The purpose of the study was to assess knowledge and beliefs regarding vaccines and willingness to participate in HIV vaccine trials. A baseline survey assessed knowledge and attitudes toward vaccination and potential HIV vaccines among 14,177 participants aged 15-49 years, in a population cohort. Willingness to participate in HIV-preventive vaccine trials was assessed during a follow-up survey 10 months later after providing community education on HIV vaccines. Knowledge of the preventive utility of vaccines was high (71%), but higher in men than women (P<0.001), and increased with education levels (P<0.001). Vaccines were considered appropriate for children and women (99 and 88%, respectively), but not for adult men (28%). Participants felt that adolescents were the most appropriate subjects for HIV preventive vaccine trials (93.7%) but also thought that HIV-positive persons were eligible for trials (60.2%), and only 20% thought a preventive vaccine could help control HIV. HIV vaccine awareness increased from 68% at baseline to 81% at follow-up (P<0.001). Willingness to participate in HIV-preventive vaccine trials was 77%. Vaccine knowledge and willingness to participate in trials are high in this population. However, there still is need for education on the potential role of preventive HIV vaccines in the control of the epidemic and the importance of vaccination for men, especially in the context of an HIV vaccine. PMID:15167291
Kiwanuka, Noah; Robb, Merlin; Kigozi, Godfrey; Birx, Deborah; Philips, James; Wabwire-Mangen, Fred; Wawer, Maria J; Nalugoda, Fred; Sewankambo, Nelson K; Serwadda, David; Gray, Ronald H
In the first preventative human immunodeficiency virus (HIV) vaccine study to be carried out in Africa, 40 HIV-seronegative Ugandan volunteers were randomly assigned to receive a canarypox vector containing HIV-1 clade B (env and gag-pro) antigens (ALVAC-HIV; n = 20), control vector containing the rabies virus glycoprotein G gene (n = 10), or saline placebo (n = 10). Cytotoxic T lymphocyte activity against target cells expressing clade A, B, and D antigens was assessed using standard chromium-release and confirmatory interferon-gamma enzyme-linked immunospot (ELISPOT) assays. Neutralizing antibody responses to cell line-adapted strains and primary isolates in all 3 clades were also tested. Twenty percent of vaccine recipients generated detectable cytolytic responses to either Gag or Env, and 45% had vaccine-induced HIV-specific CD8(+) T cell responses, as measured by the ELISPOT assay. In contrast, only 5% of the control group had vaccine-specific responses. Neutralizing antibodies against primary and laboratory-adapted HIV-1 clade B strains were seen in 10% and 15% of vaccine recipients, respectively, but responses against clades A and D were not detected. Although the immunogenicity of this clade B-based vaccine was low, ALVAC-HIV elicited CD8(+) T cell responses with detectable cross-activity against clade A and D antigens in a significant proportion of vaccine recipients. PMID:12660934
Cao, H; Kaleebu, P; Hom, D; Flores, J; Agrawal, D; Jones, N; Serwanga, J; Okello, M; Walker, C; Sheppard, H; El-Habib, R; Klein, M; Mbidde, E; Mugyenyi, P; Walker, B; Ellner, J; Mugerwa, R
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.
Bailey, Theodore C.; Sugarman, Jeremy
In the intention-to-treat analysis involving 16,402 subjects, there was a trend toward the prevention of HIV-1 infection among the vaccine recipients, with a vaccine ef- ficacy of 26.4% (95% confidence interval (CI), ?4.0 to 47.9; P = 0.08). In the per- protocol analysis involving 12,542 subjects, the vaccine efficacy was 26.2% (95% CI, ?13.3 to 51.9; P = 0.16). In
Supachai Rerks-Ngarm; Punnee Pitisuttithum; Sorachai Nitayaphan; Jaranit Kaewkungwal; Joseph Chiu; Robert Paris; Nakorn Premsri; Chawetsan Namwat; Mark de Souza; Elizabeth Adams; Michael Benenson; Sanjay Gurunathan; Jim Tartaglia; John G. McNeil; Donald P. Francis; Donald Stablein; Deborah L. Birx; Supamit Chunsuttiwat; Chirasak Khamboonruang; Prasert Thongcharoen; Merlin L. Robb; Nelson L. Michael; Prayura Kunasol; Jerome H. Kim
In the intention-to-treat analysis involving 16,402 subjects, there was a trend toward the prevention of HIV-1 infection among the vaccine recipients, with a vaccine ef- ficacy of 26.4% (95% confidence interval (CI), ?4.0 to 47.9; P = 0.08). In the per- protocol analysis involving 12,542 subjects, the vaccine efficacy was 26.2% (95% CI, ?13.3 to 51.9; P = 0.16). In
Supachai Rerks-Ngarm; Punnee Pitisuttithum; Sorachai Nitayaphan; Jaranit Kaewkungwal; Joseph Chiu; Robert Paris; Nakorn Premsri; Chawetsan Namwat; Mark de Souza; Elizabeth Adams; Michael Benenson; Sanjay Gurunathan; Jim Tartaglia; John G. McNeil; Donald P. Francis; Donald Stablein; Deborah L. Birx; Supamit Chunsuttiwat; Chirasak Khamboonruang; Prasert Thongcharoen; Merlin L. Robb; Nelson L. Michael; Prayura Kunasol; Jerome H. Kim
Development of a safe and preventive HIV-1 vaccine is a high priority. Recent advances in HIV vaccine development include\\u000a an improved understanding of HIV envelope structure, development of techniques that enable a detailed analysis of vaccine-induced\\u000a immune responses in humans, expansion of the pipeline of promising candidate vaccines, and completion of the first vaccine\\u000a efficacy trials. A common feature of
M. Patricia D’Souza; Mary Allen; Rebecca Sheets; Margaret I. Johnston
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.
Background Successful conduct of HIV vaccine efficacy trials entails identification and enrollment of at-risk populations, assessment of appropriate endpoints as measures of vaccine efficacy for prevention of HIV acquisition and amelioration of disease course among infected vaccinees, as well as identification of potential confounders or effect modifiers. While not invariably useful and bringing their own cost in terms of measurement and validation, a variety of biomarkers may aid at each stage of trial conduct. Methods A review of selected articles, chosen based on quality, relevance of the biomarker to HIV vaccine trials, and availability of the publication, was conducted. The authors also drew experience from current trials and other planned or ongoing trials. Conclusions Biomarkers are available to assess HIV incidence in potential study populations but care is needed in interpreting results of these assays. During trial conduct, STIs such as HSV-2 may act as effect modifiers on primary and secondary endpoints, including HIV incidence and set point viral load. The utility of STI biomarkers will likely depend heavily on local epidemiology at clinical trial sites. Analyses from recent large HIV vaccine efficacy trials point to the complexities in interpreting trial results and underscore the potential utility of biomarkers in evaluating confounding and effect modification.
MacLachlan, Ellen; Mayer, Kenneth; Barnabas, Ruanne; Sanchez, Jorge; Koblin, Beryl; Duerr, Ann
Background A safe and effective vaccine for the prevention of human immunodeficiency virus type 1 (HIV-1) infection is a global priority. We tested the efficacy of a DNA prime–recombinant adenovirus type 5 boost (DNA/rAd5) vaccine regimen in persons at increased risk for HIV-1 infection in the United States. Methods At 21 sites, we randomly assigned 2504 men or transgender women who have sex with men to receive the DNA/rAd5 vaccine (1253 participants) or placebo (1251 participants). We assessed HIV-1 acquisition from week 28 through month 24 (termed week 28+ infection), viral-load set point (mean plasma HIV-1 RNA level 10 to 20 weeks after diagnosis), and safety. The 6-plasmid DNA vaccine (expressing clade B Gag, Pol, and Nef and Env proteins from clades A, B, and C) was administered at weeks 0, 4, and 8. The rAd5 vector boost (expressing clade B Gag-Pol fusion protein and Env glycoproteins from clades A, B, and C) was administered at week 24. Results In April 2013, the data and safety monitoring board recommended halting vaccinations for lack of efficacy. The primary analysis showed that week 28+ infection had been diagnosed in 27 participants in the vaccine group and 21 in the placebo group (vaccine efficacy, ?25.0%; 95% confidence interval, ?121.2 to 29.3; P = 0.44), with mean viral-load set points of 4.46 and 4.47 HIV-1 RNA log10 copies per milliliter, respectively. Analysis of all infections during the study period (41 in the vaccine group and 31 in the placebo group) also showed lack of vaccine efficacy (P = 0.28). The vaccine regimen had an acceptable side-effect profile. Conclusions The DNA/rAd5 vaccine regimen did not reduce either the rate of HIV-1 acquisition or the viral-load set point in the population studied. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00865566.)
Hammer, Scott M.; Sobieszczyk, Magdalena E.; Janes, Holly; Karuna, Shelly T.; Mulligan, Mark J.; Grove, Doug; Koblin, Beryl A.; Buchbinder, Susan P.; Keefer, Michael C.; Tomaras, Georgia D.; Frahm, Nicole; Hural, John; Anude, Chuka; Graham, Barney S.; Enama, Mary E.; Adams, Elizabeth; DeJesus, Edwin; Novak, Richard M.; Frank, Ian; Bentley, Carter; Ramirez, Shelly; Fu, Rong; Koup, Richard A.; Mascola, John R.; Nabel, Gary J.; Montefiori, David C.; Kublin, James; McElrath, M. Juliana; Corey, Lawrence; 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.
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, Valerie; McElrath, M. Juliana; Jin, Xia; Ferrari, Guido; Defawe, Olivier D.; Mazzara, Gail P.; Montefiori, David; Pensiero, Michael; Panicali, Dennis L.; Corey, Lawrence
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.
Vaccination and the application of a vaginal microbicide have traditionally been considered independent methods to prevent the sexual transmission of HIV-1 to women. Both techniques can be effective in macaque models, and limited efficacy has been observed in clinical trials for each. Here, we have addressed whether vaccines and microbicides can be used together to provide reinforced protection against virus challenge of rhesus macaques. In two separate experiments, four groups of animals were vaccinated with a T-cell-based adenovirus (Ad) vectored vaccine aimed at reducing postinfection viral loads and/or a partially effective dose of a vaginal microbicide aimed at blocking infection of a high-dose vaginal challenge with SIVmac251 or SHIV-162P3. In the first study, the only two protected animals were in the group that received Ad26/Ad5HVR48 vaccine vectors combined with the fusion inhibitor T-1249 as the vaginal microbicide before SIVmac251 challenge. In the second study, vaccination with Ad35/Ad26 vectors combined with the CCR5 inhibitor maraviroc as the vaginal microbicide led to significant reductions of both acquisition of infection and postinfection viral loads following SHIV-SF162P3 challenge. As expected, the vaccine by itself reduced viral loads but had no acquisition effect, whereas the microbicide had a partial acquisition effect but minimal impact on viral loads. For both measures of protective efficacy, the vaccine-microbicide combination differed more from controls than did either separate intervention. Overall, the data suggest that vaccines and microbicides are complementary techniques that may protect better when used together than separately. PMID:22586094
Barouch, Dan H; Klasse, Per Johan; Dufour, Jason; Veazey, Ronald S; Moore, John P
This is a series of PDF files including an overview, a series of 5 lessons, assessments, an appendix and extended resources such as a lab activity. The lessons should span approximately 2 weeks, depending on the amount of activities and depth of review. This unit explores the scientific and ethical issues involved in clinical HIV vaccine trials using human research participants. The unit begins by examining studentsÃÂ current knowledge of HIV, and by reviewing HIV structure and transmission. Next, it familiarizes students with types of vaccines and with challenges related to creating an HIV vaccine. Students are encouraged to explore issues related to human research participants using basic ethical principles and historical case studies. Lastly, global issues regarding the pandemic are explored to give the students an understanding of cultural issues involved in the spread of HIV. This cultural context introduces students to ethical dilemmas inherent in the selection of human participants in global vaccine trials. The lessons culminate in having students design their own hypothetical HIV vaccine clinical trial, based upon knowledge of HIV structure, vaccine characteristics, human research participants considerations, and global contexts.
Joan Griswold (NWABR)
The potential for implementation of HIV vaccine trials in hard-to-reach female sex workers in an inner city area of Barcelona, Spain was assessed via a study of HIV risk, willingness to participate and the success of retention strategies. In 130 women, serological HIV status, behavioral risk exposures and willingness to participate in future HIV vaccine trials were recorded every six months using a confidential questionnaire. An enhanced retention (ER) strategy was compared with a control retention (CR) strategy comprising the recording of data on appointment cards. HIV seroincidence and retention rates were estimated. Retention rates after 6 and 12 mo of follow-up in the ER group were 76% and 69% respectively compared with 16% and 13% in the CR group. Among the ER group 97% were willing to participate in HIV vaccine trials at baseline and, after 12 mo of follow-up. Willingness was significantly associated with higher HIV risk exposure, and higher education level. Successfully retaining these cohorts over time in settings with a high HIV seroincidence rate is an ongoing challenge that will need to be addressed to ensure participation in future trials. Furthermore, as we have demonstrated, the fact that retaining hard-to-reach populations is difficult should not exclude this target population for HIV vaccine and prevention trials. PMID:23291931
Etcheverry, M Florencia; Evans, Jennifer L; Sanchez, Emilia; Mendez-Arancibia, Eva; Meroño, Mercé; Gatell, José M; Page, Kimberly; Joseph, Joan
Innovations in antiretroviral (ARV) treatment strategies have resulted in treated HIV-infected patients having life expectancies similar to those of uninfected individuals. Yet the number of individuals capable of HIV transmission is increasing—for every person in whom ARV treatment is initiated, four others are becoming newly infected with HIV. The limited progress with microbicides and vaccines for HIV prevention reinforce the need for a concentrated exploration of the utility of ARVs. Preliminary animal studies with topical and systemic ARVs show promising results. However, current clinical trials were designed without a comprehensive understanding of ARV pharmacokinetic–pharmacodynamic relationships in HIV prevention. This review focuses on current strategies for the prevention of HIV infection and on the ways in which the tools of pharmacology can be a valuable resource for determining pharmacodynamic targets, providing interspecies scaling of exposures, identifying the optimal drugs/drug combinations, doses, and dosing regimens, and designing efficient clinical trials.
Nicol, MR; Kashuba, ADM
Efficacy trials of prophylactic HIV vaccines will be among the most difficult clinical trials ever attempted. Not only will there be challenges with the recruitment and retention of high-risk uninfected individuals, there will be many statistical challenges to the design, conduct, analysis, and interpretation of these trials. General features of an efficacy trial are described, including choice for the primary endpoint and testing for and estimating vaccine efficacy. Secondary objectives of trials are also discussed. These include determining the correlates of protective immunity, assessing the impact of HIV genetic variation on vaccine efficacy, and using biological markers such as viral load and CD4+ lymphocyte cell count to gain insight on a vaccine's ability to prevent or delay disease. The use of biological markers as surrogates for disease outcome is discussed. Last, trial designs for studying several candidate vaccines or other HIV prevention strategies in a single trial are examined. PMID:7846417
Rida, W N; Lawrence, D N
Despite the use of Bacillus Calmette-Guérin (BCG) vaccination for many years, infants and young children exposed to adults with infectious forms of tuberculosis (TB) are at high risk of developing complicated TB disease. This risk is much higher among HIV-infected children, and data on BCG protective efficacy in HIV-infected children is lacking. Recent research on BCG safety in HIV-infected infants has resulted in policy shifts, but implementation is challenging. New approaches to preventing TB among infants and children, particularly HIV-infected infants, are needed. This paper briefly reviews BCG safety and efficacy considerations in HIV-infected infants and discusses other approaches to preventing TB, including new TB vaccines and vaccination strategies.
Nuttall, James J. C.; Eley, Brian S.
The development of a vaccine that can prevent infection by the Human immunodeficiency virus or prevent the Acquired Immunodeficiency Syndrome has remained elusive despite 20 years of scientific effort. This "Commentary" analyzes the reasons that the development of a vaccine has been so difficult, and proposes a plan to work towards an immunological approach to investigate the best vaccine candidates in the first world in individuals who are already infected, before taking the most promising vaccines to the developing world to attempt to prevent infection and disease. SAGA: (Old Norse) "a long, continued heroic story that is action-packed, but not especially romantic, and that is historical or legendary or both". PMID:12628020
Smith, Kendall A
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.
Objective To assess HIV vaccine acceptability among high-risk adults in Los Angeles. Study Setting Sexually transmitted disease clinics, needle/syringe exchange programs, Latino community health/HIV prevention programs. Study Design Cross-sectional survey using conjoint analysis. Participants were randomly selected using three-stage probability sampling. Data Collection Sixty-minute structured interviews. Participants rated acceptability of eight hypothetical vaccines, each with seven dichotomous attributes, and reported post-vaccination risk behavior intentions. Principal Findings Participants (n=1164; 55.7 percent male, 82.4 percent ethnic minority, mean age=37.4 years) rated HIV vaccine acceptability from 28.4 to 88.6; mean=54.5 (SD=18.8; 100-point scale). Efficacy had the greatest impact on acceptability, followed by side effects and out-of-pocket cost. Ten percent would decrease condom use after vaccination. Conclusions Findings support development of social marketing interventions to increase acceptability of “partial efficacy” vaccines, behavioral interventions to mitigate risk compensation, and targeted cost subsidies.
Newman, Peter A; Lee, Sung-Jae; Duan, Naihua; Rudy, Ellen; Nakazono, Terry K; Boscardin, John; Kakinami, Lisa; Shoptaw, Steven; Diamant, Allison; Cunningham, William E
The scope of the article is to review the different approaches that have been used for HIV vaccines. The review is based on articles retrieved by PubMed and clinical trials from 1990 up to date. The article discusses virus complexity, protective and non-protective immune responses against the virus, and the most important approaches for HIV vaccine development. PMID:24813074
Lema, D; Garcia, A; De Sanctis, J B
A safe and efficacious HIV vaccine would be a tremendous asset to halting the spread of HIV. Nevertheless, HIV vaccines face a range of social and behavioral challenges that will determine their ultimate contribution to prevention. HIV vaccine development and clinical trials raise thorny social, behavioral, and ethical issues around resource allocation, recruitment and enrollment, trial implementation, and post-trial follow-up
Peter A. Newman
Potential live vaccines for HIV were developed using an Lpp-OmpA system to target an HIV antigen, reverse transcriptase, or an immunodominant epitope of this enzyme, to the outer membrane of an attenuated strain of Salmonella SL3261. These live vaccines were administered orally to mice, and fecal IgA and helper T cell responses were measured. Results indicated a fecal IgA response
Mary Susan Burnett; Ning Wang; Matthias Hofmann; G Barrie Kitto
In spite of several attempts over many years at developing a HIV vaccine based on classical strategies, none has convincingly succeeded to date. As HIV is transmitted primarily by the mucosal route, particularly through sexual intercourse, understanding antiviral immunity at mucosal sites is of major importance. An ideal vaccine should elicit HIV-specific antibodies and mucosal CD8 cytotoxic T-lymphocyte (CTL) as a first line of defense at a very early stage of HIV infection, before the virus can disseminate into the secondary lymphoid organs in mucosal and systemic tissues. A primary focus of HIV preventive vaccine research is therefore the induction of protective immune responses in these crucial early stages of HIV infection. Numerous approaches are being studied in the field, including building upon the recent RV144 clinical trial. In this article, we will review current strategies and briefly discuss the use of adjuvants in designing HIV vaccines that induce mucosal immune responses. PMID:25009956
Pavot, Vincent; Rochereau, Nicolas; Lawrence, Philip; Girard, Marc P; Genin, Christian; Verrier, Bernard; Paul, Stéphane
Summary Adolescents globally are at high risk for HIV acquisition and are the targets of HIV prevention interventions such as HIV vaccines. In order to understand stakeholders’ attitudes towards the ethical issues of adolescent involvement in HIV vaccine trials, we conducted focus group discussions with key members of a semi-urban, informal Cape Town community with high HIV prevalence in which HIV vaccine trials are taking place. Themes were identified from focus group transcripts by four researchers, and included necessity of guardian consent, age of independent consent, and confidentiality of in-trial medical results. In general, ethical adolescent HIV vaccine trials will be feasible in this community.
Jaspan, Heather B; Soka, Nosiphiwo F; Strode, Ann E; Mathews, Catherine; Mark, Daniella; Flisher, Alan J; Wood, Robin; Bekker, Linda-Gail
Human immunodeficiency virus (HIV) infection represents one of the major health threats in the developing world. The costly treatment of infected individuals with multiple highly efficient anti-HIV drugs is only affordable in industrialized countries. Thus, an efficient vaccination strategy is required to prevent the further spread of the infection. The molecular biology of coronaviruses and particular features of the human
Klara K. Eriksson; Divine Makia; Reinhard Maier; Burkhard Ludewig; Volker Thiel
Traditional methods of vaccine development have not produced effective vaccines for several prevalent infectious diseases, including AIDS, malaria and tuberculosis. These difficult diseases call attention to the importance of new approaches that profit from modern technologies. Successful efforts in the past have typically taken advantage of naturally occurring, protective immune responses, but this avenue is not readily available in certain
Gary J Nabel
Global access to advanced vaccine technologies is challenged by the interrelated components of intellectual property (IP) management strategies, technology transfer (legal and technical) capabilities and the capacity necessary for accelerating R&D, commercialization and delivery of vaccines. Due to a negative association with the management of IP, patents are often overlooked as a vast resource of freely available, information akin to scientific journals as well as business and technological information and trends fundamental for formulating policies and IP management strategies. Therefore, a fundamental step towards facilitating global vaccine access will be the assembly, organization and analysis of patent landscapes, to identify the amount of patenting, ownership (assignees) and fields of technology covered. This is critical for making informed decisions (e.g., identifying licensees, building research and product development collaborations, and ascertaining freedom to operate). Such information is of particular interest to the HIV vaccine community where the HIV Vaccine Enterprise, have voiced concern that IP rights (particularly patents and trade secrets) may prevent data and materials sharing, delaying progress in research and development of a HIV vaccine. We have compiled and analyzed a representative HIV vaccine patent landscape for a prime-boost, DNA/adenoviral vaccine platform, as an example for identifying obstacles, maximizing opportunities and making informed IP management strategy decisions towards the development and deployment of an efficacious HIV vaccine. PMID:21496469
Clark, K; Cavicchi, J; Jensen, K; Fitzgerald, R; Bennett, A; Kowalski, S P
This is a PowerPoint Presentation providing background on the nature of HIV and AIDS as well as how vaccines are developed and tested. The purpose is to generate broad-based support of HIV vaccine research and trials.
A human immunodeficiency virus (HIV) vaccine remains a central component in the quest to control the worldwide epidemic. To examine the status of the development of HIV vaccines, we review the results of the efficacy trials carried out to date and the immunologic principles that guided them. Four vaccine concepts have been evaluated in HIV-1 vaccine efficacy trials, and the results of these trials have provided significant information for future vaccine development. While one of these trials demonstrated that a safe and effective HIV vaccine is possible, many questions remain regarding the basis for the observed protection and the most efficient way to stimulate it. Novel HIV vaccine strategies including induction of highly potent broadly neutralizing antibodies, use of novel homologous and heterologous vector systems, and vectored immunoprophylaxis seek to expand and build upon the knowledge gained from these trials.
The goal of a therapeutic HIV vaccine is to attenuate HIV disease progression in those already infected. Our objective was to establish comparative efficacy and cost-effectiveness thresholds at which a therapeutic vaccine would make a valuable contribution to HIV care. Using an HIV computer simulation model, we compared therapeutic vaccination with HIV standard of care without vaccination. Input data were
Rochelle P. Walensky; A. David Paltiel; Sue J. Goldie; Rajesh T. Gandhi; Milton C. Weinstein; George R. Seage; Heather E. Smith; Hong Zhang; Kenneth A. Freedberg
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.
Su, Bin; Moog, Christiane
Developing an effective vaccine remains a critical long-term approach to HIV prevention. Every efficacy trial should be responsive to the concerns of participating communities because the successful development of an HIV preventive vaccine will require long-term involvement of people who have been marginalized and who distrust the government and…
Kegeles, Susan M.; Johnson, Mallory O.; Strauss, Ronald P.; Ralston, Brady; Hays, Robert B.; Metzger, David S.; McLellan-Lemal, Eleanor; MacQueen, Kathleen M.
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.
Rao, Mangala; Peachman, Kristina K.; Kim, Jiae; Gao, Guofen; Alving, Carl R.; Michael, Nelson L.; Rao, Venigalla B.
Vaccinations are among the most efficient and important preventive medical procedures. Modern vaccines are well tolerated. In Germany there are no longer laws for mandatory vaccinations, either for the general public or for medical personnel. Vaccinations are now merely "officially recommended" by the top health authorities on the basis of recommendations from the Standing Committee on Vaccinations (STIKO) of the Robert Koch Institute (RKI) according to § 20 para 3 of the Protection against Infection law (IfSG). The management of vaccine damage due to officially recommended vaccinations is guaranteed by the Federal States. Whereas vaccinations in childhood are generally considered to be a matter of course, the willingness to accept them decreases markedly with increasing age. In the medical sector vaccinations against, for example, hepatitis B are well accepted while other vaccinations against, for example, whooping cough or influenza are not considered to be so important. The fact that vaccinations, besides offering protection for the medical personnel, may also serve to protect the patients entrusted to medical care from nosocomial infections is often ignored. PMID:24863331
Kerwat, Klaus; Goedecke, Marcel; Wulf, Hinnerk
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.
Tanner, Helen; Dalgleish, Angus
While there has been remarkable progress in understanding the biology of HIV-1 and its recognition by the human immune system, we have not yet developed an efficacious HIV-1 vaccine. Vaccine challenges include the genetic diversity and mutability of HIV-1 which create a plethora of constantly changing antigens, the structural features of the viral envelope glycoprotein that disguise conserved receptor-binding sites from the immune system, and the presence of carbohydrate moieties that shield potential epitopes from antibodies. Despite these challenges, there has been significant scientific progress in recent years. In 2009, a large-scale clinical trial known as RV144 demonstrated that a HIV-1 vaccine could modestly reduce the incidence of HIV-1 infection. Further, the identification of broadly neutralizing monoclonal antibodies (such as VRC01, a human monoclonal antibody capable of neutralizing over 90% of natural HIV-1 isolates, as well as PG and PGT antibodies that recognize conserved glycopeptide epitopes) has revealed new opportunities for vaccine design. Our ability to understand HIV-1 structure and antibody epitopes at the atomic level, the rapid advance of computational and bioinformatics approaches to immunogen design, and our newly acquired knowledge that it is possible for a vaccine to reduce the risk of HIV-1 infection, have all opened up new and promising pathways towards the development of an urgently needed effective HIV-1 vaccine. This article summarizes challenges to the development of an HIV-1 vaccine, lessons learned from scientific investigation and completed vaccine trials, and promising developments in HIV-1 vaccine design.
Kwong, Peter D; Mascola, John R; Nabel, Gary J
The St. Jude Children's Research Hospital (St. Jude) HIV-1 vaccine program is based on the observation that multiple antigenically distinct HIV-1 envelope protein structures are capable of mediating HIV-1 infection. A cocktail vaccine comprising representatives of these diverse structures (immunotypes) is therefore considered necessary to elicit lymphocyte populations that prevent HIV-1 infection. This strategy is reminiscent of that used to design a currently licensed and successful 23-valent pneumococcus vaccine. Three recombinant vector systems are used for the delivery of envelope cocktails (DNA, vaccinia virus, and purified protein), and each of these has been tested individually in phase I safety trials. A fourth FDA-approved clinical trial, in which diverse envelopes and vectors are combined in a prime-boost vaccination regimen, has recently begun. This trial will continue to test the hypothesis that a multi-vector, multi-envelope vaccine can elicit diverse B- and T-cell populations that can prevent HIV-1 infections in humans.
Hurwitz, Julia L.; Zhan, Xiaoyan; Brown, Scott A.; Bonsignori, Mattia; Stambas, John; Lockey, Timothy D.; Jones, Bart; Surman, Sherri; Sealy, Robert; Freiden, Pam; Branum, Kristen; Slobod, Karen S.
SUMMARY: The prevalence of adult HIV\\/AIDS in Thailand is declining due to intense prevention strategies, but it still continues to be a critical health problem with a prevalence of 1.5%. Several HIV vaccine candidates for the prevention of HIV infection or progress to AIDS were examined in clinical trials. We evaluated the cost-effectiveness of a vaccination regimen (rBCG prime-rDIs boost)
Shunsuke Ono; Takako Kurotaki; Tadashi Nakasone; Mitsuo Honda; Jotika Boon-Long; Pathom Sawanpanyalert; Kazuko Kimura
Realization of individual and public health benefit from an HIV vaccine requires clinical testing to demonstrate efficacy. To facilitate clinical testing, preclinical HIV vaccine developers should consider the realities of clinical practice and the conduct of clinical trials in product design. There are several essentially different approaches to prophylactic HIV vaccine design: (1) induce immunity that allows infection but reduces initial peak viremia and viral load set point; (2) induce immunity that allows infection but controls viremia to below the level of detection; (3) induce immunity that allows infection but promotes viral clearance before disease (classic vaccine approach); (4) induce "sterilizing immunity" that prevents acquisition of infection. Each approach presents different challenges for clinical product development. Current clinical trial practices and evolving treatment standards may make it infeasible to perform an efficacy trial of a preventive vaccine that only modestly reduces viremia. A vaccine that promotes control of viremia to below the level of detection is testable but will require extended follow-up to determine how long virus control persists; once control is lost boosting with the same vaccine may not be useful. A vaccine that permits infection but promotes subsequent complete clearance of the virus from the body will require the development and validation of an effective assay for virus clearance. A vaccine that prevents acquisition of infection is the most straightforward to test in the clinic, but escalating costs require more attention by vaccine developers to understanding how the vaccine works and the breadth of protection. All types of vaccine require attention to effect size to ensure adequate powering of efficacy trials. PMID:24168166
Shapiro, Stuart Z
The heavy glycosylation of HIV envelope constitutes a strong defense mechanism for the virus to evade host immune response, which accounts for a major barrier for HIV vaccine development. Nevertheless, the identification of a number of glycan-dependent broadly HIV-neutralizing antibodies from HIV-infected individuals, including 2G12, PG9, PG16, PGT121-123, PGT125-128, and PGT135, strongly suggests that the defensive viral 'glycan shield' can be important targets of vaccines. The novel glycan recognition mode exhibited by these antibodies provides new templates for immunogen design. This review highlights recent work on the characterization of the glycan-dependent epitopes of these neutralizing antibodies and recent advances in the synthesis of the relevant carbohydrate antigens for HIV vaccine design. PMID:24466581
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.
Frew, Paula M.; Macias, Wendy; Chan, Kayshin; Harding, Ashley C.
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)
Although the number of new infections has declined recently, women still constitute almost half of the world's 34 million people with HIV infection, and HIV remains the leading cause of death among women of reproductive age. Prevention research has made considerable progress during the past few years in addressing the biological, behavioral and social factors that influence women's vulnerability to HIV infection. Nevertheless, substantial work still must be done in order to implement scientific advancements and to resolve the many questions that remain. This article highlights some of the recent advances and persistent gaps in HIV prevention research for women and outlines key research and policy priorities.
Adimora, Adaora A.; Ramirez, Catalina; Auerbach, Judith D.; Aral, Sevgi O.; Hodder, Sally; Wingood, Gina; El-Sadr, Wafaa; Bukusi, Elizabeth Anne
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.
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
Schiffner, Torben; Sattentau, Quentin J; Dorrell, Lucy
Recognition that social, economic, political, and environmental factors directly aff ect HIV risk and vulnerability has stimulated interest in structural approaches to HIV prevention. Progress in the use of structural approaches has been limited for several reasons: absence of a clear defi nition; lack of operational guidance; and limited data on the eff ectiveness of structural approaches to the reduction
Geeta Rao Gupta; Justin O Parkhurst; Jessica A Ogden; Peter Aggleton; Ajay Mahal
Vaccination for human immunodeficiency virus type 1 (HIV-1) remains an elusive goal. Whether an unsuc- cessful vaccine might not only fail to provoke detectable immune responses but also could actually interfere with subsequent natural immunity upon HIV-1 infection is unknown. We performed detailed assessment of an HIV-1 gag DNA vaccine recipient (subject 00015) who was previously uninfected but sustained HIV-1
Arumugam Balamurugan; Martha J. Lewis; Christina M. R. Kitchen; Michael N. Robertson; John W. Shiver; Eric S. Daar; Jacqueline Pitt; Ayub Ali; Hwee L. Ng; Judith S. Currier; Otto O. Yang
Background The recent RV144 clinical trial showed that an ALVAC/AIDSVAX prime-boost HIV vaccine regimen may confer partial immunity in recipients and reduce transmission by 31%. Trial data suggest that efficacy may initially exceed 70% but decline over the following 3.5 years. Estimating the potential health benefits associated with a one-time vaccination campaign, as well as the projected benefits of repeat booster vaccination, may inform future HIV vaccine research and licensing decisions. Methods We developed a mathematical model to project the future course of the HIV epidemic in the United States under varying HIV vaccine scenarios. The model accounts for disease progression, infection transmission, antiretroviral therapy, and HIV-related morbidity and mortality. We projected HIV prevalence and incidence over time in multiple risk groups, and we estimated quality-adjusted life years (QALYs) and costs over a 10-year time horizon. We used an exponentially declining efficacy curve fit to trial data, and we assumed subsequent vaccine boosters confer similar immunity. Variations in vaccine parameters were examined in sensitivity analysis. Results Under existing HIV prevention and treatment efforts, an estimated 590,000 HIV infections occur over 10 years. One-time vaccination achieving 60% coverage of adults could prevent 9.8% of projected new infections over 10 years (and prevent 34% of new infections in the first year) and cost approximately $91,000/QALY gained relative to the status quo, assuming a vaccination price of $500. Targeted vaccination of high-risk groups results in net cost savings for vaccines costing less than $750. One-time vaccination of 60% of all adults coupled with three-year boosters only for men who have sex with men and injection drug users could prevent 21% of infections for $81,000/QALY gained relative to vaccination of high-risk groups only. A program attaining 90% vaccination coverage prevents 15% of new HIV cases over 10 years (and approximately 50% of infections in the first year). Conclusions A partially effective HIV vaccine with effectiveness similar to that observed in the RV144 trial would provide large health benefits in the United States and could meet conventionally accepted cost-effectiveness thresholds. Strategies that target high-risk groups are most efficient, but broader strategies provide greater total population health benefit.
Long, Elisa F.; Owens, Douglas K.
