Nearly everywhere that AIDS has been found, HIV infection is fast spreading. No one is known to have recovered from HIV infection. There is no vaccine to cure AIDS (Population Reports, 1989 and The Hindu, dated 9.3.2000). Until a cure or vaccine for HIV infection is found, the only way to prevent the spread of the disease is by changing
|This study forms part of the preparation of communities for HIV-preventive vaccine trials in South Africa. On the basis of the assumption that attitudes to any HIV vaccine or vaccine trials will partly be influenced by experiences of vaccination in general, this study aimed to investigate knowledge of, attitudes to, and experiences of vaccination…
Lindegger, Graham; Quayle, Michael; Ndlovu, Moses
Vaccination and post-exposure immunization against the human immunodeficiency viruses (HIV-1 and HIV-2) faces the problem of the extensive genetic and antigenic variability of these viruses. This raises the question of what fraction of all possible antigen strains of the virus must be recognized by the immune response to a vaccine to prevent development of acquired immunodeficiency disease (AIDS). The success
Martin A. Nowak; Angela R. McLean
"Families First Africa" is an international project whose main objective is to develop a pediatric vaccine that protects infants against HIV transmission during breast feeding. The vaccine being developed consists of HIV peptides matching HLA genotypes of the Western Africa population and will be administered in association with BCG vaccine which acts as a strong adjuvant. An alternative strategy is to administer a recombinant BCG vaccine with HIV gene fragments which codify for the same peptides. PMID:17206189
Pontrelli, Giuseppe; Colizzi, Vittorio
Studies investigating the effects of biologic HIV prevention technologies have been reported with promising results for slowing\\u000a the spread of the disease. Although they can reduce the rate of HIV transmission at varying levels of efficaciousness, it\\u000a is vital to anticipate their impact on subsequent sexual behaviors. Risk homeostasis theory posits that decreases in perceived\\u000a risk, which will occur with
Lisa A. Eaton; Seth C. Kalichman
Background This study aims to determine the maximum price at which HIV vaccination is cost-effective in the Thai healthcare setting. It also aims to identify the relative importance of vaccine characteristics and risk behavior changes among vaccine recipients to determine how they affect this cost-effectiveness. Methods A semi-Markov model was developed to estimate the costs and health outcomes of HIV prevention programs combined with HIV vaccination in comparison to the existing HIV prevention programs without vaccination. The estimation was based on a lifetime horizon period (99 years) and used the government perspective. The analysis focused on both the general population and specific high-risk population groups. The maximum price of cost-effective vaccination was defined by using threshold analysis; one-way and probabilistic sensitivity analyses were performed. The study employed an expected value of perfect information (EVPI) analysis to determine the relative importance of parameters and to prioritize future studies. Results The most expensive HIV vaccination which is cost-effective when given to the general population was 12,000 Thai baht (US$1 = 34 Thai baht in 2009). This vaccination came with 70% vaccine efficacy and lifetime protection as long as risk behavior was unchanged post-vaccination. The vaccine would be considered cost-ineffective at any price if it demonstrated low efficacy (30%) and if post-vaccination risk behavior increased by 10% or more, especially among the high-risk population groups. The incremental cost-effectiveness ratios were the most sensitive to change in post-vaccination risk behavior, followed by vaccine efficacy and duration of protection. The EVPI indicated the need to quantify vaccine efficacy, changed post-vaccination risk behavior, and the costs of vaccination programs. Conclusions The approach used in this study differentiated it from other economic evaluations and can be applied for the economic evaluation of other health interventions not available in healthcare systems. This study is important not only for researchers conducting future HIV vaccine research but also for policy decision makers who, in the future, will consider vaccine adoption.
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
Richard Horton has seriously questioned the possibility of developing a successful HIV- preventive vaccine and has appropriately criticised an over optimistic attitude promoted by some individuals in the HIV-vaccine research community.1 Horton's piece is, for the most part, on the mark and useful. However, there are points that I believe will benefit from clarification. Whereas he rightly points out that
We carried out a telephone survey to assess willingness to participate in HIV vaccine trials. The survey was conducted by interviewing randomly selected callers to the Italian National AIDS Help line. The questionnaire consisted of four sections: demographic information, knowledge about HIV vaccines and vaccines in general, factors related to participation in HIV vaccine trials, and acceptability of a future
F. Starace; T. M. Wagner; A. M. Luzi; L. Cafaro; P. Gallo; G. Rezza
Objectives: To assess the extent to which HIV-negative cohort study participants would be willing to participate (WTP) in future HIV vaccine trials, to explore enroll- ment into an ongoing phase 3 HIV vaccine trial, and to assess changing WTP in such trials over time. Methods: The Vanguard Project is a prospective study of gay and bisexual men in the greater
Jacqueline M. O'Connell; Robert S. Hogg; Keith Chan; Steffanie A. Strathdee; Nancy McLean; Steve L. Martindale; Brian Willoughby; Robert Remis
HIV-1, herpes simplex virus type 2 (HSV-2), and human papillomavirus (HPV), among other sexually transmitted infections, represent a major burden for global health. Initial insights into the mucosal transmission of these viral pathogens have raised optimism with regard to the rapid generation of protective vaccines. Nevertheless, setbacks for HIV-1 and HSV-2 vaccines have seriously challenged the initial enthusiasm. Recently, two
Damjan S Nikolic; Vincent Piguet
Although vaccine-preventable diseases are common in HIV, concerns about vaccine safety and lack of efficacy in this patient\\u000a population often lead to missed opportunities for vaccination. In this article, we review the literature regarding vaccine\\u000a risks and benefits and offer recommendations regarding their use and timing in patients with HIV infection.
Todd D. Gleeson; Mark R. Wallace; Sybil A. Tasker
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
M R Nicol; A D M Kashuba; ADM Kashuba
Once an effective HIV vaccine is discovered, a major challenge will be to ensure its world wide access. A preventive vaccine with low or moderate efficacy (30–50%) could be a valuable prevention tool, especially if targeted to populations at higher risk of HIV infection. High efficacy vaccines (80–90%) could be used in larger segments of the population.Estimated “needs” for future
José Esparza; Marie-Louise Chang; Roy Widdus; Yvette Madrid; Neff Walker; Peter D. Ghys
This study analyses the priorities of public donors in funding HIV prevention by either integrated condom programming or HIV preventive microbicides and vaccines in the period between 2000 and 2008. It further compares the public funding investments of the USA government and European governments, including the EU, as we expect the two groups to invest differently in HIV prevention options, because their policies on sexual and reproductive health and rights are different. We use two existing officially UN endorsed databases to compare the public donor funding streams for HIV prevention of these two distinct contributors. In the period 2000-2008, the relative share of public funding for integrated condom programming dropped significantly, while that for research on vaccines and microbicides increased. The European public donors gave a larger share to condom programming than the United States, but exhibited a similar downward trend in favour of funding research on vaccines and microbicides. Both public donor parties invested progressively more in research on vaccines and microbicides rather than addressing the shortage of condoms and improving access to integrated condom programming in developing countries.
Relatively recently, mathematical models have been applied to issues related to HIV vaccination. Significant progress has been made towards understanding how rather ineffective vaccines will perform in trials and in the community, but some areas still need research.
Angela R McLean; Sally M Blower
AIDS researchers are investigating new vaccines that would prevent infection with HIV and reduce the spread of AIDS. Some have argued that product liability concerns have discouraged investment in HIV vaccine research and development. The purpose of this ...
... Guidance for Industry: Development of Preventive HIV Vaccines for Use in Pediatric Populations. [PDF Printable Version - 53 KB]. ... More results from www.fda.gov/biologicsbloodvaccines/guidancecomplianceregulatoryinformation/guidances
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)
Summary. Vaccines with limited ability to prevent HIV infection may positively impact the HIV\\/AIDS pandemic by preventing secondary transmission and disease in vaccine recipients who become infected. To evaluate the impact of vaccination on secondary transmission and disease, efficacy trials assess vac- cine effects on HIV viral load and other surrogate endpoints measured after infection.A standard test that compares the
Peter B. Gilbert; Ronald J. Bosch; Michael G. Hudgens
The development of safe and efficacious preventive HIV vaccines offers the best long-term hope of controlling the AIDS pandemic. Nevertheless, suboptimal uptake of safe and efficacious vaccines that already exist suggest that HIV vaccine acceptability cannot be assumed, particularly among communities most vulnerable to HIV. The present study aimed to identify barriers and motivators to future HIV vaccine acceptability among low socioeconomic, ethnically diverse men and women in Los Angeles County. Participants completed a cross-sectional survey assessing their attitudes and beliefs regarding future HIV vaccines. Hypothetical HIV vaccine scenarios were administered to determine HIV vaccine acceptability. Two-sided t-tests were performed, stratified by gender, to examine the association between vaccine acceptability and potential barriers and motivators. Barriers to HIV vaccine acceptability differed between men and women. For women, barriers to HIV vaccine acceptability were related to their intimate relationships (p <0.05), negative experiences with health care providers (p <0.05) and anticipated difficulties procuring insurance (p <0.01). Men were concerned that the vaccine would weaken the immune system (p <0.005) or would affect their HIV test results (p <0.05). Motivators for women included the ability to conceive a child without worrying about contracting HIV (p <0.10) and support from their spouse/significant other for being vaccinated (p <0.10). Motivators for men included feeling safer with sex partners (p <0.05) and social influence from friends to get vaccinated (p <0.005). Family support for HIV immunization was a motivator for both men and women (p <0.10). Gender-specific interventions may increase vaccine acceptability among men and women at elevated risk for HIV infection. Among women, interventions need to focus on addressing barriers due to gendered power dynamics in relationships and discrimination in health care. Among men, education that addresses fears and misconceptions about adverse effects of HIV vaccination on health and the importance of vaccination as one component of integrated HIV prevention may increase vaccine acceptability.
Kakinami, Lisa; Newman, Peter A.; Lee, Sung-Jae; Duan, Naihua
Recent randomized controlled clinical trials in Africa have demonstrated that adult male circumcision (MC) efficiently decreases the rate of HIV, HPV and HSV-2 infections. Many studies have clearly shown that MC is a simple, safe, and cost-effective method for the prevention of sexually transmitted diseases and urinary tract infection, and for improving genital hygiene. While a 30% MC prevalence exists worldwide, only 5% or less of the Chinese males have undergone circumcision. In this review, we report recent trends in international MC and HIV prevention efforts, as well as the potential benefits and importance of promoting MC in China. We appeal to medical and public health authorities to pay close attention to the international experience in MC and HIV prevention. PMID:19514549
Ben, Kun-Long; Xu, Jian-Chun; Lu, Lin; Lü, Nian-Qing; Cheng, Yue; Tao, Jian; Liu, De-Kai; Min, Xiang-Dong; Cao, Xiao-Mei; Li, Philip S
Prevention is an important aspect of HIV care in the era of highly active antiretroviral therapy. Vaccines provide an excellent\\u000a opportunity to avert certain infectious diseases for which patients with HIV infection are at increased risk due to immunosuppression.\\u000a However, the state of immunosuppression reduces the efficacy of vaccines and increases the risk associated with certain vaccines.\\u000a The study of
Edgar Turner Overton
In November 2010, the iPrEx study reported that preexposure prophylaxis (PrEP) with daily tenofovir disoproxil fumarate/emtricitabine reduced HIV infections by 44% among men who have sex with men and subsequent trials corroborated efficacy among heterosexual men and women. During regularly scheduled follow-up visits from January to March 2011, participants in an ongoing phase 2b vaccine efficacy trial completed an anonymous Web survey about PrEP. Among 376 respondents, 17% reported they were very likely to use PrEP in the next year. Nonwhite participants were more likely to use PrEP. Among those with some level of interest, intent to use PrEP was greatest if the drug were available through the clinical trial or health insurance. Most (91%) believed taking PrEP would not change their willingness to stay in the vaccine trial and few thought it would affect recruitment. As key stakeholders, currently enrolled trial participants can offer vital input about emerging prevention technologies that may affect the design of future HIV vaccine and nonvaccine prevention trials. PMID:23614998
Fuchs, Jonathan D; Sobieszczyk, Magdalena E; Madenwald, Tamra; Grove, Doug; Karuna, Shelly T; Andrasik, Michele; Sherwat, Adam; Broder, Gail; Mayer, Kenneth; Koblin, Beryl; Hammer, Scott
The 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
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".
Smith, Kendall A
... Preventable Childhood Diseases Vaccines & Preventable Diseases: Vaccine-Preventable Childhood Diseases In our mobile society, over a million ... among children. On this page: Protect Your Child Childhood and Preteen/Teen Vaccination Schedule Descriptions of Vaccine- ...
The best long-term hope for controlling the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) pandemic is a safe, effective and affordable preventive vaccine, but its development has encountered unprecedented scientific challenges. The first phase I trial of an HIV vaccine was conducted in 1987. Subsequently, more than 30 candidate vaccines have been tested in over 60 phase I/II trials, involving approximately 10 000 healthy volunteers. Most of these trials have been conducted in the USA and Europe, but several have also been conducted in developing countries. The first phase III trials began in the USA in 1998 and in Thailand in 1999 to assess the efficacy of the first generation of HIV vaccines (based on the HIV envelope protein, gp120); the results will be available within the next 1-2 years. To accelerate the development of an HIV vaccine, additional candidate vaccines must be evaluated in parallel in both industrialized and developing countries. This will require international collaboration and coordination and critical ethical issues will need to be addressed. To ensure that future HIV vaccines contribute to the overall HIV/AIDS prevention effort, we should begin planning now on how best to use them.
Summary This investigation explored commonalities and differences in barriers and motivators to HIV vaccine trial participation and acceptability of future U.S. Food and Drug Administration (FDA)-approved HIV vaccines in order to identify implications of clinical trials for future HIV vaccine dissemination. Fifteen focus groups were conducted with 157 predominately ethnic minority and low income participants recruited using venue-based sampling in Los Angeles. Data were analyzed using narrative thematic analysis. Barriers and motivators in common across willingness to participate (WTP) in HIV vaccine trials and future HIV vaccine acceptability (e.g., concerns about vaccine-induced infection, false-positives, side effects, efficacy, mistrust and stigma) suggest clinical trials present significant opportunities to develop and evaluate empirically based interventions to support future HIV vaccine dissemination. Barriers specific to HIV vaccine acceptability (e.g., concerns about duration of protection, cross-clade protection, cost and access) also indicate the need for formative research focused specifically on future dissemination. Protection motivation, common to WTP and acceptability, highlights the need to provide and evaluate prevention counseling and education in clinical trials, which may form the basis of evidence-informed preventive interventions to be launched in tandem with dissemination of partial efficacy HIV vaccines.
Newman, Peter A.; Duan, Naihua; Kakinami, Lisa; Roberts, Kathleen
Developing and disseminating a preventive HIV vaccine is a primary scientific and public health objective. However, little is known about HIV vaccine acceptability in the high prevalence setting of South Africa—where young adults are likely to be targeted in early dissemination efforts. In 2007, we conducted six focus groups (n=42) with South Africans aged 18-24 years old. We used a deductive framework approach to identify key motivators and barriers to future HIV vaccine uptake. Participants identified HIV testing, HIV stigma, mistrust of the health care system, and concerns about sexual disinhibition as barriers to vaccine uptake. For women, family members and friends were strong motivators for vaccine uptake, while men were more likely to see vaccines as an opportunity to stop using HIV prevention strategies such as condoms and partner reductions. Implications of these findings for developing HIV vaccine dissemination strategies and policy in South Africa are discussed.
Sayles, Jennifer N.; Macphail, Catherine L.; Newman, Peter A.; Cunningham, William E.
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.
Although many new prevention modalities that include the use of antiretroviral drugs show promise, there is no question that a global solution to the HIV epidemic will not be economically or logistically feasible without the development of vaccine that provides durable protection. In the best case scenario, the vaccine has to protect against acquisition of infection, likely mediated by Env-specific B-cell responses combined with CD4+ T-cell responses to evoke full maturation and maintenance of protective antibodies. But HIV-specific CD8+ T-cell responses are also likely to be a key element, particularly for those inevitable situations in which full vaccine-induced protection from acquisition is not achieved, in which case durable control of established infection will be required. Although there is reason to be optimistic that an effective HIV vaccine is possible, one of the major constraints moving forward will likely be constraint on funding to support a diversity of concepts at a time that the correlates of protection from acquisition and disease progression are still unknown. Given the scope of the epidemic and the economic climate, we must strive to do much more with less and seek to access additional resources, both scientific and monetary, from every possible source. PMID:22772390
McElrath, M Juliana; Walker, Bruce D
Twenty years after the discovery of HIV, there is still no vaccine. This year, an envelope vaccine aimed at stimulating neutralizing antibodies was unable to protect against infection in phase 3 trials. But more than 20 HIV vaccines designed to stimulate T-cell responses are being developed. Will any of them work?
Tomas Hanke; Andrew J McMichael
Background Phase I and phase II HIV-1 vaccine trials have revealed increases in risky sexual activity among study subjects during the trials, perhaps because the subjects believe that the vaccine being tested is efficacious; subjects may thus suffer harm from their participation. We evaluated the sexual behaviour of Canadian men who have sex with men (MSM) who participated in the phase III Vax004 trial of an HIV-1 vaccine. Methods Using self-reports of sexual behaviours during the 6 months before trial entry as a baseline, we determined changes in reported sexual behaviour after 6, 12 and 18 months of participation in the trial. Results Of 291 HIV-seronegative MSM enrolled from July to October 1999, 260 (89%) completed 18 months of follow-up, 19 (7%) experienced seroconversion, and 12 (4%) did not complete follow-up. Unprotected receptive anal intercourse during the previous 6 months with partners whose HIV-1 serostatus was positive or unknown was reported by 21% of men at enrolment and by 27% at any point during 18 months of follow-up. No increase in this behaviour from baseline was reported by participants, including among men who were motivated to enrol because of expected protection from HIV-1 infection, men who believed they had received the vaccine, men who believed that the vaccine had greater than 50% efficacy, or men who believed that they had received the vaccine and that vaccine efficacy was greater than 50%. Interpretation MSM can be successfully enrolled in HIV-1 vaccine efficacy trials without evident increases in those sexual behaviours most associated with HIV-1 risk.
Lampinen, Thomas M.; Chan, Keith; Remis, Robert S.; Fikre Merid, Maraki; Rusch, Melanie; Vincelette, Jean; Logue, Ken; Popovic, Vladimir; Alary, Michel; Schechter, Martin T.; Hogg, Robert S.
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
? Abstract The development,of an HIV vaccine is proving to be an unprecedented challenge. The difficulty in creating this vaccine arises from the enormous,genetic variation of the virus and the unusual importance,of cytotoxic T lymphocytes,(CTL) in controlling its spread. Whereas traditional vaccine strategies are unlikely to confer safe and effective HIV protection, novel strategies for eliciting CTL have provided sub-
Norman L. Letvin
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
HIV vaccine trials present significant challenges related to trial endpoints, vaccine efficacy measurement, and the role of nonvaccine interventions. Infection is a valid endpoint for detecting sterilizing immunity. But if the vaccine prevents AIDS without preventing infection, infection may be a misleading surrogate. Appropriate endpoints must be defined for other mechanisms of vaccine action. Direct, indirect, behavioral, and biological effects all determine vaccine efficacy. False security among HIV-vaccine recipients may make negative behavioral effects an important component of vaccine performance. Both biological potency and a more comprehensive program effectiveness should be measured. These goals may require unblinded designs or community randomization. Nonvaccine interventions are currently the only HIV-prevention strategy. Support for larger scale implementation requires more rigorous evaluation that is less dependent on self-reported behavioral changes. The vaccine trial cohorts provide a unique opportunity to cost-effectively evaluate behavioral interventions. PMID:7639865
Schaper, C; Fleming, T R; Self, S G; Rida, W N
Demographic and behavioral contextual risk groups among men who have sex with men participating in a phase 3 HIV vaccine efficacy trial: implications for HIV prevention and behavioral/biomedical intervention trials.
Recent outbreaks of syphilis and gonorrhea coupled with reported increases in HIV-risk behavior among men who have sex with men (MSM) have raised concerns about a potential resurgence of HIV among MSM. These concerns have led some to suggest the need for a paradigm shift in how HIV-prevention programs are designed and implemented. In this analysis, baseline demographic, sexual partnership, and substance use information was used to identify contextual-risk groups among 5,095 HIV-seronegative MSM enrolled in a 36-month phase 3 HIV vaccine efficacy trial across 61 sites primarily in North America. Eight demographic and behavioral contextual risk groups were identified, with annualized HIV seroincidence ranging from 1.8% to 6.3% across groups. Men in primary HIV-serodiscordant relationships had the lowest HIV seroincidence (1.8%), while an older group of men with many sex partners had the highest (6.3%). Visit-schedule compliance and study retention were lowest among younger non-White men and highest among older popper users, with annualized HIV seroincidence of 2.9% and 3.5%, respectively. Differences in HIV incidence, study compliance, and retention observed among contextual-risk groups suggest that responsiveness to heterogeneity within risk group (eg, MSM) could benefit screening, enrollment, and retention of HIV-prevention programs and intervention trials, reducing the time and cost related to their design, implementation, and conclusion. PMID:17003693
Bartholow, Bradford N; Goli, Vamshidar; Ackers, Marta; McLellan, Eleanor; Gurwith, Marc; Durham, Marcus; Greenberg, Alan E
lassic preventive vaccines are designed to mimic the effects of natural exposure to microbes. They provide a high level of long-lasting pro- tection against infection in the vast majority of recipients and serve as free- standing preventive measures. Although a classic preventive vaccine remains the ultimate goal of efforts to develop a vaccine for protection against the human im- munodeficiency
Margaret I. Johnston; Anthony S. Fauci
|Developing and disseminating a preventive HIV vaccine is a primary scientific and public health objective. However, little is known about HIV vaccine acceptability in the high-prevalence setting of South Africa--where young adults are likely to be targeted in early dissemination efforts. This study reports on six focus groups (n = 42) conducted…
Sayles, Jennifer N.; Macphail, Catherine L.; Newman, Peter A.; Cunningham, William E.
