vaccines can potentially have adverse effects leading to enhancement of infection. Here, we discuss previously reported evidence of antibody-dependent enhancement of HIV infection. We also describe how a structure-based epitope-specific sieve-analysis can be employed to mine the molecular mechanism underlying this phenomenon. PMID:25483466
Shmelkov, Evgeny; Nadas, Arthur; Cardozo, Timothy
The effect of attenuated Histomonas meleagridis on pullets was investigated and the protection of vaccinated adult laying hens against a severe challenge was studied in the same experimental setting. Four groups of 25 pullets were set up at 18 weeks of life and birds in two groups were vaccinated with in vitro-attenuated H. meleagridis. Chickens in two groups (vaccinated and non-vaccinated) were challenged 5 weeks later with virulent histomonads, while the remaining groups were retained until termination of the study 11 weeks post vaccination. Vaccination of pullets did not have any impact on their subsequent performance. Egg production of non-vaccinated but challenged birds dropped significantly (P ? 0.05) between 2 and 4 weeks post challenge (p.c.) to 58.7%, compared with 90% in control chickens. At 4 weeks p.c., the drop in egg production in vaccinated and challenged birds was significantly lower (P=0.02) than in non-protected layers. Pathological changes were found only in challenged birds 2 and 6 weeks p.c. Several non-vaccinated birds showed severe lesions in the caeca with sporadic involvement of the liver and atrophy of the reproductive tract. Vaccination prior to challenge reduced the incidence of pathological findings. For the first time, vaccination of pullets with in vitro-attenuated histomonads could be shown to be an effective and safe prophylactic tool to prevent a severe drop in egg production of commercial layers following experimental infection. PMID:23391185
Liebhart, D; Sulejmanovic, T; Grafl, B; Tichy, A; Hess, M
Study Design A randomized, double-blind, placebo controlled phase I trial. Methods The trial was conducted in 32 HIV-uninfected healthy volunteers to assess the safety and immunogenicity of prime-boost vaccination regimens with either 2 doses of ADVAX, a DNA vaccine containing Chinese HIV-1 subtype C env gp160, gag, pol and nef/tat genes, as a prime and 2 doses of TBC-M4, a recombinant MVA encoding Indian HIV-1 subtype C env gp160, gag, RT, rev, tat, and nef genes, as a boost in Group A or 3 doses of TBC-M4 alone in Group B participants. Out of 16 participants in each group, 12 received vaccine candidates and 4 received placebos. Results Both vaccine regimens were found to be generally safe and well tolerated. The breadth of anti-HIV binding antibodies and the titres of anti-HIV neutralizing antibodies were significantly higher (p<0.05) in Group B volunteers at 14 days post last vaccination. Neutralizing antibodies were detected mainly against Tier-1 subtype B and C viruses. HIV-specific IFN-? ELISPOT responses were directed mostly to Env and Gag proteins. Although the IFN-? ELISPOT responses were infrequent after ADVAX vaccinations, the response rate was significantly higher in group A after 1st and 2nd MVA doses as compared to the responses in group B volunteers. However, the priming effect was short lasting leading to no difference in the frequency, breadth and magnitude of IFN-?ELISPOT responses between the groups at 3, 6 and 9 months post-last vaccination. Conclusions Although DNA priming resulted in enhancement of immune responses after 1st MVA boosting, the overall DNA prime MVA boost was not found to be immunologically superior to homologous MVA boosting. Trial Registration Clinical Trial Registry CTRI/2009/091/000051 PMID:23418465
Mehendale, Sanjay; Thakar, Madhuri; Sahay, Seema; Kumar, Makesh; Shete, Ashwini; Sathyamurthi, Pattabiraman; Verma, Amita; Kurle, Swarali; Shrotri, Aparna; Gilmour, Jill; Goyal, Rajat; Dally, Len; Sayeed, Eddy; Zachariah, Devika; Ackland, James; Kochhar, Sonali; Cox, Josephine H.; Excler, Jean-Louis; Kumaraswami, Vasanthapuram; Paranjape, Ramesh; Ramanathan, Vadakkuppatu Devasenapathi
The informed consent process (ICP) for HIV vaccine trials poses unique challenges and would benefit from improvements to its historically based structure and format. Here, we propose a theoretical framework that provides a basis for systematically evaluating and addressing these challenges. The proposed framework follows a linear pathway, starting with the precondition of voluntariness, three main variables of valid decision-making (competency, provision of information and understanding) and then the consequential outcome of either refusal or consent to participate. The existing literature reveals that culturally appropriate provision of information and resultant understanding by the vaccine trial participant are among the most significant factors influencing the authenticity of valid decision-making, though they may be overridden by other considerations, such as individual altruism, mistrust, and HIV-related stigma. Community collaborations to foster bidirectional transmission of information and more culturally tailored consenting materials, therefore, represent a key opportunity to enhance the ICP. By providing a visual synopsis of the issues most critical to IC effectiveness in a categorical and relational manner, the framework provided here presents HIV vaccine researchers a tool by which the ICP can be more systematically evaluated and consequently improved. PMID:24865892