In this introductory essay on the landscape of HIV prevention, my intent is to provide context for the subsequent topics discussed at the Symposium on Hormone Regulation of the Mucosal Environment in the female reproductive tract (FRT) and the Prevention of HIV infection: FRT immunity, mucosal microenvironment and HIV prevention, and the risk and impact of hormonal contraceptives on HIV transmission. PMID:24702688
Haase, Ashley T
HIV prevalence is increasing worldwide because people on antiretroviral therapy are living longer, although new infections decreased from 3.3 million in 2002, to 2.3 million in 2012. Global AIDS-related deaths peaked at 2.3 million in 2005, and decreased to 1.6 million by 2012. An estimated 9.7 million people in low-income and middle-income countries had started antiretroviral therapy by 2012. New insights into the mechanisms of latent infection and the importance of reservoirs of infection might eventually lead to a cure. The role of immune activation in the pathogenesis of non-AIDS clinical events (major causes of morbidity and mortality in people on antiretroviral therapy) is receiving increased recognition. Breakthroughs in the prevention of HIV important to public health include male medical circumcision, antiretrovirals to prevent mother-to-child transmission, antiretroviral therapy in people with HIV to prevent transmission, and antiretrovirals for pre-exposure prophylaxis. Research into other prevention interventions, notably vaccines and vaginal microbicides, is in progress. PMID:24907868
Maartens, Gary; Celum, Connie; Lewin, Sharon R
Researchers and representatives from more than 12 developed and developing countries convened in Boston for a three-day conference to discuss how to tailor HIV vaccines to developing countries, where more than 90% of all HIV-infected people live. The conference was sponsored by the Harvard AIDS Institute with major support from the Fogarty International Center of the US National Institutes of Health. Most of the research technology is in developed countries, but the greatest need exists in developing countries. Participants thus agreed that collaboration between developed and developing countries is the best and perhaps only way to realize the development of an effective vaccine. They were optimistic that safe, effective, and affordable vaccines can be developed for use around the world if enough funding, researchers, and political will are committed. Although safety was noted by conference participants as their top priority, the pace of research and development must be accelerated given the current rate of HIV spread in the developing world. They recommend that human efficacy trials begin as soon as a viable vaccine is developed and that human trials proceed even in the absence of animal model data. Further, when a vaccine is ready for widespread testing, the rules may need to be eased for Phase III trials. The participants identified criteria essential for a trial's success and considered the need to ensure vaccine appropriateness and availability, the importance of collaboration, and enlisting a global response. PMID:12319991
Importance of the field There are currently over thirty million people infected with HIV and there are no vaccines available to prevent HIV infections or disease. The genitourinary, rectal and oral mucosa are the mucosal HIV transmission routes. An effective vaccine that can induce both systemic and local mucosal immunity is generally accepted as a major means of protection against mucosal HIV transmission and AIDS. What the reader will gain Structure and cells that comprise the oral, vaginal and rectal mucosa pertaining to HIV transmission and vaccination strategies through each mucosal route to prevent mucosal and systemic infection will be discussed. Areas covered in this review Covering publications from 1980’s through 2010, mucosal transmission of HIV and current and previous approaches to vaccinations are discussed. Take home message Although oral transmission of HIV is far less common than vaginal and rectal transmissions, infections through this route do occur through oral sex as well as vertically from mother to child. Mucosal vaccination strategies against oral and other mucosal HIV transmissions are under intense research but the lack of consensus on immune correlates of protection and lack of safe and effective mucosal adjuvants and delivery systems hamper progress towards a licensed vaccine.
Yu, Mingke; Vajdy, Michael
Background A vaccine could substantially impact the HIV epidemic, but inadequate uptake is a serious concern. Unfortunately, people who use drugs, particularly those residing in rural communities, have been underrepresented in previous research on HIV vaccine acceptability. This study examined HIV vaccine acceptability among high-risk drug users in a rural community in the United States. Methods Interviewer-administered questionnaires included questions about risk behavior and attitudes toward HIV vaccination from 433 HIV-negative drug users (76% with history of injection) enrolled in a cohort study in Central Appalachia. HIV vaccine acceptability was measured on a 4-point Likert scale. Generalized linear mixed models were used to determine correlates to self-report of being “very likely” to receive a 90% effective HIV vaccine (i.e. “maximum vaccine acceptability”, or MVA). Adjusted odds ratios (AORs) and corresponding 95% confidence intervals (CIs) are reported. Results Most (91%) reported that they would accept a preventive HIV vaccine, but concerns about cost, dosing, transportation constraints, vaccine-induced seropositivity, and confidentiality were expressed. Cash incentives, oral-administration, and peer/partner encouragement were anticipated facilitators of uptake. In multivariate analysis, men were significantly less likely to report MVA (AOR: 0.33, CI: 0.21 – 0.52). MVA was more common among participants who believed that they were susceptible to HIV (AOR: 2.31, CI: 1.28 – 4.07), that an HIV vaccine would benefit them (AOR: 2.80, CI: 1.70 – 4.64), and who had positive experiential attitudes toward HIV vaccination (AOR: 1.85, CI: 1.08 – 3.17). MVA was also more common among participants who believed that others would encourage them to get vaccinated and anticipated that their behavior would be influenced by others' encouragement (AOR: 1.81, 95% 1.09 – 3.01). Conclusions To our knowledge, this study was among the first to explore and provide evidence for feasibility of HIV vaccination in a rural, high-risk population in the United States. This study provides preliminary evidence that gender-specific targeting in vaccine promotion may be necessary to promoting vaccine uptake in this setting, particularly among men. The data also underscore the importance of addressing perceived risks and benefits, social norms, and logistical constraints in efforts to achieve widespread vaccine coverage in this high-risk population.
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.HIVA222. 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.HIVA222–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.
Hopkins, Richard; Bridgeman, Anne; Joseph, Joan; Gilbert, Sarah C.; McShane, Helen; Hanke, Tomas
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
SUMMARY We have entered a new era in HIV prevention whereby priorities have expanded from biomedical discovery to include implementation, effectiveness, and the effect of combination prevention at the population level. However, gaps in knowledge and implementation challenges remain. In this Review we analyse trends in the rapidly changing landscape of HIV prevention, and chart a new path for HIV prevention research that focuses on the implementation of effective and efficient combination prevention strategies to turn the tide on the HIV pandemic.
Padian, Nancy S.; McCoy, Sandra I.; Karim, Salim Abdool; Hasen, Nina; Kim, Julia; Bartos, Michael; Katabira, Elly; Bertozzi, Stefano; Schwartlander, Bernhard; Cohen, Myron S.
An effective prophylactic HIV-1 vaccine is needed to eradicate the HIV/AIDS pandemic but designing such a vaccine is a challenge. Despite many advances in vaccine technology and approaches to generate both humoral and cellular immune responses, major phase-II and -III vaccine trials against HIV/AIDS have resulted in only moderate successes. The modest achievement of the phase-III RV144 prime-boost trial in Thailand re-emphasized the importance of generating robust humoral and cellular responses against HIV. While antibody-directed approaches are being pursued by some groups, others are attempting to develop vaccines targeting cell-mediated immunity, since evidence show CTLs to be important for the control of HIV replication. Phase-I and -IIa multi-epitope vaccine trials have already been conducted with vaccine immunogens consisting of known CTL epitopes conserved across HIV subtypes, but have so far fallen short of inducing robust and consistent anti-HIV CTL responses. The concepts leading to the development of T-cell epitope-based vaccines, the outcomes of related clinical vaccine trials and efforts to enhance the immunogenicity of cell-mediated approaches are summarized in this review. Moreover, we describe a novel approach based on the identification of SIV and FIV antigens which contain conserved HIV-specific T-cell epitopes and represent an alternative method for developing an effective HIV vaccine against global HIV isolates.
Sanou, Missa P; De Groot, Anne S; Murphey-Corb, Michael; Levy, Jay A; Yamamoto, Janet K
Objective: To examine behavioral history, beliefs, and vaccine characteristics as predictors of HIV vaccine acceptability. Methods: Two hundred forty-five US under graduates were surveyed regarding their sexual history, risk beliefs, and likelihood of accepting hypothetical HIV vaccines. Results: Multivariate regression analysis indicated that…
Ravert, Russell D.; Zimet, Gregory D.
Vaccine-preventable diseases have historically caused much illness and death in South Dakota. Sixty-seven diphtheria deaths were reported in 1892 and 1,017 polio cases were reported at the peak of the polio epidemic in 1952. As vaccines have been developed, licensed and put into wide use, the rates of diphtheria, polio, measles, smallpox and other diseases have successfully decreased leading to control, statewide elimination or eradication. Other diseases, such as pertussis, have been more difficult to control by vaccination alone. Although current vaccination coverage rates for South Dakota's kindergarten children surpass the Healthy People 2020 targets of 95 percent, the coverage rates for 2-year-old children and teenagers are below the target rates. Until vaccine-preventable diseases are eradicated globally, we must vigilantly maintain high vaccination coverage rates and aggressively apply control measures to limit transmission when diseases do occur in South Dakota. PMID:23444597
The adenovirus type 5 (Ad5)-based vaccine developed by Merck failed to either prevent HIV-1 infection or suppress viral load in subsequently infected subjects in the STEP human Phase 2b efficacy trial. Analogous vaccines had previously also failed in the simian immunodeficiency virus (SIV) challenge–rhesus macaque model. In contrast, vaccine protection studies that used challenge with a chimeric simian-human immunodeficiency virus
David I Watkins; Dennis R Burton; Esper G Kallas; John P Moore; Wayne C Koff
Summary A global human immunodeficiency virus-1 (HIV-1) vaccine will have to elicit immune responses capable of providing protection against a tremendous diversity of HIV-1 variants. In this review, we first describe the current state of the HIV-1 vaccine field, outlining the immune responses that are desired in a global HIV-1 vaccine. In particular, we emphasize the likely importance of Env-specific neutralizing and non-neutralizing antibodies for protection against HIV-1 acquisition and the likely importance of effector Gag-specific T lymphocytes for virologic control. We then highlight four strategies for developing a global HIV-1 vaccine. The first approach is to design specific vaccines for each geographic region that include antigens tailor-made to match local circulating HIV-1 strains. The second approach is to design a vaccine that will elicit Env-specific antibodies capable of broadly neutralizing all HIV-1 subtypes. The third approach is to design a vaccine that will elicit cellular immune responses that are focused on highly conserved HIV-1 sequences. The fourth approach is to design a vaccine to elicit highly diverse HIV-1-specific responses. Finally, we emphasize the importance of conducting clinical efficacy trials as the only way to determine which strategies will provide optimal protection against HIV-1 in humans.
Stephenson, Kathryn E; Barouch, Dan H
This unit explores the scientific and ethical issues involved in clinical HIV vaccine trials using human research participants. The unit begins by examining students current knowledge of HIV, and by reviewing HIV structure and transmission. Next, it familiarizes students with types of vaccines and with challenges related tocreating an HIV vaccine. Students are encouraged to explore issues related to human research participants using basic ethical principles and historical case studies. Lastly, global issues regarding the pandemic are explored to give the students an understanding of cultural issues involved in the spread of HIV. This cultural context introduces students to ethical dilemmas inherent in the selection of human participants in global vaccine trials. The lessons culminate in having students design their own hypothetical HIV vaccineclinical trial, based upon knowledge of HIV structure, vaccine characteristics, human research participants considerations, and global contexts.
Joan Griswold (Northwest Association for Biomedical Research;); JeanneTing Chowning (Northwest Association for Biomedical Research;)
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.
Shattock, Robin J.; Rosenberg, Zeda
This contract involves clinical research of vaccine studies on Chimpanzees. Twelve chimpanzees housed in the LEMSIP facility are assigned to this project involving research on HIV vaccine efficacy. These animals are part of a 'dynamic' pool whereby chimpa...
A. W. Rowe E. Muchmore
Objectives To determine the incidence of and risk factors for HIV acquisition in a cohort of HIV-uninfected partners from HIV discordant couples in Masaka, Uganda, and to establish its suitability for HIV vaccine trials. Methods HIV-uninfected adults living in HIV discordant couple relationships were enrolled and followed for 2 years. Interviews, medical investigations, HIV counseling and testing, syphilis and urine pregnancy (women) tests were performed at quarterly visits. Sexual risk behaviour data were collected every 6 months. Results 495 participants were enrolled, of whom 34 seroconverted during 786.6 person-years of observation (PYO). The overall HIV incidence rate [95% confidence interval (CI)] was 4.3 [3.1–6]; and 4.3 [2.8–6.4] and 4.4 [2.5–8] per 100 PYO in men and women respectively. Independent baseline predictors for HIV acquisition were young age [18–24 (aRR?=?4.1, 95% CI 1.6–10.8) and 25–34 (aRR?=?2.7, 95% CI 1.2–5.8) years]; alcohol use (aRR?=?2.6, 95% CI 1.1–6); and reported genital discharge (aRR?=?3.4, 95% CI 1.6–7.2) in the past year. Condom use frequency in the year preceding enrolment was predictive of a reduced risk of HIV acquisition [sometimes (aRR?=?0.4, 95% CI 0.2–0.8); always (aRR?=?0.1, 95% CI 0.02–0.9)]. In the follow-up risk analysis, young age [18–24 (aRR?=?6.2, 95% CI 2.2–17.3) and 25-34 (aRR?=?2.3, 95% CI 1.1–5.0) years], reported genital discharge (aRR?=?2.5, 95% CI 1.1–5.5), serological syphilis (aRR 3.2, 95% CI 1.3–7.7) and the partner being ART naïve (aRR?=?4.8, 95% CI 1.4–16.0) were independently associated with HIV acquisition. There were no seroconversions among participants who reported consistent condom use during the study. Conclusions The study has identified important risk factors for HIV acquisition among HIV discordant couples. HIV-uninfected partners in discordant couples may be a suitable population for HIV vaccine efficacy trials. However, recent confirmation that ART reduces heterosexual HIV transmission may make it unfeasible to conduct HIV prevention trials in this population.
Ruzagira, Eugene; Wandiembe, Symon; Abaasa, Andrew; Bwanika, Agnes N.; Bahemuka, Ubaldo; Amornkul, Pauli; Price, Matthew A.; Grosskurth, Heiner; Kamali, Anatoli
An examination of actual HIV vaccine trials can contribute to an understanding of motivators for participation in these studies. Analysis of these motivators reveals that they can be categorized as social and personal benefits. Social benefits are generally altruistic, whereas personal benefits are psychological, physical, and financial. In this systematic review, the authors performed a literature search for actual preventive HIV vaccine trials reporting motivators to participation. Of studies conducted in the Organization for Economic Co-operation and Development (OECD) countries, the authors retrieved 12 studies reporting on social benefits and seven reporting on personal benefits. From the non-OECD countries, nine studies reported on social benefits and eight studies on personal benefits. Social benefits were most frequently described on macroscopic, altruistic levels. Personal benefits were most frequently psychological in nature. Rates of participation were compared between the OECD and the non-OECD countries. Knowledge of actual motivators in specific countries and regions can help target recruitment in various types of actual HIV vaccine trials. PMID:23736885
Dhalla, Shayesta; Poole, Gary
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
Shabbir, Majid; Barod, Ravi; Hegarty, Paul K; Minhas, Suks
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.
Barod, Ravi; Hegarty, Paul K.; Minhas, Suks
Secondary infectious diseases contribute substantially to morbidity and mortality of people infected with human immunodeficiency virus (HIV). The authors developed comprehensive, practical recommendations for prevention of infectious complications in HIV-infected people. Recommendations are concerned with the pathogens that are more common or more severe in HIV-infected people. Several infectious complications can be prevented by avoiding ingestion of contaminated food or water. Zoonoses can be prevented by precautions to be taken in contacts with animals. The risk of several fungal diseases can be reduced if activities likely to lead to inhalation of spores are avoided. HIV-infected people should be advised how to lower adverse health effects of travel, especially international travel. The potential for infectious complications of sexual activity and illicit drug use should be stressed, and recommendations to reduce the risk are discussed. Recommendations for use of vaccines in HIV-infected people are reviewed. Blood CD4+ lymphocyte concentrations, tuberculin skin testing, Toxoplasma serology, and sexually transmitted disease screening should be performed in certain subsets of HIV-infected people. Guidelines for chemoprophylaxis against Pneumocystis carinii and tuberculosis are presented. Recent data suggest that intravenous immunoglobulin therapy may prevent bacterial infections in HIV-infected children.
Filice, G A; Pomeroy, C
Objective To assess knowledge of and attitudes towards human papillomavirus (HPV), Pap testing, and the HPV vaccine. Methods In a multicenter U.S. cohort study, women with the human immunodeficiency virus (HIV) and at-risk comparison women completed 44-item standardized self-report questionnaires exploring their knowledge of cervical cancer prevention, HPV, and HPV vaccination. Results were correlated with demographic variables, measures of education and attention, and medical factors. Data were clustered using principal component analysis. Significant associations were assessed in multivariable models. Results Among 1588 women, HIV seropositive women better understood facts about cervical cancer prevention and HPV than seronegative women, but both had substantial knowledge deficits. Almost all women considered Pap testing important, although 53% of HIV seropositive and 48% of seronegative women considered cervical cancer not preventable (P=0.21). Only 44% of HIV seropositive women knew Paps assess the cervix, versus 42% of HIV seronegative women (P=0.57). Both groups understood that HPV causes genital warts and cervical cancer (67% of HIV seropositive vs. 55% of seronegative women, P=0.002). About half of both groups considered HPV vaccination extremely important for cervical cancer prevention. HIV seronegative women were more likely to report learning of HPV vaccination through advertising than from clinicians (81% vs. 64%, P<0.0001). Conclusion High risk women need effective education about cervical cancer prevention, HPV, and HPV vaccination.
Massad, L. Stewart; Evans, Charlesnika T.; Wilson, Tracey E.; Goderre, Johanna L.; Hessol, Nancy A.; Henry, Donna; Colie, Christine; Strickler, Howard D.; Levine, Alexandra M.; Watts, D. Heather; Weber, Kathleen M.
Biomedical, logistic, economic, social, and psychosocial issues related to the successful distribution and use of a vaccine for human immunodeficiency virus (HIV) are reviewed. A mathematical model is introduced as an aid in conceptualizing these issues. The HIV vaccine should be seen as an adjunct to behavioral modification. (SLD)
Pinkerton, Steven D.; Abramson, Paul R.
HIV-1 prevalence in Guangxi, China, has been growing since 1996, when the first case was reported. Over half of HIV-1 positive patients in Guangxi Province were injecting drug users (IDUs), possibly because of the province’s location near drug-trafficking routes. Since a phase II HIV vaccine trial is ongoing there, a current characterization of the subtypes of HIV-1 among IDUs in Guangxi would provide critical information for future HIV vaccine trials, as well as further control and prevention of HIV-1 transmission. Thus, we conducted a molecular epidemiological investigation of HIV-1 samples from 2008–2010 among IDUs in multiple cities in Guangxi Province. Our results, based on the gag/pol fragment, indicated a very high proportion (78.47%) of HIV-1 CRF08_BC recombinants, some CRF01_AE (15.38%) recombinants, and a low proportion of CRF07_BC (6.15%) recombinants among the IDUs. The high proportion of CRF08 HIV-1 strains among recent IDUs matches the vaccine candidate constructs. However, future vaccine development should also incorporate CRF01-targeted vaccine candidates. Distinct Env sequence evolution patterns were observed for CRF08_BC and CRF01_AE, indicating that different local selection pressures have been exerted on these two HIV-1 subtypes. Unique drug-resistant mutations were also detected, and our data indicate that HIV treatment programs should consider pre-existing drug-resistant mutations.
Qi, Haiyan; Zhao, Ke; Xu, Fei; Zhang, Xuzhao; Zhang, Zhiyong; Yang, Li; Li, Chunling; Liang, Xu; Guo, Weigui; Chen, Shihai; Liu, Zhihao; Zhang, Wenyan; Yu, Xiao-Fang
South Africa has more people living with HIV than any other nation. The HIV epidemic in South Africa is being driven by new infections among adolescents. Inclusion of adolescents in HIV vaccine trials is essential for successful vaccine development, however, recruitment and retention of at-risk South African adolescents into these trials poses a number of legal, ethical and operational challenges. This article discusses the South African ethico-legal context in which future adolescent HIV vaccine trials would be conducted followed by a review of available data regarding strategies for recruitment into these trials and retention of trial participants.
Adler, David H.
HIV/AIDS is an important public health problem globally. An affordable, easy-to-deliver and protective HIV vaccine is therefore required to curb the pandemic from spreading further. Recombinant Salmonella bacteria can be harnessed to vector HIV antigens or DNA vaccines to the immune system for induction of specific protective immunity. These are capable of activating the innate, humoral and cellular immune responses at both mucosal and systemic compartments. Several studies have already demonstrated the utility of live recombinant Salmonella in delivering expressed foreign antigens as well as DNA vaccines to the host immune system. This review gives an overview of the studies in which recombinant Salmonella bacteria were used to vector HIV/AIDS antigens and DNA vaccines. Most of the recombinant Salmonella-based HIV/AIDS vaccines developed so far have only been tested in animals (mainly mice) and are yet to reach human trials. PMID:24478808
Chin'ombe, Nyasha; Ruhanya, Vurayai
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.
Hutnick, Natalie A; Myles, Devin JF; Bian, Chaoran Billie; Muthumani, Karuppiah; Weiner, David B
PurposeTo determine human immunodeficiency virus (HIV) prevalence, sexual risk behaviors, and attitudes toward HIV vaccine trials among 11–19 year-olds in a peri-urban community near Cape Town, South Africa.
Heather B. Jaspan; Jessica R. Berwick; Landon Myer; Catherine Mathews; Alan J. Flisher; Robin Wood; Linda-Gail Bekker
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
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.
Objectives. We investigated how persons from key populations at higher risk of HIV exposure interpreted the process and outcomes of the Step Study HIV-1 vaccine trial, which was terminated early, and implications for willingness to participate in and community support for HIV vaccine research. Methods. We used qualitative methods and a community-based approach in 9 focus groups (n = 72) among ethnically and sexually diverse populations and 6 semistructured key informant interviews in Ontario, Canada, in 2007 to 2008. Results. Participants construed social meaning from complex clinical and biomedical phenomena. Social representations and mental models emerged in fears of vaccine-induced infection, conceptualizations of unfair recruitment practices and increased risk behaviors among trial participants, and questioning of informed consent. Narratives of altruism and the common good demonstrated support for future trials. Conclusions. Public discourse on HIV vaccine trials is a productive means of interpreting complex clinical trial processes and outcomes in the context of existing beliefs and experiences regarding HIV vaccines, medical research, and historical disenfranchisement. Strategic engagement with social representations and mental models may promote meaningful community involvement in biomedical HIV prevention research.
Logie, Carmen; James, LLana; Charles, Tamicka; Maxwell, John; Salam, Khaled; Woodford, Michael
No single HIV prevention strategy will be sufficient to control the HIV pandemic. However, a growing number of interventions have shown promise in partially protecting against HIV transmission and acquisition, including knowledge of HIV serostatus, behavioral risk reduction, condoms, male circumcision, needle exchange, treatment of curable sexually transmitted infections, and use of systemic and topical antiretroviral medications by both HIV-infected and uninfected persons. Designing the optimal package of interventions that matches the epidemiologic profile of a target population, delivering that package at the population level, and evaluating safety, acceptability, coverage, and effectiveness, all involve methodological challenges. Nonetheless, there is an unprecedented opportunity to develop “prevention packages” that combine various arrays of evidence-based strategies, tailored to the needs of diverse subgroups and targeted to achieve high coverage for a measurable reduction in population-level HIV transmission. HIV prevention strategies that combine partially effective interventions should be scaled up and evaluated.
Celum, Connie; Baeten, Jared M.; Vermund, Sten H.; Wasserheit, Judith N.
More than a decade ago, the pathogenesis of AIDS was reviewed in this journal, using the subtitle 'classical and alternative views', when evidence was accumulating that HIV could not cause AIDS simply through direct cytopathic mechanisms alone. Generalised immune activation after infection with HIV is now understood to be associated with and predictive of disease progression and probably represents the single most important difference between rapid progression and slow or non-progression. However, the fundamental source of this phenomenon remains undetermined. Do pathogenic events after acute infection promote an environment susceptible to increased hyperactivity or does inherent reactivity towards HIV in susceptible individuals ultimately influence these processes? New strategies aimed at eliminating HIV-induced immune activation are required, as is investigation into the clinical and immunological influence of antibodies that target HIV epitopes associated with disease and that are not necessarily neutralising. Therapeutic vaccines to prevent disease may be more practical and effective than classic prophylactic vaccination. PMID:18624032
Cadogan, Martin; Dalgleish, Angus G
Many vaccine approaches emphasize producing HIV-1-specific CD8+ T-lymphocyte (CTL) responses. Towards this goal, many studies simply classify vaccinees as "responders" or "nonresponders," based on arbitrary cutoff criteria. HIV-1-uninfected participants receiving the TBC-3B vaccine were assessed for HIV-1-specific CTL by interferon-gamma ELISpot, and compared to HIV-1-infected control subjects not on antiretroviral therapy. Vaccinees also were tested for HIV-1-specific antibody responses and generalized CD8+ T-lymphocyte activation. Different criteria for vaccine "responder" status were applied to the measured CTL values. The vaccinees showed evidence of vaccine exposure by CD8+ T-lymphocyte activation and HIV-1-specific antibodies. Considering any single positive HIV-1-specific CTL measurement a vaccine "response," all vaccinees could be classified as "responders," but even slight increases in the stringency of response criteria resulted in a steep decline of the "response" rate. In contrast, HIV-1-infected persons were clearly "responders" against the same proteins by the same criteria. Quantitative assessment of CTL demonstrated low and transient HIV-1-specific CTL compared to natural infection. These analyses emphasize the pitfalls of summarizing vaccine study results using simple cutoff criteria to define response rates, and suggest the utility of more comprehensive descriptions to describe vaccine immunogenicity and persistence of responses. PMID:16545508
Jamieson, Beth D; Ibarrondo, F Javier; Wong, Johnson T; Hausner, Mary Ann; Ng, Hwee L; Fuerst, Marie; Price, Charles; Shih, Roger; Elliott, Julie; Hultin, Patricia M; Hultin, Lance E; Anton, Peter A; Yang, Otto O
A sizable number of individuals at risk of becoming HIV infected or infecting others either do not access or drop out of AIDS prevention programs. Attrition is a relevant concern for HIV prevention research and practice alike as nonparticipation (enrolling in but never attending an intervention) and dropout (beginning but not completing an intervention) can affect internal and external validity,
Scott E. Rutledge; Roger A. Roffman; Joseph F. Picciano; Seth C. Kalichman; James P. Berghuis
An effective vaccine for human immunodeficiency virus (HIV) is needed to stimulate the immune response of the genital mucus to prevent mucosal transmission of the virus. We have developed a macromolecular multicomponent peptide vaccine candidate, VC1. Both rectal and vaginal immunization of VC1 mixed with cholera toxin (CT) induced HIV-1-specific IgA antibody in mouse fecal extract solution and vaginal wash.
Hidenori Kato; Hiroki Bukawa; Eri Hagiwara; Ke-Qin Xin; Kenji Hamajima; Susumu Kawamoto; Mitsugu Sugiyama; Mitsuru Sugiyama; Etsunosuke Noda; Masanosuke Nishizaki; Kenji Okuda
Neisseria meningitidis is the leading cause of bacterial meningitis in the United States and worldwide. A serogroup A/C/W-135/Y polysaccharide meningococcal vaccine has been licensed in the United States since 1981 but has not been used universally outside of the military. On 14 January 2005, a polysaccharide conjugate vaccine that covers meningococcal serogroups A, C, W-135, and Y was licensed in the United States for 11- to 55-year-olds and is now recommended for the routine immunization of adolescents and other high-risk groups. This review covers the changing epidemiology of meningococcal disease in the United States, issues related to vaccine prevention, and recommendations on the use of the new vaccine.
Harrison, Lee H.
Background It has not been clearly demonstrated whether HIV vaccination can complicate routine HIV testing. In this report, we describe the laboratory data of two prisoners who received rgp120 vaccine in a phase III trial underway in Thailand. These data indicate that previous vaccination may complicate the interpretation of screening HIV diagnostic tests. Case presentation The participants were identified from a cohort study on "Health factors related to HIV-1 and other viral infections among incarcerated people" that was approved by The Ethical Committee for Research in Human Subjects, Ministry of Public Health, Thailand. HIV diagnosis was definitively established with serial specimens using multi-screening tests, Western blot and diagnostic PCR. Anti-HIV screening tests consistently exhibited either weakly reactive or inconclusive results. The band patterns of the Western blot analysis corresponded to those found in individuals who received the rgp120 vaccination. Definite results were established using diagnostic PCR, which exhibited consistently negative results with follow-up specimens. Such problems in HIV testing are not easily resolved in the routine clinical setting in Thailand. Conclusions These data demonstrate that HIV-1 vaccination interferes with routine diagnostic tests. Similar cases will not be uncommon in Thailand, where 2,545 people have already participated in a phase III trial.
Suthon, Vongsheree; Archawin, Rojanawiwat; Chanchai, Chardbanchachai; John, Lerwitworapong; Wichuda, Kongpromsook; Wiroj, Paungtubtim; Hansa, Thaisri; Pathom, Sawanpanyalert; Pongnuwat, Sri-ngam; Silaporn, Pithak; Wimala, Inunchot
Worldwide, HIV disproportionately affects women who are often unable to negotiate traditional HIV preventive strategies such as condoms. In the absence of an effective vaccine or cure, chemoprophylaxis may be a valuable self-initiated alternative. Topical microbicides have been investigated as one such option. The first generation topical microbicides were non-specific, broad-spectrum antimicrobial agents, including surfactants, polyanions, and acid buffering gels, that generally exhibited contraceptive properties. After extensive clinical study, none prevented HIV infection, and their development was abandoned. Second generation topical microbicides include agents with selective mechanisms of antiviral activity. Most are currently being used for, or have previously been explored as, drugs for treatment of HIV. The most advanced of these is tenofovir 1% gel: the first topical agent shown to significantly reduce HIV infection by 39% compared to placebo. This review summarizes the evolution of topical microbicides for HIV chemoprophylaxis, highlights important concepts learned, and offers current and future considerations for this area of research. PMID:24664786
Cottrell, Mackenzie L; Kashuba, Angela D M
Current evidence on routine immunization of HIV-1 infected children point out the need for a special vaccine schedule in this population. However, optimal strategies for identifying individuals susceptible to infections, and then offering them sustained protection through appropriate immunization schedule, both in terms of timing and number of vaccine doses, still remain to be elucidated. Understanding the degree of immune recovery after HAART initiation is important in guiding administration of routine vaccination in HIV-1 infected children. Although quantitative measures (e.g., CD4+ T-cell counts and immunoglobulin levels) are frequently performed to evaluate immune parameters, these measures do not fully mirror functional immune recovery. Here, we will review the status of single mandatory and recommended vaccines for HIV-1 infected children in relation to immune recovery after HAART initiation with the aim of identifying new means to help design personalized vaccine schedules for this population.
Cagigi, Alberto; Cotugno, Nicola; Giaquinto, Carlo; Nicolosi, Luciana; Bernardi, Stefania; Rossi, Paolo; Douagi, Iyadh; Palma, Paolo
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
We analyzed HIV-1 genome sequences from 68 newly infected volunteers in the STEP HIV-1 vaccine trial. To determine whether the vaccine exerted selective T cell pressure on breakthrough viruses, we identified potential T cell epitopes in the founder sequences and compared them to epitopes in the vaccine. We found greater distances to the vaccine sequence for sequences from vaccine recipients
Morgane Rolland; Sodsai Tovanabutra; Allan C deCamp; Nicole Frahm; Peter B Gilbert; Eric Sanders-Buell; Laura Heath; Craig A Magaret; Meera Bose; Andrea Bradfield; Annemarie O'Sullivan; Jacqueline Crossler; Teresa Jones; Marty Nau; Kim Wong; Hong Zhao; Dana N Raugi; Stephanie Sorensen; Julia N Stoddard; Brandon S Maust; Wenjie Deng; John Hural; Sheri Dubey; Nelson L Michael; John Shiver; Lawrence Corey; Fusheng Li; Steve G Self; Jerome Kim; Susan Buchbinder; Danilo R Casimiro; Michael N Robertson; Ann Duerr; M Juliana McElrath; Francine E McCutchan; James I Mullins
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.
Mucosal immune responses induced by HIV-1 vaccines are likely critical for prevention. We report a Phase 1 safety and immunogenicity trial in 8 participants using the vaccinia-based TBC-3B vaccine given subcutaneously to determine the relationship between HIV-1 specific systemic and gastrointestinal mucosal responses. Across all subjects, detectable levels of blood vaccinia- and HIV-1-specific antibodies were elicited but none were seen mucosally. While the vaccinia component was immunogenic for CD8+ T lymphocyte (CTL) responses in both blood and mucosa, it was greater in blood. The HIV-1 component of the vaccine was poorly immunogenic in both blood and mucosa. Although only 8 volunteers were studied intensively, the discordance between mucosal and blood responses may highlight mechanisms contributing to recent vaccine failures.
Anton, Peter A.; Ibarrondo, F Javier; Boscardin, W. John; Zhou, Ying; Schwartz, Elissa J.; Ng, Hwee L.; Hausner, Mary Ann; Shih, Roger; Elliott, Julie; Hultin, Patricia M.; Hultin, Lance E.; Price, Charles; Fuerst, Marie; Adler, Amy; Wong, Johnson T.; Yang, Otto O.; Jamieson, Beth D.
Mucosal immune responses induced by HIV-1 vaccines are likely critical for prevention. We report a Phase 1 safety and immunogenicity trial in eight participants using the vaccinia-based TBC-3B vaccine given subcutaneously to determine the relationship between HIV-1 specific systemic and gastrointestinal mucosal responses. Across all subjects, detectable levels of blood vaccinia- and HIV-1-specific antibodies were elicited but none were seen mucosally. While the vaccinia component was immunogenic for CD8(+) T lymphocyte (CTL) responses in both blood and mucosa, it was greater in blood. The HIV-1 component of the vaccine was poorly immunogenic in both blood and mucosa. Although only eight volunteers were studied intensively, the discordance between mucosal and blood responses may highlight mechanisms contributing to recent vaccine failures. PMID:18621451
Anton, Peter A; Ibarrondo, F Javier; Boscardin, W John; Zhou, Ying; Schwartz, Elissa J; Ng, Hwee L; Hausner, Mary Ann; Shih, Roger; Elliott, Julie; Hultin, Patricia M; Hultin, Lance E; Price, Charles; Fuerst, Marie; Adler, Amy; Wong, Johnson T; Yang, Otto O; Jamieson, Beth D
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
Epidemiologic studies have revealed that HIV-1 infections occur through contact with contaminated blood or during unprotected vaginal or anal intercourse. Hence, to protect against HIV infection, vaccines should induce both mucosal and systemic immune responses. We present a brief review of the different delivery systems and adjuvants which can be used to elicit mucosal immune responses. Oral or nasal administration
Dominique Velin; Sally Hopkins; Jean-Pierre Kraehenbuhl
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.