The greatest hope for controlling the expanding HIV epidemic is the development of a preventive HIV vaccine. Despite almost twenty years of effort, the search for an effective HIV vaccine continues at the present time. Advances in the understanding of HIV immunopathogenesis, and especially viral immune evasion mechanisms, have provided important insights into HIV vaccine design. HIV vaccine approaches based solely on recombinant monomeric envelope glycoproteins have failed dramatically and have been discarded. Modern vector technologies with the potential for generating protective cellular immune responses against HIV are undergoing intensive evaluation in clinical trials. Adenoviral vector systems appear to be very promising for this purpose, while the ability of poxvirus-based regimens to elicit potent HIV-specific cellular immune responses in humans is less certain. A number of novel live vector-based approaches are in development. This review presents the current state of the HIV vaccine field, with an emphasis on those vaccines that are in clinical trials or in an advanced stage of preclinical testing. The HIV vaccine field is a very active and challenging one that will continue to push forward our understanding of basic immunology and drive the development of new vaccine technologies. New breakthroughs in methods to generate effective neutralizing antibody responses against HIV are urgently needed. PMID:16515492
Attenuated poxviruses have been developed for use as candidate vaccine vectors. ALVAC, a strain of the Avipoxvirus canarypox, has been extensively evaluated as a vector for vaccines against the human immunodeficiency virus type 1 (HIV-1). This report presents the safety and reactogenicity data derived from 11 multicenter, randomized controlled trials of ALVAC-HIV vaccines conducted by the HIV Vaccine Trials Network
Guy de Bruyn; Anthony J Rossini; Ya-Lin Chiu; Drienna Holman; Marnie L Elizaga; Sharon E Frey; Donald Burke; Thomas G Evans; Lawrence Corey; Michael C Keefer
Hungary is a country with relatively low HIV prevalence. Since 1989, a wide range of HIV prevention projects has been developed both by government agencies and by an increasingly active voluntary sector. While energy and resources continue to be invested in HIV information and education, some senior public health officials have argued that it is the country's compulsory HIV testing and compulsory reporting system which have enabled it to maintain its low seroprevalence levels. The testing and reporting system are soon to be reformed, however, in response to growing demands for better protection of personal privacy and confidentiality. Whether or not the forthcoming reforms will have an impact on HIV prevention, and what the nature of this impact will be, remain to be seen. PMID:10168754
A safe and efficacious preventive HIV vaccine would be a tremendous asset for low- and middle-income country (LMIC) settings, which bear the greatest global impact of AIDS. Nevertheless, substantial gaps between clinical trial efficacy and real-world effectiveness of already licensed vaccines demonstrate that availability does not guarantee uptake. In order to advance an implementation science of HIV vaccines centred on
Peter A. Newman; Surachet Roungprakhon; Suchon Tepjan; Suzy Yim; Rachael Walisser
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
The design of epitope-driven vaccines that address the global variability of HIV has been significantly hampered by concerns about conservation of the vaccine epitopes across clades of HIV. We developed two computer-driven methods for improving epitope-driven HIV vaccines: the Epi-Assembler, which derives representative or “immunogenic consensus sequence” (ICS) epitopes from multiple viral variants, and VaccineCAD, which reduces junctional immunogenicity when
Anne S. De Groot; Luisa Marcon; Elizabeth A. Bishop; Daniel Rivera; Michele Kutzler; David B. Weiner; William Martin
The development of a safe and effective HIV vaccine remains a challenge. The modest efficacy seen in the RV144 vaccine trial represented an important milestone for the field. Results from all efficacy studies done to date have generated new information, which has advanced the HIV vaccine field in important ways. In this article, we review the translational research insights from the vaccine efficacy trials completed and fully analyzed to date. We also describe the recent advances in the search for broadly neutralizing antibodies and discuss potential approaches to circumvent the challenge posed by the enormous diversity of HIV-1. The experience from the past 5 years highlights the importance of conducting efficacy studies that continue to move us closer toward the goal of a safe, effective, durable, and universal HIV preventive vaccine. PMID:23764628
Tieu, Hong-Van; Rolland, Morgane; Hammer, Scott M; Sobieszczyk, Magdalena E
A safe and efficacious preventive HIV vaccine would be a tremendous asset for low- and middle-income country (LMIC) settings, which bear the greatest global impact of AIDS. Nevertheless, substantial gaps between clinical trial efficacy and real-world effectiveness of already licensed vaccines demonstrate that availability does not guarantee uptake. In order to advance an implementation science of HIV vaccines centred on LMIC settings, we explored sociocultural and structural contexts of HIV vaccine acceptability among most-at-risk populations in Thailand, the site of the largest HIV vaccine trial ever conducted. Cross-cutting challenges for HIV vaccine uptake - social stigma, discrimination in healthcare settings and out-of-pocket vaccine cost - emerged in addition to population-specific barriers and opportunities. A 'social vaccine' describes broad sociocultural and structural interventions - culturally relevant vaccine promotion galvanised by communitarian norms, mitigating anti-gay, anti-injecting drug user and HIV-related stigma, combating discrimination in healthcare, decriminalising adult sex work and injecting drug use and providing vaccine cost subsidies - that create an enabling environment for HIV vaccine uptake among most-at-risk populations. By approaching culturally relevant social and structural interventions as integral mechanisms to the success of new HIV prevention technologies, biomedical advances may be leveraged in renewed opportunities to promote and optimise combination prevention. PMID:22780324
Newman, Peter A; Roungprakhon, Surachet; Tepjan, Suchon; Yim, Suzy; Walisser, Rachael
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
Abstract This article discusses HIV vaccine discovery and candidate vaccine testing in the context of current realities of funding and clinical trial practice. Lacking perfect animal models for testing candidate HIV vaccines, clinical investigators have proposed a strategy of iterative exploratory clinical trials in the model of cancer chemotherapy development. Problems with the appropriateness of this model to HIV vaccine development are discussed. Also, the future feasibility of this strategy in the context of increasing clinical trial costs and emerging new, efficacious prevention modalities is questioned. Strategies for making better use of animal models are presented as an alternative to iterative exploratory clinical efficacy testing. Some ways in which better data from preclinical studies can refine clinical product development are described. Finally, development of an HIV vaccine under the FDA's "Animal Rule" pathway to licensure when human efficacy studies are not feasible is discussed as a fall-back approach. Not making a preventive vaccine against HIV infection is simply not an option because eradication of AIDS will require a preventive vaccine. PMID:23379343
Shapiro, Stuart Z
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.
HIV vaccine preparedness studies (VPS) are important precursors to HIV vaccine trials. As well, they contribute to an understanding of motivators and barriers for participation in hypothetical HIV vaccine trials. Motivators can take the form of altruism and a desire for social benefits. Perceived personal benefits, including psychological, personal, and financial well-being, may also motivate participation. The authors performed a
Shayesta Dhalla; Gary Poole
Like other sub-Saharan countries Nigeria is ravaged by HIV\\/AIDS. The author is a general surgeon with some training in Immunology and practises in central Nigeria. He conceived and developed a safe therapeutic HIV vaccine prepared from the blood of HIV-infected persons and applied the remedy to over 3500 such patients with their informed and written consent. He also developed a
Jeremiah Ojonemi Alabi Abalaka
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.
|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.
HIV and hepatitis B virus co-infection leads to substantially increased morbidity and mortality compared with either infection alone. Immunisation with hepatitis B virus vaccine is the most effective way to prevent the infection in people with HIV; however, these patients have decreased vaccine responses and a short duration of protection compared with immunocompetent individuals. Control of HIV replication with highly active antiretroviral therapy and increased CD4 cell counts are associated with improved immune responses to hepatitis B vaccination. New vaccination strategies, such as increased vaccine dose, use of the intradermal route, and addition of adjuvants, could improve response rates in adults with HIV. PMID:23174382
Whitaker, Jennifer A; Rouphael, Nadine G; Edupuganti, Srilatha; Lai, Lilin; Mulligan, Mark J
With HIV persisting lifelong in infected persons, therapeutic vaccination is a novel alternative concept to control virus replication. Even though CD8 and CD4 cell responses to such immunizations have been demonstrated, their effects on virus replication are still unclear. In view of this fact, we studied the impact of a therapeutic vaccination with HIV nef deliv- ered by a recombinant
Dieter Hoffmann; Judith Seebach; Antonio Cosma; Frank D. Goebel; Korbinian Strimmer; Hermann M. Schatzl; Volker Erfle
For the purposes of vaccination, persons with asymptomatic HIV infection and CD4+ cell counts of 200/?L to 500/?L are considered to have limited immune deficits and are generally candidates for immunization. HIVinfected persons with CD4+ cell counts less than 200/?L or history of an AIDS-defining illness should not receive live-attenuated viral or bacterial vaccines because of the risk of serious systemic disease and suboptimal response to vaccination. Available data indicate that immunization during antiretroviral therapy restores vaccine immunogenicity, improves the rate and persistence of immune responses, and reduces risk of vaccine-related adverse events, although vaccine responses often are suboptimal. Major issues for travelers to the developing world are vaccine-preventable illnesses (hepatitis A virus, yellow fever, and typhoid fever), traveler's diarrhea, and malaria. This article summarizes a presentation by D. Scott Smith, MD, at the IAS-USA continuing medical education program held in San Francisco in April 2012. PMID:22954612
Smith, D Scott
2 , and their co-workers indicate that male circumcision can have a sig nifi cant protective eff ect against HIV infection. Although these results are clearly important for HIV prevention, the benefi ts of male circumcision could be negated by behaviour that increases HIV risk, especially by a drop in condom use or a rise in sexual partners. In Bailey
Devon D Brewer; John J Potterat; Stuart Brody
Background The AIDS epidemic in Brazil remains concentrated in populations with high vulnerability to HIV infection, and the development of an HIV vaccine could make an important contribution to prevention. This study modeled the HIV epidemic and estimated the potential impact of an HIV vaccine on the number of new infections, deaths due to AIDS and the number of people receiving ARV treatment, under various scenarios. Methods and Findings The historical HIV prevalence was modeled using Spectrum and projections were made from 2010 to 2050 to study the impact of an HIV vaccine with 40% to 70% efficacy, and 80% coverage of adult population, specific groups such as MSM, IDU, commercial sex workers and their partners, and 15 year olds. The possibility of disinhibition after vaccination, neglecting medium- and high-risk groups, and a disease-modifying vaccine were also considered. The number of new infections and deaths were reduced by 73% and 30%, respectively, by 2050, when 80% of adult population aged 15–49 was vaccinated with a 40% efficacy vaccine. Vaccinating medium- and high-risk groups reduced new infections by 52% and deaths by 21%. A vaccine with 70% efficacy produced a great decline in new infections and deaths. Neglecting medium- and high-risk population groups as well as disinhibition of vaccinated population reduced the impact or even increased the number of new infections. Disease-modifying vaccine also contributed to reducing AIDS deaths, the need for ART and new HIV infections. Conclusions Even in a country with a concentrated epidemic and high levels of ARV coverage, such as Brazil, moderate efficacy vaccines as part of a comprehensive package of treatment and prevention could have a major impact on preventing new HIV infections and AIDS deaths, as well as reducing the number of people on ARV. Targeted vaccination strategies may be highly effective and cost-beneficial.
Fonseca, Maria Goretti P.; Forsythe, Steven; Menezes, Alexandre; Vuthoori, Shilpa; Possas, Cristina; Veloso, Valdilea; de Fatima Lucena, Francisca; Stover, John
The search for an HIV vaccine began following the discovery of the virus more than 25 years ago. Despite important progress, an effective vaccine remains an elusive goal that will likely require many more years of R&D to achieve. Following recent advances in research, however, there has been increased optimism that a prophylactic HIV vaccine is feasible. A consensus is forming among researchers to support a larger role for proof-of-concept efficacy clinical trials, conducted in parallel with invigorated basic research efforts and testing in animal models, to accelerate the discovery of key principles that will guide rational vaccine development. PMID:21154142
Robb, Merlin L
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 performed to implement scientific advancements and to resolve 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. PMID:23764631
Adimora, Adaora A; Ramirez, Catalina; Auerbach, Judith D; Aral, Sevgi O; Hodder, Sally; Wingood, Gina; El-Sadr, Wafaa; Bukusi, Elizabeth A
A series of expression vectors based on attenuated vaccine strains of Venezuelan equine encephalitis virus (VEE) have been constructed with the ultimate goal of expressing immunizing antigens derived from HIV- 1 in vivo, thus protecting against subsequent...
R. E. Johnston
HIV-1 Tat B-cell epitope vaccination was ineffectual in preventing viral rebound after ART cessation: HIV rebound with current ART appears to be due to infection with new endogenous founder virus and not to resurgence of pre-existing Tat-dependent viremia.
CD4 T cell activation, essential for productive HIV infection, is provided initially in acute HIV infection by innate immune system secretion of activating cytokines. This cytokine response wanes with time and long-term activation of CD4 cells is maintained by HIV Tat protein secreted by HIV infected cells. Structured treatment interruption (STI) in well-controlled antiretroviral-treated (ART) subjects was explored a decade ago with a consensus finding that, in most subjects, HIV levels rebounded within four weeks to pre-ART levels. Based on these observations we initiated a randomized placebo-controlled study of a universal anti-Tat epitope vaccine, TUTI-16, to determine if immunological blockade of Tat would prevent HIV rebound after ART cessation. TUTI-16 immunization was safe, with predominantly mild local and systemic injection-related adverse reactions. TUTI-16 was also immunogenic, with high levels of anti-Tat antibodies compared with levels previously shown to reduce HIV replication in vivo. Of 21 subjects analyzed, 13 (62%) had HIV rebounds vs. 8 (38%) that remained aviremia, but this distribution was not vaccine-related (p = 0.61 log-rank (Mantel-Cox) test), nullifying our hypothesis that anti-Tat antibodies would block rebound of Tat-dependent set-point HIV viremia after ART cessation. Our present findings are consistent with recent molecular findings that rebounding virus following STI is homogeneous and unrelated to previous circulating HIV, suggesting that rebounding HIV represents new founder virus, akin to the original acute HIV infection. We propose, therefore, that STI may have potential as a practical and economical approach to testing the safety and efficacy of candidate prophylactic HIV vaccines. PMID:23095869
Goldstein, Gideon; Damiano, Eve; Donikyan, Mardik; Pasha, Malika; Beckwith, Erik; Chicca, John
During the past two decades of the HIV/AIDS pandemic, several recruitment campaigns were designed to generate community involvement in preventive HIV vaccine clinical trials. These efforts utilized a blend of advertising and marketing strategies mixed with public relations and community education approaches to attract potential study participants to clinical trials (integrated marketing communications). Although more than 30,000 persons worldwide have participated in preventive HIV vaccine studies, no systematic analysis of recruitment campaigns exists. This content analysis study was conducted to examine several United States and Canadian recruitment campaigns for one of the largest-scale HIV vaccine trials to date (the “Step Study”). This study examined persuasive features consistent with the Elaboration Likelihood Model (ELM) including message content, personal relevance of HIV/AIDS and vaccine research, intended audiences, information sources, and other contextual features. The results indicated variation in messages and communication approaches with gay men more exclusively targeted in these regions. Racial/ethnic representations also differed by campaign. Most of the materials promote affective evaluation of the information through heuristic cueing. Implications for subsequent campaigns and research directions are discussed.
Frew, Paula M.; Macias, Wendy; Chan, Kayshin; Harding, Ashley C.
HIV exceptionalism (and disease-specific programs generally) garner both unbalanced funding and the most talented personnel, distorting local health priorities. In support of HIV exceptionalism, the successful mobilization of significant global health sector resources was not possible prior to HIV. Both sides of the debate have merits; rather than perpetuating polarization, we suggest that sustained improvements in global health require creating a prevention infrastructure to meet multiple health challenges experienced by local communities. We propose four fundamental shifts in HIV and disease prevention: (1) horizontally integrating prevention at one site locally, with priorities tailored to local health challenges and managed by local community leaders; (2) using a family wellness metaphor for services, not disease prevention; (3) implementing evidence-based prevention programs (EBPP) based on common principles, factors, and processes, rather than replication of specific programs; and (4) utilizing the expertise of private enterprise to re-design EBPP into highly attractive, engaging, and accessible experiences. PMID:19148744
Rotheram-Borus, Mary Jane; Swendeman, Dallas; Flannery, Diane
This study examined HIV vaccine acceptability among immigrant Thai residents in Los Angeles, California. We combined a qualitative research method (focus groups) with an innovative market research method (conjoint analysis). Focus groups explored social issues, concerns, barriers and motivators associated with HIV vaccine acceptability. Conjoint analysis was used to assess preferences among eight hypothetical HIV vaccines with varying attribute profiles and the impact of various attributes on acceptability. Five main themes were identified in the focus groups regarding acceptance and utilization of preventive HIV vaccines: (1) vaccine characteristics, such as efficacy, physical side-effects and cost, (2) fear of a vaccine, (3) vaccine acceptability and optimism, (4) social and family responses and (5) behavioral disinhibition. Conjoint analysis revealed HIV vaccine acceptability ranging from 7.4 (SD = 19.4) to 85.2 (SD = 24.3) across eight hypothetical vaccines. The vaccine with the highest acceptability had the following attributes: 99% efficacy, no side-effects, 10 years of protection, protects against one sub-type, free, one dose and given by injection. Vaccine efficacy had the greatest impact on acceptability (51.4, p = .005), followed by side-effects (11.1, p = .005) and duration of protection (8.3, p = .005). Despite some apprehensions and concerns, Thai residents perceived an HIV vaccine as making an important contribution to society and to protecting oneself and one’s family from HIV infection. Nevertheless, acceptability of a partially efficacious vaccine may be low, suggesting the need for tailored social marketing interventions that might emphasize a collectivistic rather than an individualistic focus. Assessing HIV vaccine acceptability using a mixed-method approach is feasible with Thai residents and should lend itself to HIV vaccine research with other Asian Pacific Islander populations in the US.
Lee, Sung-Jae; Brooks, Ronald A.; Newman, Peter A.; Seiden, Danielle; Sangthong, Rassamee; Duan, Naihua
A substantial proportion of HIV-1-infected individuals in sub-Saharan Africa are in stable relationships with HIV-1-uninfected partners, and HIV-1 serodiscordant couples thus represent an important target population for HIV-1 prevention. Couple-based HIV-1 testing and counseling facilitates identification of HIV-1 serodiscordant couples, counseling about risk reduction, and referrals to HIV-1 treatment, reproductive health services, and support services. Maximizing HIV-1 prevention for HIV-1 serodiscordant couples requires a combination of strategies, including counseling about condoms, sexual risk, fertility, contraception, and the clinical and prevention benefits of antiretroviral therapy (ART) for the HIV-1-infected partner; provision of clinical care and ART for the HIV-1-infected partner; antenatal care and services to prevent mother to child transmission for HIV-1- infected pregnant women; male circumcision for HIV-1-uninfected men; and, pending guidelines and demonstration projects, oral pre-exposure prophylaxis (PrEP) for HIV-1-uninfected partners.
Curran, Kathryn; Baeten, Jared M.; Coates, Thomas J.; Kurth, Ann; Mugo, Nelly R.
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)
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
Zaynab Essack; Jennifer Koen; Catherine Slack; Graham Lindegger; Peter A. Newman
Two vaccine trials that were conducted 50 years apart are reviewed and compared: the 1954 field trial of the Salk inactivated polio vaccine and the RV144 HIV vaccine trial conducted in Thailand between 2003 and 2009. Despite the obvious differences in science and historical periods, several lessons were identified that could inform the future HIV vaccine effort. Those lessons are related to paradigm changes that occur when science progresses, the need to test scientific hypothesis in efficacy trials, the controversies surrounding those trials, the need for strong community and political support, the participation of government and nongovernment institutions, the balance between implementation of other preventive and therapeutic interventions, and the priority given by society to develop a vaccine. If we have the humility and courage to apply some of those lessons, we may be able accelerate the development of an urgently needed HIV vaccine. PMID:23018439
In preparation for HIV vaccine trials, knowledge about vaccines, willingness to participate in a vaccine study, and motivations for participation must be assessed. The Preparation for AIDS Vaccine Evaluation study assessed knowledge about vaccines and vaccine trials and willingness to participate in a hypothetical trial in 1,182 Ugandan military men (aged 18-30 years). Participants received education about vaccine trials and were interviewed during 24 months of follow-up observation. Its key findings are that: 1) throughout follow-up, most participants expressed willingness to participate in a hypothetical HIV vaccine trial; 2) participants are familiar with vaccines but do not clearly distinguish the use of vaccines for prevention or curing; 3) the most common reason given for being interested in participating in a vaccine trial was to be protected from HIV/AIDS; 4) trials' procedures (e.g., placebos, randomization, and blinding) were unfamiliar; and 5) knowledge about trials' procedures increased incrementally over follow-up, but at different rates for different concepts. These data demonstrate that potential vaccine trials' participants may benefit from vaccine trial education if adequate time is allowed to ensure that participants are able to master the complex information required for trial participation. PMID:11468427
McGrath, J W; George, K; Svilar, G; Ihler, E; Mafigiri, D; Kabugo, M; Mugisha, E
Condom use is the best available strategy to prevent HIV infection during sexual intercourse. However, since many people choose not to use condoms in circumstances in which HIV risk exists, alternatives to condom use for HIV prevention are needed. Currently there are several alternative bio-medical HIV-prevention products in different stages of development: microbicides, vaccines, post-exposure prophylaxis (PEP) and pre-exposure prophylaxis
N. Nodin; A. Carballo-Diéguez; A. M. Ventuneac; I. C. Balan; R. Remien
|Existing knowledge and beliefs related to HIV vaccines provide an important basis for the development of risk communication messages to support future HIV vaccine dissemination. This study explored HIV vaccine mental models among adults from segments of the population disproportionately affected by HIV/AIDS. Nine focus groups were conducted with…
Newman, Peter A.; Seiden, Danielle S.; Roberts, Kathleen J.; Kakinami, Lisa; Duan, Naihua
Successful conduct of HIV vaccine trials in a population of great cultural diversity like India could be a challenge. Concerns, knowledge gaps and willingness to participate in future HIV vaccine trials were studied among 349 patients attending three sexually transmitted infections clinics and one reproductive tract infections clinic. Overall willingness to volunteer for HIV vaccine trials was 48%. Women and
Seema Sahay; Sanjay Mehendale; Suvarna Sane; Radhika Brahme; Amishah Brown; Karen Charron; Chris Beyrer; Robert Bollinger; Ramesh Paranjape
This study assessed various factors that may contribute to the likelihood of getting vaccinated for HIV. Three sets of determining factors were explored. Health beliefs, based on the Health Belief Model, looked at perceived susceptibility towards HIV disease, benefits to vaccination, pragmatic barriers to vaccination, fear of the vaccine causing AIDS, perceived non-membership in traditionally defined high-risk groups, and perceived
Compared with nonindigenous people, indigenous people in first-world countries have experienced much higher rates of many vaccine preventable diseases. This systematic review of published scientific literature, government reports, and immunization guidelines from Australia, Canada, New Zealand, and the United States compares pre- and postvaccination disease rates and vaccination policy for indigenous people in these four countries. Nationally funded universal vaccination
Robert Menzies; Peter McIntyre
Reducing the incidence of HIV remains one of our greatest public health challenges. However, there is growing optimism that\\u000a preexposure prophylaxis (PrEP) could have a major impact on preventing incident HIV infection. Recently presented data on\\u000a the use of oral PrEP in men who have sex with men (MSM) have provided proof-of-principle for this strategy. Additional clinical\\u000a trials are evaluating
Theodoros Kelesidis; Raphael J. Landovitz
Adenoviral 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. For effective vaccine development it is often necessary to express or present multiple antigens to the immune system to elicit an optimal vaccine as observed preclinically with mosaic/polyvalent HIV vaccines or malaria vaccines. Due to the wide flexibility of Ad vectors they are an ideal platform for expressing large amounts of antigen and/or polyvalent mosaic antigens. Ad vectors that display antigens on their capsid surface can elicit a robust humoral immune response, the “antigen capsid-incorporation” strategy. The adenoviral hexon protein has been utilized to display peptides in the majority of vaccine strategies involving capsid incorporation. Based on our abilities to manipulate hexon HVR2 and HVR5, we sought to manipulate HVR1 in the context of HIV antigen display for the first time ever. More importantly, peptide incorporation within HVR1 was utilized in combination with other HVRs, thus creating multivalent vectors. To date this is the first report where dual antigens are displayed within one Ad hexon particle. These vectors utilize HVR1 as an incorporation site for a seven amino acid region of the HIV glycoprotein 41, in combination with six Histidine incorporation within HVR2 or HVR5. Our study illustrates that these multivalent antigen vectors are viable and can present HIV antigen as well as His6 within one Ad virion particle. Furthermore, mouse immunizations with these vectors demonstrate that these vectors can elicit a HIV and His6 epitope-specific humoral immune response.