Lewis, Cindi A; Dewhurst, Stephen; McMahon, James M; Bunce, Catherine A; Keefer, Michael C; Alio, Amina P
In 2004, parliamentarians from 12 countries in West and Central Africa created a template for legislation aimed at protecting the rights of people with HIV and stemming rising HIV infection rates by criminalizing HIV transmission. Since then, the template has been adopted as national law in 15 African countries, including Burkina Faso in 2008. The Burkina Faso law offers a number of protections for people with HIV, such as confidentiality of HIV test results, and holds the government accountable for providing health services for people with HIV and education about HIV in schools. However, other articles in the law, which criminalize HIV transmission and mandate disclosure of HIV status, may contribute to violations of the human rights of women and men with HIV. This article reviews the two cases brought in Burkina Faso under the 2008 HIV law to date, both against women, and explores the implications of specific elements of the legislation. It recommends that Burkina Faso use guidance provided by UNAIDS and the Southern Africa Development Community to repeal harmful articles in the HIV-specific legislation and implement the positive provisions. Prioritizing HIV prevention over punishment is the best way to respect the rights of people living with HIV and AIDS. PMID:19962648
Sanon, Patrice; Kaboré, Simon; Wilen, Jennifer; Smith, Susanna J; Galvão, Jane
We studied HIV prevalence and risk factors for HIV infection among fertile women in Luanda for the purposes of obtaining background data for planning of interventions as well as to look into the association of armed conflicts and HIV prevalence in sub-Saharan Africa. The HIV-1 prevalence was 1.7% in an antenatal care group (n = 517) and 1.9% in a family planning group (n = 518). Socioeconomic and sexual background factors did not significantly differ HIV-positive from HIV-negative women. Data on armed conflict factors were matched with HIV prevalence figures among pregnant women in sub-Saharan Africa. The level of armed conflicts was found to be inversely related to HIV prevalence. The low HIV seroprevalence in Luanda is in sharp contrast to the capitals of neighbouring countries. While the spread of HIV may have been hampered by the long armed conflict in the country, it is feared to increase rapidly with the return of soldiers and refugees in a post-war situation. The challenge for preventive actions is urgent. This example may be relevant to other areas with a recent end-of-war situation. PMID:17623504
Strand, R T; Fernandes Dias, L; Bergström, S; Andersson, S
Through the current analysis, we aimed to better understand the relationship between congregational support and HIV prevention behaviors among a sample of high risk, HIV negative Black women. Participants were 434 Black women who were at high risk for contracting HIV through heterosexual sex. They were recruited from a city in the Mid Atlantic Region. Data were collected through face-to-face interviews and Audio-Computer-Assisted Self-Interviews (ACASI). Results revealed three congregational characteristics were important for Black women's comfort level discussing HIV and their likelihood of returning for their HIV test results: feeling loved by their congregation, having ministries that helped people with their problems and feeling listened to by their congregation. Thus, religious congregational support was a significant correlate of Black women's comfort discussing HIV prevention and treatment as well as their motivation to return to get their HIV test results. PMID:25435597
Williams, Terrinieka T; Pichon, Latrice C; Latkin, Carl A; Davey-Rothwell, Melissa
Creation of a successful HIV vaccine will require the development of a strategy to generate cellular immunity with sufficient cross-clade breadth to deal with the extreme genetic diversity of the virus. Polyvalent mosaic immunogens derived from in silica recombination of natural strains of HIV are designed to induce cellular immune responses that maximally cover the sequence diversity of circulating virus isolates. Immunization of rhesus monkeys with plasmid DNA and recombinant vaccinia virus vaccine constructs expressing either consensus immunogens or polyvalent mosaic immunogens elicited a CD4+ T lymphocyte-biased response with comparably broad epitope-specific total T lymphocyte specificities. However, immunization with the mosaic immunogens induced HIV-specific CD8+ T lymphocyte responses with markedly greater depth and breadth. Therefore, the use of polyvalent mosaic immunogens is a promising strategy for a global vaccine for HIV.