Rotheram-Borus, Mary Jane; Swendeman, Dallas; Chovnick, Gary
The development of a preventive vaccine to neutralize the highly variable and antigenically diverse human immunodeficiency virus type 1 (HIV-1) has been an indomitable goal. The recent discovery of a number of cross-neutralizing and potent monoclonal antibodies from elite neutralizers has provided important insights in this field. Neutralizing antibodies (NAbs) are useful in identifying neutralizing epitopes of vaccine utility and for understanding the mechanism of potent and broad cross-neutralization thus providing a modality of preventive and therapeutic value. In this article we review the current understanding on the potential use of broadly neutralizing antibodies (bNAbs) in their full-length IgG structure, engineered domain antibody or bispecific versions towards preventive and therapeutic applications. The potential implications of NAbs are discussed in the light of the recent developments as key components in vaccination against HIV-1. The development of a vaccine immunogen which elicits bNAbs and confers protective immunity remains a real challenge.
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.
Seth M. Noar; Jessica Fitts Willoughby
Concerns about the impact of risk compensation on advances in biomedical Human Immunodeficiency Virus (HIV) prevention technologies have been documented. We conducted an exploratory qualitative study using focus group discussions with young South African men and women (aged 18–24 years) to explore perceptions of risk compensation among young South Africans with regard to a hypothetical posttrial HIV vaccine. During the discussions participants expressed their disquiet about the potential for risk compensation and the manner in which this might manifest among young people. Discussions specifically focused on reductions in condom use, an increase in multiple partners and increased frequency of sex. The discussions also indicated contradictory feelings about HIV vaccines: appreciation for their development tempered by concerns about loss of control and undermining morality. Women were particularly concerned with the possibility of increased partner concurrency and infidelity. We suggest that concerns in HIV vaccine target populations about the impact of possible risk compensation be incorporated into strategies to for vaccine introduction once vaccines move from the hypothetical to reality.
MacPhail, Catherine L.; Sayles, Jennifer N.; Cunningham, William; Newman, Peter
Concerns about the impact of risk compensation on advances in biomedical human immunodeficiency virus (HIV) prevention technologies have been documented. We conducted an exploratory qualitative study using focus group discussions with young South African men and women (aged 18 to 24 years) to explore perceptions of risk compensation with regard to a hypothetical posttrial HIV vaccine. During the discussions, participants expressed their disquiet about the potential for risk compensation and the manner in which this might manifest among young people. Discussions specifically focused on reductions in condom use, an increase in multiple partners, and increased frequency of sex. The discussions also revealed contradictory feelings about HIV vaccines: appreciation for their development tempered by concerns about loss of control and undermining morality. Women were particularly concerned with the possibility of increased partner concurrency and infidelity. We suggest that concerns in HIV vaccine target populations about the impact of possible risk compensation be incorporated into strategies for vaccine introduction once vaccines move from the hypothetical to reality. PMID:22218269
Macphail, Catherine L; Sayles, Jennifer N; Cunningham, William; Newman, Peter A
During the mid-1980s Australia experienced a remarkable decline in HIV incidence that can rightly be considered a public health milestone of global importance. The effects of this decline lasted for about 20 years and greatly benefited all Australians. In contrast, as we enter the mid-2000s, we see the global epidemic continues to intensify, HIV vaccines remain a distant possibility, and Australia is experiencing rising HIV incidence again. Clearly, better understanding of HIV prevention has important implications both for Australia and the world. Therefore, we believe, it is timely to revisit Australian experiences of the mid-1980s in order to understand those early events better. To gauge the influence (if any) of government strategies, funding levels and other events during a period of dramatic decline in HIV transmission, incidence figures are mapped against Federal HIV/AIDS funding patterns and the occurrence of key national interventions and events. The analysis reveals that the greatest decline in HIV preceded almost all substantive initiatives undertaken at the national level, which are often held responsible for Australia's successful early containment of HIV. In particular, dramatic declines were already well advanced and/or preceded (i) substantive growth in national HIV/AIDS prevention education funding, (ii) publication of the first National AIDS Strategy, (iii) establishment of key national HIV/AIDS bodies and (iv) promulgation of the 'Ottawa Charter'. Explanations for, and lessons learned from Australia's dramatic early declines in HIV incidence are discussed. PMID:17212850
Plummer, D; Irwin, L
The role of volunteer recruitment in HIV vaccine trials has recently been considered particularly with respect to critical issues, such as motivation, psychological assessment and social impact. The preventative and therapeutic phase I trials based on the recombinant biologically active Tat vaccine candidate, sponsored in Italy by the Istituto Superiore di Sanità, included a specific centralised procedure (SCP) developed to
Anna Maria Luzi; Pietro Gallo; Anna Colucci; Simone Marcotullio; Stefania Bellino; Olimpia Longo; Barbara Ensoli
Abstract A vital part of the renewed hope for a vaccine against the human immunodeficiency virus (HIV-1) is based on recent studies that have highlighted major sites of HIV-1 vulnerability that could be effectively targeted by a preventive vaccine. One of these potential vulnerabilities includes the dense cluster of carbohydrates surrounding HIV-1's envelope glycoproteins gp120 and gp41, typically referred to as the “glycan shield.” Recent data from several laboratories have shown that glycans on the HIV-1 envelope form key epitopes for broadly neutralizing antibodies (bNAb). Moreover, HIV-1 envelope glycans play an important role in viral transmission, antigenicity, and immunogenicity. The recent availability of novel tools and technologies has now allowed investigators to leverage glycomic structure–function relationships in the design of candidate HIV-1 vaccines. Additionally, glycans modulate the immune response, playing an essential role in Fc receptor and complement activity. To promote cross-disciplinary collaboration and promote synergistic HIV-1- glycomics research, the National Institutes of Health (NIH) cosponsored and convened a 1.5-day workshop entitled “Functional Glycomics in HIV-1 Vaccine Design.” The meeting focused on the role of glycan interactions with neutralizing antibodies, the influence of immunoglobulin G (IgG) Fc receptor glycosylation, newly available glycomics technologies, and how new information on the role of glycans could be applied in HIV-1 immunogen design strategies. This report summarizes the discussions of this workshop.
Collins, Brenda S.; Dell, Anne; Alter, Galit
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.
Keating, Sheila M.; Jacobs, Evan S.; Norris, Philip J.
The science is clear: HIV prevention can and does save lives. Scores of scientific studies have identified effective prevention interventions for numerous populations, and it is estimated that prevention efforts have averted more than 350,000* HIV infecti...
Accurate methods for estimating HIV incidence from cross-sectional samples would have great utility in prevention research. This report describes recent improvements in cross-sectional methods that significantly improve their accuracy. These improvements are based on the use of multiple biomarkers to identify recent HIV infections. These multi-assay algorithms (MAAs) use assays in a hierarchical approach for testing that minimizes the effort and cost of incidence estimation. These MAAs do not require mathematical adjustments for accurate estimation of the incidence rates in study populations in the year prior to sample collection. MAAs provide a practical, accurate, and cost-effective approach for cross-sectional HIV incidence estimation that can be used for HIV prevention research and global epidemic monitoring.
Brookmeyer, Ron; Laeyendecker, Oliver; Donnell, Deborah; Eshleman, Susan H.
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.
Nutan; Gupta, Satish K.
The HIV/AIDS pandemic continues its spread at a rate of over 15,000 new infections every day. Sexual transmission of HIV-1 is the dominant mode of this pandemic spread. For the first time since the disease emerged in the early 1980s, about half the 42 million people now living with HIV/AIDS worldwide are women. Worldwide, more than 90 percent of all adolescent and adult HIV infections have resulted from heterosexual intercourse. The "feminization" of the pandemic largely driven by the social, economic, and biological factors warrants urgent attention particularly for the adolescent female population. In the absence of an effective prophylactic anti-HIV therapy or vaccine, current efforts are aimed at developing intravaginal/intrarectal topical formulations of anti-HIV agents or microbicides to curb the mucosal and perinatal HIV transmission. Microbicides would provide protection by directly inactivating HIV or preventing HIV from attaching, entering or replicating in susceptible target cells as well as dissemination from target cells present in semen or the host cells that line the vaginal/rectal wall. Thus, ideally, anti-HIV microbicides should be capable of attacking HIV from different angles. In addition, a contraceptive microbicide could help prevent unintended pregnancies worldwide. To be a microbicide, these agents must be safe, effective following vaginal or rectal administration, and should cause minimal or no genital symptoms following long-term repeated usage. 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, 18 of which have advanced to clinical testing. Targeting HIV entry has been a favored approach because it is the first step in the process of infection and several readily available anionic polymeric products seem to variably interfere with these processes are the primary candidates for potential microbicides. Formulations of some anionic polymeric antiviral agents have been tested at various doses and various durations for safety, tolerability, and acceptability in Phase I/II clinical trials (vaginal, rectal, or penile studies) in HIV-uninfected and/or HIV-infected populations. Current multicenter Phase I/II safety and Phase II/III efficacy studies that are being conducted or planned in different geographical locations by various special interest groups are designed for rapid clinical development of candidate products. The currently marketed detergent-type spermicide, nonoxynol-9 (N-9), has failed in Phase III clinical trials, due to the drug-induced formation of localized genital lesions that might in fact actually promote virus transmission. Alternative "first-generation" microbicides that have undergone Phase I/II safety and tolerability studies in HIV-uninfected and/or HIV-infected volunteers include polymeric viral fusion inhibitors (dextrin sulfate/Emmelle, carrageenans [PC-213, PC-503, PC-515/Carraguard], cellulose sulfate/Ushercell, polystyrene sulfonate, naphthalene sulfonate [PIC 024-4/PRO 2000/5], acidifying gel [Carbomer 974P/BufferGel], Lactobacillus (L. crispatus) suppository/CTV-05, detergent-type dual-function barriers [ACIDFORM, GEDA Plus, SURETE, Glyminox/C31G/Savvy, Invisible Condom], herbal extracts [Praneem], and viral replication inhibitors [PMPA/Tenofovir]. For majority of these products, no information is available regarding their long-term mucosal safety, carcinogenicity potential, bioavailability, or efficacy following their extended vaginal or rectal exposure. The irritative genitourinary symptoms reported for a number of these first-generation products in Phase I clinical trials implies that the "soft" preclinical endpoints for mucosal safety established for the use and development of vaginal spermicides may not be rigorous enough for vaginal and rectal microbicides because of the efficient sexual tra virus diversity, and genetic environment. It is now apparent that sexually transmitted R5 HIV-1 viruses have less positive c
D'Cruz, Osmond J; Uckun, Fatih M
Recombinant vesicular stomatitis virus (rVSV) is currently under evaluation as a human immunodeficiency virus (HIV)-1 vaccine vector. The most compelling reasons to develop rVSV as a vaccine vector include a very low seroprevalence in humans, the ability to infect and robustly express foreign antigens in a broad range of cells, and vigorous growth in continuous cell lines used for vaccine manufacture. Numerous preclinical studies with rVSV vectors expressing antigens from a variety of human pathogens have demonstrated the versatility, flexibility, and potential efficacy of the rVSV vaccine platform. When administered to nonhuman primates (NHPs), rVSV vectors expressing HIV-1 Gag and Env elicited robust HIV-1-specific cellular and humoral immune responses, and animals immunized with rVSV vectors expressing simian immunodeficiency virus (SIV) Gag and HIV Env were protected from AIDS after challenge with a pathogenic SIV/HIV recombinant. However, results from an exploratory neurovirulence study in NHPs indicated that these prototypic rVSV vectors might not be adequately attenuated for widespread use in human populations. To address this safety concern, a variety of different attenuation strategies, designed to produce a range of further attenuated rVSV vectors, are currently under investigation. Additional modifications of further attenuated rVSV vectors to upregulate expression of HIV-1 antigens and coexpress molecular adjuvants are also being developed in an effort to balance immunogenicity and attenuation. PMID:16977404
Clarke, David K; Cooper, David; Egan, Michael A; Hendry, R Michael; Parks, Christopher L; Udem, Stephen A
Summary A successful HIV vaccine would have a substantial impact on acquisition of infection, progression of disease among the infected, or infectiousness of the infected. Current vaccine candidates are anticipated to have their major effect on viremia, however, with the expectation that this would induce or be concordant with a reduced rate of AIDS, death, or infectiousness. Although direct assessment of disease progression or infectiousness may be impractical, available potential surrogates for these endpoints may be misleading. This article summarizes the proceedings of a National Institute of Allergy and Infectious Disease–sponsored workshop to explore the use of surrogate endpoints for licensure of an HIV vaccine. Early, medium, and late endpoints were discussed, along with challenges such as surrogate validity, the confounding effect of antiretroviral therapy initiation, and potential selection bias in the vaccine and placebo recipients who become infected. Results from 5 hypothetic HIV vaccine clinical trials with ambiguously successful results were presented to an expert panel for interpretation and discussion of next steps. Key recommendations included assessing magnitude and durability of surrogate effects, generalization across populations, and directed improvement of vaccines. Use of acquisition and a postinfection surrogate as coprimary endpoints was supported, along with use of composite endpoints and exploration of heterogeneity in vaccine efficacy by characteristics of the host and virus.
Follmann, Dean; Duerr, Ann; Tabet, Stephen; Gilbert, Peter; Moodie, Zoe; Fast, Patricia; Cardinali, Massimo; Self, Steve
The International HIV/AIDS Alliance works to support "community action on AIDS in developing countries" through advocacy efforts, research, and outreach programs. Over the past several years, they have also released a number of papers designed to assist non-governmental organizations and service providers with providing quality health care to those living with HIV. This 36-page guide was released in September 2007, and is divided into four sections, including "Community Mobilisation" and "Individually focused health education and support". Each section contains concrete suggestions, along with examples drawn from case studies in Mexico, Senegal, and other places. After reading through this publication, visitors are welcome to offer their own comments and feedback on the International HIV/AIDS Alliance website.
Bacterial infection is a major cause of morbidity and mortality among patients with HIV living in Africa. Broadening the scope\\u000a of cotrimoxazole (CTX) prophylaxis to cover patients whose CD4 counts are above 200 cells\\/mm3 has been suggested as a means of improving the control of infectous disease on the continent. CTX has demonstrated antimalarial\\u000a benefit in Central and West Africa,
David C. Spencer
... receive HIV medicines to prevent mother-to-child transmission of HIV? Within 6 to 12 hours after ... advancing and to reduce the risk of sexual transmission of HIV . The recommendation is strongest for those ...
The goal of antiretroviral therapy for the prevention of mother-to-child transmission (PMTCT) of HIV is to achieve maximal suppression of maternal viral load with minimal maternal, fetal and infant toxicity during pregnancy, delivery and postpartum. In addition to the efficacy and toxicity of antiretroviral therapy, the consideration of HIV resistance in mothers and infected newborns further complicates therapeutic choices for PMTCT. This manuscript summarizes current approaches to PMTC in diverse international settings. PMID:24709447
Rakhmanina, Natella Y; van den Anker, Johannes N
The HIV/AIDS pandemic continues to challenge the African American community with disproportionate rates of infection, particularly among young women ages 25 to 34 years. Development of a preventive HIV vaccine may bring a substantial turning point in this health crisis. Engagement of the African American community is necessary to improve awareness of the effort and favorably influence attitudes and referent norms. The Theory of Reasoned Action (TRA) may be a useful framework for exploration of community engagement outcomes including future attendance, community mobilization, and study participation. Within the context of HIV vaccine outreach, we conducted a cross-sectional survey in early 2007 with 175 African-American adults (>/= 18 years). Confirmatory factor analysis and structural equation modeling were performed and the findings support the potential of the model in understanding behavioral intentions toward HIV vaccine research. PMID:20686675
Frew, Paula M; Archibald, Matthew; Martinez, Nina; del Rio, Carlos; Mulligan, Mark J
The HIV/AIDS pandemic continues to challenge the African American community with disproportionate rates of infection, particularly among young women ages 25 to 34 years. Development of a preventive HIV vaccine may bring a substantial turning point in this health crisis. Engagement of the African American community is necessary to improve awareness of the effort and favorably influence attitudes and referent norms. The Theory of Reasoned Action (TRA) may be a useful framework for exploration of community engagement outcomes including future attendance, community mobilization, and study participation. Within the context of HIV vaccine outreach, we conducted a cross-sectional survey in early 2007 with 175 African-American adults (? 18 years). Confirmatory factor analysis and structural equation modeling were performed and the findings support the potential of the model in understanding behavioral intentions toward HIV vaccine research.
Frew, Paula M.; Archibald, Matthew; Martinez, Nina; del Rio, Carlos; Mulligan, Mark J.
Successful recruitment and retention of HIV-uninfected at-risk participants are essential for HIV vaccine efficacy trials. A multicountry vaccine preparedness study was started in 2003 to assess enrollment and retention of HIV-negative high-risk participants and to assess their willingness to participate in future vaccine efficacy trials. HIV-negative high-risk adults were recruited in the Caribbean, in Southern Africa, and in Latin America, and were followed for 1 year. Participants included men who have sex with men, heterosexual men and women, and female sex workers. History of sexually transmitted infections and sexual risk behaviors were recorded with HIV testing at 0, 6, and 12 months, and willingness to participate in future vaccine trials was recorded at 0 and 12 months. Recruitment, retention, and willingness to participate in future trials were excellent at 3 of the 6 sites, with consistent declines in risk behaviors across cohorts over time. Although not powered to measure seroincidence, HIV seroincidence rates per 100 person-years (95% confidence interval [CI]) were as follows: 2.3 (95% CI: 0.3 to 8.2) in Botswana, 0.5 (95% CI: 0 to 2.9) in the Dominican Republic, and 3.1 (95% CI: 1.1 to 6.8) in Peru. The HIV Vaccine Trials Network 903 study helped to develop clinical trial site capacity, with a focus on recruitment and retention of high-risk women in the Americas, and improved network and site expertise about large-scale HIV vaccine efficacy trials. PMID:18391750
Djomand, Gaston; Metch, Barbara; Zorrilla, Carmen D; Donastorg, Yeycy; Casapia, Martin; Villafana, Tonya; Pape, Jean; Figueroa, Peter; Hansen, Marianne; Buchbinder, Susan; Beyrer, Chris
Health behaviours are individual acts by which people aim to preserve or enhance their health. Theories commonly used to understand health behaviour include the Health Belief Model, the Theories of Reasoned Action and Planned Behaviour, the Transtheoretical Model of Change, Social Cognitive Theory and Problem-Behaviour Theory. Targets for health-promotion interventions include exercise, smoking cessation and condom use. Some behaviours that may contribute to changes in population health, however, are not health behaviours as traditionally understood. For example, participating in an HIV vaccine trial may have the potential to contribute long-term to lowering HIV incidence. To what extent, though, can or should we apply models of health behaviour to HIV vaccine trial participation? This article grapples with the theoretical challenges facing social scientists who conduct research related to HIV vaccine trial participation. We initially consider decision making regarding trial participation from both the participant and investigator perspectives, before considering how these alternate decision-making narratives might impact on the conduct of HIV vaccine trials. We conclude by arguing that social scientists need to move beyond a narrow focus on health promotion theory and to engage in the interrelated scientific activities of theory testing and theory building. PMID:18071976
Kafaar, Z; Kagee, A; Lesch, A; Swartz, L
\\u000a Epidemiological studies have revealed that HIV-1 infections occur through contact with contaminated blood or during unprotected\\u000a vaginal or anal intercourse. Hence, to protect against HIV infection, vaccines should ideally induce both mucosal and systemic\\u000a immune responses. We present a brief review of the different delivery systems and adjuvants which can be used to elicit mucosal\\u000a immune responses. Oral or nasal
Velin Dominique; Jean-Pierre Kraehenbuhl
Recently it has been shown that immunization with plasmid DNA encoding genes for viral or bacterial antigens can elicit both humoral and cellular immune responses in rodents and nonhuman primates. In this study, mice and nonhuman primates were vaccinated by intramuscular injection with plasmids that express either a secreted form of HIV-1 gp120 or rev proteins. Mice receiving the tPA-gp120 DNA developed antigen-specific antibody responses against recombinant gp120 protein and the V2 peptide neutralization epitope as determined by ELISA. Vaccinated mice also exhibited gp120-specific T cell responses, such as in vitro proliferation of splenocytes and MHC Class I-restricted cytotoxic T lymphocyte (CTL) activities, following antigen restimulation. In addition, supernatants from these lymphocyte cultures showed high levels of gamma-interferon production compared with IL-4, suggesting that primarily type 1-like helper T (Th1) lymphocyte responses were induced by both vaccines. Th1-like responses were also obtained for mice vaccinated with rev DNA. Immune responses induced by gp120 or rev vaccines were dose-dependent, boostable, and long-lived (> or = 6 months). Nonhuman primates vaccinated with tPA-gp120 DNA also showed antigen-specific T lymphocyte proliferative and humoral responses, including moderate levels of neutralizing sera against homologous HIV. These results suggest that plasmid DNA may provide a powerful means for eliciting humoral and cellular immune responses against HIV. PMID:8961146
Shiver, J W; Davies, M E; Perry, H C; Freed, D C; Liu, M A
The early immune response to HIV-1 infection is likely to be an important factor in determining the clinical course of disease. Recent data indicate that the HIV-1 quasispecies that arise following a mucosal infection are usually derived from a single transmitted virus. Moreover, the finding that the first effective immune responses drive the selection of virus escape mutations provides insight into the earliest immune responses against the transmitted virus and their contributions to the control of acute viraemia. Strong innate and adaptive immune responses occur subsequently but they are too late to eliminate the infection. In this Review, we discuss recent studies on the kinetics and quality of early immune responses to HIV-1 and their implications for developing a successful preventive HIV-1 vaccine.
McMichael, Andrew J.; Borrow, Persephone; Tomaras, Georgia D.; Goonetilleke, Nilu; Haynes, Barton F.
The nation's HIV prevention efforts are guided by a single, ambitious strategy for combating the epidemic: the National HIV/AIDS Strategy (NHAS). Recent scientific breakthroughs have equipped us with an unprecedented number of effective tools to prevent i...
Background Infections with HIV still represent a major human health problem worldwide and a vaccine is the only long-term option to fight efficiently against this virus. Standardized assessments of HIV-specific immune responses in vaccine trials are essential for prioritizing vaccine candidates in preclinical and clinical stages of development. With respect to neutralizing antibodies, assays with HIV-1 Env-pseudotyped viruses are a high priority. To cover the increasing demands of HIV pseudoviruses, a complete cell culture and transfection automation system has been developed. Methodology/Principal Findings The automation system for HIV pseudovirus production comprises a modified Tecan-based Cellerity system. It covers an area of 5×3 meters and includes a robot platform, a cell counting machine, a CO2 incubator for cell cultivation and a media refrigerator. The processes for cell handling, transfection and pseudovirus production have been implemented according to manual standard operating procedures and are controlled and scheduled autonomously by the system. The system is housed in a biosafety level II cabinet that guarantees protection of personnel, environment and the product. HIV pseudovirus stocks in a scale from 140 ml to 1000 ml have been produced on the automated system. Parallel manual production of HIV pseudoviruses and comparisons (bridging assays) confirmed that the automated produced pseudoviruses were of equivalent quality as those produced manually. In addition, the automated method was fully validated according to Good Clinical Laboratory Practice (GCLP) guidelines, including the validation parameters accuracy, precision, robustness and specificity. Conclusions An automated HIV pseudovirus production system has been successfully established. It allows the high quality production of HIV pseudoviruses under GCLP conditions. In its present form, the installed module enables the production of 1000 ml of virus-containing cell culture supernatant per week. Thus, this novel automation facilitates standardized large-scale productions of HIV pseudoviruses for ongoing and upcoming HIV vaccine trials.
Fuss, Martina; Mazzotta, Angela S.; Sarzotti-Kelsoe, Marcella; Ozaki, Daniel A.; Montefiori, David C.; von Briesen, Hagen; Zimmermann, Heiko; Meyerhans, Andreas
Adenoviral (Ad) vectors have been used for a variety of vaccine applications including cancer and infectious diseases. Traditionally, Ad-based vaccines are designed to express antigens through transgene expression of a given antigen. However, in some cases these conventional Ad-based vaccines have had sub-optimal clinical results. These sub-optimal results are attributed in part to pre-existing Ad serotype 5 (Ad5) immunity. In order to circumvent the need for antigen expression via transgene incorporation, the “antigen capsid-incorporation” strategy has been developed and used for Ad-based vaccine development in the context of a few diseases. This strategy embodies the incorporation of antigenic peptides within the capsid structure of viral vectors. The major capsid protein hexon has been utilized for these capsid incorporation strategies due to hexon's natural role in the generation of anti-Ad immune response and its numerical representation within the Ad virion. Using this strategy, we have developed the means to incorporate heterologous peptide epitopes specifically within the major surface-exposed domains of the Ad capsid protein hexon. Our study herein focuses on generation of multivalent vaccine vectors presenting HIV antigens within the Ad capsid protein hexon, as well as expressing an HIV antigen as a transgene. These novel vectors utilize HVR2 as an incorporation site for a twenty-four amino acid region of the HIV membrane proximal ectodomain region (MPER), derived from HIV glycoprotein gp41 (gp41). Our study herein illustrates that our multivalent anti-HIV vectors elicit a cellular anti-HIV response. Furthermore, vaccinations with these vectors, which present HIV antigens at HVR2, elicit a HIV epitope-specific humoral immune response.
Matthews, Qiana L.; Fatima, Aiman; Tang, Yizhe; Perry, Brian A.; Tsuruta, Yuko; Komarova, Svetlana; Timares, Laura; Zhao, Chunxia; Makarova, Natalia; Borovjagin, Anton V.; Stewart, Phoebe L.; Wu, Hongju; Blackwell, Jerry L.; Curiel, David T.
HIV vaccines offer the best long-term hope of controlling the AIDS pandemic. We explored HIV vaccine knowledge and beliefs among communities at elevated risk for HIV/AIDS. Participants (N=99; median age=33 years; 48% female; 22% African-American; 44% Latino; 28% white; 6% other) were recruited from seven high-risk venues in Los Angeles, California, using purposive, venue-based sampling. Results from nine focus groups revealed: 1) mixed beliefs and conspiracy theories about the existence of HIV vaccines; 2) hopefulness and doubts about future HIV vaccine availability; 3) lack of information about HIV vaccines; and 4) confusion about vaccines and how they work. Tailored HIV vaccine education that addresses the current status of HIV vaccine development and key vaccine concepts is warranted among communities at risk. Ongoing dialogue among researchers, public health practitioners and communities at risk may provide a vital opportunity to dispel misinformation and rumors and to cultivate trust, which may facilitate HIV vaccine trial participation and uptake of future HIV vaccines. PMID:16396058
Roberts, Kathleen Johnston; Newman, Peter A; Duan, Naihua; Rudy, Ellen T
Introduction Extensive observational data suggest that HSV-2 infection may facilitate HIV acquisition, increase HIV viral load, and accelerate HIV progression and onward transmission. To explore these relationships, we examined the impact of pre-existing HSV-2 infection in an international HIV vaccine trial. Methods We analyzed the associations between prevalent HSV-2 infection and HIV-1 acquisition and progression among 1836 men who have sex with men (MSM). We used Cox proportional hazards regression models to estimate the association between HSV-2 infection and both HIV acquisition and ART initiation, and linear regression to explore the effect of HSV-2 on pre-ART viral load. Results HSV-2 infection increased risk of HIV-1 acquisition among all volunteers (adjusted hazard ratio 2.2; 95% CI, 1.4 to 3.5). Adjusting for demographic variables, circumcision, Ad5 titer and significant risk behaviors, the risk of HIV acquisition among HSV-2 infected placebo recipients was three fold higher than HSV-2 seronegatives (hazard ratio 3.3; 95% CI, 1.6 to 6.9). Past HSV-2 infection was associated with a 0.2 log10 copies/ml higher adjusted mean set point viral load (95% CI, 0.3 lower to 0.6 higher). HSV-2 infection was not associated with time to ART initiation. Conclusions Among MSM in an HIV-1 vaccine trial, pre-existing HSV-2 infection was a major risk factor for HIV acquisition. Past HSV-2 did not significantly increase HIV viral load or early disease progression. HSV-2 seropositive persons will likely prove more difficult than HSV-2 seronegative persons to protect against HIV infection using vaccines or other prevention strategies.
Barnabas, Ruanne V; Wasserheit, Judith N; Huang, Yunda; Janes, Holly; Morrow, Rhoda; Fuchs, Jonathan; Mark, Karen E; Casapia, Martin; Mehrotra, Devan V; Buchbinder, Susan P; Corey, Lawrence
Twelve chimpanzees housed in the LEMSIP facilities have been assigned to this project involving research on HIV vaccine studies. The attached table indicates the chimpanzees that are currently in the assigned pool of animals. This is a 'dynamic' pool of a...
A. W. Rowe E. Muchmore
Streptococcus pneumoniae infection is a common and serious health problem that is best prevented by the pneumococcal vaccine. The first vaccine approved by the U.S. Federal Drug Administration in 1977 contained 14 polysaccharide antigens. An improved vaccine introduced in 1983 included 23 polysaccharide antigens. Both vaccines were effective for immunocompetent adults; however, young children and immunocompromised adults remained susceptible. A pediatric vaccine was developed consisting of the capsular antigens of seven pneumococcal serotypes commonly found in children. The antigens in this preparation are covalently conjugated to diphtheria protein to make them more antigenic. The conjugate vaccine was expanded to include 13 serotypes by 2010. Although more immunogenic, the conjugate vaccine has fewer serotypes than the older 23-valent vaccine. The U.S. Centers for Disease Control and Prevention recommend that children at risk for pneumococcal pneumonia as defined by the presence of chronic disease should receive the 13-valent conjugated vaccine. Adults at risk for pneumococcal pneumonia, which includes those over 65 years of age and those who have a chronic disease, should receive the 23-polysaccharide vaccine. Immunosuppressed patients of any age should receive both vaccines. Adults should be revaccinated once at age 65 years or older with the 23-polysaccharide vaccine provided that at least 5 years have elapsed since the previous vaccination. PMID:25032872
Mirsaeidi, Mehdi; Schraufnagel, Dean E
There has been considerable debate over what evidence from preclinical and clinical studies is required to advance an HIV vaccine candidate to phase III efficacy testing. Given this situation, conduct of intermediate-size trials is proposed as a method for assessing the plausibility that a vaccine candidate would prevent chronic HIV infection. Designed to observe 45 incident infections in the control group, these preliminary efficacy trials could rule out candidates with low or no efficacy while advancing those candidates with some evidence of protection to definitive trials. In addition, these trials could provide clues about correlates of immunity. A threefold or greater difference in the postvaccination geometric mean titer of neutralizing antibody can be readily detected between infected and uninfected vaccinees. Differences in CD8+ cytotoxic T lymphocytes, however, are more difficult to detect. Intermediate-size trials could also discern a 0.5 log10 or greater difference in plasma HIV-1 RNA levels between infected vaccinees and infected controls. Such differences in viral load might suggest disease amelioration or reduction in infectiousness. Given the large variability in CD4 count and its relatively modest average decline in the year after infection, a slower decline in CD4 count among infected vaccinees would not be detectable. With limited resources, intermediate-size trials could contribute significantly to HIV vaccine development. PMID:9390572
Rida, W; Fast, P; Hoff, R; Fleming, T
The development of an effective vaccine preventing HIV-1 infection remains elusive. Thus, the development of novel approaches capable of preventing HIV-1 transmission is of paramount importance. However, this is partly hindered by the lack of an easily accessible small-animal model to rapidly measure viral entry. Here, we report the generation of a human CD4- and human CCR5-expressing transgenic luciferase reporter mouse that facilitates measurement of peritoneal and genitomucosal HIV-1 pseudovirus entry in vivo. We show that antibodies and antiretrovirals mediate preexposure protection in this mouse model and that the serum antibody concentration required for protection from cervicovaginal infection is comparable to that required to protect macaques. Our results suggest that this system represents a model for the preclinical evaluation of prophylactic or vaccine candidates. It further supports the idea that broadly neutralizing antibodies should be evaluated for use as preexposure prophylaxis in clinical trials.
Gruell, Henning; Bournazos, Stylianos; Ravetch, Jeffrey V.; Ploss, Alexander
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
BACKGROUND: Though influenza vaccines are the cornerstone of medical interventions aimed at protecting individuals against epidemic influenza, their effectiveness in HIV infected individuals is not certain. With the recent detection of influenza strains in countries with high HIV prevalence rates, we aimed at evaluating the current evidence on the efficacy and clinical effectiveness of influenza vaccines in HIV-infected individuals. METHODS:
Julius Atashili; Linda Kalilani; Adaora A Adimora
Purpose of review We review the current state of evidence-based prevention strategies for reducing sexual transmission of HIV. The combined programmatic and scientific efforts through 2008 to reduce sexual transmission of HIV have failed to reduce substantially the global pandemic. Recent findings Prevention interventions to reduce HIV infection target behavioral, biomedical, and structural risk factors. Some of these prevention strategies have been evaluated in randomized clinical trials (RCTs) with HIV seroincidence endpoints. When RCTs are not feasible, a variety of observational and quasiexperimental research approaches can provide insight as to program effectiveness of specific strategies. Only five RCTs have demonstrated a notable decrease in sexually acquired HIV incidence. These include the Mwanza study of syndromic management of sexually transmitted diseases and three male circumcision trials in East Africa; a microbicide trial reported in 2009 shows substantial promise for the efficacy of PRO 2000 (0.5% gel). Summary The combined programmatic and scientific efforts to reduce sexual transmission of HIV have made incremental progress. New prevention tools are needed to stem the continued spread of HIV, though microbicides and vaccines will take many more years to develop, test, and deploy. Combination strategies of existing modalities should be tested to evaluate the potential for more proximate prevention benefits.