Gu, Linlin; Li, Zan C.; Krendelchtchikov, Alexandre; Krendelchtchikova, Valentina; Wu, Hongju; Matthews, Qiana L.
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.
A class of synthetic peptide immunogens for the cell surface HIV receptor complex has been developed to elicit antibodies that block viral entry by inhibiting gp120-CD4 interaction. These peptides extend our HIV receptor-directed approach from passive immunotherapy with mAb B4 (Proc. Natl. Acad. Sci. U.S.A. 96 (1999) 10367) to active immunization by a synthetic peptide-based vaccine. A peptide site from
Chang Yi Wang; Ming Shen; Gary Tam; Xin De Fang; John Ye; Fan Shen; Alan M. Walfield; James J. G. Wang; Ming Lie Li; Xuan Mao Lia; Maria Salas; Michael H. Shearer; Ronald C. Kennedy; Carl V. Hanson
We all know about the "feminization" of AIDS. Approximately 8000 women and girls are infected with HIV daily, the vast majority by their husbands or boyfriends. In Africa, women make up 60% of all people living with HIV/AIDS, and girls make up 6% of HIV positive African youth. While fewer than half of all new HIV infections in the United States occur among women, the transmission pattern is similar. Heterosexual contact is the source of at least 78% of all new infections among U.S. women. Biologically, a woman is at least twice as likely as a man to contract HIV from a single act of unprotected vaginal intercourse. Even with the "female condom," a woman cannot protect herself during heterosexual sex without the cooperation of her partner. The "ABCs" (abstain, be faithful, use condoms) fail millions of women who lack the social and economic power to negotiate when and how sex occurs and whether protection is used. Microbicides could change this picture with just a simple cream, foam, or gel that can be inserted vaginally to protect women condom use isn't possible. Five candidate microbicides are now in large-scale efficacy trials and dozens more are in the preclinical and clinical trial pipeline. Research to develop rectal microbicides is also finally underway. We now have the scientific means and the public health motivation to put the first totally new HIV prevention technology into the hands of receptive sex partners--male and female--in the very near future. PMID:17019789
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
Efficacy studies of investigational HIV vaccines require enrollment of individuals at ‘high risk’ for HIV. This paper examines participation in HIV vaccine trials among women at ‘high risk’ for HIV acquisition. In-depth interviews were conducted with 17 African-American women who use crack cocaine and/or exchange sex for money/drugs to elicit attitudes toward medical research and motivators and deterrents to HIV vaccine trial participation. Interviews were digitally recorded and transcribed; data were coded and compiled into themes. Most women expressed favorable attitudes toward medical research in general. Motivators for trial participation included compensation; personal benefits including information, social services, and the possibility that the trial vaccine could prevent HIV; and altruism. Deterrents included: dislike of needles; distrust; concern about future consequences of participating. In addition, contingencies, caregiving responsibilities, and convenience issues constituted barriers which could impede participation. Respondents described varied, complex perspectives, and individual cases illustrate how these themes played out as women contemplated trial participation. Understanding factors which influence vaccine research participation among women at ‘high risk’ can aid sites to tailor recruitment procedures to local contexts. Concerns about future reactions can be addressed through sustained community education. Convenience barriers can be ameliorated by providing rides to study visits when necessary, and/or conducting study visits in accessible neighborhood locations. Women in this sample thought carefully about enrolling in HIV vaccine trials given the structural constraints within which they lived. Further research is needed regarding structural factors which influence personal agency and individuals’ thinking about research participation.
Voytek, Chelsea D.; Jones, Kevin T.; Metzger, David S.
Since human immunodeficiency virus (HIV) was identified as the causative agent of AIDS the pressing challenge that researchers are facing is the development of a vaccine against this disease. Although progress has been made in the study of the biology of ...
P. Verani S. Butto B. Taddeo M. Federico G. B. Rossi
The need to broaden research directed at answering fundamental questions in HIV vaccine discovery through laboratory, nonhuman primate (NHP), and clinical research has recently been emphasized. In addition, the importance of attracting and retaining young researchers, developing better NHP models, and more closely linking NHP and clinical research is being stressed. In an era of a level budget for biomedical
Anthony S. Fauci; Margaret I. Johnston; Carl W. Dieffenbach; Dennis R. Burton; Scott M. Hammer; James A. Hoxie; Malcolm Martin; Julie Overbaugh; David I. Watkins; Adel Mahmoud; Warner C. Greene
The prevention of human immunodeficiency virus (HIV) associated tuberculosis (TB) remains challenging. Several vaccines against TB have advanced to clinical trials in patients with HIV infection. The DarDar Trial, a large, randomized, placebo-controlled efficacy trial conducted in Tanzania, has demonstrated that a multiple dose series of an inactivated whole cell mycobacterial vaccine is safe in HIV and can prevent HIV-associated TB in patients with childhood bacille Calmette-Guérin vaccination and CD4 counts of ?200 cells/mm(3). These developments offer promise that in the not too distant future immunization with an effective vaccine against TB can be added to other strategies for the prevention of HIV-associated TB. This expanded approach is referred to as the Five 'I's': intensified case finding, infection control, isoniazid preventive therapy (IPT), initiation of antiretroviral therapy (ART), and immunization against TB. We encourage additional studies of new TB vaccines in HIV, and propose a strategy to reduce the risk of TB by integrating IPT, ART and immunization into routine HIV care. At the time of HIV diagnosis, patients with CD4 counts of ?200 cells/mm(3) could receive immunization, IPT and, as appropriate, ART. In patients presenting with lower CD4 counts or already on ART, immunization could be initiated at CD4 counts of ?200 cells/mm(3) to add to the protection afforded by IPT and ART. PMID:22507085
von Reyn, C F; Bakari, M; Arbeit, R D; Lahey, T; Ramadhani, A; Egwaga, S
Human papillomavirus (HPV) is the etiological agent for cervical cancer and a large majority of anal cancers worldwide. In 2006 two preventive vaccines against the HPV were approved by the US Food and Drug Administration and have since been approved in over 100 countries. HIV-infected populations are at an increased risk for HPV-related cancers. None of the efficacy trials for these vaccines included HIV-infected populations. However, studies in HIV-infected children and adult men show that the vaccine is safe and highly immunogenic. Studies evaluating the vaccine in HIV-infected women are in progress. Based on these studies, the American Council on Immunization Practices recommends HPV vaccination for all HIV-infected children and young adults up to age 26 years. HPV vaccine policies in resource-limited countries, many of which have a high prevalence of HIV infection, are still being developed. Future studies should examine the role of HPV vaccination for older HIV-infected adults who likely have ongoing HPV infection. PMID:22744002
Firnhaber, Cynthia; Wilkin, Timothy
|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.
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
HIV vaccines offer the best long-term hope of controlling the AIDS pandemic; yet, the advent of HIV vaccines will not ensure their acceptability. We conducted a cross-sectional survey (n=143), incorporating conjoint analysis, to assess HIV vaccine acceptability among participants recruited using multi-site (n=9), venue-based sampling in Los Angeles. We used a fractional factorial experimental design to construct eight hypothetical HIV
Peter A. Newman; Naihua Duan; Sung-Jae Lee; Ellen T. Rudy; Danielle S. Seiden; Lisa Kakinami; William E. Cunningham
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
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. PMID:23772627
Stephenson, Kathryn E; Barouch, Dan H
Human Papillomavirus (HPV) has been associated with several human cancers, including cervical cancer, vulvar cancer, vaginal and anal cancer, and a subset of head and neck cancers. Thus effective vaccination against HPV provides an opportunity to reduce the morbidity and mortality associated with HPV. The Food and Drug Administration of the United States has approved two preventive vaccines to limit the spread of HPV. However, these are unlikely to impact upon HPV prevalence and cervical cancer rates for many years. Furthermore, preventive vaccines do not exert therapeutic effects on pre-existing HPV infections and HPV-associated lesions. In order to further impact upon the burden of HPV infections worldwide, therapeutic vaccines are being developed. These vaccines aim to generate a cell-mediated immune response to infected cells. This review discusses current preventive and therapeutic HPV vaccines and their future directions. PMID:20123582
Lin, Ken; Doolan, Kimberley; Hung, Chien-Fu; Wu, T C
Cervical cancer is the second most common cause of female cancer death worldwide. Persistent infection with `high risk' HPV genotypes is the major etiological factor in cervical cancer and thus effective vaccination against HPV provides an opportunity to reduce the morbidity and mortality associated with HPV. The FDA has approved two preventive vaccines to limit the spread of HPV. However, these are unlikely to impact upon HPV prevalence and cervical cancer rates for many years. Furthermore, preventive vaccines do not exert therapeutic effects on pre-existing HPV infections and HPV-associated lesions. In order to further impact upon the burden of HPV infections worldwide, therapeutic vaccines are being developed. These vaccines aim to generate a cell-mediated immune response to infected cells. This review discusses current preventive and therapeutic HPV vaccines and their future directions.
Lin, Ken; Doolan, Kimberley; Hung, Chien-Fu; Wu, T-C
In 2011, the Centers for Disease Control and Prevention identified the reduction in vaccine-preventable diseases (VPDs) as one of the greatest achievements of the previous decade. During that time, several new pediatric and adult vaccines were introduced including rotavirus, quadrivalent meningococcal conjugate, herpes zoster, human papillomavirus, pneumococcal conjugate, and adult tetanus, diphtheria, acellular pertussis. Despite the impact of immunization and its public health priority, vaccine coverage among adults in the United States remains suboptimal. Incorporation of adult immunization into routine obstetric and gynecologic care may be one innovative approach to vaccinate women. Pregnancy is a particularly vulnerable period for VPD-associated complications for both mother and baby, as demonstrated by the influenza pandemic of 2009. In addition to preventing maternal and congenital disease, maternal immunization can also provide direct fetal/infant protection via passive immunity. This article summarizes vaccine classification, specific vaccines recommended during pregnancy/postpartum, and barriers to maternal immunization. PMID:23271378
Swamy, Geeta K; Garcia-Putnam, Rebecca
A safe and effective HIV vaccine to prevent infection and\\/or to moderate disease is urgently needed. Research progress has been slower than anticipated for a variety of reasons including uncertainty over which immunogen to use (i.e. recombinant subunit envelope proteins or whole HIV-1 products), confusion on which immunological markers best correlate with protection, the relevance of the HIV-1 chimpanzee model
R. M. Anderson; J. Swinton; G. P. Garnett
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
... HIV, Influenza, and Smallpox Vaccines: Development of New Assays and Animal Models for Evaluation of Vaccine Safety and Efficacy. ... More results from www.fda.gov/biologicsbloodvaccines/scienceresearch/biologicsresearchareas
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
Tuberculosis (TB) has emerged as the most prominent bacterial disease found in human immunodeficiency virus (HIV)-positive individuals worldwide. Due to high prevalence of asymptomatic Mycobacterium tuberculosis (Mtb) infections, the future HIV vaccine in areas highly endemic for TB will often be administrated to individuals with an ongoing Mtb infection. The impact of concurrent Mtb infection on the immunogenicity of a HIV vaccine candidate, MultiHIV DNA/protein, was investigated in mice. We found that, depending on the vaccination route, mice infected with Mtb before the administration of the HIV vaccine showed impairment in both the magnitude and the quality of antibody and T cell responses to the vaccine components p24Gag and gp160Env. Mice infected with Mtb prior to intranasal HIV vaccination exhibited reduced p24Gag-specific serum IgG and IgA, and suppressed gp160Env-specific serum IgG as compared to respective titers in uninfected HIV-vaccinated controls. Importantly, in Mtb-infected mice that were HIV-vaccinated by the intramuscular route the virus neutralizing activity in serum was significantly decreased, relative to uninfected counterparts. In addition mice concurrently infected with Mtb had fewer p24Gag-specific IFN-?-expressing T cells and multifunctional T cells in their spleens. These results suggest that Mtb infection might interfere with the outcome of prospective HIV vaccination in humans.
Ignatowicz, Lech; Mazurek, Jolanta; Leepiyasakulchai, Chaniya; Skold, Markus; Hinkula, Jorma; Kallenius, Gunilla; Pawlowski, Andrzej
Failure of immunization with the HIV-1 envelope to induce broadly neutralizing antibodies against conserved epitopes is a major barrier to producing a preventive HIV-1 vaccine. Broadly neutralizing monoclonal antibodies (BnAbs) from those subjects who do produce them after years of chronic HIV-1 infection have one or more unusual characteristics, including polyreactivity for host antigens, extensive somatic hypermutation and long, variable heavy-chain third complementarity-determining regions, factors that may limit their expression by host immunoregulatory mechanisms. The isolation of BnAbs from HIV-1–infected subjects and the use of computationally derived clonal lineages as templates provide a new path for HIV-1 vaccine immunogen design. This approach, which should be applicable to many infectious agents, holds promise for the construction of vaccines that can drive B cells along rare but desirable maturation pathways.
Haynes, Barton F; Kelsoe, Garnett; Harrison, Stephen C; Kepler, Thomas B
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
Individuals homozygous for a 32-basepair deletion mutation (null mutation) in CCR5, a chemokine receptor, are nearly immune to developing HIV infection. Recently based on molecular dating evidence it has been proposed that the bacterium Yersinia pestis, cause of plague, may have been the selective pressure which selected for a high prevalence of the 32-basepair null mutation. An association of a
E. L. Altschuler
Purpose of review This review covers the role of the Global HIV Vaccine Enterprise (the Enterprise), an alliance of independent organizations committed to development of a safe and effective HIV vaccine. It discussesthe history, impact on the field and future directions and initiatives of the alliance, in the context of recent progress in HIV vaccine research and development. Recent Findings Significant progress has been made in the field since the release of the 2005 Scientific Strategic Plan (The Plan) of the Enterprise. Over the last year, the Enterprise embarked on an impact assessment of the 2005 Planand the development of the 2010 Plan. Enterprise Working Groups identified key priorities in the field, several of which are discussed in this review, including: changing the nature, purpose and process of clinical trials; increasing and facilitating data sharing; and optimizing existing and attracting new resources. Summary This isan important moment in HIV vaccine research. New clinical trial and laboratory results have created new opportunities to advance the search for an HIV vaccineand reinvigorated the field. The Enterprise will publish its 2010 Scientific Strategic Planthis year, providinga framework for setting new priorities and directions, and encouraging new and existing partners to embark on a shared scientific agenda.
Voronin, Yegor; Manrique, Amapola; Bernstein, Alan
Background Gene-based vaccine delivery is an important strategy in the development of a preventive vaccine for acquired immunodeficiency syndrome (AIDS). Vaccine Research Center (VRC) 004 is the first phase 1 dose-escalation study of a multiclade HIV-1 DNA vaccine. Methods VRC-HIVDNA009?00-VP is a 4-plasmid mixture encoding subtype B Gag-Pol-Nef fusion protein and modified envelope (Env) constructs from subtypes A, B, and C. Fifty healthy, uninfected adults were randomized to receive either placebo (n = 10) or study vaccine at 2 mg (n = 5), 4 mg (n = 20), or 8 mg (n = 15) by needle-free intramuscular injection. Humoral responses (measured by enzyme-linked immunosorbant assay, Western blotting, and neutralization assay) and T cell responses (measured by enzyme-linked immunospot assay and intracellular cytokine staining after stimulation with antigen-specific peptide pools) were measured. Results The vaccine was well tolerated and induced cellular and humoral responses. The maximal CD4+ and CD8+ T cell responses occurred after 3 injections and were in response to Env peptide pools. The pattern of cytokine expression by vaccine-induced HIV-specific T cells evolved over time, with a diminished frequency of interferon-?–producing T cells and an increased frequency of interleukin-2–producing T cells at 1 year. Conclusions DNA vaccination induced antibody to and T cell responses against 3 major HIV-1 subtypes and will be further evaluated as a potential component of a preventive AIDS vaccine regimen.
Graham, Barney S.; Koup, Richard A.; Roederer, Mario; Bailer, Robert T.; Enama, Mary E.; Moodie, Zoe; Martin, Julie E.; McCluskey, Margaret M.; Chakrabarti, Bimal K.; Lamoreaux, Laurie; Andrews, Charla A.; Gomez, Phillip L.; Mascola, John R.; Nabel, Gary J.
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
Currently, there is no cure and no preventive vaccine for HIV/AIDS. Combination antiretroviral therapy has dramatically improved treatment, but it has to be taken for a lifetime, has major side effects and is ineffective in patients in whom the virus develops resistance. Nanotechnology is an emerging multidisciplinary field that is revolutionizing medicine in the 21st century. It has a vast potential to radically advance the treatment and prevention of HIV/AIDS. In this review, we discuss the challenges with the current treatment of the disease and shed light on the remarkable potential of nanotechnology to provide more effective treatment and prevention for HIV/AIDS by advancing antiretroviral therapy, gene therapy, immunotherapy, vaccinology and microbicides.
Mamo, Tewodros; Moseman, E Ashley; Kolishetti, Nagesh; Salvador-Morales, Carolina; Shi, Jinjun; Kuritzkes, Daniel R; Langer, Robert; von Andrian, Ulrich
Preventive vaccination strategy around the birth is a global approach requiring the coordination of several actors. To be efficacious, general practitioners are in the front line to provide preventive care and health education. The perinatal period represents a privileged situation from listening to this approach of vaccine prevention. The raising awareness around the birth contains several additional steps to bring to the future mother and child the best protection against infectious diseases with vaccine prevention. By being vaccinated, parents and other family members indirectly provide protection to very young infants until they are old enough to be vaccinated and so directly protected themselves. Numerous opportunities exist to make sensitive the parents in this preventive way, for them and their child, whether it is from the adolescence in the adulthood above all parental project, on the occasion of a pregnancy, at birth, during the stay in maternity hospital, or along the first weeks of the postpartum. The general practitioner is the key actor to coordinate this global approach in perinatal health around the mother, his child and his family. The arrival of the newborn will be the opportunity to update vaccinations of the whole family particularly according chicken pox, measles, rubella, whooping cough and flu vaccines. PMID:21425528
Pinquier, Didier; Gagneur, Amaud; Gaudelus, Joël; Marret, Stéphane
The rapidly changing media landscape and proliferation of new technologies creates vast new opportunities for HIV prevention. The fast growth of the relatively new eHealth field is a testament to the excitement and promise of these new technologies. eHealth interventions in HIV prevention tested to date include computer- and Internet-based interventions; chat room interventions; text messaging interventions; and social media. The current article provides a brief review of these types of interventions in HIV prevention, including their unique advantages and evidence of efficacy. Implications for future research in the eHealth HIV prevention field are discussed. PMID:22519523
Noar, Seth M; Willoughby, Jessica Fitts
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
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. PMID:23869225
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
|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.
High HIV rates among cohabiting couples in many African countries have led to greater programmatic emphasis on spousal communication in HIV prevention. This study examines how demographic and socioeconomic characteristics of cohabiting adults influence their dyadic communication about HIV. A central focus of this research is on how the position of women relative to their male partners influences spousal communication
Chi Chiao; Vinod Mishra; Kate Ksobiech
BackgroundThe Expanded Program on Immunization (EPI) is the most cost-effective measures to control vaccine-preventable diseases. Currently, the EPI schedule is similar for HIV-infected children; the introduction of antiretroviral therapy (ART) should considerably prolong their life expectancy.Methods and Principal FindingsTo evaluate the persistence of antibodies to the EPI vaccines in HIV-infected and HIV-exposed uninfected children who previously received these vaccines in
Mathurin C. Tejiokem; Ionela Gouandjika; Lydie Béniguel; Marie-Claire Endegue Zanga; Gilbert Tene; Jean C. Gody; Elisabeth Njamkepo; Anfumbom Kfutwah; Ida Penda; Catherine Bilong; Dominique Rousset; Régis Pouillot; Frédéric Tangy; Laurence Baril; Landon Myer
Cognitive barriers to participation in actual HIV vaccine trials have not been previously comprehensively reviewed. In this review article, barriers in actual early phase, phase 2B, and phase 3 HIV vaccine trials are quantified and categorized, and compared between the Organization for Economic Co-operation and Development (OECD) countries and the non-OECD countries. Participation rates were standardized to allow for comparisons. In both the OECD and the non- OECD countries, barriers included subjective norms and discrimination, vaccine safety concerns, and logistical concerns. More actual HIV vaccine trials can incorporate questions about and quantify barriers to participation, and this may aid future recruitment strategies. PMID:23721228
Dhalla, Shayesta; Poole, Gary
Background: Hepatitis B (HBV) vaccination is an important preventive intervention for HIV-infected population. Data regarding booster HBV vaccine for persons with low HBV surface antibody (sAb) titers after vaccination in this immunocompromised population is lacking. Methods: We randomized 60 HIV-infected subjects lacking HBV protection after completion of 3 doses of HBV vaccine to receive a booster dose of HBV vaccine with 250mcg GM-CSF as an adjuvant or booster vaccine alone. Results: GM-CSF was safe with expected side effects. However, only 35% of persons receiving GM-CSF developed protective sAb while 50% in vaccine only arm developed protection (P = 0.47). Overall, only 28% of subjects maintained protective sAb 1 year after vaccination. Conclusions: GM-CSF failed to improve responses to the booster HBV vaccination. Overall, response was poor with only 42% of persons responding at one month post-vaccination confirming booster vaccination with the current HBV vaccine has poor immunogenicity among HIV-infected persons. Further research is needed to develop optimal vaccination strategies in HIV-infected persons.
Overton, Edgar T; Sungkanuparph, Somnuek; Klebert, Michael; Royal, Michael; Demarco-Shaw, Debra; Powderly, William G; Aberg, Judith A
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.
This paper examines South African Muslim women's opinions of the acceptability of microbicidal products to prevent HIV infection if these were to become available in the future. In the context of the HIV pandemic, prophylactic methods such as male circumcision, vaccines and microbicidal preparations are increasingly thought of as ways to reduce the incidence of infection. We examine the extent
Nina Hoel; Sadiyya Shaikh; Ashraf Kagee
In HIV Prevention Community Planning, communities and health departments come together to address HIV prevention through an established planning process. This collaborative process was developed according to the principle that local HIV prevention priorit...