Fischer, Will [Los Alamos National Laboratory; Korber, Bette [Los Alamos National Laboratory
Federal HIV prevention strategy seeks to increase efforts by health care providers to identify and reduce their HIV-positive patients’ transmission-related behaviors. Implementation of these recommendations will be hindered if providers perceive these efforts have the potential to harm their relationships with patients. Because transmission-related behaviors (unsafe sex and sharing needles) and the related issues of drug and alcohol use also jeopardize the health of HIV-positive patients, providers can use patient-centered counseling when addressing those behaviors. We suggest efforts to increase provider-delivered transmission-prevention counseling be reframed so that “prevention with positives” includes the goal of protecting HIV-positive patients’ health. We review the specific consequences of these risky behaviors on HIV-positive patients’ health and review brief counseling strategies appropriate for HIV care providers. PMID:16426152
GERBERT, BARBARA; DANLEY, DALE W.; HERZIG, KAREN; CLANON, KATHLEEN; CICCARONE, DANIEL; GILBERT, PAUL; ALLERTON, MICHAEL
Background We explored rural African American youths' perceptions about the role of community social institutions in addressing HIV. Methods We conducted four focus groups with African Americans aged 16 to 24 years in two rural counties in North Carolina. Groups were stratified by gender and risk status. We used a grounded theory approach to content analysis. Results Participants identified four social institutions as primary providers of HIV-related health promotion efforts: faith organizations, schools, politicians, and health agencies. They reported perceiving a lack of involvement in HIV prevention by faith-based organizations, constraints of abstinence-based sex education policies, politicians' lack of interest in addressing broader HIV determinants, and inadequacies in health agency services, and viewed all of these as being counter-productive to HIV prevention efforts. Conclusions youth have important insights about local social institutions that should be considered when designing HIV prevention interventions that partner with local organizations. PMID:20453373
Youmans, Selena; Lloyd, Stacy W.; Coker-Appiah, Dionne S.; Banks, Bahby; Blumenthal, Connie; Albritton, Tashuna; Ellison, Arlinda; Smith, Giselle Corbie; Adimora, Adaora A.
The Children's Vaccine Initiative (CVI), which was founded after the World Summit for Children held in New York in September 1990, had three goals: 1) immunization of all children; 2) research to determine the feasibility of a single-dose multivalent vaccine; and 3) introduction of new vaccines for infectious diseases. UNICEF, UNDP, WHO, the World Bank, and the Rockefeller Foundation co-sponsored the CVI. The following has been achieved since 1990: 1) coverage with 6 EPI vaccines has risen above 80% in many countries; 2) the number of vaccines in the research pipeline has increased; 3) there is better planning of the global vaccine supply; and 4) governments of developing countries are assuming more responsibility for national immunization. The new strategic plan for CVI, which is the work of experts from government, industry, and international organization, establishes the following goals: 1) development of greater consensus on priorities regarding vaccine development and application; 2) definition of needs and strategies for action; 3) communication of the health and economic value of vaccines; and 4) mobilization of resources. Executive Secretary Dr. Lee and CVI coordinator Roy Widdus are responsible for the new role for CVI. 4 million children die annually from diseases preventable by existing vaccines; another 8 million die annually from diseases that could be prevented by new vaccines. Measles, hepatitis B, and Hib vaccines are underused. Vaccines against rotavirus diarrhea and pneumococcal pneumonia should be available soon, while research continues on vaccines against malaria and HIV. PMID:12348372
Targeted delivery of vaccine candidates to the gastrointestinal (GI) tract holds potential for mucosal immunization, particularly against mucosal pathogens like the human immunodeficiency virus (HIV). Among the different strategies for achieving targeted release in the GI tract, namely the small intestine, pH sensitive enteric coating polymers have been shown to protect solid oral dosage forms from the harsh digestive environment of the stomach and dissolve relatively rapidly in the small intestine by taking advantage of the luminal pH gradient. We developed an enteric polymethacrylate formulation for coating hydroxy-propyl-methyl-cellulose (HPMC) capsules containing lyophilized Adenoviral type 5 (Ad5) vectors expressing HIV-1 gag and a string of six highly-conserved HIV-1 envelope peptides representing broadly cross-reactive CD4+ and CD8+ T cell epitopes. Oral immunization of rhesus macaques with these capsules primed antigen-specific mucosal and systemic immune responses and subsequent intranasal delivery of the envelope peptide cocktail using a mutant cholera toxin adjuvant boosted cellular immune responses including, antigen-specific intracellular IFN-?-producing CD4+ and CD8+ effector memory T cells in the intestine. These results suggest that the combination of oral adenoviral vector priming followed by intranasal protein/peptide boosting may be an effective mucosal HIV vaccination strategy for targeting viral antigens to the GI tract and priming systemic and mucosal immunity. PMID:18063450
Mercier, George T.; Nehete, Pramod N.; Passeri, Marco F.; Nehete, Bharti N.; Weaver, Eric A.; Templeton, Nancy Smyth; Schluns, Kimberly; Buchl, Stephanie S.; Sastry, K. Jagannadha; Barry, Michael A.