Vermund, Sten H.; Allen, Katherine L.; Karim, Quarraisha Abdool
Trials to evaluate the efficacy of preventive HCV vaccines will need participation from high risk HCV seronegative injection drug users (IDUs). To guide trial planning, we assessed willingness of young IDU in San Francisco to participate in HCV vaccine efficacy trials and evaluate knowledge of vaccine trial concepts: placebo, randomization and blinding. During 2006 and 2007, a total of 67 participants completed the survey. A substantial proportion (88%) would definitely (44%) or probably (44%) be willing to participate in a randomized trial, but knowledge of vaccine trial concepts was low. Reported willingness to participate in an HCV vaccine trial decreased with increasing trial duration, with 67% of participants surveyed willing to participate in a trial of one year duration compared to 43% of participants willing to participate in a trial of 4 years duration. Willingness to enroll in HCV vaccine trials was higher in young IDU than reported by most at-risk populations in HIV vaccine trials. Educational strategies will be needed to ensure understanding of key concepts prior to implementing HCV vaccine trials.
Levy, Vivian; Evans, Jennifer L.; Stein, Ellen S.; Davidson, Peter J.; Lum, Paula J.; Hahn, Judith A.; Page, Kimberly
The human immunodeficiency virus (HIV) prevention continuum is a framework that illustrates the interconnectedness of each step in the spectrum of prevention services, while emphasizing that all steps are needed to decrease HIV acquisition and transmission. This continuum, similar to the HIV care continuum, begins with HIV testing followed by linkage of HIV-uninfected persons to prevention services, retention in such services, and adherence to prevention interventions with repeated HIV testing to monitor for HIV acquisition. To advance the global goal of zero new HIV infections, individuals must receive the entire continuum of prevention services, and no partial credit can be given to achievement of one step in isolation of all steps in the continuum. PMID:24926026
McNairy, Margaret L; El-Sadr, Wafaa M
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.
Chanzu, Nadia; Ondondo, Beatrice
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
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
This second special issue of the Health Education Monograph Series on HIV/AIDS Prevention in Rural Communities presents seven articles: (1) "Preventing Maternal-Infant Transmission of HIV: Social and Ethical Issues" (James G. Anderson, Marilyn M. Anderson, and Tara Booth); (2) "HIV Infection in Diverse Rural Population: Migrant Farm Workers in…
Torabi, Mohammad R., Ed.
The successful demonstration that antiretroviral (ARV) drugs can be used in diverse ways to reduce HIV acquisition or transmission risks - either taken as pre-exposure prophylaxis (PrEP) by those who are uninfected or as early treatment for prevention (T4P) by those living with HIV - expands the armamentarium of existing HIV prevention tools. These findings have implications for the design of future HIV prevention research trials. With the advent of multiple effective HIV prevention tools, discussions about the ethics and the feasibility of future HIV prevention trial designs have intensified. This article outlines arguments concerning the inclusion of newly established ARV-based HIV prevention interventions as standard of prevention in HIV prevention trials from multiple perspectives. Ultimately, there is a clear need to incorporate stakeholders in a robust discussion to determine the appropriate trial design for each study population.
Haire, Bridget; Folayan, Morenike Oluwatoyin; Hankins, Catherine; Sugarman, Jeremy; McCormack, Sheena; Ramjee, Gita; Warren, Mitchell
Vaccination is traditionally considered as a measure addressed to infants and children. Indeed, in natural conditions, vaccine-preventable infections are mainly spread at a young age. The implementation of routine and mass vaccination programmes has led to the eradication of smallpox and to the elimination of poliomyelitis in many regions of the world, together with the control of once life-threatening diseases like diphtheria and tetanus. In more recent times, the development of new generation vaccines and the changing epidemiological profile of many vaccine-preventable diseases have greatly changed the objectives and the target of today's immunization strategies. The objective of this article is to highlight and discuss the evolution of vaccination strategies from measures aimed at protecting children to a practice that is needed throughout life. Adolescents and adults need immunization for several reasons: they may not have received the vaccines usually administered in childhood; new vaccines tailored for adolescents and adults have become available; immunity acquired thanks to immunization in childhood can fade; and older adults or those who are chronically ill are more susceptible to vaccine-preventable diseases and to their complications. The changing demographic profile of both industrialized countries and of countries in transition towards an 'aging' population, and the shift of several infectious diseases towards adulthood make it imperative that new infrastructures to deliver vaccines and new investments in immunization are investigated. Such a change of perspective is needed both to preserve health and to guarantee the sustainability of health systems. PMID:24829938
Bonanni, P; Sacco, C; Donato, R; Capei, R
A vaccine that would engage the mucosal immune system against a broad range of HIV-1 subtypes and prevent epithelial transmission is highly desirable. Here we report fusing the mucosal targeting B subunit of cholera toxin to the conserved galactosylceramide-binding domain (including the ELDKWA-neutralizing epitope) of the HIV-1 gp41 envelope protein, which mediates the transcytosis of HIV-1 across the mucosal epithelia. Chimeric protein expressed in bacteria or plants assembled into oligomers that were capable of binding galactosyl-ceramide and GM1 gangliosides. Mucosal (intranasal) administration in mice of the purified chimeric protein followed by an i.p. boost resulted in transcytosis-neutralizing serum IgG and mucosal IgA responses and induced immunological memory. Plant production of mucosally targeted immunogens could be particularly useful for immunization programs in developing countries, where desirable product traits include low cost of manufacture, heat stability, and needle-free delivery.
Matoba, Nobuyuki; Magerus, Aude; Geyer, Brian C.; Zhang, Yunfang; Muralidharan, Mrinalini; Alfsen, Annette; Arntzen, Charles J.; Bomsel, Morgane; Mor, Tsafrir S.
The Tat protein is essential for HIV type 1 (HIV-1) replication and may be an important virulence factor in vivo. We studied the role of Tat in viral pathogenesis by immunizing rhesus macaques with chemically inactivated Tat toxoid and challenging these animals by intrarectal inoculation with the simian/human immunodeficiency virus 89.6PD. Immune animals had significantly attenuated disease with lowered viral RNA, interferon-?, and chemokine receptor expression (CXCR4 and CCR5) on CD4+ T cells; these features of infection have been linked to in vitro effects of Tat and respond similarly to extracellular Tat protein produced during infection. Immunization with Tat toxoid inhibits key steps in viral pathogenesis and should be included in therapeutic or preventive HIV-1 vaccines.
Pauza, C. David; Trivedi, Parul; Wallace, Marianne; Ruckwardt, Tracy J.; Le Buanec, Helene; Lu, Wei; Bizzini, Bernard; Burny, Arsene; Zagury, Daniel; Gallo, Robert C.
Latinos are under-represented in HIV/AIDS medical research in the US. Although they are disproportionately impacted by HIV/AIDS, Latinos may be reluctant to participate in HIV vaccine trials. Three focus groups were conducted with 32 Spanish-speaking Latinos recruited from two community-based healthcare organizations in Los Angeles, California. A qualitative focus group interview guide was developed to explore concerns, motivators and intentions in regard to participation in HIV vaccine trials. Mistrust and fear of government emerged as important themes related to reluctance to participate in an HIV vaccine trial. Specific concerns regarding trial participation included: (1) fear of vaccine-induced HIV infection, (2) physical side effects, (3) stigma and (4) false-induced HIV-positive test results and their social repercussions. Motivators for enrolling in an HIV vaccine trial included: (1) incentives, (2) convenience of participating in a study, (3) sufficient and appropriate study information, (4) personal benefits and (5) altruism. Interventions to facilitate participation by Latinos in HIV vaccine trials should address mistrust and fear of government-sponsored HIV/AIDS medical research, increase access to and convenience of clinical trials, address fear of vaccine-induced infection, combat HIV/AIDS stigma and raise awareness of the relevance of HIV/AIDS to Latino communities. PMID:17129857
Brooks, R A; Newman, P A; Duan, N; Ortiz, D J
The HIV/AIDS epidemic remains a global health problem, especially in Sub-Saharan Africa. An effective HIV-1 vaccine is therefore badly required to mitigate this ever-expanding problem. Since HIV-1 infects its host through the mucosal surface, a vaccine for the virus needs to trigger mucosal as well as systemic immune responses. Oral, attenuated recombinant Salmonella vaccines offer this potential of delivering HIV-1 antigens to both the mucosal and systemic compartments of the immune system. So far, a number of pre-clinical studies have been performed, in which HIV-1 Gag, a highly conserved viral antigen possessing both T- and B-cell epitopes, was successfully delivered by recombinant Salmonella vaccines and, in most cases, induced HIV-specific immune responses. In this review, the potential use of Salmonella enterica serovar Typhimurium as a live vaccine vector for HIV-1 Gag is explored. PMID:23989890
The HIV/AIDS epidemic remains a global health problem, especially in Sub-Saharan Africa. An effective HIV-1 vaccine is therefore badly required to mitigate this ever-expanding problem. Since HIV-1 infects its host through the mucosal surface, a vaccine for the virus needs to trigger mucosal as well as systemic immune responses. Oral, attenuated recombinant Salmonella vaccines offer this potential of delivering HIV-1 antigens to both the mucosal and systemic compartments of the immune system. So far, a number of pre-clinical studies have been performed, in which HIV-1 Gag, a highly conserved viral antigen possessing both T- and B-cell epitopes, was successfully delivered by recombinant Salmonella vaccines and, in most cases, induced HIV-specific immune responses. In this review, the potential use of Salmonella enterica serovar Typhimurium as a live vaccine vector for HIV-1 Gag is explored.
In Australia, unlike much of the rest of the world, HIV transmission through heterosexual contact remains a relatively rare occurrence. In consequence, HIV-prevention efforts have been firmly focused on male-to-male sex as the most frequent source of HIV transmission. There are emerging signs that this epidemiological landscape may be shifting, which raises questions about current and future HIV prevention strategies. Over the past decade, national surveillance data have shown an increase in HIV notifications for which exposure to HIV was attributed to heterosexual contact. This paper offers an epidemiological and sociocultural picture of heterosexual HIV transmission in Australia. We outline recent trends in heterosexually acquired HIV and discuss specific factors that shape transmission and prevention among people at risk of HIV infection through heterosexual contact. To illustrate the contextual dynamics surrounding HIV in this diverse population, we detail two key examples: HIV among people from minority ethnic backgrounds in New South Wales; and overseas-acquired HIV among men in Western Australia. We argue that, despite their differences, there are significant commonalities across groups at risk of HIV infection through heterosexual contact, which not only provide opportunities for HIV prevention, but also call for a rethink of the dominant HIV response in Australia. PMID:24846487
Persson, Asha; Brown, Graham; McDonald, Ann; Körner, Henrike
We analyzed HIV-1 genome sequences from 68 newly-infected volunteers in the Step HIV-1 vaccine trial. To determine whether the vaccine exerted selective T-cell pressure on breakthrough viruses, we identified potential T-cell epitopes in the founder sequences and compared them to epitopes in the vaccine. We found greater distances for sequences from vaccine recipients than from placebo recipients (p-values ranging from < 0.0001 to 0.09). The most significant signature site distinguishing vaccine from placebo recipients was Gag-84, a site encompassed by several epitopes contained in the vaccine and restricted by HLA alleles common in the cohort. Moreover, the extended divergence was confined to the vaccine components of the virus (Gag, Pol, Nef) and not found in other HIV-1 proteins. These results represent the first evidence of selective pressure from vaccine-induced T-cell responses on HIV-1 infection.
Rolland, Morgane; Tovanabutra, Sodsai; deCamp, Allan C.; Frahm, Nicole; Gilbert, Peter B.; Sanders-Buell, Eric; Heath, Laura; Magaret, Craig A.; Bose, Meera; Bradfield, Andrea; O'Sullivan, Annemarie; Crossler, Jacqueline; Jones, Teresa; Nau, Marty; Wong, Kim; Zhao, Hong; Raugi, Dana N.; Sorensen, Stephanie; Stoddard, Julia N.; Maust, Brandon S.; Deng, Wenjie; Hural, John; Dubey, Sheri; Michael, Nelson L.; Shiver, John; Corey, Lawrence; Li, Fusheng; Self, Steve G.; Kim, Jerome; Buchbinder, Susan; Casimiro, Danilo R.; Robertson, Michael N.; Duerr, Ann; McElrath, M. Juliana; McCutchan, Francine E.; Mullins, James I.
During the second half of the 20th century, vaccinations led to the control or even eradication of several vaccine-preventable diseases (VPDs) in Europe. However, outbreaks of VPDs continue to occur even in countries with well-established vaccination programs. Reasons include the existence of under-vaccinated populations, the increasing anti-vaccination movement and the increasing movement of populations across borders. Ensuring adequate levels of herd immunity is the only reliable method for preventing epidemics and a re-emergence of VPDs. In order to achieve this, more flexible vaccine delivery platforms are needed targeting the less-privileged people, especially in the context of the current economic crisis. Healthcare personnel and healthcare systems should be prepared to address these challenges in the following years. PMID:24958075
Wicker, Sabine; Maltezou, Helena C
Prevention of influenza transmission and containment of epidemics and pandemics require effective strategies that can be efficiently and easily addressed to the whole population. Annual vaccination is undoubtedly the most effective way to provide protection against influenza infection. Numbers of vaccines are actually available for yearly immunisation. However, the continuous increasing demand for rapidly available vaccine doses for immunisation of a larger proportion of population represents the stimulus for study and development of more efficient vaccine production technologies, which can guarantee reduction of vaccine manufacture times and better compliance by availability of easier routes of administration. New perspectives in influenza vaccination technology are making their way in the future panorama of influenza prevention strategies. PMID:21133814
Zuccotti, Gian Vincenzo; Fabiano, Valentina
The most up-to-date estimates demonstrate very heterogeneous spread of HIV-1, and more than 30 million people are now living with HIV-1 infection, most of them in sub-Saharan Africa. The efficiency of transmission of HIV-1 depends primarily on the concentration of the virus in the infectious host. Although treatment with antiviral agents has proven a very effective way to improve the health and survival of infected individuals, as we discuss here, the epidemic will continue to grow unless greatly improved prevention strategies can be developed and implemented. No prophylactic vaccine is on the horizon. However, several behavioral and structural strategies have made a difference — male circumcision provides substantial protection from sexually transmitted diseases, including HIV-1, and the application of antiretroviral agents for prevention holds great promise.
Cohen, Myron S.; Hellmann, Nick; Levy, Jay A.; DeCock, Kevin; Lange, Joep
DNA prime and recombinant fowlpox virus (rFPV) boost vaccines were designed to express multiple HIV or SIV antigens for use in human clinical trials and in pre-clinical trials in macaques. Three sets of vaccines with matching HIV or SIV antigen sets, modified for vaccine safety considerations, were constructed and shown to express the relevant proteins. The rFPV vaccines with inserts
Barbara E. H. Coupar; Damian F. J. Purcell; Scott A. Thomson; Ian A. Ramshaw; Stephen J. Kent; David B. Boyle
Women are biologically more susceptible to HIV infection than men through heterosexual penile-vaginal intercourse, and transmission by heterosexual means seems to be increasing. The use of male condoms and partner reduction are currently recommended to reduce the risk of contracting and transmitting HIV. Women can, however, only indirectly influence these behaviors. Many face social and emotional factors which make it impossible to negotiate condom use with an unwilling partner. Scientists are therefore paying greater attention to female barrier methods such as the female condom and spermicides as potential female- controlled ways to help women avoid infection. Noncontraceptive chemical methods in the form of jellies and topical creams are being explored. Limited in vivo scientific data exists on how these methods may prevent the transmission of HIV. The female condom is a thin, plastic sheath which covers the cervix, vagina, and women's external genitalia. It has gone to clinical trials in 1700 women at 71 sites. While many women are in favor of the method, objections to its use have been voiced due to its appearance, the noise made during intercourse, slippage, how it feels during intercourse, expense, reduced sensitivity, and embarrassment. Its potential for re-use must be explored. Only inconclusive results are available on the effectiveness of spermicides. While lab and animal research show nonoxynol-9 can kill HIV, it remains to be seen how much or how often it may be used before mucosal linings become irritated and potentially facilitate the entry of HIV. Many unresolved questions about the mechanics of HIV infection remain to be answered before these methods may be fully endorsed by a wide array of scientists. PMID:12344882
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 most common cause of hearing loss in early childhood is otitis media with effusion (OME). Prevention of OME in preschool children will improve quality of life. The authors aimed to determine, by the best available published evidence, whether vaccination against pneumococci effectively prevents OME. The study design was based on systematic review (SR) of randomized controlled trials (Level 1a evidence). The medical literature available through searching Medline database was reviewed using the following keywords "Otitis media with effusion," "secretory otitis media," or "glue ear," and "vaccination" limiting the search to randomized controlled trials (RCTs) conducted on children (0-18 years), published in English, in the last 10 years. Results of effects of vaccination on prevention of OME from the included RCTs were utilized to conduct a meta-analysis to find out the preventive value of antipneumococcal vaccination. Three RCTs were identified conforming to the inclusion criteria. Meta-analysis of results showed no significant preventive advantage for antipneumococcal vaccination. Based on the results it was confirmed that neither primary nor secondary prevention by antipneumococcal vaccination has a beneficial impact on OME. More RCTs should be conducted to study the effect of vaccination on OME. PMID:22389091
El-Makhzangy, Aly M N; Ismail, Naema M; Galal, Salma B; Sobhy, Tamer S; Hegazy, Amal A
Reducing mother to child transmission (MTCT) of HIV in resource poor countries continues to be a major challenge. Here, we construct a hazard model to assess the effectiveness of combinations of HIV vaccine, Nevirapine (NVP), and HIV-specific monoclonal antibody (HIVAB) in reducing MTCT of HIV during the intrapartum and breastfeeding periods. The model shows that an intervention that uses three
Myung Shin K. Sim; William G. Cumberland; Naihua Duan; Yvonne J. Bryson
Induction of HIV-specific T-cell responses by vaccines may facilitate efficient control of HIV. Plasmid DNA vaccines and recombinant fowlpoxvirus (rFPV) vaccines are promising HIV-1 vaccine candidates, although either vaccine alone may be insufficient to protect against HIV-1. A consecutive immunisation strategy involving priming with DNA and boosting with rFPV vaccines encoding multiple common HIV-1 antigens was further evaluated in 30 macaques. The DNA vaccine vector included CpG immunostimulatory molecules, and rFPV vaccines were compared with rFPV vaccines co-expressing the pro-T cell cytokines IFNgamma or IL-12. Vaccines expressed multiple HIV-1 genes, mutated to remove active sites of the HIV proteins. The vaccines were well tolerated, and a significant enhancement of DNA-vaccine primed HIV-1 specific T lymphocyte responses was observed following rFPV boosting. Co-expression of IFNgamma or IL-12 by the rFPV vaccines did not further enhance immune responses. Non-sterilising protection from a non-pathogenic HIV-1 challenge was observed. This study provides evidence of a safe, optimised, strategy for the generation of T-cell mediated immunity to HIV-1. PMID:15531036
Dale, C Jane; De Rose, Robert; Wilson, Kim M; Croom, Hayley A; Thomson, Scott; Coupar, Barbara E H; Ramsay, Alistair; Purcell, Damian F J; Ffrench, Rosemary; Law, Matthew; Emery, Sean; Cooper, David A; Ramshaw, Ian A; Boyle, David B; Kent, Stephen J
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.
Tarimo, Edith A. M.; Thorson, Anna; Kohi, Thecla W.; Bakari, Muhammad; Mhalu, Fred; Kulane, Asli
The past two decades have witnessed substantial advances in the science of preventing HIV infection. Although important issues remain and there is a need for continuing research, arguably the biggest challenge in preventing HIV transmission is the full implementation of existing preventive interventions worldwide.
Lydia L Ogden; Eugene McCray; Ronald O Valdiserri
The rationale behind current worldwide human papilloma virus (HPV) vaccination programs starts from two basic premises, 1) that HPV vaccines will prevent cervical cancers and save lives and, 2) have no risk of serious side effects. Therefore, efforts should be made to get as many pre-adolescent girls vaccinated in order to decrease the burden of cervical cancer. Careful analysis of HPV vaccine pre- and post-licensure data shows however that both of these premises are at odds with factual evidence and are largely derived from significant misinterpretation of available data.
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.
Brenner, Bluma G.; Wainberg, Mark A.
GSK`s Synflorix: Highly effective at preventing invasive pneumococcal disease Positive phase 1 interim results for killed whole-virus HIV vaccine Therapeutic HBV vaccine drives immune responses in liver New tuberculosis vaccine candidate to enter the clinic Novartis receives positive CHMP opinion for MenB vaccine Bexsero New research points way to faster flu vaccines New Meth vaccine shows promise in animals RTS,S malaria vaccine reduces malaria by approximately one-third in African infants
Riedmann, Eva M.
... can offer important insights into where the HIV epidemic may grow, making STD surveillance data helpful in forecasting where HIV rates are likely to increase. Better linkages are needed between HIV and STD prevention ... both epidemics. In the context of persistently high prevalence of ...
The Muxe are an indigenous transgender group living in Juchitan in the State of Oaxaca in Southern Mexico. Despite many HIV prevention efforts from governmental and non governmental organizations during the past 20 years, the spread of the HIV epidemic has not been halted amongst the Muxe. Causes and consequences for the high HIV and AIDS prevalence among the Muxe
Background & Objectives: HIV is a major health challenge for prison authorities. HIV in prisons has implications for HIV in the general community. The aim of this paper was to gather information on HIV risk, prevalence, prevention and treatment in prisons in India. Methods: Relevant published and unpublished reports and information were sought in order to provide a coherent picture of the current situation relating to HIV prevention, treatment and care in prisons in India. Information covered prison management and population statistics, general conditions in prisons, provision of general medical care and the HIV situation in prison. Results: No data on drug injection in prison were identified. Sex between men was reported to be common in some Indian prisons. A national study found that 1.7 per cent of inmates were HIV positive. Some prisons provided HIV education. Condom provision was considered illegal. A few prisoners received drug treatment for drug use, HIV infection or co-infection with sexually transmitted infections (STIs). Interpretation & conclusions: HIV prevalence in prisons in India was higher than that in the general community. Regular monitoring of information on HIV risk behaviours and prevalence in Indian prisons is strongly recommended. Evidence based treatment for drug injectors and nation-wide provision of HIV prevention strategies are urgently required. Voluntary counselling, testing and treatment for HIV and STIs should be provided.
Dolan, Kate; Larney, Sarah
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
Acquired Immunodeficiency Syndrome (AIDS) is one of the most critically acclaimed endemic diseases, caused by two lentiviruses HIV-1 and 2. HIV-2 displays intimate serological and antigenic resemblance to Simian Immunodeficiency Virus (SIV) along with less pathogenicity, lower infectivity and appreciable cross reactivity with HIV-1 antigens. The present era is confronted with the challenge to fabricate a vaccine effective against all clades of both the species of HIV. But vaccine development against HIV-1 has proven highly intricate, moreover the laborious and deficient conventional approaches has slackened the pace regarding the development of new vaccines. These concerns may be tackled with the development of HIV-2 vaccine as a natural control of HIV-1 that has been found in ancestors of HIV-2 i.e. African monkeys, mangabeys and macaques. Thereby, suggesting the notion of cross protection among HIV-2 and HIV-1. Assistance of bioinformatics along with vaccinomics strategy can bring about a quantum leap in this direction for surpassing the bottleneck in conventional approaches. These specifics together can add to our conception that HIV-2 vaccine design by in silico strategy will surely be a constructive approach for HIV-1 targeting. PMID:23483108
Diwan, Batul; Saxena, Rupali; Tiwari, Archana
Rationale: Novel tuberculosis (TB) vaccines should be safe and effective in populations infected with Mycobacterium tuberculosis (M.tb) and/or HIV for effective TB control. Objective: To determine the safety and immunogenicity of MVA85A, a novel TB vaccine, among M.tb- and/or HIV-infected persons in a setting where TB and HIV are endemic. Methods: An open-label, phase IIa trial was conducted in 48 adults with M.tb and/or HIV infection. Safety and immunogenicity were analyzed up to 52 weeks after intradermal vaccination with 5 × 107 plaque-forming units of MVA85A. Specific T-cell responses were characterized by IFN-? enzyme-linked immunospot and whole blood intracellular cytokine staining assays. Measurements and Main Results: MVA85A was well tolerated and no vaccine-related serious adverse events were recorded. MVA85A induced robust and durable response of mostly polyfunctional CD4+ T cells, coexpressing IFN-?, tumor necrosis factor-?, and IL-2. Magnitudes of pre- and postvaccination T-cell responses were lower in HIV-infected, compared with HIV-uninfected, vaccinees. No significant effect of antiretroviral therapy on immunogenicity of MVA85A was observed. Conclusions: MVA85A was safe and immunogenic in persons with HIV and/or M.tb infection. These results support further evaluation of safety and efficacy of this vaccine for prevention of TB in these target populations.
Tameris, Michele; Smit, Erica; van der Merwe, Linda; Hughes, E. Jane; Kadira, Blessing; Mauff, Katya; Moyo, Sizulu; Brittain, Nathaniel; Lawrie, Alison; Mulenga, Humphrey; de Kock, Marwou; Makhethe, Lebohang; Janse van Rensburg, Esme; Gelderbloem, Sebastian; Veldsman, Ashley; Hatherill, Mark; Geldenhuys, Hendrik; Hill, Adrian V. S.; Hawkridge, Anthony; Hussey, Gregory D.; Hanekom, Willem A.; McShane, Helen; Mahomed, Hassan
Background: both the current NHMRC guidelines of Australia and the USPHS\\/IDSA guidelines recommend pneumococcal vaccine be given to all patients with HIV infection despite a paucity of data to support these recommendations. Objectives: the aim of this study was to assess the incidence of invasive pneumococcal disease and use of pneumococcal vaccine in HIV-infected patients at The Alfred Hospital, Melbourne,
Anna B. Pierce; Jennifer F. Hoy
The conserved oligomannose epitope, Man9GlcNAc2, recognized by the broadly neutralizing human mAb 2G12 is an attractive prophylactic vaccine candidate for the prevention of HIV-1 infection. We recently reported total chemical synthesis of a series of glycopeptides incorporating one to three copies of Man9GlcNAc2 coupled to a cyclic peptide scaffold. Surface plasmon resonance studies showed that divalent and trivalent, but not
Joseph G. Joyce; Isaac J. Krauss; Hong C. Song; David W. Opalka; Karen M. Grimm; Deborah D. Nahas; Mark T. Esser; Renee Hrin; Meizhen Feng; Vadim Y. Dudkin; Michael Chastain; John W. Shiver; Samuel J. Danishefsky
Background Increased sexual risk behaviour in participants enrolled in HIV prevention trials has been a concern. The HVTN 503/Phambili study, a phase 2B study of the Merck Ad-5 multiclade HIV vaccine in South Africa, suspended enrollment and vaccinations following the results of the Step study. Participants were notified of their treatment allocation and continue to be followed. We investigated changes in risk behaviour over time and assessed the impact of study unblinding. Methods 801 participants were enrolled. Risk behaviors were assessed with an interviewer-administered questionnaire at 6-month intervals. We assessed change from enrolment to the first 6-month assessment pre-unblinding and between enrolment and at least 6 months post-unblinding on all participants with comparable data. A one-time unblinding risk perception questionnaire was administered post-unblinding. Results A decrease in participants reporting unprotected sex was observed in both measured time periods for men and women, with no differences by treatment arm. At 6 months (pre-unblinding), 29.6% of men and 35.8% of women reported changing from unprotected to protected sex (p <0.0001 for each).Men (22%) were more likely than women (14%) to report behavior change after unblinding (p=0.009). Post-enrolment, 142 (45%) of 313 previously uncircumcised men underwent medical circumcision. 663 participants completed the unblinding questionnaire. More vaccine (24.6%) as compared to placebo recipients (12.0%) agreed that they were more likely to get HIV than most people (p<0.0001), and attributed this to receiving the vaccine. Conclusion We did not find evidence of risk compensation during this clinical trial. Some risk behaviour reductions including male circumcision were noted irrespective of treatment allocation.
Gray, GE; Metch, B; Churchyard, G; Mlisana, K; Nchabeleng, M; Allen, M; Moodie, Z; Kublin, J; Bekker, L-G
Targeting canarypox (CP)-HIV vaccine to dendritic cells (DCs) elicits anti-HIV-1 immune responses in vitro. We conducted a phase I/II clinical trial to evaluate whether adding DC to a CP-HIV vaccine improved virologic control during analytic treatment interruption (ATI) in HIV-1-infected subjects. Twenty-nine subjects on suppressive antiretroviral therapy were randomized to vaccination with autologous DCs infected with CP-HIV+keyhole limpet hemocyanin (KLH) (arm A, n=14) or CP-HIV+KLH alone (arm B, n=15). The mean viral load (VL) setpoint during ATI did not differ between subjects in arms A and B. A higher percentage of subjects in the DC group had a VL setpoint < 5,000 c/mL during ATI (4/13 or 31% in arm A compared with 0/13 in arm B, p=0.096), but virologic control was transient. Subjects in arm A had a greater increase in KLH lymphoproliferative response than subjects in arm B; however, summed ELISPOT responses to HIV-1 antigens did not differ by treatment arm. We conclude that a DC-CP-HIV vaccine is well-tolerated in HIV-1-infected patients, but does not lower VL setpoint during ATI compared with CP-HIV alone. New methods to enhance the immunogenicity and antiviral efficacy of DC-based vaccines for HIV-1 infection are needed. PMID:19450647
Gandhi, Rajesh T; O'Neill, David; Bosch, Ronald J; Chan, Ellen S; Bucy, R Pat; Shopis, Janet; Baglyos, Lynn; Adams, Elizabeth; Fox, Lawrence; Purdue, Lynette; Marshak, Ann; Flynn, Theresa; Masih, Reena; Schock, Barbara; Mildvan, Donna; Schlesinger, Sarah J; Marovich, Mary A; Bhardwaj, Nina; Jacobson, Jeffrey M
A safe and effective vaccine against human immunodeficiency virus type 1 (HIV-1) is urgently needed to combat the worldwide AIDS pandemic, but still remains elusive. The fact that uncontrolled replication of an attenuated vaccine can lead to regaining of its virulence creates safety concerns precluding many vaccines from clinical application. We introduce a novel approach to control HIV-1 replication, which entails the manipulation of essential HIV-1 protein biosynthesis through unnatural amino acid (UAA*)-mediated suppression of genome-encoded blank codon. We successfully demonstrate that HIV-1 replication can be precisely turned on and off in?vitro. PMID:24715496
Wang, Nanxi; Li, Yue; Niu, Wei; Sun, Ming; Cerny, Ronald; Li, Qingsheng; Guo, Jiantao
This Extended Plan maintains the focus on core prevention priorities expressed in the 2001 Plan: reducing the number of new infections, increasing knowledge of HIV status, and promoting linkages to care, treatment, and prevention services. In addition, ne...
US prison inmates are disproportionately indigent young men of color. These individuals are severely affected by HIV/AIDS, largely owing to the high-risk behavior that they engage in prior to incarceration. Researchers and practitioners have issued a call for the importance of offering HIV prevention services in prison settings. However, this call has largely been ignored. In this article, we outline reasons why these recommendations have been largely ignored, discuss innovative HIV prevention programs that are currently being implemented in prison settings, and offer recommendations for securing support for HIV prevention services in correctional settings.
Braithwaite, Ronald L.; Arriola, Kimberly R. J.
Issues of quantity, quality and location impact the ability of CD8 T cells to mediate protection from infection. These issues are considered in light of human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) vaccination. Methods are reviewed that result in 100- to 1000-fold higher frequencies of vaccine-specific memory CD8 T cells than that achieved by current HIV/SIV vaccine approaches. Data demonstrating that location within mucosal tissues has a direct impact on memory CD8 T-cell function are discussed. Arguments are made that establishing memory CD8 T cells within mucosal sites of transmission, a priori to natural infection, may be essential for conferring optimal and rapid protection. Lastly, it is proposed that heterologous prime-boost vaccination with recombinant live replicating vectors, which has the potential to induce tremendous numbers of cytolytic memory CD8 T cells within mucosal tissues, would provide a far more stringent test of the hypothesis that memory CD8 T cells could, in principal, form the basis for a preventative HIV vaccine. PMID:19093965
Antibody-dependent cell-mediated cytotoxicity (ADCC) was assessed in volunteers participating in an ALVAC-HIV (vCP1521)/AIDSVAX B/E gp120 prime-boost vaccine trial in Thailand. ADCC activity was measured using chromium release from gp120 subtype B- and CRF01_AE-coated targets in 95 vaccinees and 28 placebo recipients. There was a significant difference in the magnitude of the ADCC response to both targets between vaccinees and placebo recipients. The frequency of responders to subtype B and to CRF01_AE was 96% and 84% in the vaccine group versus 11% and 7% in the placebo group. The results demonstrate that this HIV vaccine is a potent inducer of ADCC activity and may be an additional protection of this prime-boost vaccine in preventing HIV disease. PMID:15752839
Karnasuta, Chitraporn; Paris, Robert M; Cox, Josephine H; Nitayaphan, Sorachai; Pitisuttithum, Punnee; Thongcharoen, Prasert; Brown, Arthur E; Gurunathan, Sanjay; Tartaglia, James; Heyward, William L; McNeil, John G; Birx, Deborah L; de Souza, Mark S
Much of the literature has been conducted on innovation; this research provides new insights for preventive innovations that increase our understanding of vaccination diffusion and the reasons underlying the complexity of preventive diffusion. The research uses adoption of Rogers' ( 1983 ) perceived characteristics and considers the rate by which a product diffuses in a market. Qualitative empirical evidence collected via focus groups is used to identify human papillomavirus vaccine issues against the salience of perceived characteristics. Several impediments are identified and the application of marketing strategies is suggested for preventive innovations to improve the diffusion process and for designing proactive adoption. PMID:23924220
D'Souza, Clare; Mort, Gillian Sullivan; Zyngier, Suzanne; Robinson, Priscilla; Schlotterlein, Morgan
The success of vaccine regimens against viral pathogens hinges on the elicitation of protective responses. Hypervariable pathogens such as HIV avoid neutralization by masking protective epitopes with more immunogenic decoys. The identification of protective, conserved epitopes is crucial for future vaccine candidate design. The strategies employed for identification of HIV protective epitopes will also aid towards rational vaccine design for other viral pathogens. PMID:24964950
Kramer, Victor G; Byrareddy, Siddappa N
We have previously described designing of polyepitope immunogens TBI and TCI, to stimulate the humoral and cellular immune responses to HIV-1. Here, immunogens TBI and TCI were used to create new vaccine construct named CombiHIVvac (Combined HIV-1 vaccine). CombiHIVvac is a virus-like particles (VLP) containing the DNA vaccine pcDNA-TCI as a core encapsulated within a spermidine-polyglucin-TBI conjugate. The immunogenic and
Larisa I. Karpenko; Alexander A. Ilyichev; Alexey M. Eroshkin; Leonid R. Lebedev; Roman V. Uzhachenko; Nadezhda A. Nekrasova; Olga A. Plyasunova; Pavel A. Belavin; Sergei V. Seregin; Nadezhda K. Danilyuk; Boris N. Zaitsev; Elena D. Danilenko; Valentina I. Masycheva; Sergei I. Bazhan
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.