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
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
Purpose of the review There have been over 30 HIV-prevention trials of which only four reported evidence of efficacy. The reasons for these failures may be due to ineffective interventions, but in part reflect the inappropriate selection of study populations and epidemiologic settings. Recent findings Three trials showed that male circumcision reduces HIV acquisition in men by 50–60%. In contrast, seven out of eight trials of bacterial and viral sexually transmitted infection (STI) control, and multiple microbicide trials show no efficacy for HIV prevention. Several microbicide trials found vaginal irritation and microulceration, which may increase HIV risk. Three vaccine trials failed to show efficacy and one trial suggested increased HIV risk in a subgroup of uncircumcised men. Summary The failure of most prevention trials reflects inadequate pretrial screening of potentially efficacious interventions, insufficient information on background HIV incidence, selection of high-risk populations with poor compliance and lack of generalizability, and treatment interruption during pregnancy all of which compromises power.
Gray, Ronald H.
The HIV-1 pandemic is a complex mix of diverse epidemics within and between countries and regions of the world, and is undoubtedly the defining public-health crisis of our time. Research has deepened our understanding of how the virus replicates, manipulates, and hides in an infected person. Although our understanding of pathogenesis and transmission dynamics has become more nuanced and prevention options have expanded, a cure or protective vaccine remains elusive. Antiretroviral treatment has transformed AIDS from an inevitably fatal condition to a chronic, manageable disease in some settings. This transformation has yet to be realised in those parts of the world that continue to bear a disproportionate burden of new HIV-1 infections and are most a% ected by increasing morbidity and mortality. This Seminar provides an update on epidemiology, pathogenesis, treatment, and prevention interventions pertinent to HIV-1.
Simon, Viviana; Ho, David D; Karim, Quarraisha Abdool
Human papillomaviruses (HPVs) are the primary etiologic agents of cervical cancer. Thus, cervical cancer and other HPV-associated malignancies might be prevented or treated by HPV vaccines. Transmission of papillomavirus may be prevented by the generation of antibodies to capsid proteins L1 and L2 that neutralize viral infection. However, because the capsid proteins are not expressed at detectable levels by infected
Richard B. S Roden; Morris Ling; T.-C Wu
Efficacy studies of investigational HIV vaccines require enrollment of individuals at 'high risk' for HIV. This paper examines participation in HIV vaccine trials among women at 'high risk' for HIV acquisition. In-depth interviews were conducted with 17 African-American women who use crack cocaine and/or exchange sex for money/drugs to elicit attitudes toward medical research and motivators and deterrents to HIV vaccine trial participation. Interviews were digitally recorded and transcribed; data were coded and compiled into themes. Most women expressed favorable attitudes toward medical research in general. Motivators for trial participation included compensation; personal benefits including information, social services, and the possibility that the trial vaccine could prevent HIV; and altruism. Deterrents included: dislike of needles; distrust; concern about future consequences of participating. In addition, contingencies, care-giving responsibilities, and convenience issues constituted barriers which could impede participation. Respondents described varied, complex perspectives, and individual cases illustrate how these themes played out as women contemplated trial participation. Understanding factors which influence vaccine research participation among women at 'high risk' can aid sites to tailor recruitment procedures to local contexts. Concerns about future reactions can be addressed through sustained community education. Convenience barriers can be ameliorated by providing rides to study visits when necessary, and/or conducting study visits in accessible neighborhood locations. Women in this sample thought carefully about enrolling in HIV vaccine trials given the structural constraints within which they lived. Further research is needed regarding structural factors which influence personal agency and individuals' thinking about research participation. PMID:21704110
Voytek, Chelsea D; Jones, Kevin T; Metzger, David S
Streptococcus pneumoniae is the leading bacterial opportunistic infection in HIV-infected individuals. Anti-retroviral treatment (ART) of HIV-infected individuals reduces their risk of invasive pneumococcal disease (IPD), however, it remains 20- to 40-fold greater compared with age-matched general population. This review summarizes the available published data on the immunogenicity, safety and efficacy of pneumococcal polysaccharide-protein conjugate vaccines (PCV) in HIV-infected children and adults. Several studies have demonstrated that PCV are safe in the HIV-infected persons. Although PCV are immunogenic in HIV-infected infants, the antibodies produced are functionally impaired, there is possibly a lack or loss of anamnestic responses and immunity declines in later life However, quantitative and qualitative antibody responses to PCV in HIV-infected infants are enhanced when vaccination occurs whilst on ART, as well as if vaccination occurs when the CD4+ cell percentage is ? 25% and if the nadir CD4+ is >15%. Although the efficacy of PCV was lower, the vaccine preventable burden of hospitalization for IPD and clinical pneumonia were 18-fold and 9-fold greater, respectively, in HIV-infected children compared with –uninfected children. In HIV-infected adults, PCV vaccination induces more durable and functional antibody responses in individuals on ART at the time of vaccination than in ART-naive adults, independently of baseline CD4+ cell count, although there does not appear to be much benefit from a second-dose of PCV. PCV has also been shown to reduce the risk of recurrent IPD by 74% in HIV-infected adults not on ART, albeit, also with subsequent decline in immunity and protection.
Nunes, Marta C.; Madhi, Shabir A.
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
BACKGROUND: Patients with HIV infection are at risk of co-infection with HBV, as the routes of transmission are shared and thus immunization with HBV vaccine could be protective in them. The aim of the present study was to assess the efficacy of recombinant vaccine in treatment-naive HIV positive patients and healthy controls, and to dissect out differences if any, in
Neelam Pasricha; Usha Datta; Yogesh Chawla; Surjit Singh; Sunil K Arora; Archana Sud; Ranjana W Minz; Biman Saikia; Haqeeqat Singh; Isaac James; Shobha Sehgal
Group A streptococci (GAS) are responsible for numerous human illnesses, ranging from pharyngitis to severe invasive infections,\\u000a such as necrotizing fascitis and toxic shock syndrome to the postinfectious sequelae, acute rheumatic fever (ARF), and glomerulonephritis.\\u000a To date, to develop a vaccine, studies have focused on the M protein. However, designing a vaccine to prevent GAS infection\\u000a based on this molecule
Evelyn R. Brandt; Michael F. Good
Novel, exciting intervention strategies to prevent infection with HIV have been tested in the past year, and the field is\\u000a rapidly evolving. EUROPRISE is a network of excellence sponsored by the European Commission and concerned with a wide range\\u000a of activities including integrated developmental research on HIV vaccines and microbicides from discovery to early clinical\\u000a trials. A central and timely
Sarah Brinckmann; Kelly da Costa; Marit J van Gils; David Hallengärd; Katja Klein; Luisa Madeira; Lara Mainetti; Paolo Palma; Katharina Raue; David Reinhart; Marc Reudelsterz; Nicolas Ruffin; Janna Seifried; Katrein Schäfer; Enas Sheik-Khalil; Annette Sköld; Hannes Uchtenhagen; Nicolas Vabret; Serena Ziglio; Gabriella Scarlatti; Robin Shattock; Britta Wahren; Frances Gotch
This study aimed to determine and describe HIV-negative gay men's willingness to participate in HIV vaccine trials. Data were from participants who completed face-to-face interviews during the first 18 months (to the end of 2002) of recruitment into the Health in Men cohort of HIV-negative gay men in Sydney. A key outcome measure was a scale of Willingness to Participate in HIV Vaccine Trials, with scores ranging from 1 (unwilling) to 4 (willing). The 903 participants ranged in age from 18 to 75 years (median = 36). Mean of Willingness to Participate in HIV Vaccine Trials was 2.53 (standard deviation = 0.54), with approximately 51% of the men having a score greater than the midpoint of 2.50. A reduced linear regression model yielded four significant independent associations with Willingness to Participate in HIV Vaccine Trials: lack of tertiary education (P < 0.001),having engaged 'in the previous six months' in any unprotected anal intercourse with casual or non-concordant regular partners (P < 0.001), higher self-rated likelihood of HIV infection (P < 0.01), and higher mean scores on a scale of Comfort with Participation in HIV Vaccine Trials (P < 0.001). The willingness of HIV-negative gay men at potentially higher risk for HIV to participate in HIV vaccine trials augurs well for enrolment in HIV vaccine efficacy trials. Recruitment into trials is likely to be enhanced by addressing salient concerns such as confidentiality and vaccine-induced antibody positivity. Also, it will be important to ensure that gay men are educated and fully informed about HIV vaccines and trial processes. PMID:15899086
Van de Ven, Paul; Mao, Limin; Crawford, June; Prestage, Garrett; Grulich, Andrew; Kaldor, John; Kippax, Susan
BackgroundHIV 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
Mary H. Latka; Katherine Fielding; Glenda E. Gray; Linda-Gail Bekker; Maphoshane Nchabeleng; Koleka Mlisana; Tanya Nielson; Surita Roux; Baningi Mkhize; Matsontso Mathebula; Nivashnee Naicker; Guy de Bruyn; James Kublin; Gavin J. Churchyard
High HIV rates among cohabiting couples in many African countries have led to greater programmatic emphasis on spousal communication in HIV prevention. This study examines how demographic and socioeconomic characteristics of cohabiting adults influence their dyadic communication about HIV. A central focus of this research is on how the position of women relative to their male partners influences spousal communication about HIV prevention. The authors analyze gaps in spousal age and education and females' participation in household decision making as key factors influencing spousal communication about HIV, while controlling for sexual behaviors of both partners as well as other individual and contextual factors. Data were obtained from the 2003 Kenya Demographic and Health Survey for 1,388 cohabiting couples. Information regarding spousal communication was self-reported, assessing whether both, either, or neither partner ever discussed HIV prevention with the other. Analyses showed higher levels of education for the female partner and participation in household decision making are positively associated with spousal communication about HIV prevention. With females' education and other factors controlled, couples with more educated male partners were more likely to have discussed HIV prevention than couples in which both partners have the same level of education. Spousal communication was also positively associated with household wealth status and exposure to the mass media, but couples in which male partners reported having nonspousal sex in the past year were less likely to have discussed HIV prevention with their spouses. Findings suggest HIV prevention programs should promote female empowerment and encourage male participation in sexual health discussion. PMID:21644167
Chiao, Chi; Mishra, Vinod; Ksobiech, Kate
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 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 HIVprevention coverage decisions, assesses possible legal grounds on which insurers may initially deny coverage for these technologies, and evaluates the extent to which these denials may survive external and judicial review. Because several of these legal grounds may be persuasive, particularly denials on the basis of medical necessity, this Article also explores alternative strategies for financing biomedical HIV prevention efforts. PMID:23356098
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.
Botulism is a severe neuroparalytic disease caused by toxins produced by several Clostridium species. Botulinum toxin has been of concern to the US military and its allies as a biowarfare weapon since World War II and, in more recent times, by the Centers for Disease Control and Prevention (CDC) as a potential bioterrorist threat to the public. The most effective means of defending against the toxin is by inducing a protective immune response through vaccination. Vaccination with an appropriate antigen will produce neutralizing antibodies that will bind to and clear toxin from the circulation before it can enter nerve cells and block neurotransmission. Immunity from botulism, however, has the disadvantage of precluding an individual from realizing the potential benefits of therapeutic botulinum toxin, if such a need were to arise. Botulinum toxin has been used in the treatment of numerous neuromuscular, autonomic, and sensory disorders since it was first approved for the management of strabismus and blepharospasm by the Food and Drug Administration (FDA) in 1989. Notwithstanding the value of the neurotoxin as a therapeutic drug, vaccines have been and will continue to be an important line of defense for those who work with the toxin (at-risk workers) and a select population of the military, law enforcement, and first responders. The first vaccine used to protect against botulinum neurotoxin was a chemically detoxified extract from Clostridium botulinum. A Pentavalent botulinum toxoid (PBT) vaccine in service today is administered under an Investigational New Drug (IND) application held by the CDC. Recombinant subunit vaccines are in development and a bivalent H(c) vaccine (rBV A/B (Pichia pastoris)) is presently being evaluated in a phase II clinical trial. This review focuses on botulism and the development of vaccines for its prevention. PMID:19837283
Smith, Leonard A
A World Health Organization (WHO) advisory committee meeting in Geneva at the end of last month approved phase III trials for HIV vaccines in developing countries. What is the justification for this decision?
John Moore; Roy Anderson
Human immunodeficiency virus (HIV) prevention programs and agencies are fighting growing rates of infection with decreasing resources. Identification of gaps in HIV prevention services can help inform prevention funding and program policies. To describe HIV prevention needs in a southern U.S. state, we conducted face-to-face interviews with prevention agencies and persons considered by others in their community to be "influential informants" of the community's HIV prevention services in a sample of counties in North Carolina. Using county as the unit of analysis (n = 10), we investigated differences in gaps by community characteristics, such as disparities in sexually transmitted disease rates. Lack of programs and problems with service program coordination/cooperation were reported frequently by rural counties. The most commonly reported barrier to meeting the needs of persons at risk for HIV was funding, followed by stigma. Findings from this study can inform local and regional planners on how to efficiently target prevention programs, including programs aimed at reducing racial and geographic disparities in sexually transmitted diseases, such as HIV. PMID:20446179
Torrone, Elizabeth A; Levandowski, Brooke A; Thomas, James C; Isler, Malika Roman; Leone, Peter A
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 purpose of this exploratory study was to examine personal characteristics, socio-environmental conditions, and motivational\\u000a factors that potentially influence HIV vaccine research community engagement. Specifically, the study identified predictive\\u000a aspects that may aid in future community program development on HIV vaccine issues. A cross-sectional survey consisting of\\u000a evaluative measures, demographics, social interaction, and health information-seeking behaviors was conducted. Participants\\u000a were
Paula M. Frew; Carlos del Rio; Sarah Clifton; Matthew Archibald; Joseph T. Hormes; Mark J. Mulligan
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.
We assessed the potential for anticipated changes in sexual risk-taking behaviour following hypothetical administration of a low-efficacy preventive HIV vaccine. We developed a survey and collected self-reported data from 158 HIV-negative volunteers in a cohort undergoing prescreening for Phase I/II HIV vaccine trials in Soweto. Overall, 22% reported they might use condoms less frequently; 9% reported that they might increase their frequency of sex with casual/anonymous partners; and 55% reported their sexual partners might want to use condoms less frequently knowing they were vaccinated. Multivariate analyses revealed that anticipated decrease in condom use was predicted by poor comprehension and by young age. Individuals may increase their risk-taking behaviour knowing that a vaccine would provide only incomplete protection against HIV transmission. In HIV vaccine trials and future vaccination programmes, education and risk-reduction counselling will be needed for vaccinated individuals and their partners, and mass media education campaigns may be necessary. PMID:23104749
Andersson, K M; Vardas, E; Niccolai, L M; Van Niekerk, R M; Mogale, M M; Holdsworth, I M; Bogoshi, M; McIntyre, J A; Gray, G E
VaxGen is developing prophylactic vaccines against HIV-1 consisting of two recombinant gp120 surface proteins from different HIV-1 strains.This profile has been selected from R&D Insight, a pharmaceutical intelligence database produced by Adis International Ltd. The bivalent vaccines [AIDSVAX B/B and AIDSVAX B/E] are being evaluated in two phase III trials. The first multicentre phase III trial of AIDSVAX B/B, was conducted principally in Canada and the US but also at some sites in the Netherlands and Puerto Rico. The trial was completed at the end of 2002. The second phase III trial is being conducted in Thailand with the AIDSVAX B/E vaccine. VaxGen announced in July 2002 that it would be delaying its Biologics License Application (BLA) for AIDSVAX until 2004 to enable the company to fulfil pre-approval manufacturing requirements. AIDSVAX is based on an earlier monovalent gp120 vaccine developed by Genentech that was shown to be safe in humans. VaxGen (formerly Genenvax) was formed as a spin-off company from Genentech with the sole purpose of developing the gp120 vaccine. VaxGen announced in July 2002 that the original License and Supply agreement with Genentech, signed in May 1997, had been amended. Under the revised agreement, Genentech maintains its right to market and sell AIDSVAX in North America, but has relinquished its options to commercialise the vaccine candidate in the rest of the world. Genentech's earlier decision to waive its option to manufacture AIDSVAX has also been formalised in this agreement. Additionally, VaxGen's royalty payments to Genentech for sales to the WHO or UN for underdeveloped nations have also been reduced by up to 50% and Genentech has extended the milestone date associated with VaxGen submitting an NDA. A $US120 million joint venture (Celltrion) has been formed between VaxGen and South Korean investors to manufacture more than 200 million doses of AIDSVAX a year. Celltrion will build and operate two biotechnology manufacturing facilities: a pilot plant in South San Francisco and a larger plant in Incheon, South Korea. VaxGen will retain a 44% interest in the new company, as well as any profit generated by the AIDS vaccine. If AIDSVAX wins regulatory approval, VaxGen is committed to purchasing a minimum of 87 million doses a year. Celltrion announced in July 2002 that it had acquired 24 acres of land in Incheon, South Korea, for the site of its major biologics manufacturing facility. The facility is scheduled to be ready for commercial operation by 2005. The US FDA granted fast-track designations to the two vaccines AIDSVAX B/B and AIDSVAX B/E in December 2002. The study volunteers included 5108 men who have sex with men and 309 at-risk women, all of whom were meant to be HIV negative when they joined the trial. During the 36-month trial, a total of seven injections were administered at months 0, 1, 6, 12, 18, 24 and 30. The ratio of vaccine to placebo recipients was 2:1. On February 24 2003, VaxGen announced that AIDSVAX B/B did not prove effective in the trials conducted in North America and Europe. The study did not show a statistically significant reduction of HIV infection within the study population as a whole, which was the primary endpoint of the trial. However, the study did show a statistically significant reduction of HIV infection in certain vaccinated groups. Trial data indicate that black and Asian volunteers appeared to produce higher levels of antibodies against HIV. White and Hispanic volunteers appeared to develop consistently lower levels of protective antibodies following vaccination. VaxGen intends to conduct additional analyses to confirm if there was a direct correlation between the level of antibodies and the prevention of infection. The company intends to continue development of the vaccine through licensure, including any studies necessary to evaluate the protective riticism in the media about the statistical analysis of the non-Caucasian data, VaxGen issued a statement on 27 February 2003 claiming that the analysis of data from the trial followed a statistica
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.
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
David K. Clarke; David Cooper; Michael A. Egan; R. Michael Hendry; Christopher L. Parks; Stephen A. Udem
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
Infants born to HIV-infected mothers are at high risk of becoming infected during gestation or the breastfeeding period. A search is thus warranted for vaccine formulations that will prevent mother-to-child HIV transmission. The LAMP\\/gag DNA chimeric vaccine encodes the HIV-1 p55gag fused to the lysosome-associated membrane protein-1 (LAMP-1) and has been shown to enhance anti-Gag antibody (Ab) and cellular immune
Paula Ordonhez Rigato; Milton Maciel; Adriana Letícia Goldoni; Orlando Guerra Piubelli; Noemia Mie Orii; Ernesto Torres Marques; Joseph Thomas August; Alberto José da Silva Duarte; Maria Notomi Sato
We report on the adverse reactions to the Bacillus Calmette-Guérin (BCG) vaccine in BCG-vaccinated children. We examined children\\u000a exposed to the vertical transmission of human immunodeficiency virus (HIV) (n?=?141), who participated in a prevention program of vertical transmission, and HIV-infected children (n?=?66) in a setting endemic for HIV and tuberculosis (TB) in Brazil from August 2000 to February 2008. No
Regina Célia de Souza Campos Fernandes; Luciana Cordeiro de Araújo; Enrique Medina-Acosta
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 multiassay 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 before 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. PMID:23764641
Brookmeyer, Ron; Laeyendecker, Oliver; Donnell, Deborah; Eshleman, Susan H
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
Despite 30 years of study, there is no HIV-1 vaccine and, until recently, there was little hope for a protective immunization. Renewed optimism in this area of research comes in part from the results of a recent vaccine trial and the use of single-cell antibody-cloning techniques that uncovered naturally arising, broad and potent HIV-1-neutralizing antibodies (bNAbs). These antibodies can protect against infection and suppress established HIV-1 infection in animal models. The finding that these antibodies develop in a fraction of infected individuals supports the idea that new approaches to vaccination might be developed by adapting the natural immune strategies or by structure-based immunogen design. Moreover, the success of passive immunotherapy in small-animal models suggests that bNAbs may become a valuable addition to the armamentarium of drugs that work against HIV-1. PMID:24031012
Klein, Florian; Mouquet, Hugo; Dosenovic, Pia; Scheid, Johannes F; Scharf, Louise; Nussenzweig, Michel C
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. PMID:23767872
Malaspina, Angela; Collins, Brenda S; Dell, Anne; Alter, Galit; Onami, Thandi M
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
From early in the HIV epidemic it was appreciated that many inflammatory markers such as neopterin and TNF-? were elevated in patients with AIDS. With the advent of modern technology able to measure a broad array of cytokines, we now know that from the earliest points of infection HIV induces a cytokine storm. This review will focus on how cytokines are disturbed in HIV infection and will explore potential therapeutic uses of cytokines. These factors can be used directly as therapy during HIV infection, either to suppress viral replication or prevent deleterious immune effects of infection, such as CD4+ T cell depletion. Cytokines also show great promise as adjuvants in the development of HIV vaccines, which would be critical for the eventual control of the epidemic. PMID:22743035
Keating, Sheila M; Jacobs, Evan S; Norris, Philip J
The 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.
Objective:To analyze the policies of isoniazid prophylaxis for human immunodeficiency virus (HIV)-infected tuberculin reactors and for\\u000a HIV-infected anergic patients with unknown tuberculin status.\\u000a \\u000a Methods:Transition-state model of clinical immune deterioration of HIV-infection over ten years, review of published data, and a survey\\u000a of AIDS experts. Outcome measures are the numbers of tuberculosis cases and deaths prevented and isoniazid toxicity cases\\u000a and
David N. Rose; Clyde B. Schechter; Henry S. Sacks
We assessed attitudes to medicines, HIV treatments and antiretroviral-based prevention in a national, online survey of 1,041 Australian gay men (88.3% HIV-negative and 11.7% HIV-positive). Multivariate analysis of variance was used to identify the effect of HIV status on attitudes. HIV-negative men disagreed with the idea that HIV drugs should be restricted to HIV-positive people. HIV-positive men agreed and HIV-negative men disagreed that taking HIV treatments was straightforward and HIV-negative men were more sceptical about whether HIV treatment or an undetectable viral load prevented HIV transmission. HIV-negative and HIV-positive men had similar attitudes to pre-exposure prophylaxis but divergent views about 'treatment as prevention'. PMID:23001412
Holt, Martin; Murphy, Dean; Callander, Denton; Ellard, Jeanne; Rosengarten, Marsha; Kippax, Susan; de Wit, John
To date, preventive care and prevention services have not been included in our conceptualization or operationalization of\\u000a prisoners’ “right to health care.” Given the potential public health impact of focusing on prevention for prisoners, however,\\u000a the time has come to examine this issue. Although not specifically a right under the Constitution, correctional systems should\\u000a be obligated to offer comprehensive HIV
We propose a set of common factors in evidence-based interventions (EBI) for HIV prevention, which cut across theoretical\\u000a models of behavior change. Three existing literatures support this agenda: (1) Common factors in psychotherapy; (2) core elements\\u000a from the Centers for Disease Control and Prevention EBIs; and (3) component analyses of EBI. To stimulate discussion among\\u000a prevention researchers, we propose a
Mary Jane Rotheram-Borus; Dallas Swendeman; Diane Flannery; Eric Rice; David M. Adamson; Barbara Ingram
The purpose of this article is to illustrate how an ecodevelopmental perspective on risk and protection can be applied to the study and prevention of unsafe sexual behavior in Hispanic immigrant adolescents. Special attention is given to culturally based ecodevelopmental risk and protective processes that may influence unsafe sexual behavior among Hispanic adolescents. Principles for designing prevention programs to offset these risks are offered on the basis of an ecodevelopmental HIV prevention program that has been developed and is currently being tested.