Subjects Twenty vertically HIV-infected children, 6–16 years of age, with stable viral load control and CD4+ values above 400 cells/mm3. Intervention Ten subjects continued their ongoing antiretroviral treatment (ART, Group A) and 10 were immunized with a HIV-DNA vaccine in addition to their previous therapy (ART and vaccine, Group B). The genetic vaccine represented HIV-1 subtypes A, B and C, encoded Env, Rev, Gag and RT and had no additional adjuvant. Immunizations took place at weeks 0, 4 and 12, with a boosting dose at week 36. Monitoring was performed until week 60 and extended to week 96. Results Safety data showed good tolerance of the vaccine. Adherence to ART remained high and persistent during the study and did not differ significantly between controls and vaccinees. Neither group experienced either virological failure or a decline of CD4+ counts from baseline. Higher HIV-specific cellular immune responses were noted transiently to Gag but not to other components of the vaccine. Lymphoproliferative responses to a virion antigen HIV-1 MN were higher in the vaccinees than in the controls (p?=?0.047), whereas differences in reactivity to clade-specific Gag p24, RT or Env did not reach significance. Compared to baseline, the percentage of HIV-specific CD8+ lymphocytes releasing perforin in the Group B was higher after the vaccination schedule had been completed (p?=?0.031). No increased CD8+ perforin levels were observed in control Group A. Conclusions The present study demonstrates the feasibility, safety and moderate immunogenicity of genetic vaccination in vertically HIV-infected children, paving the way for amplified immunotherapeutic approaches in the pediatric population. Trial registration clinicaltrialsregister.eu _2007-002359-18IT PMID:24312194
Palma, Paolo; Romiti, Maria Luisa; Montesano, Carla; Santilli, Veronica; Mora, Nadia; Aquilani, Angela; Dispinseri, Stefania; Tchidjou, Hyppolite K.; Montano, Marco; Eriksson, Lars E.; Baldassari, Stefania; Bernardi, Stefania; Scarlatti, Gabriella
Although HIV information is widely available in this country, little is known about how commonly used HIV prevention activities reach persons at highest risk for HIV. In this paper, we describe the extent to which HIV prevention strategies reach a sample of high-risk persons and whether such exposure correlates with having been tested for HIV. Data are from the 2000 HIV Testing Survey, an anonymous interview study of men who have sex with men (MSM), injection drug users (IDU), and high-risk heterosexuals (HRH), recruited from appropriate venues in seven states and New York City. We report the proportion of persons exposed to three types of interventions: information (media messages, brochures), counseling or skills-building (group counseling, role play, calling an AIDS hotline), and prevention supplies (provision of condoms, bleach kits), stratified by HIV testing status (ever, never). Exposure to information interventions was high among 2491 respondents (85%-96%) and did not differ by testing status. Use of counseling or skills-building interventions varied by testing status for IDU (8% untested versus 41% tested, p < 0.01) and HRH (14% versus 20%, p = 0.03) but not MSM (15% versus 23%, p = 0.08). Among tested IDU, those receiving bleach kits were more likely to report consistent bleach use when injecting with nonsterile needles (25% versus 9%, p = 0.003). Exposure to HIV prevention information is high but exposure to counseling or skills-building interventions is less common and more prevalent among those previously tested. Prevention initiatives should focus on counseling and testing, skills-building, and prevention supplies. PMID:16789852
Kellerman, Scott E; Drake, Amy; Lansky, Amy; Klevens, R Monina
Gay bathhouses (including sex clubs) contributed to HIV prevention from the early days of the AIDS epidemic, but the extent to which prevention interventions are implemented in bathhouses is unknown. Using telephone survey methodology, bathhouse managers provided data about HIV prevention in their bathhouses. All the bathhouses provided free condoms, and nearly all displayed educational posters in public areas and had informational pamphlets available for patrons. A few of the bathhouses offered outreach services and counseling services. Almost all promoted HIV/STI testing (which included providing information about where to get tested), and 75.5% had HIV testing programs in their venues. Most of the HIV testing programs were started during the previous 5 years, initiated by the bathhouse management or a community agency and operated by community-based agencies. About a third of the programs offered rapid HIV testing. The results of the telephone survey revealed that all the bathhouses engaged in prevention and many offered a wide range of prevention services, suggesting that managers have embraced the issue of HIV and collaborated in bringing prevention to high-risk men. The absence of studies evaluating these prevention efforts remains a concern and an obstacle to efficient use of prevention resources. PMID:21406994