Pirrone, Vanessa; Thakkar, Nina; Jacobson, Jeffrey M.; Wigdahl, Brian; Krebs, Fred C.
The World Health Organization estimates that 50% of the 30 million HIV infections worldwide occurred in young people between the ages of 15 and 24 years. In the United States, national statistics estimate that almost 40% of new HIV cases occur in youth ages 13-29 (Centers for Disease Control and Prevention, 2011). Therefore, a focus on preventing…
This study evaluated the effectiveness of Positive Prevention, a theory-based, HIV/STD prevention education curriculum for high school youth. Three hundred fifty-three students participated in a longitudinal experimental design to determine the impact of the curriculum on HIV/AIDS knowledge, self-efficacy to abstain from sex, self-efficacy of…
LaChausse, Robert G.
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
Women's and men's gender roles and expectations regarding romantic and sexual encounters have been shifting, and the need to develop HIV preventive strategies has underscored the importance of understanding the contextual dynamics related to sexuality. Urban women's gender scripts were investigated as part of a comprehensive study that evaluated the efficacy of a theory-driven HIV\\/STI prevention programme. One hundred and
Blanca Ortiz-Torres; Samantha P. Williams; Anke A. Ehrhardt
Vaccination is currently considered as an additional therapeutic approach to stimulate HIV-specific immune response in subjects that could not naturally control HIV. Ten chronically HIV infected individuals have been vaccinated with a modified vaccinia Ankara (MVA)-HIV-1LAI-nef vector in order to assess safety and immunogenicity. No significant adverse effects were observed during the course of vaccination indicating for the first time
Antonio Cosma; Rashmi Nagaraj; Silja Bühler; Jorma Hinkula; Dirk H. Busch; Gerd Sutter; Frank D. Goebel; Volker Erfle
Cytokines play important roles in regulating immune response. This study evaluated the adjuvant effect of an expression plasmid encoding RANTES (regulated on activation normal T-cell expressed and secreted) chemokine on the immunity induced by a DNA vaccine. This vaccine consists of expression plasmids encoding the env and rev genes of human immunodeficiency virus type 1 (HIV-1). DNA vaccination with RANTES
Ke-Qin Xin; Yuan Lu; Kenji Hamajima; Jun Fukushima; Jun Yang; Keiji Inamura; Kenji Okuda
Antiviral agents can be used to prevent HIV transmission before exposure as preexpo-sure prophylaxis (PrEP), after exposure as postexposure prophylaxis, and as treatment of infected people for secondary prevention. Considerable research has shed new light on antiviral agents for PrEP and for prevention of secondary HIV transmission. While promising results have emerged from several PrEP trials, the challenges of poor adherence among HIV-negative clients and possible increase in sexual risk behaviors remain a concern. In addition, a broader pipeline of antiviral agents for PrEP that focuses on genital tract pharmacology and safety and resistance issues must be developed. Antiretroviral drugs have also been used to prevent HIV transmission from HIV-infected patients to their HIV-discordant sexual partners. The HIV Prevention Trials Network 052 trial demonstrated nearly complete prevention of HIV transmission by early treatment of infection, but the generalizability of the results to other risk groups – including intravenous drug users and MSM – has not been determined. Most importantly, the best strategy for use of antiretroviral agents to reduce the spread of HIV at either the individual level or the population level has not been developed, and remains the ultimate goal of this area of investigation.
Cohen, Myron S.; Muessig, Kathryn E.; Smith, M. Kumi; Powers, Kimberly A.; Kashuba, Angela D.M.
HIV preferentially infects activated T cells, and activated mucosal CD4+ T cells are the primary sites of viral replication. One potential explanation for increased HIV acquisition rates in the STEP study is that vaccination with adenoviral (Ad) vectors increased CD4+ T cell activation levels at the site of infection, a concept that others and we continue to explore.1,2 Whether vaccination with HIV vaccine platforms increases the activation state of CD4+ T cells within peripheral tissues, such as the gastro-intestinal (GI) mucosa, is exceptionally important to determine as a vaccine safety measure, given the susceptibility of activated CD4+ T cells to HIV infection. In this study we examined whether vaccination with DNA plasmids and chemokine adjuvants alter the activation state of T cells within the GI mucosa, inguinal LN, and peripheral blood. T cell activation state was measured by expression of CD25, CD69, and HLA-DR over the course of the prime/boost study. DNA plasmid vaccination did not increase expression of any of these markers in the 3 tissues studied. Addition of the gut-homing chemokine TECK during DNA plasmid vaccination did not alter activation levels of CD4+ T cells at any of these sites. These findings indicate that DNA vaccines do not elicit generalized mucosal T cell activation. Thus, DNA platforms may be especially suitable for HIV vaccine development, where bystander activation could promote increased HIV transmission.
Reuter, Morgan A.; Yuan, Sally; Marx, Preston A.; Kutzler, Michele A.; Weiner, David B.; Betts, Michael R.
Summary: ?-Defensins have been observed to have anti-HIV activity but have not been investigated in relation to mother-to-child HIV transmission. We measured the concentration of ?-defensins in breast milk of HIV-positive mothers and tested whether the concentrations were associated with HIV transmission. A nested case-control study of 32 HIV-positive women who transmitted HIV to their infants and 52 randomly selected HIV-positive women who did not transmit HIV to their infants was conducted in Lusaka, Zambia. ?-Defensins were detected in most (79%) of the milk samples tested. Concentrations of ?-defensins increased as breast milk HIV RNA quantity increased, and breast milk HIV RNA quantity was, in turn, a strong and significant predictor of HIV transmission. After adjustment for milk HIV RNA quantity, however, ?-defensin concentration was significantly associated with a decreased risk of intrapartum and postnatal HIV transmission (odds ratio = 0.3, 95% confidence interval: 0.09-0.93). Our data suggest that there may be a role for ?-defensins in prevention of HIV transmission to breastfed infants.
Kuhn, Louise; Trabattoni, Daria; Kankasa, Chipepo; Semrau, Katherine; Kasonde, Prisca; Lissoni, Francesca; Sinkala, Moses; Ghosh, Mrinal; Vwalika, Cheswa; Aldrovandi, Grace M.; Thea, Donald M.; Clerici, Mario
Given the shared risk factors for transmission, co-infection of hepatitis B virus (HBV) with hepatitis C virus (HCV) and/or human immunodeficiency virus (HIV) is quite common, and may lead to increases in morbidity and mortality. As such, HBV vaccine is recommended as the primary means to prevent HBV super-infection in HCV- and/or HIV-infected individuals. However, vaccine response (sero-conversion with a hepatitis B surface antibody titer >10 IU/L) in this setting is often blunted, with poor response rates to standard HBV vaccinations in virally infected individuals when compared to the healthy subjects. This phenomenon also occurs to other vaccines in adults, such as pneumococcal and influenza vaccines, in other immunocompromised hosts who are really at risk for opportunistic infections, such as individuals with hemodialysis, transplant, and malignancy. In this review, we summarize the underlying mechanisms involving vaccine failure in these conditions, focusing on immune exhaustion and immune senescence - two distinct signaling pathways regulating cell function and fate. We raise the possibility that blocking these negative signaling pathways might improve success rates of immunizations in the setting of chronic viral infection.
Yao, Zhi Q.; Moorman, Jonathan P.
Aims: We review recent evidence of trends in HIV infection, risk behaviour and HIV prevention associated with injecting drug use in the Russian Federation. Methods: Findings draw on a review of English and Russian language research, published international conference abstracts, international agency and assessment reports, and centrally registered HIV surveillance data. Findings: We note the continued major importance of injecting
Tim Rhodes; Anya Sarang; Alexei Bobrik; Eugene Bobkov; Lucy Platt
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.
Spokes, Paula; Gilmour, Robin
Background HIV prevention trials are increasingly being conducted in sub-Saharan Africa. Women at risk for HIV are also at risk of pregnancy. To maximize safety, women agree to avoid pregnancy during trials, yet pregnancies occur. Using data from the HVTN 503/“Phambili” vaccine trial, we report pregnancy incidence during and after the vaccination period and identify factors, measured at screening, associated with incident pregnancy. Methods To enrol in the trial, women agreed and were supported to avoid pregnancy until 1 month after their third and final vaccination (“vaccination period”), corresponding to the first 7 months of follow-up. Unsterilized women, pooled across study arms, were analyzed. Poisson regression compared pregnancy rates during and after the vaccination period. Cox proportional hazards regression identified associations with first pregnancy. Results Among 352 women (median age 23 yrs; median follow-up 1.5 yrs), pregnancy incidence was 9.6/100 women-years overall and 6.8/100 w-yrs and 11.3/100 w-yrs during and after the vaccination period, respectively [Rate Ratio?=?0.60 (0.32–1.14), p?=?0.10]. In multivariable analysis, pregnancy was reduced among women who: enrolled at sites providing contraception on-site [HR?=?0.43, 95% CI (0.22–0.86)]; entered the trial as injectable contraceptive users [HR?=?0.37 (0.21–0.67)] or as consistent condom users (trend) [HR?=?0.54 (0.28–1.04)]. Compared with women with a single partner of HIV-unknown status, pregnancy rates were increased among women with: a single partner whose status was HIV-negative [HR?=?2.34(1.16–4.73)] and; 2 partners both of HIV-unknown status [HR?=?4.42(1.59–12.29)]. Women with 2 more of these risk factors: marijuana use, heavy drinking, or use of either during sex, had increased pregnancy incidence [HR?=?2.66 (1.24–5.72)]. Conclusions It is possible to screen South African women for pregnancy risk at trial entry. Providing injectable contraception for free on-site and supporting consistent condom use may reduce incident pregnancy. Screening should determine the substance use, partnering, and HIV status of both members of the couple for both pregnancy and HIV prevention. Trial Registration SA National Health Research Database DOH-27-0207-1539; Clinicaltrials.gov NCT00413725
Latka, Mary H.; Fielding, Katherine; Gray, Glenda E.; Bekker, Linda-Gail; Nchabeleng, Maphoshane; Mlisana, Koleka; Nielson, Tanya; Roux, Surita; Mkhize, Baningi; Mathebula, Matsontso; Naicker, Nivashnee; de Bruyn, Guy; Kublin, James; Churchyard, Gavin J.
Cervical cancer is, globally known to be, one of the most common cancers among women especially in developing countries. More than 90% of cervical cancers are associated with high-risk human papillomaviruses (HPVs) particularly HPV types 16 and 18. Two major strategies have been developed for prevention and treatment of cervical cancer and other HPV-associated malignancies; the first one is based on HPV virus-like particles (VLPs) containing HPV structural proteins. VLP based vaccines can induce genotype specific virus neutralizing antibodies for preventing HPV infections. The other strategy is based on HPV early genes especially E6 and E7 for eliminating the established HPV infections; therefore they are classified as HPV therapeutic vaccines. This article reviews the preventive and therapeutic vaccines against HPV infections and cervical cancer.
Nayereh, Khadem Ghaebi; Khadem, Ghaeb
A cross-sectional study was performed to determine the prevalence and risk factors for HIV-1 infection among agricultural plantation residents in Kericho, Kenya. Volunteers were recruited, interviewed, and phlebotomized for HIV-1 serologic testing. Sex-specific adjusted odds ratios were estimated using logistic regression. The overall HIV-1 prevalence was 9.9% (81/820), with prevalence in women more than twice that in men (17.4% vs 8.0%, P=0.001). Among men, elevated HIV-1 prevalence was seen with increasing age, peaking in those older than 30 years (10.3%), marriage (10.4%), Luo tribe affiliation (23.5%), employment (8.9%), travel (11.0%), and being uncircumcised (29.2%). Among women, elevated HIV-1 prevalence was seen in those with no formal education (36.8%) and those who received goods in exchange for sex (36.0%). More than 97% of volunteers expressed a willingness to participate in future HIV-1 studies requiring semiannual visits. HIV prevention efforts have been implemented, along with further research to characterize this population for future cohort feasibility studies and HIV-1 vaccine efficacy trials. PMID:16885773
Sateren, Warren B; Foglia, Ginamarie; Renzullo, Philip O; Elson, Lynne; Wasunna, Monique; Bautista, Christian T; Birx, Deborah L
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.
We report here results of clinical trials on a birth control vaccine, consisting of a heterospecies dimer of the beta subunit of human chorionic gonadotropin (hCG) associated noncovalently with the alpha subunit of ovine luteinizing hormone and conjugated to tetanus and diphtheria toxoids as carriers, that induces antibodies of high avidity (K(a) approximately 10(10) M-1) against hCG. Fertile women exposed to conception over 1224 cycles recorded only one pregnancy at antibody titers of > 50 ng/ml (hCG bioneutralization capacity). The antibody response declines with time; fertility was regained when titers fell to < 35 ng/ml. This study presents evidence of the feasibility of a vaccine for control of human fertility.
Talwar, G P; Singh, O; Pal, R; Chatterjee, N; Sahai, P; Dhall, K; Kaur, J; Das, S K; Suri, S; Buckshee, K
Tat and Nef are very important regulatory proteins of HIV-1. They enhance viral replication and down-regulate expression of MHC Class I molecules, respectively. The antigens are now considered to be targets for HIV vaccine development. The expression of Tat and Nef in Salmonella vaccines has not previously been investigated. In this study, HIV-1 Subtype C tat and nef genes were cloned into an expression plasmid and their expression investigated in Salmonella. Very high-level expression of the two HIV-1 antigens was demonstrated in the recombinant Salmonella. The antigens were also successfully purified in bulk from the bacterium.Salmonella can therefore potentially be used to overexpress HIV-1 antigens and used as a possible delivery system in HIV-1 vaccine development. PMID:24498468
Chin'ombe, Nyasha; Lebeko, Maribanyana; Kgatle, Mankgopo
We obtained sealed vials of two different polio vaccine lots, expiration date 1955, which were used in the first U.S. polio vaccine campaign. These early lots were pulled from the market because they contained live infectious poliovirus which caused polio in some of the vaccines. Theoretically, these vaccines could have contained other infectious retroviruses, including HIV. No viral sequences were
Paola Rizzo; Christine Matker; Amy Powers; Paul Setlak; Jonathan L. Heeney; Herbert Ratner; Michele Carbone
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.
Lippman, Sheri A.; Maman, Suzanne; MacPhail, Catherine; Twine, Rhian; Peacock, Dean; Kahn, Kathleen; Pettifor, Audrey
The development of an effective HIV vaccine has become a crucial national healthcare goal. To develop a worldwide AIDS vaccine, an international collaboration with developing countries is needed. The global approach rationale is threefold: millions of lives can be saved, a vaccine preparation can be tested more rapidly and economically among populations with high rates of infections; and the HIV epidemic comprises at least ten different subtypes. Although a number of barriers to the successful development of an HIV vaccine exist, the polio vaccine can be used as an example to show researchers how to overcome the obstacles. Jonas Salk, the polio vaccine developer, used killed whole virus in a technique that critics argued would not be fully effective. However, the Salk vaccine reduced polio-related paralysis by 72 percent, while the more effective Sabin oral vaccine did not become available until several years later. The lesson to be learned is that any percent of effectiveness is better than nothing, and researchers should not abandon uncertain HIV vaccine development efforts because they believe a better solution may develop in the future. The existence of traditional research should not preclude the development of new solutions that might prove more effective. For example, in the case of polio, the March of Dimes campaign pushed both the Salk and Sabin vaccines despite the skepticism of many academic research groups. PMID:11364812
Testing and counseling, along with community outreach, have been identified as valuable in the prevention of human immunodeficiency virus (HIV) and other blood-borne diseases. This article assesses the extent to which outpatient substance abuse treatment (OSAT) programs provide such services. Longitudinal data for 1988-2000 were analyzed from the National Drug Abuse Treatment System Survey (NDATSS). Random-effects regression was used to examine factors associated with the provision of prevention services. HIV testing, which had became more common between 1990 and 1995, continued to proliferate between 1995 and 2000. The proportion of units that provide HIV testing and counseling increased from 66% to 86%. The proportion of units that provide HIV community outreach increased significantly before 1995 but then slightly decreased from 77% to 73% between 1995 and 2000. In conclusion, HIV testing and counseling widely proliferated in OSAT care. However, OSAT units remain less likely to offer HIV community outreach services. PMID:16377451
Pollack, Harold A; D'Aunno, Thomas; Lamar, Barbara
This study examined how individual differences in personality style influenced children's receptivity to HIV primary prevention. Prior to taking part in a HIV prevention program, 123 fifth graders from an ethnically diverse inner city school district were administered the Weinberger Adjustment Inventory (WAI) and scales measuring HIV-related beliefs, attitudes, and knowledge. The HIV scales were readministered at the conclusion of the program. WAI groups (formed by contrasting dimensions of restraint and distress) were found to differ significantly on measures of knowledge about HIV, HIV-related fears, safe behavior attitudes, and risk behavior at pre-test. The intervention's impact, as reflected in scale change scores, did not show significant differences among WAI groups. Although subtle differences were evident among groups, findings suggest that HIV primary prevention programs may be equally effective among children with differing degrees of self-restraint and distress. PMID:24254753
Wagner, E F; Brown, L K; Brenman, A J
CD8+ T-cell responses provide beneficial antiviral immunity against human immunodeficiency virus 1 (HIV-1). In this study, we show that intragastric vaccination with a Salmonella HIV-1 Env DNA vaccine vector generates Env-specific CD8+ T-cells, both in mucosal and systemic lymphoid tissue. By contrast, intramuscular vaccination with the Env DNA vaccine alone only induced systemic CD8+ T-cells. To our knowledge, this is
Mohamed T. Shata; Marvin S. Reitz Jr.; Anthony L. DeVico; George K. Lewis; David M. Hone
Enormous effort has been devoted to the development of a vaccine against human immunodeficiency virus (HIV). But it is proving to be an unprecedented challenge to create an effective vaccine mainly due to the high genetic variability of the virus and the necessity of cytotoxic T lymphocytes (CTL) for containing the infection. Currently pursued vaccine strategies appear to induce CTL in nonhuman primate models but in the early clinical trials, these strategies fail to fully control the viral infection. New strategies that can cover the vast genetic diversity of HIV are needed for the development of a potent vaccine.
Several recent large clinical trials evaluated HIV vaccine candidates that were based on recombinant adenovirus serotype 5 (rAd-5) vectors expressing HIV-derived antigens. These vaccines primarily elicited T-cell responses, which are known to be critical for controlling HIV infection. In the current study, we present a meta-analysis of epitope mapping data from 177 participants in three clinical trials that tested two different HIV vaccines: MRKAd-5 HIV and VRC-HIVAD014-00VP. We characterized the population-level epitope responses in these trials by generating population-based epitope maps, and also designed such maps using a large cohort of 372 naturally infected individuals. We used these maps to address several questions: (1) Are vaccine-induced responses randomly distributed across vaccine inserts, or do they cluster into immunodominant epitope hotspots? (2) Are the immunodominance patterns observed for these two vaccines in three vaccine trials different from one another? (3) Do vaccine-induced hotspots overlap with epitope hotspots induced by chronic natural infection with HIV-1? (4) Do immunodominant hotspots target evolutionarily conserved regions of the HIV genome? (5) Can epitope prediction methods be used to identify these hotspots? We found that vaccine responses clustered into epitope hotspots in all three vaccine trials and some of these hotspots were not observed in chronic natural infection. We also found significant differences between the immunodominance patterns generated in each trial, even comparing two trials that tested the same vaccine in different populations. Some of the vaccine-induced immunodominant hotspots were located in highly variable regions of the HIV genome, and this was more evident for the MRKAd-5 HIV vaccine. Finally, we found that epitope prediction methods can partially predict the location of vaccine-induced epitope hotspots. Our findings have implications for vaccine design and suggest a framework by which different vaccine candidates can be compared in early phases of evaluation.
Hertz, Tomer; Ahmed, Hasan; Friedrich, David P.; Casimiro, Danilo R.; Self, Steven G.; Corey, Lawrence; McElrath, M. Juliana; Buchbinder, Susan; Horton, Helen; Frahm, Nicole; Robertson, Michael N.; Graham, Barney S.; Gilbert, Peter
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.
Solorio, Rosa; Forehand, Mark; Aguirre, Joel
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; Norton-Shelpuk, Pamela; Forehand, Mark; Martinez, Marcos; Aguirre, Joel
A safe, efficacious vaccine is required to stop the AIDS pandemic. Disappointing results from the STEP trial implied a need to include humoral anti-HIV-1 responses, a notion supported by RV144 trial data even though correlates of protection are unknown. We vaccinated rhesus macaques with recombinant simian immunodeficiency virus (SIV) Gag-Pol particles, HIV-1 Tat and trimeric clade C (HIV-C) gp160, which
Samir K. Lakhashe; Wendy Wang; Nagadenahalli B. Siddappa; Girish Hemashettar; Patricia Polacino; Shiu-Lok Hu; François Villinger; James G. Else; Francis J. Novembre; John K. Yoon; Sandra J. Lee; David C. Montefiori; Ruth M. Ruprecht; Robert A. Rasmussen
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.
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
Interrogating immune correlates of infection risk for efficacious and non-efficacious HIV-1 vaccine clinical trials have provided hypotheses regarding the mechanisms of induction of protective immunity to HIV-1. To date, there have been six HIV-1 vaccine efficacy trials (VAX003, Vaxgen, Inc., San Francisco, CA, USA), VAX004 (Vaxgen, Inc.), HIV-1 Vaccine Trials Network (HVTN) 502 (Step), HVTN 503 (Phambili), RV144 (sponsored by the U.S. Military HIV Research Program, MHRP) and HVTN 505). Cellular, humoral, host genetic and virus sieve analyses of these human clinical trials each can provide information that may point to potentially protective mechanisms for vaccine-induced immunity. Critical to staying on the path toward development of an efficacious vaccine is utilizing information from previous human and non-human primate studies in concert with new discoveries of basic HIV-1 host-virus interactions. One way that past discoveries from correlate analyses can lead to novel inventions or new pathways toward vaccine efficacy is to examine the intersections where different components of the correlate analyses overlap (e.g., virus sieve analysis combined with humoral correlates) that can point to mechanistic hypotheses. Additionally, differences in durability among vaccine-induced T- and B-cell responses indicate that time post-vaccination is an important variable. Thus, understanding the nature of protective responses, the degree to which such responses have, or have not, as yet, been induced by previous vaccine trials and the design of strategies to induce durable T- and B-cell responses are critical to the development of a protective HIV-1 vaccine.
Tomaras, Georgia D.; Haynes, Barton F.
Rabies, being a major zoonotic disease, significantly impacts global public health. It is invariably fatal once clinical signs\\u000a are apparent. The majority of human rabies deaths occur in developing countries. India alone reports more than 50% of the\\u000a global rabies deaths. Although it is a vaccine-preventable disease, effective rabies prevention in humans with category III\\u000a bites requires the combined administration
T. Nagarajan; Charles E. Rupprecht; Scott K. Dessain; P. N. Rangarajan; D. Thiagarajan; V. A. Srinivasan
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
We assess the cost-effectiveness of maintenance treatment for heroin addiction, with emphasis on its role in preventing HIV infection. The analysis is based on a dynamic compartmental model of the HIV epidemic among a population of adults, ages 18 to 44. The population is divided into nine compartments according to infection status and risk group. The model takes into account
Gregory S. Zaric; Margaret L. Brandeau; Paul G. Barnett
The best HIV prevention programs--those that effect change on a multiplicity of levels by changing knowledge, attitudes, and behaviors and that are sustained over time--are also those that place HIV-positive people at the center of program design, implementation, and evaluation.
Allan, Brent; Leonard, William
Abstract HIV prevalence is the most commonly used measure to prioritize communities for HIV prevention. We show that data on two HIV infection stages (early vs. nonearly and late vs. nonlate) allow estimation of two better measures of prevention need: HIV incidence (for prevention of HIV acquisition) and expected probability of HIV transmission in unprotected sex acts between HIV-infected community members and susceptible individuals (for prevention of HIV transmission). The three ranking schemes—by prevalence, incidence, and transmission probability—lead to significantly different community rank orders. Disease stage information should be collected in HIV surveys.
Tanser, Frank; Hallett, Timothy; Newell, Marie-Louise
Background In the last decade, several large-scale, clinical trials evaluating the efficacy of novel HIV prevention products have been completed, and 8 are currently underway or about to be reported. Little attention has been given in the literature to the level of protection sufficient to warrant introduction, and there is concern that using the term “efficacy” to describe the effect of user-controlled methods such as microbicides may mislead policymakers. Design We review how the fields of family planning, vaccine science, and mathematical modelling understand and use the terms efficacy and effectiveness and explore with simple mathematical models, how trial results of user-controlled products relate to common understandings of these terms. Results Each field brings different assumptions, a different evidence base, and different expectations to interpretations of efficacy and effectiveness—a reality that could cloud informed assessment of emerging data. Conclusion When making judgments on the utility of new health technologies, it is important to use standards that yield appropriate comparisons for the innovation and that take into account the local epidemic and available alternatives.
Heise, Lori L.; Watts, Charlotte; Foss, Anna; Trussell, James; Vickerman, Peter; Hayes, Richard; McCormack, Sheena
Since at least the late 1980s, policymakers have questioned which strategies are most cost-effective in preventing further HIV infection. Only in recent years has sufficient evidence of the efficacy and effectiveness of specific interventions accumulated ...
J. E. Sisk
The search for intervention strategies appropriate for young adolescents has recently led to the use of digital games. Digital gaming interventions are promising because they may be developmentally appropriate for adolescent populations. The gaming approach also capitalizes on an inherent interest to adolescents and circumvents traditional barriers to access to prevention interventions faced in some geographical areas. Notwithstanding, research on gaming in HIV prevention is quite limited. In this review article, we examine the need for contextually relevant HIV prevention interventions among young adolescents. From this, we provide a theoretical framework for exploring contextually relevant HIV risk factors and a foundation for gathering and using input from the target population to adapt an existing game or to create a developmentally appropriate and contextually relevant HIV prevention game. PMID:22871481
Enah, Comfort; Moneyham, Linda; Vance, David E; Childs, Gwendolyn
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.
Bekker, Linda-Gail; Beyrer, Chris; Quinn, Thomas C.
We review drug abuse treatment as a means of preventing infection with HIV. Thirty-three studies, with an aggregate of over seventeen thousand subjects, were published in peer-reviewed journals from 1988–1998. Research on the utility of drug abuse treatment as an HIV prevention strategy has focused primarily on methadone maintenance treatment (MMT) rather than other modalities such as residential or outpatient
James L. Sorensen; Amy L. Copeland
The current analysis considers the HIV prevention research record in the social sciences. We do so with special reference to what has been termed “AIDS Exceptionalism”— departures from standard public health practice and prevention research priorities in favor of alternative approaches to prevention that, it has been argued, emphasize individual rights at the expense of public health protection. In considering this issue, we review the historical context of the HIV epidemic; empirically demonstrate a pattern of prevention research characterized by systematic neglect of prevention interventions for HIV-infected persons; and articulate a rationale for “Prevention for Positives,” supportive prevention efforts tailored to the needs of HIV+ individuals. We then propose a social psychological conceptualization of processes that appear to have influenced developments in HIV prevention research and directed its focus to particular target populations. Our concluding section considers whether there are social and research policy lessons to be learned from the record of HIV prevention research that might improve our ability to addresses effectively, equitably, and in timely fashion future epidemics that play out, as HIV does, at the junction of biology and behavior. At the first quarter century of the AIDS epidemic, it is important to weigh our accomplishments against our failures in the fight against AIDS…Future historians will conclude that we cannot escape responsibility for our failure to use effective, scientifically proven strategies to control the AIDS epidemic…They will also likely regard as tragic those instances when we allowed scarce resources to be used to support ideologically driven “prevention” that only served a particular political agenda. Editorial: A Quarter Century of AIDS. American Journal of Public Health. (Stall & Mills, 2006, p. 961)
Fisher, William A.; Kohut, Taylor; Fisher, Jeffrey D.
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.
Lippman, Sheri A.; Treves-Kagan, Sarah; Gilvydis, Jennifer M.; Naidoo, Evasen; Khumalo-Sakutukwa, Gertrude; Darbes, Lynae; Raphela, Elsie; Ntswane, Lebogang; Barnhart, Scott
Recent evidence suggests that live oral Salmonella-HIV vaccine vectors have the potential to elicit HIV-specific T cell-mediated immunity in both the mucosal and systemic compartments. We are using the mouse-typhoid model to identify Salmonella::HIV vaccine vector constructs that elicit HIV-specific mucosal and systemic immune responses. Oral immunization of mice with a Salmonella strain that expresses recombinant gp120 (rgp120) in the
David M. Hone; Shaoguang Wu; Robert J. Powell; David W. Pascual; John Van Cott; Jerry McGhee; Timothy R. Fouts; Robert G. Tuskan; George K. Lewis
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.
Reis, Janet S.; Weber, Kathleen M.
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
Universal HIV testing and immediate antiretroviral therapy for infected individuals has been proposed as a way of reducing the transmission of HIV and thereby bringing the HIV epidemic under control. It is unclear whether transmission during early HIV infection—before individuals are likely to have been diagnosed with HIV and started on antiretroviral therapy—will compromise the effectiveness of treatment as prevention.
Myron S. Cohen; Christopher Dye; Christophe Fraser; William C. Miller; Kimberly A. Powers; Brian G. Williams
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
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
Background An HIV vaccine could substantially impact the epidemic. However, risk compensation (RC), or post-vaccination increase in risk behavior, could present a major challenge. The methodology used in previous studies of risk compensation has been almost exclusively individual-level in focus, and has not explored how increased risk behavior could affect the connectivity of risk networks. This study examined the impact of anticipated HIV vaccine-related RC on the structure of high-risk drug users' sexual and injection risk network. Methods A sample of 433 rural drug users in the US provided data on their risk relationships (i.e., those involving recent unprotected sex and/or injection equipment sharing). Dyad-specific data were collected on likelihood of increasing/initiating risk behavior if they, their partner, or they and their partner received an HIV vaccine. Using these data and social network analysis, a "post-vaccination network" was constructed and compared to the current network on measures relevant to HIV transmission, including network size, cohesiveness (e.g., diameter, component structure, density), and centrality. Results Participants reported 488 risk relationships. Few reported an intention to decrease condom use or increase equipment sharing (4% and 1%, respectively). RC intent was reported in 30 existing risk relationships and vaccination was anticipated to elicit the formation of five new relationships. RC resulted in a 5% increase in risk network size (n?=?142 to n?=?149) and a significant increase in network density. The initiation of risk relationships resulted in the connection of otherwise disconnected network components, with the largest doubling in size from five to ten. Conclusions This study demonstrates a new methodological approach to studying RC and reveals that behavior change following HIV vaccination could potentially impact risk network connectivity. These data will be valuable in parameterizing future network models that can determine if network-level change precipitated by RC would appreciably impact the vaccine's population-level effectiveness.
Young, April M.; Halgin, Daniel S.; DiClemente, Ralph J.; Sterk, Claire E.; Havens, Jennifer R.
Objectives. We explored the relative effects of 2 awareness components-exposure and attention-on racial/ethnic differences in HIV vaccine trial awareness among men who have sex with men (MSM). Methods. Surveys assessing awareness of and attitudes toward HIV vaccine trials were administered to 1723 MSM in 6 US cities. Proxy measures of exposure included use of HIV resources and other health care services, community involvement, income, and residence. Attention proxy measures included research attitudes, HIV susceptibility, and HIV message fatigue. Using logistic regression models, we assessed the extent to which these proxies accounted for racial/ethnic differences in vaccine trial awareness. Results. White MSM reported significantly (P?.01) higher rates of HIV vaccine trial awareness (22%) compared with Latino (17%), Black (13%) and "other" (13%) MSM. Venue-based exposure proxies and research-directed attitudinal attention proxies were significantly associated with awareness, but only accounted for the White-Latino disparity in awareness. No proxies accounted for the White-Black or White-"other" differentials in awareness. Conclusions. Sources of disparities in awareness of HIV vaccine trials remain to be explained. Future trials seeking to promote diverse participation should explore additional exposure and attention mediators. PMID:24922153
Arnold, Michael P; Andrasik, Michele; Landers, Stewart; Karuna, Shelly; Mimiaga, Matthew J; Wakefield, Steven; Mayer, Kenneth; Buchbinder, Susan; Koblin, Beryl 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.
Vermund, Sten H.; Tique, Jose A.; Cassell, Holly M.; Johnson, Megan E.; Ciampa, Philip J.; Audet, Carolyn M.
HIV-1 sequencing has been used extensively in epidemiologic and forensic studies to investigate patterns of HIV-1 transmission. However, the criteria for establishing genetic linkage between HIV-1 strains in HIV-1 prevention trials have not been formalized. The Partners in Prevention HSV/HIV Transmission Study (ClinicaITrials.gov NCT00194519) enrolled 3408 HIV-1 serodiscordant heterosexual African couples to determine the efficacy of genital herpes suppression with acyclovir in reducing HIV-1 transmission. The trial analysis required laboratory confirmation of HIV-1 linkage between enrolled partners in couples in which seroconversion occurred. Here we describe the process and results from HIV-1 sequencing studies used to perform transmission linkage determination in this clinical trial. Consensus Sanger sequencing of env (C2-V3-C3) and gag (p17-p24) genes was performed on plasma HIV-1 RNA from both partners within 3 months of seroconversion; env single molecule or pyrosequencing was also performed in some cases. For linkage, we required monophyletic clustering between HIV-1 sequences in the transmitting and seroconverting partners, and developed a Bayesian algorithm using genetic distances to evaluate the posterior probability of linkage of participants sequences. Adjudicators classified transmissions as linked, unlinked, or indeterminate. Among 151 seroconversion events, we found 108 (71.5%) linked, 40 (26.5%) unlinked, and 3 (2.0%) to have indeterminate transmissions. Nine (8.3%) were linked by consensus gag sequencing only and 8 (7.4%) required deep sequencing of env. 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.