Pantin, Hilda; Schwartz, Seth J.; Sullivan, Summer; Prado, Guillermo; Szapocznik, Jose
This paper describes a study among HIV-negative gay men in London to examine willingness to volunteer for an HIV vaccine trial. HIV-negative gay men (n=506) were surveyed in central London gyms in February–March 2002. Information was collected on willingness to volunteer for an HIV vaccine trial, attitudes toward HIV vaccines and sexual risk behaviour. Men reporting unprotected anal intercourse (UAI)
L. Sherr; G. Bolding; J. Elford
This study examined HIV vaccine acceptability among immigrant Thai residents in Los Angeles, California. We combined a qualitative research method (focus groups) with an innovative market research method (conjoint analysis). Focus groups explored social issues, concerns, barriers and motivators associated with HIV vaccine acceptability. Conjoint analysis was used to assess preferences among eight hypothetical HIV vaccines with varying attribute profiles
Sung-Jae Lee; Ronald A. Brooks; Peter A. Newman; Danielle Seiden; Rassamee Sangthong; Naihua Duan
No form of disease prevention has had greater success than prophylactic immunization. Whereas therapeutic cancer vaccines have only marginal evidence of clinical efficacy, prophylactic vaccination against tumor- associated antigens can confer life-long pr...
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
Cash payments to improve health outcomes have been used for many years, however, their use for HIV prevention is new and the impact not yet well understood. We provide a brief background on the rationale behind using cash to improve health outcomes, review current studies completed or underway using cash for prevention of sexual transmission of HIV, and outline some key considerations on the use of cash payments to prevent HIV infections. We searched the literature for studies that implemented cash transfer programs and measured HIV or HIV-related outcomes. We identified 16 studies meeting our criteria; 10 are completed. The majority of studies have been conducted with adolescents in developing countries and payments are focused on addressing structural risk factors such as poverty. Most have seen reductions in sexual behavior and one large trial has documented a difference in HIV prevalence between young women getting cash transfers and those not. Cash transfer programs focused on changing risky sexual behaviors to reduce HIV risk suggest promise. The context in which programs are situated, the purpose of the cash transfer, and the population will all affect the impact of such programs; ongoing RCTs with HIV incidence endpoints will shed more light on the efficacy of cash payments as strategy for HIV prevention.
Pettifor, Audrey; MacPhail, Catherine; Nguyen, Nadia; Rosenberg, Molly
The International AIDS Vaccine Initiative has established a consortium to elucidate mechanisms of protection conferred by live attenuated simian immunodeficiency virus vaccines in monkeys. Here, the strategies defining key components of the protective immune response elicited by these vaccines are discussed.
Wayne C Koff; Philip R Johnson; David I Watkins; Dennis R Burton; Jeffrey D Lifson; Kim J Hasenkrug; Adrian B McDermott; Alan Schultz; Timothy J Zamb; Rosanne Boyle; Ronald C Desrosiers
The RV144 phase III clinical trial with the combination of the poxvirus vector ALVAC and the HIV gp120 protein has taught us that a vaccine against HIV/AIDS is possible but further improvements are still needed. Although the HIV protective effect of RV144 was modest (31.2%), these encouraging results reinforce the use of poxvirus vectors as HIV/AIDS vaccine candidates. In this review we focus on the prophylactic clinical studies thus far performed with the more widely studied poxvirus vectors, ALVAC, MVA, NYVAC and fowlpox expressing HIV antigens. We describe the characteristics of each vector administered either alone or in combination with other vectors, with emphasis on the immune parameters evaluated in healthy volunteers, percentage of responders and triggering of humoral and T cell responses. Some of these immunogens induced broad, polyfunctional and long-lasting CD4+ and CD8+ T cell responses to HIV-1 antigens in most volunteers, with preference for effector memory T cells, and neutralizing antibodies, immune parameters that might be relevant in protection. Finally, we consider improvements in immunogenicity of the poxvirus vectors by the selective deletion of viral immunomodulatory genes and insertion of host range genes in the poxvirus genome. Overall, the poxvirus vectors have proven to be excellent HIV/AIDS vaccine candidates, with distinct behavior among them, and the future implementation will be dictated by their optimized immune profile in clinical trials.
Elena Gomez, Carmen; Perdiguero, Beatriz; Garcia-Arriaza, Juan; Esteban, Mariano
HIV vaccine availability does not guarantee uptake. Given suboptimal uptake of highly efficacious and already accessible vaccines in the United States, low vaccine coverage in the developing world, and the expectation that initial HIV vaccines will be only partially efficacious, the public health community will face formidable challenges in disseminating U.S. Food and Drug Administration (FDA)-approved HIV vaccines. HIV/AIDS stigma, fear of vaccine- induced HIV infection, social side effects of testing HIV-positive, and mistrust of government and research present additional obstacles to HIV vaccine dissemination. Increased risk behaviors because of HIV vaccine availability can undermine the effectiveness of partially efficacious vaccines in reducing HIV incidence. HIV vaccine efficacy trials also face significant challenges in recruitment of sufficient volunteers and possible increases in risk behaviors due to trial participation. Planning and designing interventions to facilitate successful recruitment for large-scale phase 3 efficacy trials is a vital step towards U.S. FDA-approved HIV vaccines. Rather than despair in the face of momentous HIV vaccine dissemination challenges, or presume unrealistically that vaccine uptake will ensue automatically and that risk behavior increases will not occur, let us deem the estimated 10-year window to an approved HIV vaccine as an opportunity to investigate and confront these challenges. A consumer research agenda founded on social marketing principles is needed to facilitate the design of empirically-based interventions tailored to the unique needs and preferences of specific segments of consumers. Social marketing interventions may increase future HIV vaccine uptake and clinical trial participation, and mitigate increases in HIV risk behaviors. PMID:15659880
Newman, Peter A; Duan, Naihua; Rudy, Ellen T; Anton, Peter A
This research used open-ended and true-false questions to assess the preparedness of 96 ethnically diverse, economically and socially marginalized adult street drug users to consent to participate in HIV vaccine trials (HVT). Specific areas of consent vulnerability included misconceptions about: (1) the recuperative value and risk of vaccines in general; (2) the presence of the HIV virus within the vaccine and the possibility of contracting or transmitting HIV as a consequence of participation; (3) inclusion criteria and experimental blinds; and (4) distrust in the medical and research establishments. A brief HVT lesson administered to 30 participants was effective in correcting specific HVT knowledge misperceptions and increasing certain, but not all areas of HVT trust. Assessment of post-lesson responses to ethics-relevant questions provides information on respondents' attitudes toward AIDS safe behavior, research risks and benefits, monetary compensation, and willingness to participate. Implications for enhancing informed consent for HVT involving active drug users are discussed. PMID:20569151
Fisher, Celia B
This research used open-ended and true-false questions to assess the preparedness of 96 ethnically diverse, economically and socially marginalized adult street drug users to consent to participate in HIV vaccine trials (HVT). Specific areas of consent vulnerability included misconceptions about: (1) the recuperative value and risk of vaccines in general; (2) the presence of the HIV virus within the vaccine and the possibility of contracting or transmitting HIV as a consequence of participation; (3) inclusion criteria and experimental blinds; and (4) distrust in the medical and research establishments. A brief HVT lesson administered to 30 participants was effective in correcting specific HVT knowledge misperceptions and increasing certain, but not all areas of HVT trust. Assessment of post-lesson responses to ethics-relevant questions provides information on respondents' attitudes toward AIDS safe behavior, research risks and benefits, monetary compensation, and willingness to participate. Implications for enhancing informed consent for HVT involving active drug users are discussed.
Fisher, Celia B.
The purpose of this study was to explore local perceptions and experiences regarding vaccines in general and HIV vaccines and vaccine trials in the Dominican Republic. In-depth interviews were carried out with 25 participants representing two study groups: (1) individuals considered at high risk for HIV infection including female sex workers and male STI clinic attendees and (2) individuals considered
C. Barrington; L. Moreno; D. Kerrigan
... Google Bookmarks Occupational HIV Transmission and Prevention Among Health Care Workers Fast Facts Occupational transmission of HIV to ... every hour counts. Building Better Prevention Programs for Health Care Workers Continued diligence in the following areas is ...
Evaluation of: Liao H, Bonsignori M, Alam M et al. Vaccine induction of antibodies against a structurally heterogeneous site of immune pressure within HIV-1 envelope protein variable regions 1 and 2. Immunity 38, 176-186 (2013). In 2009, results from the Phase III HIV-1 vaccine clinical trial RV144 applying a prime/boost regimen with a canarypox vaccine vector ALVAC-HIV plus the AIDSVAX B/E subunit envelope vaccine conducted in Thailand were reported. The priming canarypox vector carried the HIV-1 vaccine genes gp120 linked to the transmembrane-anchoring portion of subtype B gp41, HIV-1 Gag and protease; the boosting vaccine was composed of clades B and E of HIV-1 gp120. A 31.2% vaccine efficacy could be seen in this trial, an encouraging result in HIV-1 vaccine research that had been previously plagued with little clinical efficacy. In this paper, results from tests of four monoclonal antibodies isolated from RV144 vaccinees are reported. The antibodies recognize a certain HIV-1 envelope residue (169), neutralize laboratory-adapted HIV-1 strains and mediate killing of CD4(+) cells infected with HIV-1 laboratory isolates. Crystal structure analysis suggests that the recognized HIV-1 envelope epitope can exist in different conformations. It is thought that the immune pressure elicited by the monoclonal antibodies targets a HIV-1 envelope region with variable sequence structure. PMID:23638741
A simplified version of the HIVNET prototype HIV vaccine process was developed for adolescents at risk of HIV by: (1) reducing reading level; (2) reorganizing; (3) adding illustrations; and (4) obtaining focus group feedback. Then adolescents (N?=?187) in three cities were randomly assigned to the standard or simplified version. Adolescents receiving the simplified version had significantly higher comprehension scores (80%
D. A. Murphy; D. Hoffman; G. R. Seage Iii; M. Belzer; J. Xu; S. J. Durako; M. Geiger; Aids Interventions
In the United States, the number and proportion of HIV\\/AIDS cases among black\\/African Americans continue to highlight the\\u000a need for new biomedical prevention interventions, including an HIV vaccine, microbicide, or new antiretroviral (ARV) prevention\\u000a strategies such as pre-exposure prophylaxis (PrEP) to complement existing condom usage, harm reduction methods, and behavioral\\u000a change strategies to stem the HIV epidemic. Although black\\/African Americans
Paula M. Frew; Matthew Archibald; Dazon Dixon Diallo; Su-I Hou; Takeia Horton; Kayshin Chan; Mark J. Mulligan; Carlos del Rio
Abstract Well-defined correlates of protective immunity are an essential component of rational vaccine development. Despite years of basic science and three HIV vaccine efficacy trials, correlates of immunological protection from HIV infection remain undefined. In December 2010, a meeting of scientists engaged in basic and translational work toward developing HIV-1 vaccines was convened. The goal of this meeting was to discuss current opportunities and optimal approaches for defining correlates of protection, both for ongoing and future HIV-1 vaccine candidates; specific efforts were made to engage young scientists. We discuss here the highlights from the meeting regarding the progress made and the way forward for a protective HIV-1 vaccine.
Burgers, Wendy A.; Manrique, Amapola; McKinnon, Lyle R.; Reynolds, Matthew R.; Rolland, Morgane; Blish, Catherine; Chege, Gerald K.; Curran, Rhonda; Fischer, William; Herrera, Carolina; Sather, D. Noah
This digest summarizes available information on the importance of HIV (human immunodeficiency virus) prevention education efforts for students with disabilities. The digest notes these students' increased risk of HIV infection due to their lack of knowledge, misinformation, poor social skills, low self-esteem, poor judgement, and tendency to let…
Council for Exceptional Children, Reston, VA.
Abstract Vaccination against hepatitis A is an important intervention to prevent disease in HIV-patients. There are insufficient data on the association of the response to hepatitis A vaccine with immunological parameters, including subpopulations of T-cells. We studied HIV-infected adults with CD4 T-cells>200 cells/mm(3) who received two doses of hepatitis A vaccine (Havrix or Vaqta). The counts of CD3, CD4, CD8, CD4+T-cells, NK, NK CD8+, NK CD8 - cells, and HIV RNA were measured at the time of first dose administration and one month after the end of the vaccination period. The geometric mean titer of antibodies to hepatitis A virus (anti-HAV) and factors affecting response were evaluated. 113 patients (50 antiretroviral treatment-naïve and 63 treatment-experienced) were enrolled in the study. There was no change in the immunological parameters and in the HIV-RNA post-vaccination, except for a decrease in CD8 and in double positive CD4+CD8+t-cell count. The immune response and geometric mean titer of anti-HAV were similar among treated and naïve patients (78% vs. 76% and 237?mIU/mL vs. 158?mIU/mL). Vaccine response was achieved in 71% of patients with CD4=200-499 cells/mm(3) compared with 80% of participants with CD4 ?500 cells/mm(3) (p>0.05). Logistic regression revealed that immunological cells tested do not affect response differently in treatment-naïve vs. experienced patients. The only factor affecting response is the CD4 T-cell count at vaccination (OR 1.320; 95% CI 1.052-1.656; p=0.016). Patients with CD4 T-cell count ?500 cells/mm(3) were 4.3 times more likely to respond to the vaccine than patients with CD4 T-cell count 200-499 cells/mm(3) (p=0.005). In conclusion, successful vaccination is associated with CD4 T-cells. The count of other immune cells or the administration of antiretroviral therapy does not predict response to hepatitis A vaccine in HIV patient with baseline CD4 T-cell>200 cells/mm(3). PMID:24044625
Kourkounti, Sofia; Papaizos, Vassilios; Leuow, Kirsten; Kordosis, Theodoros; Antoniou, Christina
The success of the HIV Prevention Trials Network 052 trial has led to revisions in HIV-1 treatment guidelines. Antiretroviral therapy 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 men who have sex with men and intravenous drug user 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 men who have sex with men epidemic over the last decade. High rates of coclustering of primary infections are associated with 1 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 antiretroviral therapy initiation to avert transmission cascades. PMID:23764643
Brenner, Bluma G; Wainberg, Mark A
The importance of cultural competence in social work practice is becoming increasingly more evident as the dividing lines between countries and cultures continue to fade away. Successful practice in today's global environment hinges on the ability to accept differences and to work towards a shared future. The necessity of cultural competence is painfully obvious when considering HIV prevention and care.
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
A method is proposed for computing the coverage required to prevent epidemics by age-specific vaccination schedules. The method applies in a very general setting and provides explicit expressions in many cases. It can accommodate vaccination doses administered at different ages, heterogeneity among individuals of different ages, a community structured into households, and waning of vaccine-induced immunity. A comparison of results
Niels G. Becker; Abbas Bahrampour
The role of worry, regret, and perceived risk in preventive health decisions was explored in a longitudinal questionnaire study on influenza vaccination among 428 university employees. The study yielded 3 main findings. First, ratings of anticipated worry and regret were stronger predictors of vaccination than perceived risk and mediated the effect of risk on vaccination. Second, the anticipated level of
Gretchen B. Chapman; Elliot J. Coups
Background Observational data and non-human primate challenge studies suggest that cell-mediated immune (CMI) responses may provide control of HIV replication. The Step Study is the first direct assessment of the efficacy of a CMI vaccine to protect against HIV infection or alter early plasma HIV levels in humans. Method HIV-seronegative participants (3000) were randomized (1:1) to receive 3 injections of MRKAd5 HIV-1 gag/pol/nef vaccine or placebo. Randomization was pre-stratified by gender, baseline adenovirus type 5 (Ad5) titer, and study site. Participants were tested ~every 6 months for HIV acquisition; early plasma HIV RNA was measured ~3 months post-HIV diagnosis. Findings The vaccine elicited IFN-? ELISPOT responses in 75% of vaccinees. In a pre-specified interim analysis among participants with baseline Ad5 ?200, 24 of 741 vaccinees became HIV infected, versus 21 of 762 placebo recipients. All but one infection occurred in men. The early geometric mean plasma HIV RNA was comparable in infected vaccine and placebo recipients. In exploratory multivariate analyses, HIV incidence was higher in vaccinees versus placebo recipients among Ad5 seropositive men (5.1% versus 2.2% per year, respectively) and uncircumcised men (5.2% versus 1.4% per year, respectively). HIV incidence was similar in vaccinees versus placebo recipients among Ad5 seronegative men and circumcised men. Interpretation This CMI vaccine did not prevent HIV infection or lower early viral level. Mechanisms for failure of the vaccine to protect and for the increased HIV infection rates in subgroups of vaccinees are being explored. Additional follow-up will determine if elevated HIV incidence in vaccinee subgroups persists.
Buchbinder, Susan P.; Mehrotra, Devan V.; Duerr, Ann; Fitzgerald, Daniel W.; Mogg, Robin; Li, David; Gilbert, Peter B.; Lama, Javier R.; Marmor, Michael; Rio, Carlos del; McElrath, M. Juliana; Casimiro, Danilo R.; Gottesdiener, Keith M.; Chodakewitz, Jeffrey A.; Corey, Lawrence; Robertson, Michael N.
Background The prime-boost HIV vaccine regimen used in the recent RV144 trial resulted in modest efficacy of 31% over 3.5 years, but was substantially higher in the first year post-vaccination. We sought to explore the potential impact of a vaccine with rapidly waning efficacy in a South African population. Methods We explored two strategies using a dynamic compartmental epidemic model for heterosexual transmission of HIV: (1) vaccination of a single cohort (30%, 60% or 90% of the initial population), with potential booster vaccinations at 5-year or 2-year intervals over time, and (2) vaccination of the overall population at coverage levels (30%, 60% or 90%) that are constant over time, such that individuals are vaccinated or revaccinated to maintain effective coverage levels, given the rapidly waning protection of the vaccine. We also examined potential changes in post-vaccination condom use. Results The single cohort vaccination strategies did not have a substantial impact on HIV prevalence, although without boosters they still prevented 2–6% of the expected infections at 20 years, depending on the population coverage. The 5-year and 2-year booster strategies prevented 8–24% and 17–45% of the expected infections, respectively. The continuous vaccination strategies resulted in more substantial reductions in population HIV prevalence and greater numbers of infections prevented: HIV prevalence at 20 years was reduced from 23% to 8–14% and the number of expected infections was decreased by 34–59%, depending on the population coverage level. Moderate changes in post-vaccination condom use did not substantially affect these outcomes. Conclusions An HIV vaccine with partial efficacy and declining protection similar to the RV144 vaccine could prevent a substantial proportion of HIV infections if booster vaccinations were effective and available. Our estimates of the population impact of vaccination would be improved by further understanding of the duration of protection, the effectiveness of booster vaccination, and whether the vaccine efficacy varies between subpopulations at higher and lower risk of exposure.
Andersson, Kyeen M.; Paltiel, A. David; Owens, Douglas K.
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.
Roberts, Kathleen Johnston; Newman, Peter A.; Duan, Naihua; Rudy, Ellen T.
The latest developments in the HIV vaccine field were aired at a Keystone Symposium recently. This Commentary summarizes some of the highlights from this meeting, and focuses on some of the developments that appeared particularly promising, as well as those that do not. Unfortunately, the "saga" continues.
Smith, Kendall A
|In contrast to other countries in Southeast Asia, the HIV/ AIDS epidemic is in the initial stages in Viet Nam, although the rates have increased notably since 1997. This study examined attitudes towards the use of an HIV vaccine (when one becomes available) as a means for preventing the disease. Since injecting drug users are the great majority…
African Americans experience HIV and AIDS at a rate 10 times greater than the U.S. White population. Although there have been advances in HIV risk-reduction strategies, these efforts have not been as successful in decreasing HIV infection in the African American population. This article reviews the research base of HIV prevention interventions to identify research that will lead to the
Lula A. Beatty; Darrell Wheeler; Juarlyn Gaiter
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
Potent virus-specific cytotoxic T lymphocyte (CTL) responses elicited by candidate AIDS vaccines have been shown to provide short-term control of viral replication following pathogenic viral challenges in rhesus monkeys. We have recently shown that vaccines that control rather than prevent immunodeficiency virus infections are still subject to immune escape. In particular, viral mutations can develop that result in viral escape
Dan H Barouch; Norman L Letvin
CD4(+) T cells can perform a panoply of tasks to shape an effective response against a pathogen. Limited attention has been paid to the potential importance of functional CD4(+) T cell responses in the context of the development of next-generation vaccines, including HIV vaccines. Many CD4(+) T cell functions are newly appreciated and only partially understood. A workshop was held as a forum to bring together a small group of experts to exchange ideas on the role of CD4(+) T cells in developing durable functional antibody responses, via follicular helper T cells, as well as on the roles of CD4(+) T cells in other aspects of protective immunity. Here we discuss whether CD4(+) T cell responses may represent a beneficial component of an efficacious HIV vaccine. PMID:23389614
Streeck, Hendrik; D'Souza, M Patricia; Littman, Dan R; Crotty, Shane
|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.