Woods, William J.; Euren, Jason; Pollack, Lance M.; Binson, Diane
Recent FDA approval of tenofovir-emtricitabine for prevention of human immunodeficiency virus (HIV) as a form of pre-exposure prophylaxis (PrEP) has led to concern about implementation of this strategy. Fifty years ago, a very similar national and international debate occurred when the oral contraceptive pill ("the Pill" or "OCP") was approved. Contentious issues included OCP safety, cost, and the potential impact on sexual behavior--many of the same concerns being voiced currently about PrEP. In this article, we review the social and medical history of OCP, drawing parallels with the current PrEP debate. We also explore the key areas where PrEP differs from its forbear: lower efficacy, presence of drug resistance, and a more circumscribed (and marginalized) target population. A thoughtful approach to PrEP implementation, bearing in mind the historical insights gained from the 1960s, might serve as well as we begin this new chapter in the control of the HIV epidemic. PMID:23408681
Myers, Julie E; Sepkowitz, Kent A
Background: Four observational studies and one clinical trial have suggested that influenza vaccination is associated with a >50% reduction in risk of cardiac sudden death, myocardial infarction (MI), and stroke. One observational study found no effect. Objective: To identify an association between influenza or pneumococcal vaccination and myocardial infarction. Methods: We conducted a case-control study of discharges from nine metropolitan
David G. Meyers; D. David Beahm; Peter D. Jurisich; Christopher J. Milford
Background Induction of HIV-1-specific CD4+ T cell responses by therapeutic vaccination represents an attractive intervention to potentially increase immune control of HIV-1. Methods We performed a double-blinded, randomized, placebo-controlled clinical trial to determine the safety and immunogenicity of GSK Biologicals' HIV-1 gp120/NefTat subunit protein vaccine formulated with the AS02A adjuvant in subjects with well controlled chronic HIV-1 infection on HAART. Ten individuals received the vaccine; while adjuvant alone or placebo was given to five subjects each. Immunogenicity was monitored by intracellular cytokine flow cytometry and CFSE-based proliferation assays. Results The vaccine was well tolerated with no related SAEs. Vaccine recipients had significantly stronger gp120-specific CD4+ T cell responses which persisted until week 48 and greater gp120-specific CD4+ T cell proliferation activity as compared to controls. In the vaccine group, the number of participants that demonstrated positive responses for both gp120-specific CD4+ T cell IL-2 production and gp120-specific CD8+ T cell proliferation was significantly higher at week 6. Conclusions The gp120/NefTat/AS02A vaccine induced strong gp120-specific CD4+ T cell responses, and a higher number of vaccinees developed both HIV-1-specific CD4+ T cell responses and CD8+ T cell proliferation. The induction of these responses may be important in enhancing immune-mediated viral control. PMID:21963936
Lichterfeld, Mathias; Gandhi, Rajesh T.; Simmons, Rachel P.; Flynn, Teresa; Sbrolla, Amy; Yu, Xu G.; Basgoz, Nesli; Mui, Stanley; Williams, Katie; Streeck, Hendrik; Burgett-Yandow, Nicole; Roy, Gilbert; Janssens, Michel; Pedneault, Louise; Vandepapelière, Pierre; Koutsoukos, Marguerite; Demoitié, Marie-Ange; Bourguignon, Patricia; McNally, Lisa; Voss, Gerald; Altfeld, Marcus
HIV-prevention intervention effectiveness depends on understanding whether clients with highest need for HIV-prevention counseling accept it. With this objective, a field study with a high-risk community sample from the southeastern United States (N = 350) investigated whether initial knowledge about HIV, motivation to use condoms, condom-use-relevant behavioral skills, and prior condom use correlate with subsequent acceptance of an HIV-prevention counseling session. Ironically, participants with high (vs. low) motivation to use condoms, high (vs. low) condom-use-relevant behavioral skills, and high (vs. low) prior condom use were more likely to accept the HIV-prevention counseling. Moreover, the influence of motivation to use condoms, condom-use-relevant behavioral skills, and prior condom use on acceptance of the counseling was mediated by expectations that the counseling session would be useful. Methods to reduce barriers to recruitment of clients for counseling programs are discussed. PMID:19634960
Earl, Allison; Albarracín, Dolores; Durantini, Marta R.; Gunnoe, Joann B.; Leeper, Josh; Levitt, Justin H.