Leitner, Thomas [Los Alamos National Laboratory; Campbell, Mary S [UNIV OF WASHINGTON; Mullins, James I [UNIV OF WASHINGTON; Hughes, James P [UNIV OF WASHINGTON; Wong, Kim G [UNIV OF WASHINGTON; Raugi, Dana N [UNIV OF WASHINGTON; Scrensen, Stefanie [UNIV OF WASHINGTON
Many different HIV-1 vaccine strategies have been developed, but as yet none has been completely successful. Promising results from combined DNA prime\\/protein boost vaccines have been reported. Specific immune responses generated by DNA vaccines can be modulated by the co-delivery of genes coding for cytokines. In this study, we have used the intradermal route by needle injection of a plasmid
Odile Billaut-Mulot; Thierry Idziorek; Elisabeth Ban; Laurent Kremer; Loic Dupré; Marc Loyens; Gilles Riveau; Camille Locht; André Capron; George M. Bahr
BACKGROUND: Information on cost-effectiveness of the range of HIV prevention interventions is a useful contributor to decisions on the best use of resources to prevent HIV. We conducted this assessment for the state of Andhra Pradesh that has the highest HIV burden in India. METHODS: Based on data from a representative sample of 128 public-funded HIV prevention programs of 14
Lalit Dandona; SG Prem Kumar; G Anil Kumar; Rakhi Dandona
Summary Adolescents are at high risk for HIV acquisition, and thus need to be included in HIV vaccine trials. In preparation for inclusion of adolescents in HIV vaccine trials in an urban community in Cape Town with a high antenatal HIV prevalence, the study assessed the attitudes towards the inclusion of adolescents in HIV vaccine trials. A total of 18 focus group discussions were conducted using a semistructured interview guide. The participants (n = 200) were adolescents, young adults, parents and other key informants. Participants from all groups welcomed the inclusion of adolescents in HIV vaccine trials due to their high-risk status. There were, however, concerns about sexual disinhibition, fear of side-effects, fear of HIV testing and disclosure of HIV status, mistrust of nurses and clinics. The study highlighted a number of ethical and social issues that need to be addressed before the trials.
Jaspan, H B; Soka, N F; Mathews, C; Flisher, A J; Mark, D; Middelkoop, K; Wood, R; Bekker, L-G
Background To examine immunisation information needs of teenagers we explored understandings of vaccination and vaccine-preventable diseases, attitudes towards immunisation and experiences of immunisation. Diseases discussed included nine for which vaccines are currently offered in the UK (human papillomavirus, meningitis, tetanus, diphtheria, polio, whooping cough, measles, mumps and rubella), and two not currently included in the routine UK schedule (hepatitis B and chickenpox). Methods Twelve focus groups conducted between November 2010 and March 2011 with 59 teenagers (29 girls and 30 boys) living in various parts of Scotland. Results Teenagers exhibited limited knowledge and experience of the diseases, excluding chickenpox. Measles, mumps and rubella were perceived as severe forms of chickenpox-like illness, and rubella was not associated with foetal damage. Boys commonly believed that human papillomavirus only affects girls, and both genders exhibited confusion about its relationship with cancer. Participants considered two key factors when assessing the threat of diseases: their prevalence in the UK, and their potential to cause fatal or long-term harm. Meningitis was seen as a threat, but primarily to babies. Participants explained their limited knowledge as a result of mass immunisation making once-common diseases rare in the UK, and acknowledged immunisation's role in reducing disease prevalence. Conclusions While it is welcome that fewer teenagers have experienced vaccine-preventable diseases, this presents public health advocates with the challenge of communicating benefits of immunisation when advantages are less visible. The findings are timely in view of the Joint Committee on Vaccination and Immunisation's recommendation that a booster of meningitis C vaccine should be offered to teenagers; that teenagers did not perceive meningitis C as a significant threat should be a key concern of promotional information. While teenagers’ experiences of immunisation in school were not always positive, they seemed enthusiastic at the prospect of introducing more vaccines for their age group.
Hilton, S.; Patterson, C.; Smith, E.; Bedford, H.; Hunt, K.
The morbidity and mortality related to many communicable infectious diseases have significantly decreased in Western countries largely because of the use of antibiotics, and the implementation of well-planned vaccination strategies and national immunisation schedules specifically aimed at infants and children. However, although immunisation has proved to be highly effective for public health, more effort is needed to improve the currently sub-optimal rates of vaccination against various diseases among adults who may be at risk because of their age, medical condition or occupation. The vaccines currently licenced in Western countries are safe, immunogenic and effective against many infectious diseases and their complications, but the availability of newer vaccines or vaccines with new indications, the evolving ecology and epidemiology of many infections, population ageing, and other demographic changes (i.e. the increasing prevalence of chronic comorbidities and immunodeficiencies, mass migration, new working relationships, and widespread international tourism) require changes in the approach to immunisation. There is now a need for appropriate preventive measures for adults and the elderly aimed at protecting people at risk by using every possible catch-up opportunity and recommending specific age-related schedules on the basis of local epidemiology. PMID:24389370
Esposito, Susanna; Durando, Paolo; Bosis, Samantha; Ansaldi, Filippo; Tagliabue, Claudia; Icardi, Giancarlo
Objectives: To determine the prevalence of prevention counseling discussions between HIV care providers and their patients who are newly linked to care and to assess factors that facilitate such discussions. Methods: In 2009, a probability sample of HIV care providers in 582 outpatient settings in the United States and Puerto Rico was surveyed regarding provider's HIV prevention discussions with HIV-infected patients newly linked to HIV medical care. Results: A majority of providers reported consistently discussing HIV transmission risk reduction (76%), sexually transmitted disease risk (66%), and adherence to antiretroviral regimens (87%). Only 35% of providers reported consistently discussing partner counseling services. Conclusion: The proportion of providers engaged in HIV prevention counseling with patients newly linked to HIV care is generally high, but more work is needed to encourage providers to fully participate as partners in prevention, which is central to preventing onward transmission of HIV. PMID:24429103
Valverde, Eduardo; Beer, Linda; Johnson, Christopher; Blair, Janet M; Mattson, Christine L; Sanders, Catherine; Weiser, John; Skarbinski, Jacek
Latinos are under-represented in HIV\\/AIDS medical research in the US. Although they are disproportionately impacted by HIV\\/AIDS, Latinos may be reluctant to participate in HIV vaccine trials. Three focus groups were conducted with 32 Spanish-speaking Latinos recruited from two community-based healthcare organizations in Los Angeles, California. A qualitative focus group interview guide was developed to explore concerns, motivators and intentions
R. A. Brooks; P. A. Newman; N. Duan; D. J. Ortiz
Since the human immunodeficiency virus (HIV-1) is transmitted either parenterally or sexually, both mucosal and systemic immune responses may be required to provide protective immunity. Attenuated Salmonella vectors expressing heterologous antigen can stimulate responses in both compartments. To evaluate the utility of Salmonella vectors as an HIV-1 vector vaccine, a gene expression cassette encoding recombinant HIV-1 gp120 (rgp120) was integrated
Timothy R. Fouts; Robert G. Tuskan; Sunil Chada; David M. Hone; George K. Lewis
Sex work occurs to meet the demand for sexual services and is a universal phenomenon. In Africa sex work takes many forms and is an important source of income for many women. Yet sex worker reproductive health needs remain largely unmet. The criminalisation of sex work; community and service provider stigma; violence; substance use and limited access to health services and prevention commodities contribute to the high HIV burden evident among female sex workers in Africa. Following UNAIDS' three pillar approach to HIV prevention and sex work we present an overview of current opportunities, barriers and suggestions to improve HIV prevention policy and programming for sex work in Africa. Universal access to a comprehensive package of HIV services is the first pillar. Reproductive health commodities; voluntary and anonymous HIV counselling and testing; treatment of sexually transmitted infections, HIV and opportunistic infections; harm reduction for substance use and psychosocial support services make up the recommended package of services. The second pillar is a sex worker-supportive environment. The inclusion of sex worker programmes within national HIV strategic planning; sex worker-led community mobilisation and the establishment of sex work community networks (comprised of sex workers, health service providers, law enforcers and other stakeholders) enable effective programme implementation and are recommended. The reduction of sex worker vulnerability and addressing structural issues form the final pillar. The decriminalisation of sex work; development of supportive policy; gender equality and economic development are key factors that need to be addressed to increase sex worker resilience. Evidence supports the public health benefit of human rights based approaches to HIV prevention; moralistic and restrictive policy and laws towards sex work are harmful and should be removed. The establishment of these pillars will increase sex worker safety and enhance the inclusiveness of the HIV response. PMID:23237073
Scheibe, A; Drame, F M; Shannon, K
Urinary tract infections (UTIs) are one of the most common infectious diseases of humans, with approximately 150 million cases estimated to occur globally every year. UTIs usually start as a bladder infection (cystitis), but can develop into acute kidney infection (pyelonephritis) and even infection of the bloodstream (urosepsis). The high frequency of UTIs in community and nosocomial settings places an enormous burden on healthcare systems worldwide. Multiple different pathogens cause UTI, with uropathogenic E. coli (UPEC) the most common etiological agent. UTIs caused by these pathogens are increasingly associated with antibiotic resistance, thus severely reducing treatment options and significantly increasing UTI-associated morbidity and mortality. In this review we present an overview of the recent advances in vaccine research targeted towards the prevention of UPEC-mediated UTI. In the context of multidrug resistance, we conclude that vaccination represents a viable approach for the prevention of chronic and recurrent UTI. PMID:24372245
Moriel, Danilo G; Schembri, Mark A
To address these challenges, CDC and its partners are pursuing a High-Impact Prevention approach to reducing new HIV infections. By using combinations of scientifically proven, cost-effective, and scalable interventions targeted to the right populations i...
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.
DiClemente, Ralph J.; Sales, Jessica McDermott; Borek, Nicolette
Enrollment of US women with sufficient risk of HIV infection into HIV vaccine efficacy trials has proved challenging. A cohort of 799 HIV-negative women, aged 18-45, recruited from three US cities was enrolled to assess recruitment strategies based on geographic risk pockets, social and sexual networks and occurrence of sexual concurrency and to assess HIV seroincidence during follow-up (to be reported later). Among enrolled women, 90% lived or engaged in risk behaviors within a local risk pocket, 64% had a male partner who had concurrent partners and 50% had a male partner who had been recently incarcerated. Nearly half (46%) were recruited through peer referral. At enrollment, 86% of women said they were willing to participate in a vaccine efficacy trial. Results indicate that participant and partner risk behaviors combined with a peer referral recruitment strategy may best identify an at-risk cohort willing to participate in future trials.
Metch, Barbara; Frank, Ian; Novak, Richard; Swann, Edith; Metzger, David; Morgan, Cecilia; Lucy, Debbie; Dunbar, Debora; Graham, Parrie; Madenwald, Tamra; Escamilia, Gina; Koblin, Beryl
Mathematical models of HIV prevention interventions often provide critical insights related to programmatic design and economic efficiency. One recent dynamic model by Long et al. highlights that a combination prevention approach - with testing, treatment, circumcision, microbicides and PrEP - may decrease transmissions by over 60% and may be very cost-effective in South Africa. In this analysis, the authors introduce the critical concept of joint effectiveness of preventions programs and demonstrate how some programs operate synergistically (HIV screening coupled with early treatment) while others may create redundancies (microbicides coupled with pre-exposure prophylaxis). Whether combination HIV prevention programs perform with additive, multiplicative or maximal effectiveness will be important to consider in anticipation of their combined transmission impact. PMID:23797377
Walensky, Rochelle P
As new HIV prevention tools are developed, researchers face a number of ethical and logistic questions about how and when to include novel HIV prevention strategies and tools in the standard prevention package of ongoing and future HIV prevention trials. Current Joint United Nations Programme on HIV/AIDS (UNAIDS)/World Health Organization (WHO) guidance recommends that participants in prevention trials receive 'access to all state of the art HIV risk reduction methods', and that decisions about adding new tools to the prevention package be made in consultation with 'all relevant stakeholders'. The guidance, however, leaves open questions of both process and implementation. In March 2009, the Global Campaign for Microbicides, UNAIDS and the Centers for Disease Control and Prevention convened a consultation to develop practical answers to these questions. Fifty-nine diverse participants, including researchers, ethicists, advocates and policymakers, worked to develop consensus criteria on when to include new HIV prevention tools in future trials. Participants developed a set of questions to guide decision-making, including: whether the method has been recommended by international bodies or adopted at a national level; the size of the effect and weight of the evidence; relevance to the trial population; whether the tool has been approved or introduced in the trial country; whether adding the tool might lead to trial futility; outstanding safety issues and status of the trial. Further work is needed to develop, implement and evaluate approaches to facilitate meaningful stakeholder participation in this deliberative process. PMID:21186207
Philpott, Sean; Heise, Lori; McGrory, Elizabeth; Paxton, Lynn; Hankins, Catherine
SUMMARY Little is known about long-lasting measles protective immunity when exposure to wild-type or vaccine measles virus precedes HIV infection. The results obtained suggest that measles immunity wanes and the lowest measles geometric mean titres (GMT) were significantly associated with measles vaccine-induced immunity in individuals that later developed HIV infection (86% prevalence, GMT 164 mIU/ml) compared to naturally induced immunity in HIV-infected adults (100% prevalence, GMT 340 mIU/ml, P = 0·0082) or non-HIV infected adults (100%, GMT 724 mIU/ml, P = 0·0001), and vaccine-induced immunity in non-HIV-infected adults (100%, GMT 347 mIU/ml, P = 0·017). The study was conducted in an area without wild-type virus circulation since 2000. The absence of virus circulating may alter the paradigm of lifelong immunity to measles virus after vaccination. As the proportion of HIV-infected individuals possessing only vaccine-induced immunity continues to grow, checking the status of measles immunity in this group is strongly recommended. PMID:24139476
Isa, M B; Pavan, J V; Sicilia Don, P; Grutadauria, S; Martinez, L C; Giordano, M O; Masachessi, G; Barril, P A; Nates, S V
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
Recombinant modified vaccinia virus Ankara (rMVA) expressing HIV-1 genes are promising vaccine candidates. Toward the goal of conducting clinical trials with one or a cocktail of recombinant viruses, four rMVAs expressing env and gag-pol genes from primary HIV-1 isolates representing predominant subtypes from Kenya, Tanzania, Uganda, and Thailand (A, C, D, and CRF01_AE, respectively) were constructed. Efficient expression, processing, and function of Env and Gag were demonstrated. All inserted genes were shown to be genetically stable after repeated passage in cell culture. Strong HIV-specific cellular and humoral immune responses were elicited in mice immunized with each individual vaccine candidate. The MVA/CMDR vaccine candidate expressing CRF01_AE genes has elicited HIV-specific T-cell responses in two independent Phase I clinical trials. Further testing of the other rMVA is warranted. PMID:19654066
Earl, Patricia L; Cotter, Catherine; Moss, Bernard; VanCott, Thomas; Currier, Jeffrey; Eller, Leigh Anne; McCutchan, Francine; Birx, Deborah L; Michael, Nelson L; Marovich, Mary A; Robb, Merlin; Cox, Josephine H
Therapeutic HIV vaccines represent promising strategy as an adjunct or alternative to current antiretroviral treatment options for HIV. Unlike prophylactic AIDS vaccines designed to prevent HIV infection, therapeutic vaccines are given to already infected individuals to help fight the disease by modulating their immune response. The first immunotherapeutic trial in AIDS patients was conducted in 1983. Since then several dozen conventional therapeutic vaccine trials have been carried out. Unfortunately, the results have consistently shown that while HIV-specific immune responses were evident as a result of vaccination, the clinical improvement has been seldom observed. The instances of the apparent clinical benefit were invariably associated with unconventional vaccines that acted in accord with the principles of alloimmunization and/or autologous vaccination. All such vaccines were derived from the blood of HIV carriers or a cell culture and thus they inherently contained allo- or self-antigens unrelated to HIV. This intriguing observation raises the issue whether this clinically successful approach has been unduly neglected. The current strategy biased toward vaccines, which have shown little evidence of clinical efficacy, needs to be diversified and supplemented with research on alternative vaccine approaches geared toward immune tolerance induction. PMID:16787245
Bourinbaiar, A S; Root-Bernstein, R S; Abulafia-Lapid, R; Rytik, P G; Kanev, A N; Jirathitikal, V; Orlovsky, V G
Background HIV-1 specific cellular immunity contributes to control of HIV-1 replication. HIV-1 infected volunteers on antiretroviral therapy received a replication defective Ad5 HIV-1 gag vaccine in a randomized, blinded therapeutic vaccination study. Methods HIV-1-infected vaccine or placebo recipients underwent a 16-wk analytical treatment interruption (ATI). The log10 HIV-1 RNA at the ATI set point and time averaged area under the curve (TA-AUC) served as co-primary endpoints. Immune responses were measured by intracellular cytokine staining and CFSE dye dilution. Results Vaccine benefit trends were seen for both primary endpoints, but did not reach a pre-specified p ? 0.025 level of significance. The estimated shift in TA-AUC and set point were 0.24 (unadjusted p=0.04) and 0.26 (unadjusted p=0.07) log10 copies lower in the vaccine than in the placebo arm. HIV-1 gag-specific CD4+ interferon-? producing cells were an immunologic correlate of viral control. Conclusion The vaccine was generally safe and well tolerated. Despite a trend favoring viral suppression among vaccine recipients, differences in HIV-1 RNA levels did not meet the pre-specified level of significance. Induction of HIV-1 gag-specific CD4 cells correlated with control of viral replication in vivo. Future immunogenicity studies should require a substantially higher immunogenicity threshold before an ATI is contemplated.
Schooley, Robert T.; Spritzler, John; Wang, Hongying; Lederman, Michael M.; Havlir, Diane; Kuritzkes, Daniel R.; Pollard, Richard; Battaglia, Cathy; Robertson, Michael; Mehrotra, Devan; Casimiro, Danilo; Cox, Kara; Schock, Barbara
Preventing hepatitis B by vaccination is essential in HIV-infected patients (higher progression rate of HBV infection to chronicity, lower rate of serum HBe Ag loss). However, it has been shown a decreased anti-HBs response in these individuals after a standard vaccination (3 doses of 20 micrograms). Thus, we tested the hypothesis that doubling the number of hepatitis B vaccine injections might increase anti-HBs response rate. HIV-infected patients with CD4 > 200/microliter, who were on stable antiretroviral treatment, as well as seronegative for HBV markers, and who have never been vaccinated against HBV, were given 3 intramuscular injections of Genhevac B 20 micrograms at 1 month intervals. Initial non responders were given 3 additional monthly injections. Anti-HBs titer was followed. We also evaluated the effects on HIV-1 viral load. Twenty patients with a median CD4 cell count of 470/microliter were enrolled. The response rate after three 20 micrograms injections was 55% (11/20), lower in individuals with CD4 between 200 and 500/microliter (4/12 = 33.3%), compared to patients with CD4 above 500/microliter (7/8 = 87.5%, P = 0.02). Among 9 initial non-responders, only 2 did not respond to 3 additional doses; thus, the overall response rate was 90% (18/20). Geometric mean titers of anti-HBs were 133 IU/l and 77.5 IU/l, after 3 and 6 Genhevac doses, respectively (P = 0.38). One year later, only 10/17 (58.8%) patients had protective anti-HBs. Five patients experienced a significant viral load increase, transient in 3 cases. These preliminary results suggest that doubling the number of hepatitis B vaccinations in HIV-infected patients might significantly improve anti-HBs response rate; however, close monitoring of anti-HBs is necessary because of its short-lived persistence. The effects on HIV-1 viral load are limited. PMID:10649616
Rey, D; Krantz, V; Partisani, M; Schmitt, M P; Meyer, P; Libbrecht, E; Wendling, M J; Vetter, D; Nicolle, M; Kempf-Durepaire, G; Lang, J M
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.
Pettifor, Audrey; Bekker, Linda-Gail; Hosek, Sybil; DiClemente, Ralph; Rosenberg, Molly; Bull, Sheana; Allison, Susannah; Delany-Moretlwe, Sinead; Kapogiannis, Bill G.; Cowan, Frances
...Emphasis Panel (SEP): Minority HIV/AIDS Research Initiative (MARI) To Build...and Hispanic Researchers To Conduct HIV/AIDS Epidemiologic and Prevention Research...received in response to ``Minority HIV/AIDS Research Initiative (MARI) to...
This publication was developed in response to requests by prevention service providers and planners, for science-based interventions that work in HIV/AIDS prevention. All interventions came from behavioral or social studies that had both intervention and control/comparison groups and positive results for behavioral or health outcomes. The document…
Centers for Disease Control and Prevention (DHHS/PHS), Atlanta, GA.
Meyer-Rath and Over assert in another article in the July 2012 PLoS Medicine Collection, “Investigating the Impact of Treatment on New HIV Infections”, that economic evaluations of antiretroviral therapy (ART) in currently existing programs and in HIV treatment as prevention (TasP) programs should use cost functions that capture cost dependence on a number of factors, such as scale and scope
Till Bärnighausen; Joshua A. Salomon; Nalinee Sangrujee
THE acquired immunodeficiency syndrome (AIDS) is the late-stage clinical manifestation of long-term persistent infection with the human immunodeficiency virus type 1 (HIV-1). Immune responses directed against the virus and against virus-infected cells during the persistent infection fail to mediate resolution of the infection. As a result, a successful AIDS vaccine must elicit an immune state that will prevent the establishment
E. A. Emini; W. A. Schleif; J. H. Nunberg; A. J. Conley; Y. Eda; S. Tokiyoshi; S. D. Putney; S. Matsushrta; K. E. Cobb; C. M. Jett; J. W. Eichberg; K. K. Murthy
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 = 1,581) 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
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.
Card, Josefina J.; Newman, Emily N.; Golden, Rachel E.; Kuhn, Tamara; Lomonaco, Carmela
The promising results obtained with the HIV-1 Tat-based vaccines in mice, monkeys and humans, a better understanding of Tat immunomodulatory functions, as well as evidence that vaccination with trimeric V2 loop-deleted HIV-1 Env induces cross-clade neutralizing antibodies led to the rational design of a novel vaccine based on the combination of Tat and V2-deleted Env.
Barbara Ensoli; Aurelio Cafaro; Antonella Caputo; Valeria Fiorelli; Fabrizio Ensoli; Riccardo Gavioli; Flavia Ferrantelli; Andrea Cara; Fausto Titti; Mauro Magnani
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
Community-based organizations face multiple challenges in implementing preventive intervention programs that are both evidence based and sustainable under limited resources and staffing. This article describes the development and preliminary evaluation of the theory-based Atlas HIV prevention program, which includes a unique service-learning component and capitalizes on a committed core of volunteers. Supporting research is presented for the effectiveness among the volunteers of service learning and popular opinion leader approaches; the Atlas program was developed using these principles, in alignment with state and federal HIV prevention strategies. Nearly 40% of the Atlas volunteers were retained for more than 2 years, and 25% have served more than 3 years. During their tenure with Atlas, the volunteers demonstrated improved knowledge of HIV transmission and prevention and increased sexual efficacy, and nearly all had been tested for HIV. Community-based organizations are encouraged to incorporate service-learning when implementing prevention programs and develop committed volunteers in order to increase the effectiveness and sustainability of their prevention efforts. PMID:23182859
Shepherd, Jennifer L; O'Caña, Frank
...On!: HIV/ STD Prevention Mobile Application (App) Video Game...On!: HIV/STD Prevention Mobile Application (App) Video Game...Contestants can submit game apps beginning September 13, 2013...On!: HIV/STD Prevention Mobile Application (App) Video...
Women comprise almost 50% of the population of people living with HIV and the majority of these women contracted the virus through sexual transmission in monogamous relationships in the developing world. In these environments, where women are not empowered to protect themselves through the negotiation of condom use, effective means of preventing HIV transmission are urgently needed. In the absence of an approved and effective vaccine, microbicides have become the strategy of choice to provide women with the ability to prevent HIV transmission from their infected partners. Topical microbicides are agents specifically developed and formulated for use in either the vaginal or rectal environment that prevent infection by sexually transmitted infectious organisms, including pathogenic viruses, bacteria and fungi. Although a microbicidal product will have many of the same properties as other anti-infective agents and would be similarly developed through human clinical trials, microbicide development bears its own challenges related to formulation and delivery and the unique environment in which the product must act, as well as the requirement to develop a product that is acceptable to the user. Herein, perspectives based on preclinical and clinical microbicide development experience, which have led to an evolving microbicide development algorithm, will be discussed. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, Vol 85, issue 1, 2010”.
Buckheit, Robert W.; Watson, Karen M.; Morrow, Kathleen M.; Ham, Anthony S.
A simian immunodeficiency virus (SIV) vaccine coexpressing granulocyte-macrophage colony stimulating factor (GM-CSF) prevented infection in 71% of macaques that received 12 rectal challenges. The SIVsmE660 challenge had the tropism of incident human immunodeficiency virus (HIV) infections and a similar genetic distance from the SIV239 vaccine as intraclade HIV isolates. The heterologous prime-boost vaccine regimen used recombinant DNA for priming and recombinant modified vaccinia Ankara for boosting. Co-expression of GM-CSF in the DNA prime enhanced the avidity of elicited immunoglobulin G for SIV envelope glycoproteins, the titers of neutralizing antibody for easy-to-neutralize SIV isolates, and antibody-dependent cellular cytotoxicity. Impressively, the co-expressed GM-CSF increased vaccine-induced prevention of infection from 25% in the non–GM-CSF co-expressing vaccine group to 71% in the GM-CSF co-expressing vaccine group. The prevention of infection showed a strong correlation with the avidity of the elicited Env-specific antibody for the Env of the SIVsmE660 challenge virus (r = 0.9; P < .0001).
Lai, Lilin; Kwa, SueFen; Kozlowski, Pamela A.; Montefiori, David C.; Ferrari, Guido; Johnson, Welkin E.; Hirsch, Vanessa; Villinger, Francois; Chennareddi, Lakshmi; Earl, Patricia L.; Moss, Bernard; Amara, Rama Rao
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.
Stewart, Angela; Fasciano, John; Brown, Larry K.
Although a live attenuated HIV vaccine is not currently considered for safety reasons, a strategy inducing both T cells and neutralizing antibodies to native assembled HIV-1 particles expressed by a replicating virus might mimic the advantageous characteristics of live attenuated vaccine. To this aim, we generated a live attenuated recombinant measles vaccine expressing HIV-1 Gag virus-like particles (VLPs) covered with
Mathilde Guerbois; Arnaud Moris; Chantal Combredet; Valérie Najburg; Claude Ruffié; Michèle Février; Nadège Cayet; Samantha Brandler; Olivier Schwartz; Frédéric Tangy
To stimulate the immune system's natural defenses, a post-infection HIV vaccination program to regularly boost cytotoxic T-lymphocytes has been proposed. We develop a mathematical model to describe such a vaccination program, where the strength of the vaccine and the vaccination intervals are constant. We apply the theory of impulsive differential equations to show that the model has an orbitally asymptotically stable periodic orbit, with the property of asymptotic phase. We show that, on this orbit, the vaccination frequency can be chosen so that the average number of infected CD4(+) T cells can be made arbitrarily low. We illustrate the results with numerical simulations and show that the model is robust with respect to both the parameter choices and the formulation of the model as a system of impulsive differential equations. PMID:18359048
Smith, Robert J; Schwartz, Elissa J
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
Objectives: Willingness to participate in HIV-1 vaccine trials and associated factors were investigated in a sample of 2670 Royal Thai Army conscripted recruits. Methods: Self administered questionnaires were used. Data were collected during the final visit of a longitudinal cohort study of HIV-1 epidemiology. Cross sectional analysis of data from this visit was performed. Results: 32% of the respondents reported they would "definitely" join an HIV-1 vaccine trial. Greater willingness was associated with perceived risk of HIV-1 infection and a desire to help Thai society, although tangible incentives and intentions to reduce condom use in a vaccine trial also were associated with increased willingness. Concerns about physical harm and anticipated social pressure from family not to join were the most substantial impediments to willingness. Concerns about "social harm" (for example, participation would give appearance of having AIDS virus, a partner might refuse sex) also appeared to inhibit interest in joining trials and approached significance. Conclusions: Willingness to participate was somewhat greater than in other investigations of non-injection drug user (IDU) cohorts in Thailand, with fewer concerns expressed about physical harm. Motivations appear to involve tradeoffs among perceived risk, anticipated social pressure, altruism, and tangible rewards. The absence of significant problems associated with vaccine trials to date, along with the presence of educational interventions in the study may help explain the lower level of concerns here relative to other Thai studies. Key Words: HIV; vaccine; Thailand
Jenkins, R; Torugsa, K; Markowitz, L; Mason, C; Jamroentana, V; Brown, A; Nitayaphan, S
Literature to guide HIV prevention outreach for southeastern rural blacks is limited despite the increasing prevalence of HIV infection in this population. Three men and one woman conducted HIV prevention outreach in three north Florida rural counties in teams of two. The workers received five days of training in additional homework assignments. The workers used HIV\\/AIDS outreach surveys to guide
Emma J. Brown; Joseph S. Brown
Abstract Changes in natural killer (NK) cells according to their phenotype and expression of certain regulatory receptors were analyzed in a double-blind, controlled study of antiretroviral therapy (ART)-untreated HIV-seropositive patients, who had been vaccinated with monocyte-derived dendritic cells pulsed with inactivated HIV-1 autologous virus. This work extends other recently published studies of the same group of HIV-1+ vaccinated patients, which demonstrated that the viral load significantly decreases and correlates inversely with an increase in HIV-specific T-cell responses in vaccinated patients, but not in controls who received placebo. Our results indicate that this vaccine raises the level of the NK CD56neg cell subpopulation, while levels of the NK CD56dim and NK CD56bright cells expressing the inhibitory receptor CD85j/ILT-2 fell in vaccinated patients. Taken together, these results suggest that this vaccine might enhance innate immunity by amplifying the inflammatory and cytolytic capacity.
Frias, Mario; Castro-Orgaz, Laura; Gonzalez, Rafael; Garcia, Felipe; Gallart, Teresa; Gatell, Jose Maria; Plana, Montserrat
Changes in natural killer (NK) cells according to their phenotype and expression of certain regulatory receptors were analyzed in a double-blind, controlled study of antiretroviral therapy (ART)-untreated HIV-seropositive patients, who had been vaccinated with monocyte-derived dendritic cells pulsed with inactivated HIV-1 autologous virus. This work extends other recently published studies of the same group of HIV-1(+) vaccinated patients, which demonstrated that the viral load significantly decreases and correlates inversely with an increase in HIV-specific T-cell responses in vaccinated patients, but not in controls who received placebo. Our results indicate that this vaccine raises the level of the NK CD56(neg) cell subpopulation, while levels of the NK CD56(dim) and NK CD56(bright) cells expressing the inhibitory receptor CD85j/ILT-2 fell in vaccinated patients. Taken together, these results suggest that this vaccine might enhance innate immunity by amplifying the inflammatory and cytolytic capacity. PMID:22233253
Peña, José; Frías, Mario; Castro-Orgaz, Laura; González, Rafael; García, Felipe; Gallart, Teresa; Gatell, Jose María; Plana, Montserrat
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.
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.
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.
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 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.
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
Gupta, Ravindra K; Van de Vijver, David A M C; Manicklal, Sheetal; Wainberg, Mark A
A phase I randomized, double blind, placebo-controlled trial to assess the immunogenicity of a multiclade HIV-1 DNA plasmid vaccine was conducted in 31 HIV-1-negative Ugandans. Following immunization with DNA at 0, 1, and 2 months, the frequency of HIV-specific immune responses was assessed up to 10 months using a standard chromium release assay (CRA), lymphoproliferative assay (LPA), and antibody dependent cell-mediated cytotoxicity assay (ADCC). Seven of 15 (47%) vaccinees demonstrated CTL activity using the CRA to HIV-1 Env B with responses observed 1 month following the second vaccination and as late as 7 months following complete immunization. Additionally, lymphoproliferative reponses were observed in 14/15 vaccinees against p24. No CTL or LPA responses were observed at baseline or in the placebo group. ADCC activity was minimally induced by DNA vaccination. This study demonstrates that immunization with DNA alone induces CTL and lymphoproliferative responses in a population that will participate in a phase IIb study evaluating HIV-1 DNA priming followed by boosting with a replication-defective recombinant adenovirus vector. PMID:17920731
Eller, Michael A; Eller, Leigh Anne; Opollo, Marc S; Ouma, Benson J; Oballah, Peter O; Galley, Lynee; Karnasuta, Chitraporn; Kim, Silvia Ratto; Robb, Merlin L; Michael, Nelson L; Kibuuka, Hannah; Wabwire-Mangen, Fred; Graham, Barney S; Birx, Deborah L; de Souza, Mark S; Cox, Josephine H
Until now, decisions about how to allocate ART have largely been based on maximising the therapeutic benefit of ART for patients. Since the results of the HPTN 052 study showed efficacy of antiretroviral therapy (ART) in preventing HIV transmission, there has been increased interest in the benefits of ART not only as treatment, but also in prevention. Resources for expanding
Wim Delva; Jeffrey W. Eaton; Fei Meng; Christophe Fraser; Richard G. White; Peter Vickerman; Marie-Claude Boily; Timothy B. Hallett
The rigorous evaluation of the impact of combination HIV prevention packages at the population level will be critical for the future of HIV prevention. In this review, we discuss important considerations for the design and interpretation of cluster randomized controlled trials (C-RCTs) of combination prevention interventions. We focus on three large C-RCTs that will start soon and are designed to test the hypothesis that combination prevention packages, including expanded access to antiretroviral therapy, can substantially reduce HIV incidence. Using a general framework to integrate mathematical modelling analysis into the design, conduct, and analysis of C-RCTs will complement traditional statistical analyses and strengthen the evaluation of the interventions. Importantly, even with combination interventions, it may be challenging to substantially reduce HIV incidence over the 2- to 3-y duration of a C-RCT, unless interventions are scaled up rapidly and key populations are reached. Thus, we propose the innovative use of mathematical modelling to conduct interim analyses, when interim HIV incidence data are not available, to allow the ongoing trials to be modified or adapted to reduce the likelihood of inconclusive outcomes. The preplanned, interactive use of mathematical models during C-RCTs will also provide a valuable opportunity to validate and refine model projections.
Boily, Marie-Claude; Masse, Benoit; Alsallaq, Ramzi; Padian, Nancy S.; Eaton, Jeffrey W.; Vesga, Juan F.; Hallett, Timothy B.
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; de Val Alda, Natalia; Wilson, Richard; Sundling, Christopher; Li, Yuxing; Stanfield, Robyn L; Wilson, Ian A; Ward, Andrew B; Karlsson Hedestam, Gunilla B; Wyatt, Richard T
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.