Participation of different community sectors, including the private business sector, is necessary to fight the HIV\\/AIDS epidemic. Local businesses may be reluctant to participate in HIV prevention because of fear of negative customer reactions and loss of revenue. This study examines the extent to which residents of two communities in San Diego, California, would support HIV prevention initiatives in local
Christina M. Phillips-Guzman; Ana P. Martinez-Donate; Melbourne F. Hovell; Elaine J. Blumberg; Carol L. Sipan; Liza S. Rovniak; Norma J. Kelley
This document presents a summary of three phases of a project looking at HIV prevention for youth in Vermont. Several questions were asked of interviewees in all three phases of this project: (1) Which HIV prevention interventions do you provide to youth? (2) Which HIV risks do you address with youth? (3) What resources would you need to improve…
Vermont Department of Education, 2005
A vaccine against human immunodeficiency virus (HIV) seems to be on the horizon. Correlates of risk of infection for [corrected] the RV144 vaccine trial have been found. There is understanding of what makes HIV envelope-specific antibodies broadly neutralizing and new T cell vaccine approaches can overcome virus variability. PMID:22513323
McMichael, Andrew J; Haynes, Barton F
Purpose To examine risk perceptions (perceived risk of HPV, perceived risk of other sexually transmitted infections (STIs), and need for safer sexual behaviors) and to determine factors associated with these risk perceptions after human papillomavirus (HPV) vaccination. Methods Data were collected at the baseline visit of an HPV-6, -11, -16, -18 vaccine clinical trial in 16- to 23-year-old HIV-infected young women (N=99). Immediately after receiving the first vaccine dose, participants completed a confidential questionnaire that included three 5-item scales measuring perceived risk of HPV, perceived risk of other STIs, and need for safer sexual behaviors. Linear and logistic regression models were used to examine associations between baseline characteristics (demographic characteristics; CD4+ count; HIV viral load; knowledge about HPV and HPV vaccines; sexual behaviors; and STI diagnosis) and each measure of risk perceptions. Results Most participants perceived themselves to be at lower risk for HPV (mean scale score 19.5/50), most perceived that they were not at lower risk for other STIs (mean 31.2/50), and the vast majority reported that there was still a need for safer sexual behaviors after vaccination (mean 43.1/50). Multivariable analyses indicated that knowledge about HPV and HPV vaccines was associated with perceived need for safer sexual behaviors (OR 1.05, 95% CI 1.0-1.1). Conclusions Although almost all young women in this study believed that safer sexual behaviors were still important after HPV vaccination, a subset believed they were at less risk for STIs other than HPV. Educational interventions are needed to prevent misperceptions and promote healthy behaviors after vaccination.
Kahn, Jessica A.; Xu, Jiahong; Zimet, Gregory D.; Liu, Nancy; Gonin, Rene; Dillard, Mary E.; Squires, Kathleen
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
There is an urgent need for a vaccine capable of preventing HIV infection or the development of HIV-related disease. A number of approaches designed to stimulate HIV-specific CD8+ cytotoxic T cell responses together with helper responses are presently under evaluation. In this phase 1, multi-center, placebo-controlled trial, we tested the ability of a novel multi-epitope peptide vaccine to elicit HIV-specific immunity. To enhance the immunogenicity of the peptide vaccine, half of the vaccine recipients received recombinant GM-CSF protein as a co-adjuvant. The vaccine was safe; tolerability was moderate, with a number of adverse events related to local injection site reactogenicity. Anti-GM-CSF antibody responses developed in the majority of GM-CSF recipients but were not associated with adverse hematologic events. The vaccine was only minimally immunogenic. Six of 80 volunteers who received vaccine developed HIV-specific responses as measured by interferon-gamma ELISPOT assay, and measurable responses were transient. This study failed to demonstrate that GM-CSF can substantially improve the overall weak immunogenicity of a multiepitope peptide-based HIV vaccine.
Spearman, Paul; Kalams, Spyros; Elizaga, Marnie; Metch, Barbara; Chiu, Ya-Lin; Allen, Mary; Weinhold, Kent J.; Ferrari, Guido; Parker, Scott D.; McElrath, M. Juliana; Frey, Sharon E.; Fuchs, Jonathan D.; Keefer, Michael C.; Lubeck, Michael D.; Egan, Michael; Braun, Ralph; Eldridge, John H.; Haynes, Barton F.; Corey, Lawrence
Rhesus macaques are an important animal model for the study of human disease and the development of vaccines against HIV and AIDS. HIV vaccines have been benchmarked in rhesus macaque preclinical challenge studies using chimeric viruses made up of parts of HIV and simian immunodeficency viruses. However, the lack of efficacy in a recent clinical trial calls for a re-evaluation
Devon J. Shedlock; Guido Silvestri; David B. Weiner
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
Adolescents worldwide are at high risk for HIV, which makes them essential candidates for HIV vaccine trials. However, enrollment of adolescents into such trials has implications for trial sites. Adolescents are considered vulnerable subjects and require proxy consent in addition to their assent, which brings issues of confidentiality and access into play. HIV vaccine trial sites often do not have
Linda-Gail Bekker; Heather Jaspan; James McIntyre; Robin Wood; Glenda Gray
Background: Underrepresentation of ethnic minority communities limits the generalizability of HIV vaccine trial results. We explored perceived barriers and motivators regarding HIV vaccine trial participation among low-socioeconomic ethnic minority respondents at risk for HIV. Methods: Six focus group interviews were conducted using a semistructured interview guide. Participants (N = 58, mean age = 36 years, 37% female, and 56% Latino\\/a
Peter A. Newman; Naihua Duan; Kathleen J. Roberts; Danielle Seiden; Ellen T. Rudy; Dallas Swendeman; Svetlana Popova
Every year, millions of American adolescents are infected with STDs, including HIV. The personal, social, and economic consequences of adolescent STD infection are substantial. Fortunately, school-based, individually-focused, and community-level educational and sexual risk reduction interventions can help prevent the spread of STDs among adolescents. However, very little is known about the economic efficiency, or cost-effectiveness, of such programs. Because funding
Steven D. Pinkerton; Heather Cecil; David R. Holtgrave
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
Text Version... 1055 1056 Centers for Disease Control and Prevention (CDC), 2010, HIV/AIDS Fact Sheet for HIV in the 1057 United States in Women, February. ... More results from www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation
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 ?g). Thus, we tested the hypothesis that doubling the number of hepatitis B vaccine injections might
David Rey; Véronique Krantz; Marialuisa Partisani; Marie-Paule Schmitt; Pierre Meyer; Eric Libbrecht; Marie-Josée Wendling; Denis Vetter; Margreet Nicolle; Georgette Kempf-Durepaire; Jean-Marie Lang
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
This paper describes a 16-month health education pilot program based on diffusion of innovation and social network theories. The program was implemented by volunteer community liaisons for the purposes of increasing awareness of and support for HIV vaccine research in minority populations. This theoretically driven pilot program allowed the liaisons to integrate delivery of the HIV vaccine research messages created for the program into their existing activities and routines. Through training in participatory engagement, volunteers were able to tailor and adapt an HIV prevention message for their communities. Process evaluation data showed that the acceptance of participatory engagement and HIV vaccine message dissemination far exceeded expectations. The anticipated number of community members to receive the message was estimated at 500 with 10 volunteer liaisons or 50 per person. However, the actual number of people reached was 644, with only 7 volunteer liaisons, or an average of 92 persons per liaison, almost double the original number. Further research is recommended to analyze the specific behavioral changes that can come from the use of social networks in HIV vaccine research awareness within minority populations.
Kelley, R. T.; Hannans, A.; Kreps, G. L.; Johnson, K.
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
Synopsis Despite more than two decades of research, an effective vaccine that can prevent HIV-1 infection in populations exposed to the virus remains elusive. In the pursuit of an HIV-1 vaccine, does prevention of exposure to maternal HIV-1 in utero, at birth or in early life through breast-milk require special consideration? In this article we will review what is known about the immune mechanisms of susceptibility and resistance to mother-to-child transmission (MTCT) of HIV-1 and will summarise studies that have used passive or active immunisation strategies to interrupt -MTCT of HIV-1. We will also describe potentially modifiable infectious co-factors that may enhance transmission and/or disease progression (especially in the developing world). Ultimately an effective prophylactic vaccine against HIV-1 infection will need to be deployed as part of the Extended Programme of Immunisation (EPI) recommended by the World Health Organisation (WHO) for use in developing countries, so it is important to understand how the infant immune system responds to HIV-1 antigens, both in natural infection and presented by candidate vaccines.
Lohman-Payne, Barb; Slyker, Jennifer; Rowland-Jones, Sarah L.
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.
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 G(M1) 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. PMID:15347807
Matoba, Nobuyuki; Magérus, Aude; Geyer, Brian C; Zhang, Yunfang; Muralidharan, Mrinalini; Alfsen, Annette; Arntzen, Charles J; Bomsel, Morgane; Mor, Tsafrir S
The invention provides immunogenic peptide sequences of the gp120 envelope protein of the human immunodeficiency virus (HIV). Epitopes from the conserved region which give rise to neutralizing antibodies are described.
K. Krohn A. Ranki
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.
More than a decade has passed since the human immunodeficiency virus (HIV) and the acquired immunodeficiency syndrome (AIDS) epidemic began; our failure to develop an effective vaccine and adequate medical treatments indicates that future research and practice must work to prevent the spread of HIV. We review the literature on the current HIV-prevention practices of primary care physicians and highlight opportunities for clinical prevention. Prevention is hindered in four ways: 1) by narrow conceptions of medical care and of the role of the physician; 2) by physicians' discomfort with discussing human sexuality and illicit drug use and their attitudes toward persons with HIV or AIDS; 3) by constraints on time and resources; and 4) by the ambiguity of HIV prevention messages. We suggest strategies to overcome these barriers, including modifications in public policy, health care delivery systems, and medical education. These strategies support a nonhierarchical physician-patient relationship, with attention to culture and values, that will help physicians to identify and work with persons at increased risk for HIV infection. PMID:7574227
Makadon, H J; Silin, J G
There is growing enthusiasm for increasing coverage of antiretroviral treatment among HIV-infected people for the purposes of preventing ongoing transmission. Treatment as prevention will face a number of barriers when implemented in real world populations, which will likely lead to the effectiveness of this strategy being lower than proposed by optimistic modelling scenarios or ideal clinical trial settings. Some settings, as part of their prevention and treatment strategies, have already attained rates of HIV testing and use of antiretroviral therapy—with high levels of viral suppression—that many countries would aspire to as targets for a treatment-as-prevention strategy. This review examines a number of these “natural experiments”, namely, British Columbia, San Francisco, France, and Australia, to provide commentary on whether treatment as prevention has worked in real world populations. This review suggests that the population-level impact of this strategy is likely to be considerably less than as inferred from ideal conditions.
Wilson, David P.
This report updates the 2012 recommendations by CDC's Advisory Committee on Immunization Practices (ACIP) regarding the use of influenza vaccines for the prevention and control of seasonal influenza (CDC. Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2012;61:613-8). Routine annual influenza vaccination is recommended for all persons aged ?6 months. For the 2013-14 influenza season, it is expected that trivalent live attenuated influenza vaccine (LAIV3) will be replaced by a quadrivalent LAIV formulation (LAIV4). Inactivated influenza vaccines (IIVs) will be available in both trivalent (IIV3) and quadrivalent (IIV4) formulations. Vaccine virus strains included in the 2013-14 U.S. trivalent influenza vaccines will be an A/California/7/2009 (H1N1)-like virus, an H3N2 virus antigenically like the cell-propagated prototype virus A/Victoria/361/2011, and a B/Massachusetts/2/2012-like virus. Quadrivalent vaccines will include an additional influenza B virus strain, a B/Brisbane/60/2008-like virus, intended to ensure that both influenza B virus antigenic lineages (Victoria and Yamagata) are included in the vaccine. This report describes recently approved vaccines, including LAIV4, IIV4, trivalent cell culture-based inactivated influenza vaccine (ccIIV3), and trivalent recombinant influenza vaccine (RIV3). No preferential recommendation is made for one influenza vaccine product over another for persons for whom more than one product is otherwise appropriate. This information is intended for vaccination providers, immunization program personnel, and public health personnel. These recommendations and other information are available at CDC's influenza website (http://www.cdc.gov/flu); any updates also will be found at this website. Vaccination and health-care providers should check the CDC influenza website periodically for additional information. PMID:24048214
A critical goal of HIV vaccine development is the identification of safe and immunogenic vectors. Recombinant vaccinia virus is a highly effective vaccine vector, with demonstrated capacity to protect animals from various viral pathogens, including rabies. Unlike many other candidate vaccine vectors, vast human experience exists with the parenteral smallpox vaccine. However, consideration of recombinant vaccinia virus as a modern
K. S. Slobod; T. D. Lockey; N. Howlett; R. V. Srinivas; S. D. Rencher; P. J. Freiden; P. C. Doherty; J. L. Hurwitz
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
Few Positive Prevention interventions have been implemented in Africa; however, greater attention is now being paid to interventions that include messages of personal responsibility or altruism that may motivate HIV-infected individuals towards HIV prevention behaviors in Africa. We conducted 47 in-depth interviews in 2004 with HIV-infected men and women purposefully sampled to represent a range of sexual activities among clients of an AIDS support organization in Uganda. Qualitative interviews were selected from a cross-sectional survey of 1092 HIV-infected men and women. Clients were interviewed about their concerns around sexual HIV transmission, feelings of responsibility and reasons for these feelings, as well as about the challenges and consequences of actions to prevent HIV transmission. The reasons they provided for their sense of prevention responsibility revolved around ethical and practical themes. Responsibility toward sexual partners was linked to the belief that conscious transmission of HIV equals murder, would cause physical and emotional harm, and would leave children orphaned. The primary reason specific to preventing HIV transmission to unborn children was the perception that they are 'innocent'. Most participants felt that HIV-infected individuals held a greater responsibility for preventing HIV transmission than did HIV-uninfected individuals. Respondents reported that their sense of responsibility lead them to reduce HIV transmission risk, encourage partner testing, disclose HIV test results, and assume an HIV/AIDS educator role. Challenges to HIV preventive behavior and altruistic intentions included: sexual desire; inconsistent condom use, especially in long term relationships; myths around condom use; fear of disclosure; gender-power dynamics; and social and financial pressure. Our finding that altruism played an important role in motivating preventive behaviors among HIV-infected persons in Uganda supports the inclusion of altruistic prevention and counseling messages within Positive Prevention interventions. PMID:19101063
King, Rachel; Lifshay, Julie; Nakayiwa, Sylvia; Katuntu, David; Lindkvist, Pille; Bunnell, Rebecca
The protection of human rights will be critical to the success of HIV vaccine trials throughout the world. A vaccine for HIV remains our best hope to control the global epidemic. In order to launch and sustain useful and successful human trials of HIV vaccines, a partnership between scientists, governments, pharmaceutical companies, and affected communities is essential. This article provides a review of some of the key issues relevant to human rights in the design, testing, and dissemination of HIV vaccines. The article gives specific examples from three countries -- Brazil, Thailand, and the United States -- which may initiate large-scale trials in the near future. PMID:10347374
Beloqui, Jorge; Chokevivat, Vichai; Collins, Chris
The Eighth International AIDS Symposium in Amsterdam, the Netherlands, provided updated scientific and programmatic information on the human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) to thousands of interested participants. As in the other scientific areas, the amount of information presented in epidemiology and prevention was overwhelming; however, the scientific progress described was steady but incremental. This commentary summarizes progress made in three selected areas that were highlighted during the meeting's scientific session and a fourth that received widespread media attention: (1) the epidemiology of HIV/AIDS in heterosexual women; (2) tuberculosis as an increasing opportunistic pathogen in HIV-infected persons; (3) prevention research, practice, and policy; and (4) preliminary reports of severe immunodeficiency in persons without evident HIV infection. In order to stem HIV transmission worldwide, a safe and effective vaccine is urgently needed. Currently, in the absence of such a vaccine, it is crucial for all of the world's communities to apply the best science-based prevention methods available.
Castro, K G; Valdiserri, R O; Curran, J W
In this paper we introduce the contributions included in the special section on community-level efforts to prevent HIV. Authors of several recent review papers have suggested that individual-level approaches to prevent the spread of HIV produce short-term changes in behavior among intervention participants. However, many HIV prevention researchers believe that changing individuals' behavior alone is insufficient to stem the tide
Robin Lin Miller; James G. Kelly
Summary Because increasing numbers of HIV vaccine candidates are being tested globally, it is essential to differentiate vaccine-from virus-induced antibodies. Most of the currently tested vaccines contain multiple viral components. As a result, many vaccine recipients give positive results in FDA-licensed HIV serodetection tests. We have identified conserved sequences in Env-gp41 and Gag-p6, which are recognized soon after infection but are not included in most HIV vaccine candidates. A new HIV serodetection assay, the HIVSELECTEST, was established that distinguishes between vaccine-induced antibodies and seroconversion due to true HIV infections. It is important to make this assay globally relevant, because many clinical trials are conducted around the world where most HIV infections are due to non-B subtype HIV-1. Therefore, the current study examined the reactivity of plasma samples from .3000 infections with diverse HIV subtypes worldwide. The HIVSELECTEST performed at .99% specificity and sensitivity. Both recent and established infections with clades A, B, C, D, E, F, G, J, and CRFs were detected. Antibodies elicited by other vaccinations or infections endemic to the clinical trial sites did not react in this assay. Therefore, HIV-SELECTEST could be an important differential diagnostic tool for HIV vaccine trials, blood banks, and population screening worldwide.
Khurana, Surender; Needham, James; Park, Susan; Mathieson, Bonnie; Busch, Michael P.; Nemo, George; Nyambi, Phillipe; Zolla-Pazner, Susan; Laal, Suman; Munlenga, Joseph; Chomba, Elwyn; Hunter, Eric; Allen, Susan; McIntyre, James; Hewlett, Indira; Lee, Sherwin; Tang, Shixing; Cowan, Elliot; Beyrer, Chris; Altfeld, Marcus; Yu, Xu G.; Tounkara, Anatole; Koita, Ousmane; Kamali, Anatoli; Nguyen, Nga; Graham, Barney S.; Todd, Deborah; Mugenyi, Peter; Anzala, Omu; Sanders, Eduard; Ketter, Nzeera; Fast, Patricia; Golding, Hana
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
Background As HIV infection continues to devastate low-income countries, efforts to search for an effective HIV vaccine are crucial. Therefore, participation in HIV vaccine trials will be useful for the development of a preventive vaccine that will work and thus reduce the global HIV epidemic. Objective The objective of this study was to analyse the willingness to volunteer (WTV) in a Phase I/II HIV vaccine trial among police officers in Dar es Salaam, Tanzania. Design We included a convenience sample of 329 participants (79% males) from sensitisation workshops that were held once at each of the 32 police stations. Participants were recruited from 23 stations which were included according to availability. Data about personal characteristics, general HIV and AIDS knowledge and sexual behaviour, attitudes towards vaccines and willingness to participate in the HIV vaccine trial were obtained through an interview-administered questionnaire with both closed and open-ended questions. Results Overall, 61% of the participants expressed WTV in HIV vaccine trials. WTV was significantly associated with: positive attitude towards use of effective vaccine, Odds ratio (OR), 36.48 (95% CI: 15.07–88.28); the intention to tell others about one's decision to participate in the trial, OR, 6.61 (95% CI: 3.89–11.24); Tanzania becoming a partner in developing the vaccine, OR, 4.28 (95% CI: 2.28–8.03); having an extra sexual partner, OR, 3.05 (95% CI: 1.63–5.69); perceived higher risk of getting HIV infection, OR, 2.11 (95% CI: 1.34–3.33); and high knowledge about HIV and AIDS, OR, 1.92 (95% CI: 1.22–3.01). Conclusion The results indicated that a majority of police officers in this study were willing to participate in HIV vaccine trials. However, there is a need to provide the respondents with precise information about the purpose of a Phase I/II HIV vaccine trial and the fact that it does not protect against HIV infection, in order to avoid increasing risky behaviour.
Tarimo, Edith A.M.; Thorson, Anna; Bakari, Muhammad; Mwami, Joachim; Sandstrom, Eric; Kulane, Asli
Novel, exciting intervention strategies to prevent infection with HIV have been tested in the past year, and the field is rapidly evolving. EUROPRISE is a network of excellence sponsored by the European Commission and concerned with a wide range of activities including integrated developmental research on HIV vaccines and microbicides from discovery to early clinical trials. A central and timely theme of the network is the development of the unique concept of co-usage of vaccines and microbicides. This review, prepared by the PhD students of the network captures much of the research ongoing between the partners. The network is in its 5th year and involves over 50 institutions from 13 European countries together with 3 industrial partners; GSK, Novartis and Sanofi-Pasteur. EUROPRISE is involved in 31 separate world-wide trials of Vaccines and Microbicides including 6 in African countries (Tanzania, Mozambique, South Africa, Kenya, Malawi, Rwanda), and is directly supporting clinical trials including MABGEL, a gp140-hsp70 conjugate trial and HIVIS, vaccine trials in Europe and Africa.
Plasmid DNA vaccines encoding HIV-1 env were used to immunize mice and nonhuman primates. Plasmids were prepared that produced either secreted gp120 or full-length gp160. Mice immunized with gp120 DNA developed strong antigen-specific antibody responses, CD8+ cytotoxic T lymphocytes (CTL) (following in vitro restimulation with gp120-derived peptide), and showed in vitro proliferation and Th1-like cytokine secretion [?-interferon, interleukin (IL)-2 with
John W. Shiver; Mary-Ellen Davies; Yasuhiro Yasutomi; Helen C. Perry; Daniel C. Freed; Norman L. Letvin; Margaret A. Liu
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 core objectives of this study were to document the process by which a community-based organization replicated and adapted an experimentally developed intervention to its own use and to explore the effectiveness of that HIV prevention program for male prostitutes and other patrons in New York City “hustler” bars. The intervention model employed was based on previous research with gay
Robin Lin Miller; David Klotz; Haftan M. Eckholdt
Feline immunodeficiency virus (FIV) discovered in 1986 is a lentivirus that causes AIDS in domestic cats. FIV is classified into five subtypes (A–E), and all subtypes and circulating intersubtype recombinants have been identified throughout the world. A commercial FIV vaccine, consisting of inactivated subtype-A and –D viruses (Fel-O-Vax FIV, Fort Dodge Animal Health), was released in the United States in 2002. The United States Department of Agriculture approved the commercial release of Fel-O-Vax FIV based on two efficacy trials using 105 laboratory cats and a major safety trial performed on 689 pet cats. The prototype and commercial FIV vaccines had broad prophylactic efficacy against global FIV subtypes and circulating intersubtype recombinants. The mechanisms of cross-subtype efficacy are attributed to FIV-specific T-cell immunity. Findings from these studies are being used to define the prophylactic epitopes needed for an HIV-1 vaccine for humans.
Yamamoto, Janet K.; Sanou, Missa P.; Abbott, Jeffrey R.; Coleman, James K.