over time among women tested for HIV infection during pregnancy. We tested for HIV during pregnancy 546 HIV-infected and 393 HIV-negative women within the DITRAME Plus ANRS project in Abidjan; these women-test result to their partners, whereas only 45.6% of HIV-infected women did it (pinfected
For more than 20 years cationic surfactant Miramistin has been used in Russia and Ukraine as an antiseptic mean for individual prophylaxis of venereal diseases and for the treatment of genitourinary tract and other systems infections. Complete inhibition of HIV-1 activity in vitro by Miramistin in concentrations higher than 0.0075%, has been demonstrated, that allows to consider this detergent as a potent first-generation vaginal microbicide for the prevention of HIV transmission. Higher anti-HIV effect of Miramistin than of nonoxynol-9 and low local toxicity show good prospects of using Miramistin for individual prevention of HIV transmission. PMID:24605621
Krivorutchenko, Iu L; Andronovskaia, I B
Reliable and effective induction of cytotoxic T-lymphocytes (CTL) is one of the prime objectives of vaccine research. Previously, novel HIV vaccine candidates were constructed as a string of CTL epitopes (20 human, 3 macaque and 1 mouse) delivered using a DNA vector [Hanke T, Schneider J, Gilbert SG, Hill AVS, McMichael A. DNA multi-CTL epitope vaccines for HIV and Plasmodium falciparum: immunogenicity in mice. Vaccine 1998;16:426-435.] or modified vaccinia Ankara (MVA [Hanke T, Blanchard TJ, Schneider J, Ogg GS, Tan R, Becker MSC, Gilbert SG, Hill AVS, Smith GL, McMichael A. Immunogenicities of intravenous and intramuscular administrations of MVA-based multi-CTL epitope vaccine for HIV in mice. J Gen Virol 1998;79:83-90.]), i.e. vaccine vehicles acceptable for use in humans. In mice, a single intramuscular (i.m.) needle injection of either vaccine alone elicited good CTL responses. Here, it is demonstrated that the multi-epitope DNA also induced CTL when delivered intradermally using the Accell gene gun. The CTL responses increased after re-immunization and after three deliveries were comparable to those induced by a single i.m. injection. Recent evidence indicates that combining routes and vaccine vehicles enhances the immunogenicity of vaccine-delivered or -encoded antigens. Here, it is shown that administration of DNA by an i.m. priming/gene gun boosting more efficiently induced CTL than gene gun priming/i.m. boosting. A similar increment was obtained by sequential vaccinations using a gene gun-delivered DNA followed by recombinant MVA. Thus particular sequences of routes or vaccine vehicles rather than simple prime-boost delivery of a single vaccine is critical for an effective elicitation of CTL. PMID:10075166
Hanke, T; Neumann, V C; Blanchard, T J; Sweeney, P; Hill, A V; Smith, G L; McMichael, A
Introduction There are limited data characterizing the burden of HIV among men who have sex with men (MSM) in Malawi. Epidemiologic research and access to HIV prevention, treatment and care services have been traditionally limited in Malawi by criminalization and stigmatization of same-sex practices. To inform the development of a comprehensive HIV prevention intervention for Malawian MSM, we conducted a community-led assessment of HIV prevalence and correlates of infection. Methods From April 2011 to March 2012, 338 MSM were enrolled in a cross-sectional study in Blantyre, Malawi. Participants were recruited by respondent-driven sampling methods (RDS), reaching 19 waves. Trained staff administered the socio-behavioural survey and HIV and syphilis voluntary counselling and testing. Results Crude HIV and syphilis prevalence estimates were 15.4% (RDS-weighted 12.5%, 95% confidence interval (CI): 7.3–17.8) and 5.3% (RDS-weighted 4.4%, 95% CI: 3.1–7.6), respectively. Ninety per cent (90.4%, unweighted) of HIV infections were reported as being previously undiagnosed. Participants were predominantly gay-identified (60.8%) or bisexually identified (36.3%); 50.7% reported recent concurrent relationships. Approximately half reported consistent condom use (always or almost always) with casual male partners, and proportions were relatively uniform across partner types and genders. The prevalence of perceived and experienced stigma exceeded 20% for almost all variables, 11.4% ever experienced physical violence and 7% were ever raped. Current age >25 years (RDS-weighted adjusted odds ratio (AOR) 3.9, 95% CI: 1.2–12.7), single marital status (RDS-weighted AOR: 0.3; 95% CI: 0.1–0.8) and age of first sex with a man <16 years (RDS-weighted AOR: 4.3, 95% CI: 1.2–15.0) were independently associated with HIV infection. Conclusions Results demonstrate that MSM represent an underserved, at-risk population for HIV services in Malawi and merit comprehensive HIV prevention services. Results provide a number of priorities for research and prevention programmes for MSM, including providing access to and encouraging regular confidential HIV testing and counselling, and risk reduction counselling related to anal intercourse. Other targets include the provision of condoms and compatible lubricants, HIV prevention information, and HIV and sexually transmitted infection treatment and adherence support. Addressing multiple levels of HIV risk, including structural factors, may help to ensure that programmes have sufficient coverage to impact this HIV epidemic among MSM. PMID:24321110