Eng, Philip; Lim, Lean Huat; Loo, Chian Min; Low, James Alvin; Tan, Carol; Tan, Eng Kiat; Wong, Sin Yew; Setia, Sajita
Confronted with the recent high-profile failures of several clinical trials of promising candidate vaccines against HIV, many scientists have all but given up hope of producing a human-ready vaccine within the next decade. In this review I contend that although the scientific obstacles remain formidable, the economic challenges are just as real. The groundwork will be laid for a major scientific breakthrough in vaccine development only when there are new contractual structures that enhance private incentives for vaccine development; when we have clearly specified the rights to the profitable North American market; when we have established a system of liability protection for vaccine side effects; and when our clinical trials also test the behavioral consequences of vaccination. PMID:19887405
Harris, Jeffrey E
Alcohol use is associated with risks for sexually transmitted infections (STIs), including HIV/AIDS. People meet new sex partners at bars and other places where alcohol is served, and drinking venues facilitate STI transmission through sexual relationships within closely knit sexual networks. This paper reviews HIV prevention interventions conducted in bars, taverns, and informal drinking venues. Interventions designed to reduce HIV risk by altering the social interactions within drinking environments have demonstrated mixed results. Specifically, venue-based social influence models have reduced community-level risk in U.S. gay bars, but these effects have not generalized to gay bars elsewhere or to other populations. Few interventions have sought to alter the structural and physical environments of drinking places for HIV prevention. Uncontrolled program evaluations have reported promising approaches to bar-based structural interventions with gay men and female sex workers. Finally, a small number of studies have examined multilevel approaches that simultaneously intervene at both social and structural levels with encouraging results. Multilevel interventions that take environmental factors into account are needed to guide future HIV prevention efforts delivered within alcohol-serving establishments.
Kalichman, Seth C.
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”.
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.
Cohen, Myron S; Smith, M Kumi; Muessig, Kathryn E; Hallett, Timothy B; Powers, Kimberly A; Kashuba, Angela D
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 schoolbased 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
Despite considerable experience with single-dose, live, oral cholera vaccine CVD 103-HgR in Asia, Europe, and the Americas, the vaccine had not been evaluated in sub-Saharan Africa or on individuals infected with human immunodeficiency virus (HIV). We therefore conducted a randomized, placebo-controlled, double-blind, cross-over clinical trial in 38 HIV-seropositive (without clinical acquired immunodeficiency syndrome (AIDS)) and 387 HIV-seronegative adults in Mali to assess its safety and immunogenicity. Adverse reactions (fever, diarrhoea and vomiting) were observed with similar frequency among vaccine and placebo recipients. The vaccine strain was not isolated from the coprocultures of any subject. The baseline geometric mean titre (GMT) of serum vibriocidal antibody was significantly lower in HIV-seropositives (1:23) than in HIV-seronegatives (1:65) (P = 0.002). Significant rises in vibriocidal antibody were observed in 71% of HIV-seronegatives and 58% of HIV-seropositives, and in 40% of HIV-seropositives with CD4+ counts below 500 per microliter. Following immunization, the peak vibriocidal GMT in HIV-seronegatives was 1:584 versus 1:124 in HIV-seropositives (P = 0.0006); in HIV-seropositives with CD4+ counts < 500 per microliter, the peak vibriocidal GMT was 1:40 (P = 0.03 versus other HIV-seropositives). CVD 103-HgR was safe in HIV-infected Malian adults, although serological responses were significantly attenuated among HIV-seropositives (particularly in those with CD4+ counts < 500 per microliter) relative to HIV-seronegatives. These results encourage further evaluations of this single-dose, oral cholera vaccine in high-risk populations such as refugees in sub-Saharan Africa.
Perry, R. T.; Plowe, C. V.; Koumare, B.; Bougoudogo, F.; Kotloff, K. L.; Losonsky, G. A.; Wasserman, S. S.; Levine, M. M.
BackgroundA vaccine is needed to control the spread of human immunodeficiency virus type 1 (HIV-1). An in vitro assay that can predict the protection induced by a vaccine would facilitate the development of such a vaccine. A potential candidate would be an assay to quantify neutralization of HIV-1.Methods and FindingsWe have used sera from rhesus macaques that have been immunized
David Davis; Wim Koornstra; Daniella Mortier; Zahra Fagrouch; Ernst J. Verschoor; Jonathan L. Heeney; Willy M. J. M. Bogers
Recombinant modified vaccinia virus Ankara (MVA) is together with a few other attenuated viral vectors on the forefront of human immunodeficiency virus type 1 (HIV-1) vaccine development. As such, MVA-vectored vaccines are likely to be administered into immunocompromized individuals. Here, we demonstrated in a good laboratory practice study safety and biological clearance of candidate HIV-1 vaccine MVA·HIVA in simian immunodeficiency
Tomáš Hanke; Andrew J. McMichael; Michael J. Dennis; Sally A. Sharpe; Lindsey A. J. Powell; Lorraine McLoughlin; Steven J. Crome
Dissemination of evidence-based HIV prevention programs for adolescents will be increased if community interventionists are able to distinguish core, essential program elements from optional, discretionary ones. We selected five successful adolescent HIV prevention programs, used a qualitative coding method to identify common processes described in the procedural manuals, and then compared the programs. Nineteen common processes were categorized as structural features, group management strategies, competence building, and addressing developmental challenges of adolescence. All programs shared the same structural features (goal-setting and session agendas), used an active engagement style of group management, and built cognitive competence. Programs varied in attention to developmental challenges, emphasis on behavioral and emotional competence, and group management methods. This qualitative analysis demonstrated that successful HIV programs contain processes not articulated in their developers’ theoretical models. By moving from the concrete specifics of branded interventions to identification of core, common processes, we are consistent with the progress of “common factors” research in psychotherapy.
Ingram, Barbara L.; Flannery, Diane; Elkavich, Amy
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.
In Washington, D.C. adolescents are infected with about 1/3 of all sexually transmitted diseases, and the incidence of congenital syphilis is mounting. The District of Columbia had a reported AIDS infection rate of 132.5/100,000 residents between July 1991 and June 1992 compared with 44.8 in New York. A total of 6613 cases were reported of which 6523 afflicted adults and adolescents. Only San Francisco had more cases with 12,402 cases of adults and adolescents reported. The District of Columbia's 1991 Youth Risk Behavior Survey disclosed that 78.8% of the 1275 adolescents in grades 9 and 10 had experienced sexual intercourse, and 38.8% of these were 13 years old or younger at 1st coitus. 33% of responders had had sex with 6 or more people. .53% of adolescent military recruits from the District had HIV infection, the highest rate in the nation. The District of Columbia Public Schools (DCPS) started an AIDS education program in 1987 for grades 4-12 with support from the Centers for Disease Control. During 1987-92 a 5-year HIV/AIDS Education program's activities involved formal training for all teachers; awareness seminars for school counselors and instructors; evaluation of teachers trained; student assessment of classroom training; DCPS Advisory Board with medical specialists, AIDS educators, and AIDS victims; coalition building with more than 20 organizations in the city; and distribution of literature to the 174 schools in the system. The program resulted in significant improvement in HIV/AIDS awareness at all 3 school levels, although it was more effective with elementary students and it made the least impact on senior high school students, especially on boys. Girls in junior high school showed improvement in knowledge, attitudes, and behavior concerning HIV/AIDS than boys. Future educational efforts should concentrate more on boys both in junior and senior high school. PMID:12286191
Sadler, J W
In 1999, the Broward County Health Department and local community faith-based organizations collaborated to develop Churches United to Stop HIV (CUSH). CUSH has provided HIV prevention services to over 32,000 people, trained over 2,850 faith leaders, conducted over 1,000 risk assessments and provided HIV counseling and testing for over 825 people and technical assistance for 48 churches, including the development of a training manual. We report the development of this innovative program that demonstrates how collaborations between public health and faith-based organizations can connect science with communities. PMID:16080459
Agate, Lisa L; Cato-Watson, D'Mrtri; Mullins, Jolene M; Scott, Gloria S; Rolle, Vanice; Markland, Donna; Roach, David L
DNA vaccines require significant engineering in order to generate strong CTL responses in both non-human primates and humans. In this study, we designed a clade C env gene (EY3E1-C) to decrease the genetic distances of virus isolates within clade C and focus the induced T cell responses to conserved clade C epitopes. After generating a consensus sequence by analyzing full-length clade C env early transmitter sequences, several modifications were performed to increase the expression of the EY3E1-C, including codon/RNA optimization, addition of Kozak sequence and addition of an IgE leader sequence. We also shortened the V1 and V2 loops to approximate early transmitter isolate sequences and the cytoplasmic tail was truncated to prevent envelope recycling. When studied as a DNA vaccine in Balb/c mice, compared to a primary codon-optimized clade C envelope DNA vaccine (p96ZM651gp140-CD5), this novel construct is up to three times more potent in driving CTL responses. Importantly this construct not only induces stronger cross-reactive cellular responses within clade C, it also induces stronger immune responses against clade B and group M envelope peptide pools than p96ZM651gp140-CD5. Epitope mapping demonstrated that EY3E1-C was able to induce clade C envelope-specific immune responses against 15 peptide pools, clade B envelope-specific immune responses against 19 peptide pools and group M envelope-specific immune responses against 16 peptide pools out of 29, respectively, indicating that a significant increase in the breadth of induced immune responses. The analysis of antibody responses suggested that vaccination of pEY3E1-C could induce a clade C envelope-specific antibody response. The cellular immune responses of pEY3E1-C could be further enhanced when the DNA was delivered by using electroporation (EP). Thus, the synthetic engineered consensus EY3E1-C gene is capable of eliciting stronger and broader CTL responses than primary clade C envelopes. This finding suggests that such synthetic immunogens could be important for examination of their potential as part of an efficient HIV DNA vaccine.
Yan, Jian; Corbitt, Natasha; Pankhong, Panyupa; Shin, Thomas; Khan, Amir; Sardesai, Niranjan Y.; Weiner, David B.
DNA vaccines require significant engineering in order to generate strong CTL responses in both non-human primates and humans. In this study, we designed a clade C env gene (EY3E1-C) to decrease the genetic distances of virus isolates within clade C and focus the induced T cell responses to conserved clade C epitopes. After generating a consensus sequence by analyzing full-length clade C env early transmitter sequences, several modifications were performed to increase the expression of the EY3E1-C, including codon/RNA optimization, addition of Kozak sequence and addition of an IgE leader sequence. We also shortened the V1 and V2 loops to approximate early transmitter isolate sequences and the cytoplasmic tail was truncated to prevent envelope recycling. When studied as a DNA vaccine in Balb/c mice, compared to a primary codon-optimized clade C envelope DNA vaccine (p96ZM651gp140-CD5), this novel construct is up to three times more potent in driving CTL responses. Importantly this construct not only induces stronger cross-reactive cellular responses within clade C, it also induces stronger immune responses against clade B and group M envelope peptide pools than p96ZM651gp140-CD5. Epitope mapping demonstrated that EY3E1-C was able to induce clade C envelope-specific immune responses against 15 peptide pools, clade B envelope-specific immune responses against 19 peptide pools and group M envelope-specific immune responses against 16 peptide pools out of 29, respectively, indicating that a significant increase in the breadth of induced immune responses. The analysis of antibody responses suggested that vaccination of pEY3E1-C could induce a clade C envelope-specific antibody response. The cellular immune responses of pEY3E1-C could be further enhanced when the DNA was delivered by using electroporation (EP). Thus, the synthetic engineered consensus EY3E1-C gene is capable of eliciting stronger and broader CTL responses than primary clade C envelopes. This finding suggests that such synthetic immunogens could be important for examination of their potential as part of an efficient HIV DNA vaccine. PMID:21651948
Yan, Jian; Corbitt, Natasha; Pankhong, Panyupa; Shin, Thomas; Khan, Amir; Sardesai, Niranjan Y; Weiner, David B
HIV pseudovirion or virus-like particle vaccines represent a promising approach for eliciting humoral and cellular immune responses. Pseudovirions present the envelope glycoprotein complex in its authentic trimeric form, and thus have the potential to generate neutralizing antibodies against relevant virion-associated epitopes that may be lacking in protein subunit vaccines. The development of pseudovirion particles as a viable vaccine approach for
Jason Hammonds; Xuemin Chen; Xiugen Zhang; Francis Lee; Paul Spearman
Emergence of serogroup B meningococci of clonal complex sequence type (ST) 41/44 can cause high levels of disease, as exemplified by a recent epidemic in New Zealand. Multiplication of annual incidence rates (3.1 cases/100,000 population) of meningococcal disease in a defined German region, the city of Aachen and 3 neighboring countries (Greater Aachen) prompted us to investigate and determine the source and nature of this outbreak. Using molecular typing and geographic mapping, we analyzed 1,143 strains belonging to ST41/44 complex, isolated from persons with invasive meningococcal disease over 6 years (2001–2006) from 2 German federal states (total population 26 million) and the Netherlands. A spatially slowly moving clone with multiple-locus variable-number tandem repeat analysis type 19, ST42, and antigenic profile B:P1.7–2,4:F1–5 was responsible for the outbreak. Bactericidal activity in serum samples from the New Zealand MeNZB vaccination campaign confirmed vaccine preventability. Because this globally distributed epidemic strain spreads slowly, vaccination efforts could possibly eliminate meningococcal disease in this area.
Schouls, Leo M.; van de Pol, Ingrid; Keijzers, Wendy C.; Martin, Diana R.; Glennie, Anne; Oster, Philipp; Frosch, Matthias; Vogel, Ulrich; van der Ende, Arie
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
Background Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. Methods In nine countries, we enrolled 1763 couples in which one partner was HIV-1–positive and the other was HIV-1–negative; 54% of the subjects were from Africa, and 50% of infected partners were men. HIV-1–infected subjects with CD4 counts between 350 and 550 cells per cubic millimeter were randomly assigned in a 1:1 ratio to receive antiretroviral therapy either immediately (early therapy) or after a decline in the CD4 count or the onset of HIV-1–related symptoms (delayed therapy). The primary prevention end point was linked HIV-1 transmission in HIV-1–negative partners. The primary clinical end point was the earliest occurrence of pulmonary tuberculosis, severe bacterial infection, a World Health Organization stage 4 event, or death. Results As of February 21, 2011, a total of 39 HIV-1 transmissions were observed (incidence rate, 1.2 per 100 person-years; 95% confidence interval [CI], 0.9 to 1.7); of these, 28 were virologically linked to the infected partner (incidence rate, 0.9 per 100 person-years, 95% CI, 0.6 to 1.3). Of the 28 linked transmissions, only 1 occurred in the early-therapy group (hazard ratio, 0.04; 95% CI, 0.01 to 0.27; P<0.001). Subjects receiving early therapy had fewer treatment end points (hazard ratio, 0.59; 95% CI, 0.40 to 0.88; P = 0.01). Conclusions The early initiation of antiretroviral therapy reduced rates of sexual transmission of HIV-1 and clinical events, indicating both personal and public health benefits from such therapy.
Cohen, Myron S.; Chen, Ying Q.; McCauley, Marybeth; Gamble, Theresa; Hosseinipour, Mina C.; Kumarasamy, Nagalingeswaran; Hakim, James G.; Kumwenda, Johnstone; Grinsztejn, Beatriz; Pilotto, Jose H.S.; Godbole, Sheela V.; Mehendale, Sanjay; Chariyalertsak, Suwat; Santos, Breno R.; Mayer, Kenneth H.; Hoffman, Irving F.; Eshleman, Susan H.; Piwowar-Manning, Estelle; Wang, Lei; Makhema, Joseph; Mills, Lisa A.; de Bruyn, Guy; Sanne, Ian; Eron, Joseph; Gallant, Joel; Havlir, Diane; Swindells, Susan; Ribaudo, Heather; Elharrar, Vanessa; Burns, David; Taha, Taha E.; Nielsen-Saines, Karin; Celentano, David; Essex, Max; Fleming, Thomas R.
Background Bundling is defined as the aggregation of services to increase effectiveness (i.e., creating synergy of effort). The purpose of this commentary is to review the utilization and potential benefits of bundling in its application to HIV prevention. Methods Review of the literature to provide a broad perspective on the concept of bundling and specific examples of bundling in HIV prevention. Benefits, challenges and directions are considered. Results To be effective, bundling must offer strategic advantage: greater value, less cost. It provides an opportunity to target multiple risk behaviors simultaneously for synergistic gain. Technological advances including rapid HIV tests permit noninvasive sampling in clinical and non-clinical settings. Bundling of HIV prevention provides an opportunity to reach high-risk persons who are asymptomatic and/or may not otherwise seek care by eliminating barriers to prevention. Conclusions We must implement programs that work and consider innovative approaches to stem the AIDS epidemic; bundling provides one such opportunity to create an efficient paradigm targeting multiple risk behaviors simultaneously.
Ickovics, Jeannette R.
Conducted a formative research study designed to elicit preferences for sexually transmitted disease (STD)/HIV prevention programs from clients at a midwestern STD clinic. Responses of 126 participants show preferences for mixed group or individual meetings with counselors, with extensive intervention less favored than single sessions. Discusses…
Hennessy, Michael; Mercier, Michele M.; Williams, Samantha P.; Arno, Janet N.
The first two aims of this project were to develop a Bayesian method for computing credible intervals around the cost-effectiveness statistic for HIV prevention interventions in which effectiveness is modeled, and to apply this Bayesian method to a cost-e...
A. P. Johnson-Masotti
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.
This volume is a guide to providing effective Human Immunodeficiency Virus (HIV) and substance abuse prevention services to runaway and homeless youth. The guide is based on current research and the best programs in this field. Chapters 1 and 2 summarize what is known about runaway and homeless youth, the services these youth require if they are…
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
Recent research has highlighted the significant contribution families make in the prevention of HIV risk behaviors among adolescents. As the most proximal and fundamental social system influencing child development, families provide many of the factors that protect adolescents from engaging in sexual risk behaviors. Among these are positive family relations, effective communication about sexuality and safer sexual behaviors, enhancement and
Tatiana Perrino; Alina González-Soldevilla; Hilda Pantin; José Szapocznik
Purpose of review The purpose of this review is to describe a critical need of the HIV research community for a globally accessible database of HIV vaccine responses that stores data from multiple assay platforms in the form of lists of correlates of immune protection and vaccine efficacy. This is not a detailed review but a first step toward developing a dialogue among investigators and funding organizations to build upon existing resources to efficiently develop a HIV vaccine response and correlates database. We also discuss examples of databases that complement our needs and could be integrated into our proposed database requirements. Recent findings Several vaccine-related databases that store information at the study level currently exist, however, at the present time, a correlates of immune protection database does not exist. Summary Here, we discuss the scientific climate surrounding HIV vaccine development with the evolution of systems biology approaches, the problems at hand for analyzing and harmonizing datasets generated from preclinical and clinical studies, and the curation and accessibility of useful information to model outcomes. We also compare key database requirements of a few existing globally accessible databases and provide several illustrative correlate database submission and utilization examples.
Wilkinson, Peter; Filali-Mouhim, Abdelali; Li, Shuzhao; Ahlers, Jeffrey; Schatzle, John; Pulendran, Bali; Sekaly, Rafick-Pierre; Cameron, Mark 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.
Live attenuated viruses make potent and effective vaccines. Despite the urgent need for an HIV vaccine, this approach has not been feasible, since it has not been possible to attenuate the virus reliably and guarantee vaccine safety. Instead, live viral vectors have been proposed that could present HIV vaccine antigens in the most immunogenic way, in the context of an active infection. We have adapted the rubella vaccine strain RA27/3 as a vector to express HIV and SIV antigens, and tested the effect of insert size and composition on vector stability and viral titer. We have identified an acceptor site in the rubella nonstructural gene region, where foreign genes can be expressed as a fusion protein with the nonstructural protein P150 without affecting essential viral functions. The inserts were expressed as early genes of rubella, under control of the rubella genomic promoter. At this site, HIV and SIV antigens were expressed stably for at least seven passages, as the rubella vectors reached high titers. Rubella readily infects rhesus macaques, and these animals will provide an ideal model for testing the new vectors for replication in vivo, immunogenicity, and protection against SIV or SHIV challenge.
Virnik, Konstantin; Ni, Yisheng; Berkower, Ira
To overcome the problem of HIV-1 variability, candidate vaccine antigens have been designed to be composed of conserved elements of the HIV-1 proteome. Such candidate vaccines could be improved with a better understanding of both HIV-1 evolutionary constraints and the fitness cost of specific mutations. We evaluated the in vitro fitness cost of 23 mutations engineered in the HIV-1 subtype B Gag-p24 Center-of-Tree (COT) protein through fitness competition assays. While some mutations at conserved sites exacted a high fitness cost, as expected under the assumption that the most conserved residue confers the highest fitness, there was no overall strong relationship between sequence conservation and replicative capacity. By comparing sites that have evolved since the beginning of the epidemic to those that have remain unchanged, we found that sites that have evolved over time were more likely to correspond to HLA-associated sites and that their mutation had limited fitness costs. Our data showed no transcendent link between high conservation and high fitness cost, indicating that merely focusing on conserved segments of HIV-1 would not be sufficient for a successful vaccine strategy. Nonetheless, a subset of sites exacted a high fitness cost upon mutation—these sites have been under selective pressure to change since the beginning of the epidemic but have proved virtually nonmutable and could constitute preferred targets for vaccine design.
Manocheewa, Siriphan; Swain, J. Victor; Lanxon-Cookson, Erinn C.; Kim, Moon; Westfall, Dylan H.; Larsen, Brendan B.; Gilbert, Peter B.; Mullins, James I.
Synthetic V3 loop peptides hold numerous benefits for the development of HIV vaccines and in immunodiagnosis; however, their use is limited due to the extensive antigenic variability of this region. The effectiveness of a potential HIV vaccine component, which accounts for V3 loop variability, is evaluated here. A branched peptide construct representing multiple sequences and allowing 1.8 x 10(16) possible permutations was developed to mimic circulating HIV-1 subtype C, V3 loops. The construct was found to be immunogenic, able to induce neutralizing antibodies and sensitive to HIV-1 subtype B/C and HIV-2. This alternative antigen format also incorporates conformational epitopes. PMID:15755588
Hewer, R; Meyer, D
This study investigated provider-based complementary/alternative medicine use and its association with receipt of recommended vaccinations by children aged 1–2 years and with acquisition of vaccine-preventable disease by children aged 1–17 years. Results were based on logistic regression analysis of insurance claims for pediatric enrollees covered by two insurance companies in Washington State during 2000–2003. Primary exposures were use of chiropractic, naturopathy, acupuncture, or massage practitioner services by pediatric enrollees or members of their immediate families. Outcomes included receipt by children aged 1–2 years of four vaccine combinations (or their component vaccines) covering seven diseases, and acquisition of vaccine-preventable diseases by enrollees aged 1–17 years. Children were significantly less likely to receive each of the four recommended vaccinations if they saw a naturopathic physician. Children who saw chiropractors were significantly less likely to receive each of three of the recommended vaccinations. Children aged 1–17 years were significantly more likely to be diagnosed with a vaccine-preventable disease if they received naturopathic care. Use of provider-based complementary/alternative medicine by other family members was not independently associated with early childhood vaccination status or disease acquisition. Pediatric use of complementary/alternative medicine in Washington State was significantly associated with reduced adherence to recommended pediatric vaccination schedules and with acquisition of vaccine-preventable disease. Interventions enlisting the participation of complementary/alternative medicine providers in immunization awareness and promotional activities could improve adherence rates and assist in efforts to improve public health.
Tyree, Patrick T.; Huebner, Colleen E.; Lafferty, William E.
Background. Polysaccharide pneumococcal vaccine (PPV) is recommended among human immunodeficiency virus (HIV)-infected patients, although its effect in reducing the incidence of pneumonia or invasive pneumococcal disease is not well established. Our objective was to determine the effectiveness of 23-valent PPV in HIV-infected adults and the risk factors for pneumococcal pneumonia or invasive pneumococcal disease. Methods. We performed a retrospective case-control
Maria Penaranda; Vicenc Falco; Antoni Payeras; Queralt Jordano; Adria Curran; Antoni Pareja; Gloria Samperiz; David Dalmau; Esteve Ribera; Melcior Riera
In the third decade of the HIV/AIDS epidemic, empirically based HIV transmission risk reduction interventions for HIV infected persons are still needed. As part of a Health Resources Services Administration/Special Projects of National Significance initiative to increase prevention services among HIV infected persons, we implemented SHAPE (Supporting Healthy Alternatives through Patient Education). SHAPE is a behavioral HIV prevention intervention delivered to HIV infected persons receiving primary medical care at El Rio Health Center in Tucson, Arizona. The SHAPE intervention is based on Kalichman's "Healthy Relationships for Men and Women Living with HIV-AIDS." The intervention is interactive and uses a video discussion intervention format where educational activities, movie clips, and discussions are used to provide participants with information and skills to increase their comfort in disclosing their HIV status and in reducing HIV transmission. This paper describes the intervention in sufficient detail to replicate it in other settings. PMID:17265144
Estrada, Barbara D; Trujillo, Stephen; Estrada, Antonio L
The role of the European Centre for Disease Prevention and Control (ECDC) is to strengthen the capacity of the European Union (EU) Member States to protect human health through the prevention and control of infectious diseases. The main objective of the programme on vaccine-preventable diseases and invasive bacterial infections (VPD) is to provide robust evidence and high-quality technical support to the EU Member States to help them in their efforts to prevent and control VPD. Since the establishment of ECDC, several existing VPD surveillance networks have been transferred to ECDC, namely EU-IBIS, DIPNET and EUVAC. In addition to surveillance of diseases, ECDC is collecting information and monitoring other parameters that are of crucial importance for a well-functioning immunization system, including vaccination coverage. The VPD programme also provides independent scientific opinions in the area of immunization and initiates and coordinates scientific studies in the area of vaccination to answer specific questions of public health importance, including risk perception and analysis of behaviour in different population groups. One of the overall ECDC priorities over recent years is the Centre's involvement in measles elimination. The 'Message' tool and the 'Measles Atlas' are examples of work aiming at supporting the efforts of Member States in the elimination phase. PMID:24438673
Kramarz, P; Lopalco, P L; Huitric, E; Pastore Celentano, L
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.
Gamble, Lena J; Matthews, Qiana L
Background Hepatitis B virus (HBV) is an important cause of comorbidity in human immunodeficiency virus (HIV)–infected individuals. The immunogenicity of HBV vaccination in children receiving highly active antiretroviral therapy (HAART) was investigated. Methods HIV-infected children receiving HAART who had low to moderate HIV loads and who had previously received ?3 doses of HBV vaccine were given an HBV vaccine booster. Concentrations of antibody to hepatitis B surface antigen (anti-HBs) were determined before vaccination and at weeks 8, 48, and 96. A subset of subjects was administered a subsequent dose, and anti-HBs was measured before and 1 and 4 weeks later. Results At entry, 24% of 204 subjects were seropositive. Vaccine response occurred in 46% on the basis of seropositivity 8 weeks after vaccination and in 37% on the basis of a ?4-fold rise in antibody concentration. Of 69 subjects given another vaccination 4–5 years later, immunologic memory was exhibited by 45% on the basis of seropositivity 1 week after vaccination and by 29% on the basis of a ?4-fold rise in antibody concentration at 1 week. Predictors of response and memory included higher nadir and current CD4 cell percentage, higher CD19 cell percentage, and undetectable HIV load. Conclusions HIV-infected children frequently lack protective levels of anti-HBs after previous HBV vaccination, and a significant proportion of them do not respond to booster vaccination or demonstrate memory despite receiving HAART, leaving this population insufficiently protected from infection with HBV.
Abzug, Mark J.; Warshaw, Meredith; Rosenblatt, Howard M.; Levin, Myron J.; Nachman, Sharon A.; Pelton, Stephen I.; Borkowsky, William; Fenton, Terence
Most candidate HIV vaccines are directed at priming memory T cell responses and are being evaluated on their effects on post acquisition viremia and/or disease progression. These vaccines are being studied in areas of high HIV-1 prevalence. As such, we evaluated the frequency of CD4+ T cell decline and time course of opportunistic infections of patients presenting at a major metropolitan hospital in Lima, Peru, an area where such candidate vaccines are being tested. We examined 92 patients with untreated HIV-1 in calendar year 2002: 35% presented with CD4+ T cell counts of <200, 25% between 201 and 400, and 17% with >400 cells/mm3, 30 of 92 patients presented with overt AIDS, 6 were without an AIDS defining OI but CD4 counts <200. Over the course of follow-up, CD4 count decreased by a mean of 31 cells/mm3/year in women and 28 in men (p>0.5). Among persons presenting with CD4 counts >250 cells/mm3, the median time to first OI was 3.5 years. If clinical endpoints are required to evaluate the clinical effectiveness of T cell based vaccines, extended clinical follow-up of subjects enrolled in such trials will be required. PMID:17012861
Corey, Daniel; Kim, Hyung Woo; Salazar, Raul; Gutierrez, Luis; Sanchez, Jorge; Tabet, Stephen R
Coccidiosis in chickens is a parasitic disease with great economic significance, which has been controlled successfully for decades using mainly anticoccidial products. However, large-scale and long-term use of anticoccidial drugs has led to the worldwide development of resistance against all these drugs. In order to minimize the occurrence of resistance, the rotation of various anticoccidial drugs in single and/or shuttle programmes is used. Unfortunately, this has not solved the anticoccidial resistance problem. Recently, live anticoccidial vaccines have been incorporated into rotation programmes, resulting in an increasing incidence of anticoccidial drug-sensitive Eimeria spp. field isolates, which may ameliorate the efficacy of anticoccidial drugs. Nevertheless, possible upcoming bans restricting the use of anticoccidials as feed additives, consumer concerns on residues and increasing regulations have prompted the quest for alternative coccidiosis control strategies. Although management and biosecurity measures could halt the introduction of Eimeria spp. to a farm, in practice they do not suffice to prevent coccidiosis outbreaks. Phytotherapy, aromatherapy and pre- and probiotics either show conflicting, non-consistent or non-convincing results, and have therefore not been applied at a large scale in the field. So far, live attenuated and non-attenuated anticoccidial vaccines have proved to be the most solid and successful coccidiosis prevention and control strategy. Despite the drawbacks associated with their production and use, their popularity is increasing. If with time, the immunogenicity of subunit vaccines can be improved, they could represent the next generation of highly efficient and low-cost anticoccidial strategies. PMID:22029884
Peek, H W; Landman, W J M
Text messaging is a potential HIV-prevention tool for men who have sex with men (MSM), specifically young MSM and MSM of color. To determine the willingness of MSM to receive text messages as part of an HIV-prevention intervention, we administered an online survey to MSM recruited from MySpace.com, which included questions about mobile phone ownership and willingness to participate in a future text message-based HIV research study. Of participants, 85% (n = 5,378) reported owning a mobile phone and 49% (n = 2,483) of mobile phone owners reported being willing to receive text messages in a future HIV research study. Black and Hispanic men were more willing than White non-Hispanic men to receive text messages. Men with a college degree were less willing to receive texts than men with a high school level of education, and men >22 years old were less likely to be willing to receive texts than those younger than 22 years of age. The authors' findings demonstrate that willingness to receive text messages as part of an HIV research study is moderate, and mirrors patterns of text message use in age and race. Variations in willingness should be taken into account when designing and implementing future interventions. PMID:23905653
Khosropour, Christine M; Lake, Jason G; Sullivan, Patrick S
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.
Objective: Traveler’s diarrhea (TD) is the most frequent disease among people from industrialized countries who travel to less developed ones, especially sub-Saharan Africa, Southern Asia and South America. The most common bacteria causing TD is enterotoxigenic Escherichia coli (ETEC). The WC/rBS cholera vaccine (Dukoral®) has been shown to induce cross-protection against ETEC by means of the B subunit of the cholera toxin. The aim of the study was to evaluate the effectiveness of the WC/rBS cholera vaccine in preventing TD. Methods: Between May 1 and September 30 (2007), people seeking pre-travel advice in ten Spanish international vaccination centers were included in a prospective cohort study of travelers to cholera risk countries. The incidence rates of TD were adjusted for variables whose frequencies were statistically different (entry point 0.10) between the vaccinated and non-vaccinated cohorts. Findings: The vaccinated cohort (n = 544 travelers) included people vaccinated with the WC/rBS cholera vaccine, and the non-vaccinated cohort (n = 530 travelers) by people not vaccinated. The cumulative incidence rate of TD was 1.69 in vaccinated and 2.14 in non-vaccinated subjects. The adjusted relative risk of TD in vaccinated travelers was 0.72 (95% CI: 0.58–0.88) and the adjusted vaccination effectiveness was 28% (95% CI: 12–42). Conclusions: The WC/rBS cholera vaccine prevents TD in 2 out of 7 travelers (preventive fraction: 28%). The number needed to vaccinate (NNV) to prevent 1 case of TD is 10.
Lopez-Gigosos, Rosa; Campins, Magda; Calvo, Maria J.; Perez-Hoyos, Santiago; Diez-Domingo, Javier; Salleras, Luis; Azuara, Maria T.; Martinez, Xavier; Bayas, Jose M.; Ramon Torrell, Josep M.; Perez-Cobaleda, Maria A.; Nunez-Torron, Maria E.; Gorgojo, Lydia; Garcia-Rodriguez, Magdalena; Diez-Diaz, Rosa; Armadans, Luis; Sanchez-Fernandez, Concepcion; Mejias, Teresa; Masuet, Cristina; Pinilla, Rafael; Anton, Nieves; Segarra, Pilar
Purpose After decades of research, AIDS continues to be a major pandemic and to date, adaptive immunity vaccine designs have had little to no success. Data indicate the alloimmune response is a potent mitigator of human immunodeficiency virus (HIV) infection, for which experiments of nature should be demonstrable to justify pursuit of an alloimmune vaccine strategy. We sought to determine if large-scale alloimmune diversity correlates with lower HIV infection rates. Methods Using published data of African linguistic groups to determine sub-Saharan country ethnicity profiles as a proxy for human leukocyte antigen (HLA) diversity, a correlation analysis was performed against respective sub-Saharan country HIV infection rates. Ethnicity data from 37 sub-Saharan nations in 2003 and from 38 nations in 2005 were used to calculate the Meyers-Macintosh ethnic diversity score for each nation as the independent variable. World Health Organization data on HIV infection rates for the same countries were used as the dependent variable. The main outcome measure was the correlation coefficient of ethnic diversity versus HIV infection rate. Results A significant negative correlation was shown between ethnic diversity and HIV infection: for 2003 data, ?0.4586 (two-tailed P-value of 0.0043); and, for 2005 data, ?0.3866 (two-tailed P-value of 0.0165). Conclusion In conjunction with substantial evidence that alloimmunity confers protection against HIV transmission and recent work identifying specific anti-HIV mechanisms, this analysis strongly justifies an HLA-based alloimmune vaccine strategy against HIV.