Public health surveillance programs for vaccine preventable diseases (VPD) need functional quality assurance (QA) in order to operate with high quality activities to prevent preventable communicable diseases from spreading in the community. Having a functional QA plan can assure the performance and quality of a program without putting excessive stress on the resources. A functional QA plan acts as a
Mucosal tissues are major sites of HIV entry and initial infection. Induction of a local mucosal cytotoxic T lymphocyte response is considered an important goal in developing an effective HIV vaccine. In addition, activation and recruitment of memory CD4(+) and CD8(+) T cells in systemic lymphoid circulation to mucosal effector sites might provide the firewall needed to prevent virus spread. Therefore a vaccine that generates CD4(+) and CD8(+) responses in both mucosal and systemic tissues might be required for protection against HIV. However, optimal routes and number of vaccinations required for the generation of long lasting CD4(+) and CD8(+) CTL effector and memory responses are not well understood especially for mucosal T cells. A number of studies looking at protective immune responses against diverse mucosal pathogens have shown that mucosal vaccination is necessary to induce a compartmentalized immune response including maximum levels of mucosal high-avidity CD8(+) CTL, antigen specific mucosal antibodies titers (especially sIgA), as well as induction of innate anti-viral factors in mucosa tissue. Immune responses are detectable at mucosal sites after systemic delivery of vaccine, and prime boost regimens can amplify the magnitude of immune responses in mucosal sites and in systemic lymphoid tissues. We believe that the most optimal mucosal and systemic HIV/SIV specific protective immune responses and innate factors might best be achieved by simultaneous mucosal and systemic prime and boost vaccinations. Similar principals of vaccination may be applied for vaccine development against cancer and highly invasive pathogens that lead to chronic infection. PMID:21824096
Belyakov, I M; Ahlers, J D
We analyzed HIV viral load (VL) and CD4 count changes, and antibody responses following MMR vaccination of individuals in the U.S. Military HIV Natural History Study cohort. Cases receiving at least one dose of MMR vaccine after HIV diagnosis were matched 1:2 to HIV-positive controls not receiving the vaccine. Baseline was defined as time of vaccination for cases and indexed
Benjamin M. Stermole; Greg A. Grandits; Mollie P. Roediger; Brychan M. Clark; Anuradha Ganesan; Amy C. Weintrob; Nancy F. Crum-Cianflone; Tomas M. Ferguson; Grace E. Macalino; Michael L. Landrum
BackgroundAdenoviral based vectors remain promising vaccine platforms for use against numerous pathogens, including HIV. Recent vaccine trials utilizing Adenovirus based vaccines expressing HIV antigens confirmed induction of cellular immune responses, but these responses failed to prevent HIV infections in vaccinees. This illustrates the need to develop vaccine formulations capable of generating more potent T-cell responses to HIV antigens, such as
Daniel M. Appledorn; Yasser A. Aldhamen; William DePas; Sergey S. Seregin; Chyong-Jy J. Liu; Nathan Schuldt; Darin Quach; Dionisia Quiroga; Sarah Godbehere; Igor Zlatkin; Sungjin Kim; J. Justin McCormick; Andrea Amalfitano
Meeting the challenges of diverse cultures, numerous languages and great distances, the Northwest Territories discovered innovative ways to promote AIDS prevention. This article discusses obstacles to HIV prevention and techniques used to overcome them commonly found in health services for the NWT. For example, techniques for improved service delivery include reliance on decentralized services provided by regional health boards and Community Health Representatives. Further, the challenges posed by language diversity and cultural taboos against speaking openly about sexual matters have been partially overcome through the conversion of materials and concepts into aboriginal languages which are culturally appropriate. The article specifically discusses two AIDS education campaigns in which these techniques were utilized: namely, Health is a Community Affair Campaign (or the Door-to-Door Project) and local initiatives which hosted presentations by an Aboriginal person living with AIDS. PMID:8481873
Crown, M; Duncan, K; Hurrell, M; Ootoova, R; Tremblay, R; Yazdanmehr, S
In December 2005, the UNAIDS and WHO reported that the global epidemic known as acquired immunodeficiency syndrome (AIDS) has claimed the lives of more than 25 million adults and children over the past 26 years. These figures included an estimated 3.1 million AIDS-related deaths in 2005. Despite enormous efforts to control the spread of human immunodeficiency virus (HIV) new infection rates
David A. Hokey; David B. Weiner
Pasteurella multocida serotype B:3,4 isolated from a fallow deer in England was used as a vaccine to prevent haemorrhagic septicaemia. The deer strain was less virulent for calves than typical serotype B:2 of haemorrhagic septicaemia strains. It elicited antibodies in cattle that protected mice against serotype B:2 infection. The live deer vaccine containing 2 X 10(7) viable organisms per dose was used to immunise calves. Six months after vaccination, five of six calves were protected against serotype B:2 challenge. Two calves challenged nine months after vaccination survived the same challenge. The live vaccine was more efficacious than an alum precipitated vaccine in protecting calves against B:2 challenge. PMID:3111071
Myint, A; Carter, G R; Jones, T O
Previous modeling studies have identified the vaccination coverage level necessary for preventing influenza epidemics, but have not shown whether this critical coverage can be reached. Here we use computational modeling to determine, for the first time, whether the critical coverage for influenza can be achieved by voluntary vaccination. We construct a novel individual-level model of human cognition and behavior; individuals are characterized by two biological attributes (memory and adaptability) that they use when making vaccination decisions. We couple this model with a population-level model of influenza that includes vaccination dynamics. The coupled models allow individual-level decisions to influence influenza epidemiology and, conversely, influenza epidemiology to influence individual-level decisions. By including the effects of adaptive decision-making within an epidemic model, we can reproduce two essential characteristics of influenza epidemiology: annual variation in epidemic severity and sporadic occurrence of severe epidemics. We suggest that individual-level adaptive decision-making may be an important (previously overlooked) causal factor in driving influenza epidemiology. We find that severe epidemics cannot be prevented unless vaccination programs offer incentives. Frequency of severe epidemics could be reduced if programs provide, as an incentive to be vaccinated, several years of free vaccines to individuals who pay for one year of vaccination. Magnitude of epidemic amelioration will be determined by the number of years of free vaccination, an individuals' adaptability in decision-making, and their memory. This type of incentive program could control epidemics if individuals are very adaptable and have long-term memories. However, incentive-based programs that provide free vaccination for families could increase the frequency of severe epidemics. We conclude that incentive-based vaccination programs are necessary to control influenza, but some may be detrimental. Surprisingly, we find that individuals' memories and flexibility in adaptive decision-making can be extremely important factors in determining the success of influenza vaccination programs. Finally, we discuss the implication of our results for controlling pandemics. PMID:17480117
Vardavas, Raffaele; Breban, Romulus; Blower, Sally
HIV prevention exhaustion has occurred among MSM, with resurgence of HIV beginning in 2000 a palpable effect. A stratified snowball sample was recruited from MSM social venues including gay bars, parks, and social service agencies in order to develop targets and strategies for future prevention efforts. Three methods of data collection were used: (a) individual interviews (n = 30), (b)
Anthony P. Natale
Current efforts to prevent human immunodeficiency virus (HIV) disease, which largely focus on altering human behavior, have had some notable successes yet have failed to halt the spread of the acquired immu- nodeficiency syndrome pandemic. A greater understanding of the pathogenesis of HIV disease is providing us with the scientific rationale for additional approaches to prevention. Some of the approaches
Anthony S. Fauci
|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…
A vaccine against human immunodeficiency virus (HIV) seems to be on the horizon. Correlates of risk of infection for the RV144 trial have been found. There is understanding of what makes HIV envelope–specific antibodies broadly neutralizing and new T cell vaccine approaches can overcome virus variability.
McMichael, Andrew J; Haynes, Barton F
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 <5000 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.
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.
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
Background A safe effective and affordable HIV vaccine is the most cost effective way to prevent HIV infection worldwide. Current studies of HIV prevalence and incidence are needed to determine potentially suitable cohorts for vaccine studies. The prevalence and incidence of HIV-1 infection among the police in Dar es Salaam in 1996 were 13.8% and 19.6/1000 PYAR respectively. This study aimed at determining the current prevalence and incidence of HIV in a police cohort 10 years after a similar study was conducted. Methods Police officers in Dar es Salaam, Tanzania were prospectively enrolled into the study from 2005 and followed-up in an incidence study three years later. HIV infection was determined by two sequential enzyme linked immunosorbent assays (ELISAs) in the prevalence study and discordant results between two ELISAs were resolved by a Western blot assay. Rapid HIV assays (SD Bioline and Determine) were used for the incidence study. Results A total of 1,240 police participated in the HIV prevalence study from August 2005 to November 2008. Of these, 1101 joined the study from August 2005-September 2007 and an additional 139 were recruited between October 2007 to November 2008 while conducting the incidence study. A total of 726 (70%) out of the 1043 eligible police participated in the incidence study. The overall HIV-1 prevalence was 65/1240 (5.2%). Females had a non-statistically significant higher prevalence of HIV infection compared to males 19/253, (7.5%) vs. 46/987 (4.7%) respectively (p?=?0.07). The overall incidence of HIV-1 was 8.4 per 1000 PYAR (95% CI 4.68-14.03), and by gender was 8.8 and 6.9 per 1000 PYAR, among males and females respectively, (p?=?0.82). Conclusions The HIV prevalence and incidence among the studied police has declined over the past 10 years, and therefore this cohort is better suited for phase I/II HIV vaccine studies than for efficacy trials.
While the HIV epidemic is resurging in gay communities worldwide, HIV notification rates remain stable in NSW. This outcome demonstrates the success of a well-funded partnership approach to preventing HIV infection in gay men in NSW. However, population rates of new diagnoses of HIV are similar to those seen in comparable countries and sexual risk-taking may be increasing. As the HIV epidemic has evolved, prevention in gay men has become more complex and must effectively engage with an increasing diversity of risk reduction strategies. These strategies reflect the continual adaptation of the gay community to evolving understandings of the HIV epidemic and the diverse ways in which gay men balance pleasure and prevention. PMID:20513303
de Wit, John B F; Prestage, Garrett P; Duffin, Ian R
Background Human papillomavirus (HPV) vaccine is now approved for use in males in the United States to prevent genital warts. We conducted an experiment to see whether framing HPV vaccination as also preventing cancer in men would increase men’s vaccination willingness. Methods We conducted an online survey in January 2009 with a national sample of men aged 18–59 who self-identified as gay/bisexual (n=312) or heterosexual (n=296). In the within-subjects experiment, men read 4 randomly ordered vignettes that described hypothetical vaccines that prevented either genital warts alone, or genital warts and either anal cancer, oral cancer, or penile cancer. We analyzed data using repeated-measures analysis of variance and tested whether perceived severity or perceived likelihood mediated the effect of disease outcome framing on men’s HPV vaccination willingness Results While only 42% of men were willing to receive HPV vaccine when it was framed as preventing genital warts alone, 60% were willing to get it when it was framed as preventing cancer in addition to genital warts (p<.001). The effect of outcome framing was the same for heterosexual and gay/bisexual men and for the three cancer types examined. Perceived severity of disease partially mediated the association between disease outcome and HPV vaccination willingness. Conclusions Men may be more accepting of HPV vaccine when it is framed as preventing cancer, regardless which of the three most common HPV-related cancers in men is described. Impact Study findings may be useful in developing health communication messages that maximize HPV vaccine acceptability among young men.
McRee, Annie-Laurie; Reiter, Paul L.; Chantala, Kim; Brewer, Noel T.
A current debate in the HIV-1 vaccine field concerns the ability of an immunodeficiency virus to elicit a protective response. One argument is that HIV-1 superinfections are frequent in healthy individuals, because virus evades conventional immune surveillance, a serious obstacle to vaccine design. The opposing argument is that protection from superinfection is significant, reflecting a robust immune response that might be harnessed by vaccination to prevent disease. In an experiment designed to address the debate, two macaques received an I.V. inoculation with SHIV KU-1-d (a derivative of SHIV KU-1) and were rested for ?10 months. Infection elicited diverse neutralizing antibody activities in both animals. Animals were then exposed to SHIV 89.6P (I.V.), a virus carrying a heterologous envelope protein relative to the vaccine strain. Infection was monitored by viral load and CD4+ T-cell measurements. All control animals were infected and most succumbed to disease. In contrast, protection from superinfection was statistically significant in test monkeys; one animal showed no evidence of superinfection at any time point and the second showed evidence of virus at only one time point over a 6-month observation period. Neither animal showed signs of disease. Perhaps this protective state may serve as a ‘gold-standard’ for HIV-1 vaccine development, as a similar degree of protection against immunodeficiency virus infections in humans would be much desired.
Sealy, Robert; Zhan, Xiaoyan; Lockey, Timothy D.; Martin, Louis; Blanchard, James; Traina-Dorge, Vicki; Hurwitz, Julia L.
Background Current recommendations are that HIV-infected persons should not be given live vaccines. We set out to assess potential toxicity of three live, attenuated oral vaccines (against rotavirus, typhoid and ETEC) in a phase 1 study. Methods Two commercially available oral vaccines against rotavirus (Rotarix) and typhoid (Vivotif) and one candidate vaccine against Enterotoxigenic Escherichia coli (ACAM2017) were given to HIV seropositive (n = 42) and HIV seronegative (n = 59) adults. Gastrointestinal symptoms were sought actively by weekly interview up to 1 month of vaccination. In rotavirus vaccine recipients, intestinal biopsies were collected by endoscopy and evaluated for expression of IL-8 and pro-inflammatory cytokines. Results No difference was observed between symptoms in HIV infected and HIV uninfected vaccinees, except for diarrhoea reported more than 7 days after the last dose of vaccine. If only diarrhoea episodes within 7 days of vaccination are included, diarrhoea was not more frequent in HIV seropositive than in HIV seronegative vaccinees (OR 6.7, 95% CI 1.2–67; P = 0.09). However, if later episodes of diarrhoea are included, a significant increase in diarrhoea was demonstrated (OR 5.3, 95% CI 0.98–53; P = 0.04). All episodes were mild and transient. IL-8 was slowly up-regulated over the week following vaccination (P = 0.02), but IL-?, IFN? or TNF? were not. Conclusions No evidence was found of adverse events following administration of these three vaccines, except for late episodes of diarrhoea which may not be attributable to vaccination. Our data do not support the need for a prohibition on oral administration of live, attenuated vaccines to all HIV infected adults, though further work on severely immunocompromised adults and children are required.
Banda, Rose; Yambayamba, Vera; Lalusha, Bwalya Daka; Sinkala, Edford; Kapulu, Melissa Chola; Kelly, Paul
The acceptance of a future HIV vaccine may be influenced, in part, by the characteristics of the vaccine itself. This study evaluated the relationship of vaccine characteristics to acceptability of hypothetical HIV immunization. Subjects were 549 undergraduates (18-56 years of age); 70.3% were female, and 80.4% were non-Hispanic white. Subjects completed a self-administered questionnaire assessing a series of 12 hypothetical
A. Liau; G. D. Zimet
Prevention with Positives (PwP) is a component of the US HIV prevention strategy that targets HIV-infected persons who are aware of their seropositive status. This paper examines the use of prevention messages by clinical providers during the PwP intervention period of the US Health Resources and Services Administration's Special Projects of National Significance program. Quantitative approaches were used to learn
Carol Dawson Rose; Kimberly A. Koester; Mi-Suk Kang Dufour; Janet J. Myers; Starley B. Shade; Karen McCready; Stephen Morin
Pasteurella multocida serotype B:3,4 isolated from a fallow deer in England was used as a vaccine to prevent haemorrhagic septicaemia. The deer strain was less virulent for calves than typical serotype B:2 of haemorrhagic septicaemia strains. It elicited antibodies in cattle that protected mice against serotype B:2 infection. The live deer vaccine containing 2 X 10(7) viable organisms per dose
A Myint; GR Carter; TO Jones
Prophylactic human papillomavirus (HPV) vaccines based on intramuscular injection of non-infectious L1 virus-like particles (VLPs) are undergoing intense clinical evaluation. As documented in preceding chapters of this monograph, clinical trials of these vaccines have demonstrated their safety and high efficacy at preventing type-specific persistent cervical HPV infection and the development of type-specific cervical intraepithelial neoplasia (CIN) cervical neoplasia. There is
John T. Schiller; Denise Nardelli-Haefliger
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.
This perspective on the report by Beatty et al. in this issue of the journal (beginning on page XX) discusses the prevention of cancer through vaccination strategies that target antigens associated with tumor promotion and progression. Such approaches were first developed for treating cancer. We address cancer vaccination in the context of a mouse model of inflammatory bowel disease expressing MUC1, an epithelial mucin aberrantly expressed during chronic inflammation and in colorectal carcinogenesis, and in a broader context that includes the potential of targeting the tumor microenvironment for immunoprevention in humans. Obstacles in developing effective cancer vaccines, including antigen selection, immunoediting, and tumor-mediated immunosuppression, also are discussed.
Weiner, Louis M.; Surana, Rishi; Murray, Joseph
Advances in HIV treatment have changed the natural history of HIV disease and improved the life of infected people. But, paradoxically, the transformation of a lethal disease into a chronic condition has lead many people to pessimism regarding the future of HIV prevention. Post-exposure prophylaxis and prophylaxis of vertical transmission have added new tools, although they do not change the
Introduction: Herpes zoster (HZ) occurs as a reactivation of dormant varicella zoster virus (VZV), and occurs more frequently in the aging population or the immunocompromised due to waning cell-mediated immunity. Up to 1 million cases of HZ are reported annually in the USA with an estimated 10 - 30% of the population being affected by shingles in their lifetime. HZ is a debilitating illness, and while mortality is low, morbidity remains a significant cause for concern with prevention efforts aimed at reducing VZV reactivation and its complications. The HZ vaccine was approved by the US Food and Drug Administration for individuals aged 50-years or older. However, the Center for Disease Control and Prevention's Advisory Committee for Immunization Practices recommends the vaccine in individuals aged 60-years or older. Areas covered: Recent literature investigating the efficacy and indications of live attenuated zoster vaccine. Expert opinion: Live attenuated zoster vaccine is safe and efficacious in preventing HZ and decreasing the morbidity associated with postherpetic neuralgia. The vaccine is FDA approved in individuals aged 50-years or older but further studies are warranted to investigate the vaccine's efficacy in immunosuppressed and immunocompromised patients. PMID:23984934
Doan, Hung Q; Ung, Bothland; Ramirez-Fort, Marigdalia K; Khan, Farhan; Tyring, Stephen K
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
Neisseria meningitidis is one of the most feared infections in pediatrics as the result of its rapid progression, high fatality rate, and frequent occurrence of sequelae. The 5 major meningococcal serogroups associated with disease are A, B, C, Y, and W-135. Currently available polysaccharide vaccines are effective in preventing disease caused by serogroups A, C, Y, and W-135 in older children and adults but do not elicit good long-term protection in young children. Vaccines that protect against serogroup B disease are still in development. As with the Haemophilus influenzae type b and pneumococcal polysaccharide vaccines, conjugation of the polysaccharide vaccine to a protein carrier dramatically changes vaccine characteristics, with resulting efficacy in infants. New meningococcal conjugate vaccines against serogroups A, C, Y, and W-135 are being developed. A serogroup C conjugate vaccine has been introduced successfully into the routine childhood schedule in the United Kingdom. New meningococcal conjugate vaccines are likely to have a dramatic effect on the burden of meningococcal disease within the next decade. PMID:12199614
Soriano-Gabarró, M; Stuart, James M; Rosenstein, Nancy E
Botulism is a potentially lethal disease caused by one of seven homologous neurotoxic proteins usually produced by the bacterium, Clostridium botulinum. This neuromuscular disorder occurs through an exquisite series of molecular events, ultimately ending with the arrest of acetylcholine release and hence, flaccid paralysis. The development of vaccines that protect against botulism dates back to the 1940s. Currently, a pentavalent
Michael P Byrne; Leonard A Smith
\\u000a Injection drug use has been a major risk factor for transmission of HIV in the United States since the beginning of the HIV\\u000a epidemic (Des Jarlais & Semaan, 2008) and is a major risk factor for African Americans. While the proportion of injection\\u000a drug users (IDUs) among HIV-positive persons has decreased over time, the Centers for Disease Control and Prevention
David W. Purcell; Yuko Mizuno; Cynthia M. Lyles
Renewed enthusiasm for biomedical HIV prevention strategies has followed the recent publication of several high-profile HIV antiretroviral therapy-based HIV prevention trials. In a recent article, Roberts & Matthews (2012) accurately note some of the shortcomings of these individually targeted approaches to HIV prevention and advocate for increased emphasis on structural interventions that have more fundamental effects on the population distribution of HIV. However, they make some implicit assumptions about the extent to which structural interventions are user-independent and more sustainable than biomedical or behavioral interventions. In this article, I elaborate a simple typology of structural interventions along these two axes and suggest that they may be neither user-independent nor sustainable and therefore subject to the same sustainability concerns, costs, and potential unintended consequences as biomedical and behavioral interventions.
Tsai, Alexander C.
Background.? Vaccination provides long-term immunity to hepatitis A virus (HAV) among the general population, but there are no such data regarding vaccine durability among human immunodeficiency virus (HIV)–infected adults. Methods.? We retrospectively studied HIV-infected adults who had received 2 doses of HAV vaccine. We analyzed blood specimens taken at 1 year, 3 years, and, when available, 6–10 years postvaccination. HAV immunoglobulin G (IgG) values of ?10 mIU/mL were considered seropositive. Results.? We evaluated specimens from 130 HIV-infected adults with a median age of 35 years and a median CD4 cell count of 461 cells/mm3 at or before time of vaccination. Of these, 49% had an HIV RNA load <1000 copies/mL. Initial vaccine responses were achieved in 89% of HIV-infected adults (95% confidence interval [CI], 83%–94%), compared with 100% (95% CI, 99%–100%) of historical HIV-uninfected adults. Among initial HIV-infected responders with available specimens, 90% (104 of 116; 95% CI, 83%–95%) remained seropositive at 3 years and 85% (63 of 74; 95% CI, 75%–92%) at 6–10 years. Geometric mean concentrations (GMCs) among HIV-infected adults were 154, 111, and 64 mIU/mL at 1, 3, and 6–10 years, respectively, compared with 1734, 687, and 684 mIU/mL among HIV-uninfected persons. Higher GMCs over time among HIV-infected adults were associated with lower log10 HIV RNA levels (? = ?.12, P = .04). Conclusions.? Most adults with well-controlled HIV infections had durable seropositive responses up to 6–10 years after HAV vaccination. Suppressed HIV RNA levels are associated with durable HAV responses.
Wilkins, Kenneth; Lee, Andrew W.; Grosso, Anthony; Landrum, Michael L.; Weintrob, Amy; Ganesan, Anuradha; Maguire, Jason; Klopfer, Stephanie; Brandt, Carolyn; Bradley, William P.; Wallace, Mark R.; Agan, Brian K.
Hispanics are the fastest growing minority group in North Carolina with increasing incidence of HIV infection. Gender roles, cultural expectations, and acculturation of women may explain some of Hispanic women's risks. The perspectives of Hispanic female immigrants and community-based providers were sought to identify services they offer, understand HIV risk factors, and support the adaptation of a best-evidence HIV behavioural intervention for Hispanic women. Two sets of focus groups were conducted to explicate risks and the opportunities to reach women or couples and the feasibility to conduct HIV prevention in an acceptable manner. Salient findings were that Hispanic female immigrants lacked accurate HIV/AIDS and STI knowledge and that traditional gender roles shaped issues surrounding sexual behaviour and HIV risks, as well as condom use, partner communication, and multiple sexual partnerships. Intervention implications are discussed such as developing and adapting culturally appropriate HIV prevention interventions for Hispanics that address gender roles and partner communication.
Hernandez, Amy M.; Zule, William A.; Karg, Rhonda S.; Browne, Felicia A.; Wechsberg, Wendee M.