Wirtz, Andrea L; Jumbe, Vincent; Trapence, Gift; Kamba, Dunker; Umar, Eric; Ketende, Sosthenes; Berry, Mark; Strömdahl, Susanne; Beyrer, Chris; Baral, Stefan D
In June 2006, the Food and Drug Administration (FDA) approved the first human papillomavirus (HPV) vaccine. The vaccine was subsequently recommended by the Centers for Disease Control and Prevention's (CDC) Advisory Committee for Immunization Practices (ACIP) for routine vaccination of 11-12-year-old girls and catch-up vaccination of females 13-26 years of age. With the approval of the first HPV vaccine, cervical cancer now has a primary prevention tool. However, the availability of an HPV vaccine will not change the course of cervical cancer in this country unless there is both widespread demand by and access for the targeted populations. Demand will require recognition of the need for protection against HPV infection as well as a positive perception of the vaccine as safe and efficacious. General knowledge of HPV and its relationship to cervical cancer is limited; some parents and healthcare providers are hesitant to vaccinate preadolescent girls. Access to the expensive vaccine will not be increased without addressing financial constraints. Although the Vaccines for Children (VFC) program has added HPV to its vaccine plan, not all private insurers have approved coverage, and the uninsured and underinsured may have limited access. Moving forward will require a well-planned and executed public information campaign by trusted sources and the development of a comprehensive vaccine administration program. Although mandates would assure the broadest coverage, controversies surrounding mandates may deter work toward broad coverage. States should focus on developing a comprehensive program and then return to the mandate issue if coverage does not meet public health objectives. PMID:18001182
Vetter, Kathleen M; Geller, Stacie E
ABSTRACT The RV144 ALVAC/AIDSVax HIV-1 vaccine clinical trial showed an estimated vaccine efficacy of 31.2%. Viral genetic analysis identified a vaccine-induced site of immune pressure in the HIV-1 envelope (Env) variable region 2 (V2) focused on residue 169, which is included in the epitope recognized by vaccinee-derived V2 monoclonal antibodies. The ALVAC/AIDSVax vaccine induced antibody-dependent cellular cytotoxicity (ADCC) against the Env V2 and constant 1 (C1) regions. In the presence of low IgA Env antibody levels, plasma levels of ADCC activity correlated with lower risk of infection. In this study, we demonstrate that C1 and V2 monoclonal antibodies isolated from RV144 vaccinees synergized for neutralization, infectious virus capture, and ADCC. Importantly, synergy increased the HIV-1 ADCC activity of V2 monoclonal antibody CH58 at concentrations similar to that observed in plasma of RV144 vaccinees. These findings raise the hypothesis that synergy among vaccine-induced antibodies with different epitope specificities contributes to HIV-1 antiviral antibody responses and is important to induce for reduction in the risk of HIV-1 transmission. IMPORTANCE The Thai RV144 ALVAC/AIDSVax prime-boost vaccine efficacy trial represents the only example of HIV-1 vaccine efficacy in humans to date. Studies aimed at identifying immune correlates involved in the modest vaccine-mediated protection identified HIV-1 envelope (Env) variable region 2-binding antibodies as inversely correlated with infection risk, and genetic analysis identified a site of immune pressure within the region recognized by these antibodies. Despite this evidence, the antiviral mechanisms by which variable region 2-specific antibodies may have contributed to lower rates of infection remain unclear. In this study, we demonstrate that vaccine-induced HIV-1 envelope variable region 2 and constant region 1 antibodies synergize for recognition of virus-infected cells, infectious virion capture, virus neutralization, and antibody-dependent cellular cytotoxicity. This is a major step in understanding how these types of antibodies may have cooperatively contributed to reducing infection risk and should be considered in the context of prospective vaccine design. PMID:24807721
Pollara, Justin; Bonsignori, Mattia; Moody, M. Anthony; Liu, Pinghuang; Alam, S. Munir; Hwang, Kwan-Ki; Gurley, Thaddeus C.; Kozink, Daniel M.; Armand, Lawrence C.; Marshall, Dawn J.; Whitesides, John F.; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Pitisuttithum, Punnee; Rerks-Ngarm, Supachai; Robb, Merlin L.; O'Connell, Robert J.; Kim, Jerome H.; Michael, Nelson L.; Montefiori, David C.; Tomaras, Georgia D.; Liao, Hua-Xin; Haynes, Barton F.