Zamani, Christopher; Elzey, Jared D; Hildreth, James EK
We used, within the case study, virus-like particles (VLP) and attenuated strains of salmonella for the delivery of HIV-1 DNA vaccine encoding the multiepitope CTL-immunogene. The immunogenicity of the thus obtained vaccine constructions was comparatively analyzed. All constructions were shown to be able of inducing, in immunized animals, both the specific T-cell responses and the synthesis of virus-specific antibodies. The lowest level of immune response was registered in animals immunized by "naked" plasmid DNA. The delivery by plasmid DNA involving VLP or the attenuated strain of salmonella enhances the efficiency of the DNA-vaccine presentation to the immune system. PMID:15715155
Il'ichev, A A; Karpenko, L I; Nekrasova, N A; Lebedev, L R; Ignat'ev, G M; Agafonov, A P; Belavin, P A; Seregin, S S; Daniliuk, N K; Bazhan, S I
An immunization strategy using attenuated bacteria to deliver DNA vaccine plasmids to mucosal sites may induce protective T cell responses against sexual HIV transmission. In a murine intranasal (i.n.) immunization model, we demonstrate that transiently persistent ?asdShigella flexneri strain 15D harboring DNA vaccines induces HIV- and SIV-specific gamma interferon (IFN-?) producing CD8+ T cells among splenocytes more efficiently than either
William H. Vecino; Paul M. Morin; Rabia Agha; William R. Jacobs; Glenn J. Fennelly
This special issue of the Journal of Empirical Research on Human Research Ethics represents a sampling of projects fostered through the NIDA-funded Fordham University HIV Prevention Research Ethics Institute. The first three articles employ processes of co-learning to give voice to the experiences of individuals recovering from substance abuse and engaged in sex work who have participated in HIV prevention studies in the United States, India, and the Philippines. The fourth article describes a unique community-based approach to the development of research ethics training modules designed to increase participation of American Indian and Alaskan Native (AI/AN) tribal members as partners in research on health disparities. The last two articles focus a critical scholarly lens on two underexamined areas confronting IRB review of HIV research: The emerging and continuously changing ethical challenges of using social media sites for recruitment into HIV prevention research, and the handling of research-related complaints from participants involving perceived research harms or research experiences that do not accord with their initial expectations. Together, the articles in this special issue identify key ethical crossroads and provide suggestions for best practices that respect the values and merit the trust of research participants. PMID:24572078
Fisher, Celia B
Live attenuated measles virus is one of the most efficient and safest vaccines available, making it an attractive candidate vector for a HIV/AIDS vaccine aimed at eliciting cell-mediated immune responses (CMI). Here we have characterized the potency of CMI responses generated in mice and non-human primates after intramuscular immunisation with a candidate recombinant measles vaccine carrying an HIV-1 insert encoding Clade B Gag, RT and Nef (MV1-F4). Eight Mauritian derived, MHC-typed cynomolgus macaques were immunised with 105 TCID50 of MV1-F4, four of which were boosted 28 days later with the same vaccine. F4 and measles virus (MV)-specific cytokine producing T cell responses were detected in 6 and 7 out of 8 vaccinees, respectively. Vaccinees with either M6 or recombinant MHC haplotypes demonstrated the strongest cytokine responses to F4 peptides. Polyfunctional analysis revealed a pattern of TNF? and IL-2 responses by CD4+ T cells and TNF? and IFN? responses by CD8+ T cells to F4 peptides. HIV-specific CD4+ and CD8+ T cells expressing cytokines waned in peripheral blood lymphocytes by day 84, but CD8+ T cell responses to F4 peptides could still be detected in lymphoid tissues more than 3 months after vaccination. Anti-F4 and anti-MV antibody responses were detected in 6 and 8 out of 8 vaccinees, respectively. Titres of anti-F4 and MV antibodies were boosted in vaccinees that received a second immunisation. MV1-F4 carrying HIV-1 Clade B inserts induces robust boostable immunity in non-human primates. These results support further exploration of the MV1-F4 vector modality in vaccination strategies that may limit HIV-1 infectivity.
Stebbings, Richard; Fevrier, Michele; Li, Bo; Lorin, Clarisse; Koutsoukos, Marguerite; Mee, Edward; Rose, Nicola; Hall, Joanna; Page, Mark; Almond, Neil; Voss, Gerald; Tangy, Frederic
Cholera is a major global public health problem and remains an important threat in almost every developing country, especially in areas where population overcrowding and poor sanitation are common, such as slums and refugee camps. Cholera is one of the most dreaded diseases in the world, in some cases leading to death within 24 h if left untreated. Without treatment, severe infection has a mortality rate of 30-50%. In 2007, WHO recorded 177,963 cholera cases and 4,031 deaths worldwide. However, the estimated actual burden of cholera is in the vicinity of 3 to 5 million cases and 100,000 to 130,000 deaths per year. The disease is endemic to parts of Africa, Asia, the Middle East and South America. Large outbreaks are common after natural disasters or in populations displaced by war, where there is inadequate sewage disposal and contaminated water. In India, during the 10-y period (1997-2006) studied, the states having the highest number of reported outbreaks were West Bengal, Orissa, Maharashtra and Kerala, which together accounted for 60% of all reported outbreaks. A review of cholera cases in India reported to WHO from 2003-2007 showed that the numbers were in the few thousands with a case fatality rate of < 1%. However, it is believed that the number of cholera cases and deaths occurring annually in India is much greater than the number reported. A literature review covering a four-year period from 2003 to 2006 found reported cholera outbreaks in 18 of the 35 States and Union Territories of India. Of these, 11 had cholera outbreaks reported for multiple years. Vietnam has produced a cheaper variant of killed whole-cell vaccine devoid of the B subunit. This vaccine contains both Vibrio cholerae O1 and O139, and provides 50 per cent protection for at least three years after vaccination. For endemic cholera, population-level immunity is relatively high, making control possible with relatively low vaccine coverage levels. This vaccine should be used in areas where cholera is endemic, particularly in those at risk of outbreaks, in conjunction with other prevention and control strategies. PMID:22634452
Verma, Ramesh; Khanna, Pardeep; Chawla, Suraj
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.
Most antibodies that broadly neutralize HIV-1 are highly somatically mutated in antibody clonal lineages that persist over time. Here, we describe the analysis of human antibodies induced during an HIV-1 vaccine trial (GSK PRO HIV-002) that used the clade B envelope (Env) gp120 of clone W6.1D (gp120W6.1D). Using dual-color antigen-specific sorting, we isolated Env-specific human monoclonal antibodies (MAbs) and studied the clonal persistence of antibodies in the setting of HIV-1 Env vaccination. We found evidence of VH somatic mutation induced by the vaccine but only to a modest level (3.8% ± 0.5%; range 0 to 8.2%). Analysis of 34 HIV-1-reactive MAbs recovered over four immunizations revealed evidence of both sequential recruitment of naïve B cells and restimulation of previously recruited memory B cells. These recombinant antibodies recapitulated the anti-HIV-1 activity of participant serum including pseudovirus neutralization and antibody-dependent cell-mediated cytotoxicity (ADCC). One antibody (3491) demonstrated a change in specificity following somatic mutation with binding of the inferred unmutated ancestor to a linear C2 peptide while the mutated antibody reacted only with a conformational epitope in gp120 Env. Thus, gp120W6.1D was strongly immunogenic but over four immunizations induced levels of affinity maturation below that of broadly neutralizing MAbs. Improved vaccination strategies will be needed to drive persistent stimulation of antibody clonal lineages to induce affinity maturation that results in highly mutated HIV-1 Env-reactive antibodies.
Yates, Nicole L.; Amos, Joshua D.; Drinker, Mark S.; Eudailey, Joshua A.; Gurley, Thaddeus C.; Marshall, Dawn J.; Whitesides, John F.; Chen, Xi; Foulger, Andrew; Yu, Jae-Sung; Zhang, Ruijun; Meyerhoff, R. Ryan; Parks, Robert; Scull, Julia Cavanaugh; Wang, Lu; Vandergrift, Nathan A.; Pickeral, Joy; Pollara, Justin; Kelsoe, Garnett; Alam, S. Munir; Ferrari, Guido; Montefiori, David C.; Voss, Gerald; Liao, Hua-Xin; Tomaras, Georgia D.; Haynes, Barton F.
We compared influenza vaccine-prevented hospitalizations in adults aged ?65 years for a range of hypothetical effectiveness estimates. During 2012-2013, a vaccine with 10% effectiveness (66% coverage) would have averted approximately 13 000 hospitalizations, and a vaccine with 40% effectiveness would have averted approximately 60 000 hospitalizations. Annual vaccination is merited in this vulnerable population. PMID:24803379
Fry, Alicia M; Kim, Inkyu K; Reed, Carrie; Thompson, Mark; Chaves, Sandra S; Finelli, Lyn; Bresee, Joseph
Despite advances in HIV prevention and care, African Americans 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, and are less likely to have suppressed viral load than are Whites. The first National HIV/AIDS Strategy…
Grossman, Cynthia I.; Purcell, David W.; Rotheram-Borus, Mary Jane; Veniegas, Rosemary
This paper presents a number of deterministic models for theoretically assessing the potential impact of an imperfect prophylactic HIV-1 vaccine that has five biological modes of action, namely “take,” “degree,” “duration,” “infectiousness,” and “progression,” and can lead to increased risky behavior. The models, which are of the form of systems of nonlinear differential equations, are constructed via a progressive refinement
Elamin H. Elbasha; Abba B. Gumel
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)
Background: A comprehensive approach to preventing HIV infection in infants has been recommended, including: (a) preventing HIV in young women, (b) reducing unintended pregnancies among HIV-infected women, (c) preventing vertical transmis- sion (PMTCT), and (d) providing care, treatment, and support to HIV-infected women and their families. Most attention has been given to preventing vertical transmission based on analysis showing nevirapine
Michael D. Sweat; Kevin R. O'reilly; George P. Schmid; Julie Denison; Isabelle de Zoysa
Meyer-Rath and Over assert in another article in the July 2012 PLoS Medicine Collection, "Investigating the Impact of Treatment on New HIV Infections", that economic evaluations of antiretroviral therapy (ART) in currently existing programs and in HIV treatment as prevention (TasP) programs should use cost functions that capture cost dependence on a number of factors, such as scale and scope of delivery, health states, ART regimens, health workers' experience, patients' time on treatment, and the distribution of delivery across public and private sectors. We argue that for particular evaluation purposes (e.g., to establish the social value of TasP) and from particular perspectives (e.g., national health policy makers) less detailed cost functions may be sufficient. We then extend the discussion of economic evaluation of TasP, describing why ART outcomes and costs assessed in currently existing programs are unlikely to be generalizable to TasP programs for several fundamental reasons. First, to achieve frequent, widespread HIV testing and high uptake of ART immediately following an HIV diagnosis, TasP programs will require components that are not present in current ART programs and whose costs are not included in current estimates. Second, the early initiation of ART under TasP will change not only patients' disease courses and treatment experiences--which can affect behaviors that determine clinical treatment success, such as ART adherence and retention--but also quality of life and economic outcomes for HIV-infected individuals. Third, the preventive effects of TasP are likely to alter the composition of the HIV-infected population over time, changing its biological and behavioral characteristics and leading to different costs and outcomes for ART. PMID:22802743
Bärnighausen, Till; Salomon, Joshua A; Sangrujee, Nalinee
Biomedical approaches to HIV prevention (eg, microbicides, antiretroviral preexposure prophylaxis) are undergoing clinical\\u000a trials to test their efficacy. One key consideration emerging from completed trials is the critical role of adherence to the\\u000a investigational product. Suboptimal product adherence may compromise clinical trial results and ultimately undermine the effectiveness\\u000a of biomedical prevention methods in any future real-world use. Efforts to strengthen
Michael J. Stirratt; Christopher M. Gordon
As the science demonstrating strong evidence for voluntary medical male circumcision (VMMC) for HIV prevention has evolved, the President’s Emergency Plan for AIDS Relief (PEPFAR) has collaborated with international agencies, donors, and partner country governments supporting VMMC programming. Mathematical models forecast that quickly reaching a large number of uncircumcised men with VMMC in strategically chosen populations may dramatically reduce community-level HIV incidence and save billions of dollars in HIV care and treatment costs. Because VMMC is a 1-time procedure that confers life-long partial protection against HIV, programs for adult men are vital short-term investments with long-term benefits. VMMC also provides a unique opportunity to reach boys and men with HIV testing and counseling services and referrals for other HIV services, including treatment. After formal recommendations by WHO in 2007, priority countries have pursued expansion of VMMC. More than 1 million males have received VMMC thus far, with the most notable successes coming from Kenya’s Nyanza Province. However, a myriad of necessary cultural, political, and ethical considerations have moderated the pace of overall success. Because many millions more uncircumcised men would benefit from VMMC services now, US President Barack Obama committed PEPFAR to provide 4.7 million males with VMMC by 2014. Innovative circumcision methods—such as medical devices that remove the foreskin without injected anesthesia and/or sutures—are being rigorously evaluated. Incorporation of safe innovations into surgical VMMC programs may provide the opportunity to reach more men more quickly with services and dramatically reduce HIV incidence for all.
Reed, Jason Bailey; Njeuhmeli, Emmanuel; Thomas, Anne Goldzier; Bacon, Melanie C.; Bailey, Robert; Cherutich, Peter; Curran, Kelly; Dickson, Kim; Farley, Tim; Hankins, Catherine; Hatzold, Karin; Justman, Jessica; Mwandi, Zebedee; Nkinsi, Luke; Ridzon, Renee; Ryan, Caroline; Bock, Naomi
As the science demonstrating strong evidence for voluntary medical male circumcision (VMMC) for HIV prevention has evolved, the President's Emergency Plan for AIDS Relief (PEPFAR) has collaborated with international agencies, donors, and partner country governments supporting VMMC programming. Mathematical models forecast that quickly reaching a large number of uncircumcised men with VMMC in strategically chosen populations may dramatically reduce community-level HIV incidence and save billions of dollars in HIV care and treatment costs. Because VMMC is a 1-time procedure that confers life-long partial protection against HIV, programs for adult men are vital short-term investments with long-term benefits. VMMC also provides a unique opportunity to reach boys and men with HIV testing and counseling services and referrals for other HIV services, including treatment. After formal recommendations by WHO in 2007, priority countries have pursued expansion of VMMC. More than 1 million males have received VMMC thus far, with the most notable successes coming from Kenya's Nyanza Province. However, a myriad of necessary cultural, political, and ethical considerations have moderated the pace of overall success. Because many millions more uncircumcised men would benefit from VMMC services now, US President Barack Obama committed PEPFAR to provide 4.7 million males with VMMC by 2014. Innovative circumcision methods-such as medical devices that remove the foreskin without injected anesthesia and/or sutures-are being rigorously evaluated. Incorporation of safe innovations into surgical VMMC programs may provide the opportunity to reach more men more quickly with services and dramatically reduce HIV incidence for all. PMID:22797745
Reed, Jason Bailey; Njeuhmeli, Emmanuel; Thomas, Anne Goldzier; Bacon, Melanie C; Bailey, Robert; Cherutich, Peter; Curran, Kelly; Dickson, Kim; Farley, Tim; Hankins, Catherine; Hatzold, Karin; Justman, Jessica; Mwandi, Zebedee; Nkinsi, Luke; Ridzon, Renee; Ryan, Caroline; Bock, Naomi
The HIV vaccine strategy that, to date, generated immune protection consisted of a prime-boost regimen using a canarypox vector and an HIV envelope protein with alum, as shown in the RV144 trial. Since the efficacy was weak, and previous HIV vaccine trials designed to generate antibody responses failed, we hypothesized that generation of T cell responses would result in improved protection. Thus, we tested the immunogenicity of a similar envelope-based vaccine using a mouse model, with two modifications: a clade C CN54gp140 HIV envelope protein was adjuvanted by the TLR9 agonist IC31®, and the viral vector was the vaccinia strain NYVAC-CN54 expressing HIV envelope gp120. The use of IC31® facilitated immunoglobulin isotype switching, leading to the production of Env-specific IgG2a, as compared to protein with alum alone. Boosting with NYVAC-CN54 resulted in the generation of more robust Th1 T cell responses. Moreover, gp140 prime with IC31® and alum followed by NYVAC-CN54 boost resulted in the formation and persistence of central and effector memory populations in the spleen and an effector memory population in the gut. Our data suggest that this regimen is promising and could improve the protection rate by eliciting strong and long-lasting humoral and cellular immune responses.
Pattacini, Laura; Mize, Gregory J.; Graham, Jessica B.; Fluharty, Tayler R.; Graham, Tisha M.; Lingnau, Karen; Wizel, Benjamin; Perdiguero, Beatriz; Esteban, Mariano; Pantaleo, Giuseppe; Shen, Mingchao; Spies, Gregory A.; McElrath, M. Juliana; Lund, Jennifer M.
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
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
Background: Access and adoption of HIV prevention information are important criteria for reducing HIV infection rates among men who have sex with men. Methods: Using focus group data, researchers sought to identify sources of HIV prevention information and barriers to adopting protective behaviors among young African American men who have sex with…
Voisin, Dexter R.; Bird, Jason D. P.; Shiu, Chen-Shi; Krieger, Cathy
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.
Stigma against persons living with HIV/AIDS (PLHA) is a barrier to seeking prevention education, HIV testing, and care. Social capital has been reported as an important factor influencing HIV prevention and social support upon infection. In the study, we explored the associations between social capital and stigma among men and women who are…
Sivaram, Sudha; Zelaya, Carla; Srikrishnan, A. K.; Latkin, Carl; Go, V. F.; Solomon, Suniti; Celentano, David
Several conserved neutralizing epitopes have been identified in the HIV Env protein and among these, the MPER of gp41 has received great attention and is widely recognized as a promising target. However, little success has been achieved in eliciting MPER-specific HIV neutralizing antibodies by a number of different vaccine strategies. We investigated the ability of HA\\/gp41 chimeric protein-based vaccines, which
Ling Ye; Zhiyuan Wen; Ke Dong; Xi Wang; Zhigao Bu; Huizhong Zhang; Richard W. Compans; Chinglai Yang
Black heterosexual men (BHM) are seldom mentioned in HIV prevention research, policy, and interventions, despite evidence that heterosexual contact is becoming the leading exposure category for BHM. The disparate effect of HIV/AIDS on BHM; the debunked “down low” myth; the contexts of BHM's lives in terms of disproportionate poverty, unemployment, and incarceration; and a growing empirical base linking these factors to increased HIV risk, underscore the need to prioritize HIV risk and prevention initiatives for BHM. We highlighted the structural contexts of HIV risk for BHM, and four community-based approaches to address HIV risk and prevention for BHM: (1) men's health programs; (2) workforce and postincarceration release programs; (3) linkages to women's prevention programs; and (4) faith-based initiatives.
Identifying the earliest neutralizing antibody specificities that are elicited following infection or vaccination by HIV-1 is an important objective of current HIV\\/AIDS vaccine research. We have shown previously that transplantation of HIV-1 V3 epitopes into an HIV-2 envelope (Env) scaffold provides a sensitive and specific means to detect and quantify HIV-1 V3 epitope specific neutralizing antibodies (Nabs) in human sera.
Katie L. Davis; Elin S. Gray; Penny L. Moore; Julie M. Decker; Aidy Salomon; David C. Montefiori; Barney S. Graham; Michael C. Keefer; Abraham Pinter; Lynn Morris; Beatrice H. Hahn; George M. Shaw
Background An accurate test for Mycobacterium tuberculosis infection is urgently needed in immunosuppressed populations. The aim of this study was to investigate the diagnostic power of enzyme-linked immunospot (ELISPOT)-based IFN-? release assay in detecting active and latent tuberculosis in HIV-infected population in bacillus Calmette-Guerin (BCG)-vaccinated area. A total of 100 HIV-infected individuals including 32 active tuberculosis patients were recruited. An ELISPOT-based IFN-? release assay, T-SPOT.TB, was used to evaluate the M. tuberculosis ESAT-6 and CFP-10 specific IFN-? response. Tuberculin skin test (TST) was performed for all recruited subjects. Results The subjects were divided into group HIV+ATB (HIV-infected individuals with active tuberculosis, n = 32), group HIV+LTB (HIV-infected individuals with positive results of T-SPOT.TB assay, n = 46) and group HIV only (HIV-infected individuals with negative results of T-SPOT.TB assay and without evidence of tuberculosis infection, n = 22). In group HIV+ATB and HIV+LTB, T-SPOT.TB positive rate in subjects with TST <5 mm were 50% (16/32) and 41.3% (19/46), respectively. Individuals in group HIV+ATB and HIV+LTB with CD4+ T cells <500/?l, T-SPOT.TB showed a higher sensitivity than TST (64.5% vs. 22.6% and 62.2% vs. 29.7%, respectively, both P < 0.0001). In addition, the sensitivity of T-SPOT.TB assay in group HIV+ATB increased to >85% in patients with TB treatment for less than 1 month and CD4+ T cells ?200/?l, while for patients treated for more than 3 months and CD4+ T cells <200/?l, the sensitivity was decreased to only 33.3%. Furthermore, the results could be generated by T-SPOT.TB assay within 24 hours, which was more rapid than TST with 48–72 hours. Conclusion ELISPOT-based IFN-? release assay is more sensitive and rapid for the diagnosis of TB infection in Chinese HIV-infected individuals with history of BCG vaccination, and could be an effective tool for guiding preventive treatment with isoniazid in latently infected people and for TB control in China.
Jiang, Weimin; Shao, Lingyun; Zhang, Ying; Zhang, Shu; Meng, Chengyan; Xu, Yunya; Huang, Lingli; Wang, Yun; Wang, Ying; Weng, Xinhua; Zhang, Wenhong
We explored the feasibility of engaging young black men in a 12-week text messaging programme about HIV prevention. There were two non-randomized groups of 30 young men each. The participants were aged 16-20 years, self-identifying as black or African-American, sexually active, who owned a mobile phone and lived in Philadelphia. They received three text messages per week for 12 weeks. People in the intervention group received text messages about HIV prevention, while those in the control group received text messages about nutrition. The intervention participants showed trends in increased monogamy at follow-up compared to controls. Awareness of sexual health was significantly higher in the intervention group. Condom norms were significantly higher for the control group. There were no differences in the proportion of protected sex acts. The participants embraced the project, and were enrolled and retained in numbers that suggest such an intervention is worth examining for efficacy. PMID:21270049
Juzang, Ivan; Fortune, Thierry; Black, Sandra; Wright, Erin; Bull, Sheana
Congenital infection of human cytomegalovirus (HCMV) is the leading cause of childhood hearing loss and mental retardation. Unfortunately, a preventive vaccine remains elusive. Two strategies have been employed to develop HCMV vaccines, including (1) attenuating HCMV to generate modified virus vaccines and (2) isolating subunit viral antigen(s) to create individual antigen vaccines. The most studied candidate in each category is live attenuated Towne virus and recombinant gB/MF59 vaccine, respectively. Although both were moderately efficacious, neither could induce the durable, robust humoral and cellular immunity commonly seen in HCMV seropositive subjects. In addition, both vaccines failed to induce neutralizing antibodies against viral infection of endothelial cells, epithelial cells and leukocytes. This review summarizes the recent understanding of host natural immunity to HCMV, including the importance of antibodies targeting HCMV epithelial tropism, and discusses its implications for vaccine design. We also highlight some recent key discoveries that may lead to the development of an effective HCMV vaccine. PMID:24681264
Fu, Tong-Ming; An, Zhiqiang; Wang, Dai
The purpose of this article is to evaluate the quality of published studies conducted in North America that assessed behavior change interventions to prevent HIV'AIDS among people ages 12–24 years. A search of the Medline, HealthStar, and AIDSLINE electronic databases was completed. English language articles published between 1995 and 2000 were screened for relevance. A scoring system was developed to
Jean A. Shoveller; W. A. Wia Pietersma
Using survey and semi-structured interview data collected in various religious congregations in urban and rural areas of Mozambique, this study analyzes how gender differences in perceptions of HIV\\/AIDS and preventive behavior are mediated by religious involvement. Logistic regression is employed to examine the effects of gender and of the interactions between gender and type of denomination—“mainline” (Catholic and Presbyterian) or
Our knowledge of the host genetic factors that contribute to the acquisition of HIV infection is limited. To identify the host genetic correlates of HIV1 acquisition, we genotyped 777 participants of a randomized trial of recombinant adenovirus HIV1 vaccine for Fc? receptor IIa (Fc?RIIa), Fc?RIIIa, and several GM and KM alleles-genetic markers of immunoglobulin ? and ? chains, respectively. None of the genotypes by itself was significantly associated with the acquisition of HIV1 infection. However, particular combinations of GM and KM as well as those of GM and Fc?RIIIa loci were significantly associated with the acquisition of HIV1 infection epistatically: KM1/3-GM3/17 (interaction p=0.0246; FDR=0.2952), KM1/3-GM5/21 (interaction p=0.0016; FDR=0.0960), and GM23+/-Fc?RIIIa (interaction p=0.0060; FDR=0.1200). These results suggest the involvement of GM, KM, and Fc?RIIIa loci in the acquisition of HIV infection. Additional studies are warranted. PMID:23582638
Pandey, Janardan P; Namboodiri, Aryan M; Bu, Shizhong; De Dieu Tapsoba, Jean; Sato, Alicia; Dai, James Y
Live attenuated measles vaccine (MV) could provide a safe and efficient pediatric vaccination vector to immunize children simultaneously against measles and human immunodeficiency virus type 1 (HIV-1). To evaluate the capacity of a vector derived from the certified Schwarz measles vaccine (MVSchw) to prime effective cytotoxic T cells (CTL) and broad neutralizing antibodies against HIV-1 conserved epitopes, we generated recombinant
Clarisse Lorin; Frédéric Delebecque; Valérie Labrousse; Lucie Da Silva; François Lemonnier; Michel Brahic; Frédéric Tangy
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
During 30 years of research on human immunodeficiency virus (HIV), our knowledge of its cellular receptors - CD4, CCR5 and CXCR4 - has illuminated aspects of the pathogenesis of the acquired immune deficiency syndrome (AIDS). Studying how the HIV envelope glycoproteins interact with the receptors led to anti-retroviral drugs based on blocking the docking or fusion of virus to the host cell. Genetic polymorphisms of CCR5 determine resistance to HIV infection and the rate of progression to AIDS. Eliciting neutralizing antibodies to the sites of receptor interaction on HIV glycoproteins is a promising approach to HIV vaccine development.
Effective biomedical and structural HIV prevention approaches are being implemented throughout sub-Saharan Africa. A "lifecycle approach" to HIV prevention recognizes the interconnectedness of the health of women, children and adolescents, and prioritizes interventions that have benefits across these populations. We review new biomedical prevention strategies for women, adolescents and children, structural prevention approaches, and new modalities for eliminating infant HIV infection, and discuss the implications of a lifecycle approach for the success of these methods. Some examples of the lifecycle approach include evaluating education and HIV prevention strategies among adolescent girls not only for their role in reducing risk of HIV infection and early pregnancy, but also to promote healthy adolescents who will have healthier future children. Similarly, early childhood interventions such as exclusive breastfeeding not only prevent HIV, but also contribute to better child and adolescent health outcomes. The most ambitious biomedical infant HIV prevention effort, Option B+, also represents a lifecycle approach by leveraging the prevention benefits of optimal HIV treatment for mothers; maternal survival benefits from Option B+ may have ultimately more health impact on children than the prevention of infant HIV in isolation. The potential for synergistic and additive benefits of lifecycle interventions should be considered when scaling up HIV prevention efforts in sub-Saharan Africa. PMID:24659344
Roxby, Alison C; Unger, Jennifer A; Slyker, Jennifer A; Kinuthia, John; Lewis, Andrew; John-Stewart, Grace; Walson, Judd L
The HIV epidemic has been the most significant public health crisis of the last 2 decades. Although Experimental Social Innovation and Dissemination (ESID) principles have been used by many HIV prevention researchers, the clearest application is the series of model-building and replication experiments conducted by Kelly and colleagues. The model mobilized, trained, and engaged key opinion leaders to serve as behavior change and safe-sex endorsers in their social networks. This paper illustrates how ESID principles were used to develop, test, and disseminate an innovative social model and discusses the challenges of applying ESID methodology in the midst of a public health emergency. PMID:14703268
Fernández, M Isabel; Bowen, G Stephen; Gay, Caryl L; Mattson, Tiffany R; Bital, Evelyne; Kelly, Jeffrey A
Self-efficacy is a critical element for HIV prevention, however little is known about the predictors of self-efficacy for HIV prevention among Hispanic women. In this cross-sectional study we assessed if age, living with a partner, employment status, HIV knowledge, self-esteem, and intimate partner violence (IPV) predicted self-efficacy for HIV prevention in 548 Hispanic women in South Florida who participated in a randomized controlled trial (SEPA). The majority of Hispanic women reported high levels of self-efficacy for HIV prevention. Women who were older, living with a partner, with less HIV knowledge, and a history of IPV reported significantly lower levels of self-efficacy for HIV prevention. HIV knowledge was the most important predictor of self-efficacy for HIV prevention. Employment was not a significant predictor of self-efficacy for HIV prevention. Predictors identified in the study can be used to identify high-risk Hispanic women who are in need of HIV prevention interventions.
Villegas, Natalia; Cianelli, Rosina; Gonzalez-Guarda, Rosa; Kaelber, Lorena; Ferrer, Lilian; Peragallo, Nilda
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
The purpose of this study is to improve understanding of HIV vulnerability and opportunities for HIV prevention within the social networks of male-to-female transgender persons in San Salvador, El Salvador. We compare HIV prevalence and behavioral data from a sample of gay-identified men who have sex with men (MSM) (n = 279), heterosexual or bisexual identified MSM (n = 229) and transgender persons (n = 67) recruited using Respondent Driven Sampling. Transgender persons consistently reported higher rates of HIV risk behavior than the rest of the study population and were significantly more likely to be involved in sex work. While transgender persons reported the highest rates of exposure to HIV educational activities they had the lowest levels of HIV-related knowledge. Transgender respondents’ social networks were homophilous and efficient at recruiting other transgender persons. Findings suggest that transgender social networks could provide an effective and culturally relevant opportunity for HIV prevention efforts in this vulnerable population.
Barrington, Clare; Wejnert, Cyprian; Guardado, Maria Elena; Nieto, Ana Isabel; Bailey, Gabriela Paz
Background Despite the centrality of family in Indian society, relatively little is known about family-based communication concerning sexual behaviour and HIV/AIDS in rural Indian families. To date, very few family-based adolescent HIV-prevention interventions have been developed for rural Indian youth. This study conducted formative research with youth aged 14 to18 years and their parents in order to assess the feasibility of conducting a family-based HIV-prevention intervention for rural Indian adolescents. Methods Eight focus groups were conducted (n = 46) with mothers, fathers, adolescent females and adolescent males (two focus groups were held for each of the four groups). All focus groups consisted of same-gender participants. Adolescents aged 14 to18 years old and their parents were recruited from a tribal community in rural Maharashtra, India. Focus group transcripts were content analyzed to identify themes related to family perceptions about HIV/AIDS and participation in a family-based intervention to reduce adolescent vulnerability to HIV infection. Results Six primary thematic areas were identified: (1) family knowledge about HIV/AIDS; (2) family perceptions about adolescent vulnerability to HIV infection; (3) feasibility of a family-based programme to prevent adolescent HIV infection; (4) barriers to participation; (5) recruitment and retention strategies; and (6) preferred content for an adolescent HIV prevention intervention. Conclusion Despite suggestions that family-based approaches to preventing adolescent HIV infection may be culturally inappropriate, our results suggest that a family-based intervention to prevent adolescent HIV infection is feasible if it: (1) provides families with comprehensive HIV prevention strategies and knowledge; (2) addresses barriers to participation; (3) is adolescent friendly, flexible and convenient; and (4) is developmentally and culturally appropriate for rural Indian families.
Investigational product: Rosuvastatin (Crestor®; Astra Zeneca). Active ingredients: Rosuvastatin (5 mg). Study title: Prevention of Atherosclerosis in Patients Living with HIV. Phase of study: Phase III. Aims: Primary aim: To assess whether rosuvastatin therapy could slow the progression of the carotid intima-media thickness (C-IMT; as measured by the change in the mean IMT of the near and far walls of the distal common carotid arteries) over 2 years in HIV-infected patients (HIV-IP). Secondary aims: To assess whether rosuvastatin therapy could reduce highly sensitive C reactive protein (hs-CRP) inflammatory marker that is increased in HIV-IP.To assess the effect of rosuvastatin therapy on serum lipid levels (total cholesterol [TC], low-density lipoprotein [LDL] cholesterol, high-density lipoprotein [HDL] cholesterol and triglycerides [TG]) and apolipoproteins (APO A1, APO B and APO B/A1).To assess the safety of rosuvastatin in HIV-IP through the evaluation of clinical laboratory analyses (liver function tests and creatine kinase) and adverse events (AEs). Study design: Two-year randomized, double-blind, placebo-controlled, parallel group study. Planned sample size: 320 HIV-IP. Summary of eligibility criteria: HIV-IP who are aged between 30 and 60 years, with a CD4 count. greater than 200 cells/mm3. Patients must be stable on combination antiretroviral therapy (cART) for at least 12 months and have a 10-year CVD risk of less than 20% (using the Framingham risk score). Number of study centers: One. Duration of treatment: Two years (5 mg rosuvastatin or placebo once daily). Dose and route of administration: Oral rosuvastatin (5 mg) once daily. The incidence of cardiovascular disease (CVD) in HIV-IP is at least three times higher than in the general population and further increases each year with combination anti-retroviral therapy (cART). The carotid atherosclerosis progression rate is 10 times higher in HIV-IP than in uninfected individuals. The aim of this study is to assess whether therapy with 5 mg rosuvastatin could: 1) Slow the progression in the mean IMT of the distal common carotid arteries over two years in HIV-IP.2) Change the concentration in the inflammatory marker – hs-CRP, which is increased in HIV-IP.3) Change the concentrations of TC, LDL cholesterol, HDL cholesterol, TG, apolipoproteins (APO) B, APO A1 and APO B/A1.4) Be administered safely in the study population. Pharmacological intervention with rosuvastatin will be evaluated in a double-blind, placebo-controlled, randomized clinical trial in HIV-IP treated with cART not matching the published selection criteria for lipid-lowering therapy. For the first time, this study will investigate anti-inflammatory and anti-atherogenic effects of a pharmacological lipid-lowering agent in HIV-IP that may lead to the reduction of CVD.
De Lorenzo, Ferruccio; Boffito, Marta; Collot-Teixeira, Sophie; Gazzard, Brian; McGregor, John L; Shotliff, Kevin; Xiao, Han
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
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, S