For a country with a moderate adult HIV prevalence of just over 1% in 2012, Thailand is widely perceived as having made some extraordinary contributions to the global management of the HIV/AIDS pandemic. It has been promoted as a model of effective HIV control and applauded for its leadership in providing access to antiretroviral treatment. Thailand has also received international recognition for its contribution to biomedical HIV prevention research, which is generally perceived as exceptional. In this paper, Thailand's global role model function as an example of effective HIV/AIDS control and high-quality biomedical HIV prevention research is re-evaluated against the background of currently available data and more recent insights. The results indicate that Thailand's initial response in raising the level of the political significance of HIV/AIDS was indeed extraordinary, which probably prevented a much larger epidemic from occurring. However, this response transpired in unusual extraconstitutional circumstances and its effectiveness declined once the country returned to political normalcy. Available data confirm the country's more than exceptional contribution to biomedical HIV prevention research. Thailand has made a huge contribution to the global management and control of the HIV/AIDS pandemic. PMID:25000363
van Griensven, Frits; Phanuphak, Nittaya; Srithanaviboonchai, Kriengkrai
Using popular culture to engage students in discussions of HIV prevention is a nontraditional approach that may complement current prevention efforts and enhance the ability to reach youth who are at high risk of contracting HIV and other sexually transmitted infections. Hip-hop or rap music is the dominant genre of music among adolescents, especially Black and Latino youth who are disproportionately impacted by HIV and AIDS. This paper describes the rationale and development of the Reducing HIV and AIDS through Prevention (RHAP) program, a school-based program that uses hip-hop/rap music as a vehicle for raising awareness among adolescents about HIV/AIDS. Constructs from the Social Cognitive Theory and the Sexual Script Theory were used in developing the program. It was piloted and evaluated among 26 middle school students in East Harlem, New York. The lessons learned from a formative evaluation of the program and the implications for developing other programs targeting public health problems are discussed. The RHAP program challenges the traditional pedagogue-student paradigm and provides an alternative approach to teaching about HIV prevention and awareness. PMID:20195778
Boutin-Foster, Carla; McLaughlin, Nadine; Gray, Angela; Ogedegbe, Anthony; Hageman, Ivan; Knowlton, Courtney; Rodriguez, Anna; Beeder, Ann
Using popular culture to engage students in discussions of HIV prevention is a nontraditional approach that may complement current prevention efforts and enhance the ability to reach youth who are at high risk of contracting HIV and other sexually transmitted infections. Hip-hop or rap music is the dominant genre of music among adolescents, especially Black and Latino youth who are disproportionately impacted by HIV and AIDS. This paper describes the rationale and development of the Reducing HIV and AIDS through Prevention (RHAP) program, a school-based program that uses hip-hop/rap music as a vehicle for raising awareness among adolescents about HIV/AIDS. Constructs from the Social Cognitive Theory and the Sexual Script Theory were used in developing the program. It was piloted and evaluated among 26 middle school students in East Harlem, New York. The lessons learned from a formative evaluation of the program and the implications for developing other programs targeting public health problems are discussed. The RHAP program challenges the traditional pedagogue–student paradigm and provides an alternative approach to teaching about HIV prevention and awareness. PMID:20195778
McLaughlin, Nadine; Gray, Angela; Ogedegbe, Anthony; Hageman, Ivan; Knowlton, Courtney; Rodriguez, Anna; Beeder, Ann
With the 2010s declared the Decade of Vaccines, and Millennium Development Goals 4 and 5 focused on reducing diseases that are potentially vaccine preventable, now is an exciting time for vaccines against poverty, that is, vaccines against diseases that disproportionately affect low- and middle-income countries (LMICs). The Global Burden of Disease Study 2010 has helped better understand which vaccines are most needed. In 2012, US$1.3 billion was spent on research and development for new vaccines for neglected infectious diseases. However, the majority of this went to three diseases: HIV/AIDS, malaria, and tuberculosis, and not neglected diseases. Much of it went to basic research rather than development, with an ongoing decline in funding for product development partnerships. Further investment in vaccines against diarrheal diseases, hepatitis C, and group A Streptococcus could lead to a major health impact in LMICs, along with vaccines to prevent sepsis, particularly among mothers and neonates. The Advanced Market Commitment strategy of the Global Alliance for Vaccines and Immunisation (GAVI) Alliance is helping to implement vaccines against rotavirus and pneumococcus in LMICs, and the roll out of the MenAfriVac meningococcal A vaccine in the African Meningitis Belt represents a paradigm shift in vaccines against poverty: the development of a vaccine primarily targeted at LMICs. Global health vaccine institutes and increasing capacity of vaccine manufacturers in emerging economies are helping drive forward new vaccines for LMICs. Above all, partnership is needed between those developing and manufacturing LMIC vaccines and the scientists, health care professionals, and policy makers in LMICs where such vaccines will be implemented. PMID:25136089
MacLennan, Calman A.; Saul, Allan