The British HIV Association (BHIVA) has published guidelines for immunization of HIV-infected adults. A chart review of 200 HIV-infected patients diagnosed was conducted to determine shortcomings in previous practice and determine which vaccines should routinely be given in specialist HIV clinics and which might be able to be delegated to primary care clinics. Data were collected on administration of three categories of vaccinations: (1) vaccines used in all individuals with chronic disease (pneumococcal, influenza, swine flu H1N1); (2) targeted vaccinations used in non-immune individuals with HIV who are at risk of exposure (hepatitis A and hepatitis B); (3) routine vaccines traditionally delivered to the whole population (measles/mumps/rubella [MMR], diphtheria/tetanus/pertussis and meningitis C/ACWY). Pneumococcal vaccine was delivered to 54% of eligible patients, 52% of eligible individuals completed a full hepatitis B programme of vaccination and 21% (42/200) were naturally immune; hepatitis A vaccine was delivered to 36% of eligible individuals. With increasing demands on resources, it seems likely that HIV services will have to harness resources of primary care in vaccine programmes in relation to routine vaccines. By improving communication between primary and secondary care mistakes with live vaccination decisions could be avoided; HIV services should continue to perform targeted and chronic disease vaccines, i.e. for category 1 and category 2 vaccines. PMID:22422690
Quinn, K J; McCarty, E J; Quah, S P; Emerson, C R; Donnelly, C M
... With HIV Testing May Not Help Prevent Future STDs Study saw no decrease in infection rate among ... October 22, 2013 Related MedlinePlus Pages HIV/AIDS Sexually Transmitted Diseases TUESDAY, Oct. 22 (HealthDay News) -- Contrary to what ...
Since the mid-1990s, southern African countries have been experiencing an expansion of human immunodeficiency virus type 1 (HIV-1) infection caused by HIV-1 subtype C. To facilitate the design of an HLA-based HIV vaccine, we studied the distribution of the HLA class I antigen specificities in Botswana, a southern African country with a high prevalence of HIV infection. Botswana’s highly efficient
Vladimir Novitsky; Pedro O Flores-Villanueva; Pride Chigwedere; Sarah Gaolekwe; Hermann Bussman; Gaseene Sebetso; Richard Marlink; Edmond J Yunis; Max Essex
Since the start of the HIV epidemic we have witnessed significant advances in our understanding of the impact of HIV disease worldwide. Further, breakthroughs in treatment and the rapid expansion of HIV care and treatment programs in heavily impacted countries over the past five years are potentially critical assets in a comprehensive approach to controlling the continued spread of HIV globally. A strategic approach to controlling the epidemic requires continued and comparable expansion and integration of care, treatment, and prevention programs. As every new infection involves transmission, whether vertically or horizontally, from a person already living with HIV/AIDS (PLWHA), integration of HIV prevention into HIV care settings has the potential to prevent thousands of new infections, as well as improve the lives of PLWHAs. In this paper, we highlight how to better utilize opportunities created by the antiretroviral (ARV) roll-out to achieve more effective prevention, particularly in Sub Saharan Africa. We offer specific recommendations for action in the domains of healthcare policy and practice in order to better utilize the advances in HIV treatment to advance HIV prevention.
Remien, Robert H.; Berkman, Alan; Myer, Landon; Bastos, Francisco I.; Kagee, Ashraf; El-Sadr, Wafaa
We examined the uptake of rotavirus vaccine and its effectiveness in preventing acute gastroenteritis (AGE) in the community. Data on rotavirus vaccines purchases and AGE were extracted from the computerized database of a large health maintenance organization in Israel. The incidence of AGE requiring a physician visit during 2008–09 rotavirus season among vaccinated and non-vaccinated children were compared, and vaccine
Khitam Muhsen; Gabriel Chodick; Sophy Goren; Varda Shalev; Dani Cohen
The Centers for Disease Control and Prevention (CDC), in coordination with 65 states, cities, and territories, implemented HIV prevention community planning beginning in 1994. This large scale innovation in public health planning has involved tens of thousands of professionals and community residents. Though a single case study, Michigan provides a strong test of the implementation of this national prevention planning
James W. Dearing; R. Sam Larson; Liisa M. Randall; Randall S. Pope
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
Hepatitis E virus (HEV) is a major cause of illness and of death in the developing world and disproportionate cause of deaths among pregnant women. Although HEV vaccine trials, including trials conducted in populations in southern Asia, have shown candidate vaccines to be effective and well-tolerated, these vaccines have not yet been produced or made available to susceptible populations. Surveillance data collected during 2001–2007 from >110,000 pregnancies in a population of ?650,000 women in rural Bangladesh suggest that acute hepatitis, most of it likely hepatitis E, is responsible for ?9.8% of pregnancy-associated deaths. If these numbers are representative of southern Asia, as many as 10,500 maternal deaths each year in this region alone may be attributable to hepatitis E and could be prevented by using existing vaccines.
Sikder, Shegufta S.; Krain, Lisa J.; West, Keith P.; Christian, Parul; Rashid, Mahbubur; Nelson, Kenrad E.
Shedding of live vaccine virus, comparative safety, and influenza-specific antibody responses after administration of live attenuated and inactivated trivalent influenza vaccines to HIV-infected children.
HIV-infected children (N=243), >or=5 to <18 years old, receiving stable antiretroviral therapy, were stratified by immunologic status and randomly assigned to receive intranasal live attenuated influenza vaccine (LAIV) or intramuscular trivalent inactivated influenza vaccine (TIV). The safety profile after LAIV or TIV closely resembled the previously reported tolerability to these vaccines in children without HIV infection. Post-vaccination hemagglutination inhibition (HAI) antibody responses and shedding of LAIV virus were also similar, regardless of immunological stratum, to antibody responses and shedding previously reported for children without HIV infection. LAIV should be further evaluated for a role in immunizing HIV-infected children. PMID:18597900
Levin, Myron J; Song, Lin-Ye; Fenton, Terrence; Nachman, Sharon; Patterson, Julie; Walker, Robert; Kemble, George; Allende, Maria; Hultquist, Micki; Yi, Tingting; Nowak, Barbara; Weinberg, Adriana
Shedding of Live Vaccine Virus, Comparative Safety, and Influenza-Specific Antibody Responses after Administration of Live Attenuated and Inactivated Trivalent Influenza Vaccines to HIV-Infected Children
HIV-infected children (n = 243), ?5 to <18 years old, receiving stable antiretroviral therapy, were stratified by immunologic status and randomly assigned to receive intranasal live attenuated influenza vaccine (LAIV) or intramuscular trivalent inactivated influenza vaccine (TIV). The safety profile after LAIV or TIV closely resembled the previously reported tolerability to these vaccines in children without HIV infection. Post-vaccination hemagglutination inhibition (HAI) antibody responses and shedding of LAIV virus were also similar, regardless of immunological stratum, to antibody responses and shedding previously reported for children without HIV infection. LAIV should be further evaluated for a role in immunizing HIV-infected children.
Levin, Myron J.; Song, Lin-Ye; Fenton, Terrence; Nachman, Sharon; Patterson, Julie; Walker, Robert; Kemble, George; Allende, Maria; Hultquist, Micki; Yi, Tingting; Nowak, Barbara; Weinberg, Adriana
Dissemination of evidence-based HIV prevention programs for adolescents will be increased if community interventionists are\\u000a able to distinguish core, essential program elements from optional, discretionary ones. We selected five successful adolescent\\u000a HIV prevention programs, used a qualitative coding method to identify common processes described in the procedural manuals,\\u000a and then compared the programs. Nineteen common processes were categorized as structural
Barbara L. Ingram; Diane Flannery; Amy Elkavich; Mary Jane Rotheram-Borus
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.
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). PMID:23667386
Fisher, William A; Kohut, Taylor; Fisher, Jeffrey D
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.
ABSTRACT: Clinical and epidemiologic research has identified increasingly effective interventions to reduce mother to child HIV transmission in resource-limited settings These scientific breakthroughs have been implemented in some programmes, although much remains to be done to improve coverage and quality of these programmes. But prevention of HIV transmission is not enough. It is necessary also to consider ways to improve
Louise Kuhn; Moses Sinkala; Don M Thea; Chipepo Kankasa; Grace M Aldrovandi
The incidence of HIV infection has increased to alarming proportions among minority youth, in particular among young men who\\u000a have sex with men and among teenage girls. The unique socioeconomic, behavioral, and emotional vulnerability of adolescents\\u000a for sexually transmitted diseases, including HIV, requires early identification of HIV infection for linkage to care. Differences\\u000a in the clinical and psychosocial presentations of
Hans M. L. Spiegel; Donna C. Futterman
Background To explore Bacillus Calmette-Guérin vaccine (BCG) as a protective factor against tuberculosis (TB) and how human immunodeficiency virus (HIV) infection modifies the effect of BCG on TB. Methods Two matched case-control studies were conducted. One study compared TB cases and controls who were HIV positive. The second compared TB cases and controls who were HIV negative. The study population
María Patricia Arbeláez; Kenrad E Nelson; Alvaro Muñoz
Mkr intention is first to present a brief survey of other countries that employ BCG vaccine in the prevention of tuberculosis, with examples of results obtained; then to explain the procedure adopted in the country where it has proved most successful, namely, Sweden; and finally to touch on the need and advisability for application of the method in ]~ire. Wherever
D. Stopford Price; C. Singer; G. G. Coulton; A. L. Fisher; A. Castiglioni; Helen Waddell
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
Background Live-attenuated influenza vaccine (LAIV) prevents more cases of influenza in immune-competent children than the trivalent inactivated vaccine (TIV). We compared the antibody responses to LAIV or TIV in HIV-infected children. Methods Blood and saliva obtained at enrollment, 4 and 24 weeks post-immunization (wpi) from 243 HIV-infected children randomly assigned to TIV or LAIV were analyzed. Results Both vaccines increased the anti-influenza neutralizing antibodies at 4 and 24 wpi. At 4 wpi, TIV recipients had 2- to 3-fold higher neutralizing antibody titers than LAIV recipients, but the proportions of subjects with protective titers (?1:40) were similar between treatment groups (96% to 100% for influenza A and 81% to 88% for influenza B). Both vaccines increased salivary homotypic IgG antibodies, but not IgA antibodies. Both vaccines also increased serum heterosubtypic antibodies. Among HIV-specific characteristics, the baseline viral load correlated best with the antibody responses to either vaccine. We used LAIV-virus shedding as a surrogate of influenza infection. Influenza-specific humoral and mucosal antibody levels were significantly higher in non-shedders than in shedders. Conclusions LAIV and TIV generated homotypic and heterosubtypic humoral and mucosal antibody responses in HIV-infected children. High titers of humoral or mucosal antibodies correlated with protection against viral shedding.
Weinberg, Adriana; Song, Lin-Ye; Walker, Robert; Allende, Maria; Fenton, Terence; Patterson-Bartlett, Julie; Nachman, Sharon; Kemble, George; Yi, Ting-Ting; Defechereux, Patricia; Wara, Diane; Read, Jennifer S.; Levin, Myron
Little is known about the factors that govern the level of HIV-1 replication in infected individuals. Recent studies (using potent antiviral drugs) of the kinetics of HIV-1 replication in vivo have demonstrated that steady-state levels of viremia are sustained by continuous rounds of de novo infection and the associated rapid turnover of CD4+ T lymphocytes. However, no information is available concerning the biologic variables that determine the size of the pool of T cells that are susceptible to virus infection or the amount of virus produced from infected cells. Furthermore, it is not known whether all CD4+ T lymphocytes are equally susceptible to HIV-1 infection at a given time or whether the infection is focused on cells of a particular state of activation or antigenic specificity. Although HIV-1 replication in culture is known to be greatly facilitated by T cell activation, the ability of specific antigenic stimulation to augment HIV-1 replication in vivo has not been studied. We sought to determine whether vaccination of HIV-1-infected adults leads to activation of virus replication and the targeting of vaccine antigen- responsive T cells for virus infection and destruction. Should T cell activation resulting from exposure to environmental antigens prove to be an important determinant of the steady-state levels of HIV-1 replication in vivo and lead to the preferential loss of specific populations of CD4+ T lymphocytes, it would have significant implications for our understanding of and therapeutic strategies for HIV-1 disease. To begin to address these issues, HIV-1-infected individuals and uninfected controls were studied by measurement of immune responses to influenza antigens and quantitation of virion- associated plasma HIV-1 RNA levels at baseline and at intervals after immunization with the trivalent influenza vaccine. Influenza vaccination resulted in readily demonstrable but transient increases in plasma HIV-1 RNA levels, indicative of activation of viral replication, in HIV-1-infected individuals with preserved ability to immunologically respond to vaccine antigens. Activation of HIV-1 replication by vaccination was more often seen and of greater magnitude in individuals who displayed a T cell proliferative response to vaccine antigens at baseline and in those who mounted a significant serologic response after vaccination. The fold increase in viremia, as well as the rates of increase of HIV-1 in plasma after vaccination and rates of viral decline after peak viremia, were higher in individuals with higher CD4+ T cell counts.(ABSTRACT TRUNCATED AT 400 WORDS)
Background Local HIV epidemiology data are critical in determining the suitability of a population for HIV vaccine efficacy trials. The objective of this study was to estimate the prevalence and incidence of, and determine risk factors for HIV transmission in a rural community-based HIV vaccine preparedness cohort in Masaka, Uganda. Methods Between February and July 2004, we conducted a house-to-house HIV sero-prevalence survey among consenting individuals aged 18–60 years. Participants were interviewed, counseled and asked to provide blood for HIV testing. We then enrolled the HIV uninfected participants in a 2-year HIV sero-incidence study. Medical evaluations, HIV counseling and testing, and sample collection for laboratory analysis were done quarterly. Sexual risk behaviour data was collected every 6 months. Results The HIV point prevalence was 11.2%, and was higher among women than men (12.9% vs. 8.6%, P?=?0.007). Risk factors associated with prevalent HIV infection for men were age <25 years (aOR?=?0.05, 95% CI 0.01–0.35) and reported genital ulcer disease in the past year (aOR?=?2.17, 95% CI 1.23–3.83). Among women, being unmarried (aOR?=?2.59, 95% CI 1.75–3.83) and reported genital ulcer disease in the past year (aOR?=?2.40, 95% CI 1.64–3.51) were associated with prevalent HIV infection. Twenty-one seroconversions were recorded over 2025.8 person-years, an annual HIV incidence of 1.04% (95% CI: 0.68–1.59). The only significant risk factor for incident HIV infection was being unmarried (aRR?=?3.44, 95% CI 1.43–8.28). Cohort retention after 2 years was 87%. Conclusions We found a high prevalence but low incidence of HIV in this cohort. HIV vaccine efficacy trials in this population may not be feasible due to the large sample sizes that would be required. HIV vaccine preparatory efforts in this setting should include identification of higher risk populations.
Ruzagira, Eugene; Wandiembe, Symon; Abaasa, Andrew; Levin, Jonathan; Bwanika, Agnes; Bahemuka, Ubaldo; Price, Matthew A.; Kamali, Anatoli
The HIV Prevention Trials Network (HPTN) is supported by the NIH to conduct randomized clinical trials to assess the efficacy of HIV prevention strategies and technologies to reduce HIV transmission between adults. A special focus of attention is on the use of antiretroviral drugs to prevent HIV transmission, both by reducing infectiousness among HIV-infected persons taking combination antiretroviral therapy (cART) and also by reducing susceptibility among HIV-uninfected persons taking antiretrovirals for pre-exposure prophylaxis. Studies may be developmental in nature to assess novel ideas for interventions or for assessing trial feasibility. However, pivotal efficacy trials to test HIV-specific prevention strategies and technologies are the main HPTN priority. Examples include a major protocol investigating the impact of expanded testing and linkage to care on HIV surveillance indicators in the USA (HPTN 065). Another protocol is addressing similar issues while also investigating how combinations of prevention approaches are best deployed to make a community-level impact in southern Africa (HPTN 071). HPTN 068 is evaluating a novel conditional cash transfer structural intervention to increase school completion rates in young girls and thereby reduce their HIV risk. Studies outside the US address the epidemic in most at-risk populations and include an assessment of opiate agonist therapy to reduce risk of HIV seroconversion among injection drug users (HTPN 058), methods to increase HIV testing rates (HTPN 043), as well as methods for reducing high-risk behaviors, and increasing adherence to cART in HIV-infected individuals (HPTN 062 and HPTN 063, respectively). The recent HPTN 052 study demonstrated that a 96% reduction in HIV transmission could be achieved between serodiscordant sexual partners by providing the infected partners with cART at a CD4+ cell count (350–550/µl) above the level that would usually qualify them for therapy in low- and middle-income countries. The immediate relevance to public health policy showcased in these trials is a paradigm for the HPTN: design and conduct of clinical trials using available licensed tools that can be rapidly translated for implementation (‘Prevention NOW!’).
Sista, Nirupama Deshmane; Abdool Karim, Quarraisha; Hinson, Kathy; Donnell, Deborah; Eshleman, Susan H; Vermund, Sten H
Community research into women's experiences in the indoor commercial sex industry illustrated an urgent need for sexually transmitted infection (STI) and HIV education, prevention, testing, and treatment and culturally appropriate services to support the sexual and reproductive health of commercial sex workers (CSWs). This work also revealed that a high number of immigrant--primarily Asian--women are involved in the indoor sex industry. In response, the authors developed a community-academic research partnership to design and implement a blended outreach research program to provide STI and HIV prevention interventions for indoor CSWs and their clients. This Community Health Worker Model HIV Prevention and Health Promotion Program incorporated health education, primary care referrals, STI testing using self-swab techniques, and a point-of-care HIV screening test. Here the authors report on program implementation, design, and the experiences of participants and team members and provide research and vaccination recommendations for future work in this area. This work work affirms that community-based service providers can be a key entry point for indoor CSWs to access health care and sexual health promotion and education and may be a solution to missed opportunities to provide culturally and contextually appropriate education and services to this population. PMID:22885289
Bungay, Vicky; Kolar, Kat; Thindal, Soni; Remple, Valencia P; Johnston, Caitlin L; Ogilvie, Gina
Since the announcement of the STEP trial results in the past months, we have heard many sober pronouncements on the possibility of an HIV vaccine. On the other hand, optimistic quotations have been liberally used, from Shakespeare's Henry V's \\
Stanley A Plotkin
OBJECTIVE: This study examines whether men-who-have-sex-with-men (MSM) and transgender (TG) persons' attitudes, beliefs, and risk perceptions toward human immunodeficiency virus (HIV) vaccine research have been altered as a result of the negative findings from a phase 2B HIV vaccine study. DESIGN: We conducted a cross-sectional survey among MSM and TG persons (N = 176) recruited from community settings in Atlanta from 2007 to 2008. The first group was recruited during an active phase 2B HIV vaccine trial in which a candidate vaccine was being evaluated (the "Step Study"), and the second group was recruited after product futility was widely reported in the media. METHODS: Descriptive statistics, t tests, and chi-square tests were conducted to ascertain differences between the groups, and ordinal logistic regressions examined the influences of the above-mentioned factors on a critical outcome, future HIV vaccine study participation. The ordinal regression outcomes evaluated the influences on disinclination, neutrality, and inclination to study participation. RESULTS: Behavioral outcomes such as future recruitment, event attendance, study promotion, and community mobilization did not reveal any differences in participants' intentions between the groups. However, we observed greater interest in HIV vaccine study screening (t = 1.07, P < 0.05) and enrollment (t = 1.15, P < 0.05) following negative vaccine findings. Means on perceptions, attitudes, and beliefs did not differ between the groups. Before this development, only beliefs exhibited a strong relationship on the enrollment intention (? = 2.166, P = 0.002). However, the effect disappeared following negative trial results, with the positive assessment of the study-site perceptions being the only significant contributing factor on enrollment intentions (? = 1.369, P = 0.011). CONCLUSION: Findings show greater enrollment intention among this population in the wake of negative efficacy findings from the Step Study. The resolve of this community to find an HIV vaccine is evident. Moreover, any exposure to information disseminated in the public arena did not appear to negatively influence the potential for future participation in HIV vaccine studies among this population. The results suggest that subsequent studies testing candidate vaccines could be conducted in this population. PMID:21152413
Frew, Paula M; Mulligan, Mark J; Hou, Su-I; Chan, Kayshin; del Rio, Carlos
Adolescents continue to be at high risk for HIV infection, with young men who have sex with men and youth with drug abuse and/or mental health problems at particularly high risk. Multiple factors may interact to confer risk for these youth. Engaging vulnerable youth in HIV prevention research can present unique challenges in the areas of enrollment, retention, and trial adherence. Examples of successful engagement with vulnerable youth offer encouraging evidence for the feasibility of including these youth in clinical trials. Ethical challenges must be taken into consideration before embarking on biomedical HIV prevention studies with vulnerable youth, especially in the global context. Given the many individual and contextual factors that contribute to their high-risk status, it is essential that vulnerable youth populations be included in HIV prevention clinical research studies. PMID:20571422
Borek, Nicolette; Allison, Susannah; Cáceres, Carlos F
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
Eliciting a broadly neutralizing polyclonal antibody response against HIV-1 remains a major challenge. One approach to vaccine development is prevention of HIV-1 entry into cells by blocking the fusion of viral and cell membranes. More specifically, our goal is to elicit neutralizing antibodies that target a transient viral entry intermediate (the prehairpin intermediate) formed by the HIV-1 gp41 protein. Because this intermediate is transient, a stable mimetic is required to elicit an immune response. Previously, a series of engineered peptides was used to select a mAb (denoted D5) that binds to the surface of the gp41 prehairpin intermediate, as demonstrated by x-ray crystallographic studies. D5 inhibits the replication of HIV-1 clinical isolates, providing proof-of-principle for this vaccine approach. Here, we describe a series of peptide mimetics of the gp41 prehairpin intermediate designed to permit a systematic analysis of the immune response generated in animals. To improve the chances of detecting weak neutralizing polyclonal responses, two strategies were employed in the initial screening: use of a neutralization-hypersensitive virus and concentration of the IgG fraction from immunized animal sera. This allowed incremental improvements through iterative cycles of design, which led to vaccine candidates capable of generating a polyclonal antibody response, detectable in unfractionated sera, that neutralize tier 1 HIV-1 and simian HIV primary isolates in vitro. Our findings serve as a starting point for the design of more potent immunogens to elicit a broadly neutralizing response against the gp41 prehairpin intermediate.
Bianchi, Elisabetta; Joyce, Joseph G.; Miller, Michael D.; Finnefrock, Adam C.; Liang, Xiaoping; Finotto, Marco; Ingallinella, Paolo; McKenna, Philip; Citron, Michael; Ottinger, Elizabeth; Hepler, Robert W.; Hrin, Renee; Nahas, Deborah; Wu, Chengwei; Montefiori, David; Shiver, John W.; Pessi, Antonello; Kim, Peter S.
Although some HIV prevention programs have been successful in helping gay and bisexual men change their sexual behaviors, rates of HIV infection continue to increase. In an attempt to address this problem, social workers need to move beyond traditional HIV prevention approaches to a psychosocial model of HIV prevention. Based on the work of previous researchers, this approach assumes that
Edward J. Alessi
BACKGROUND: In South Africa, HIV prevalence among youth aged 15-24 is among the world's highest. Given the urgent need to identify effective HIV prevention approaches, this review assesses the evidence base for youth HIV prevention in South Africa. METHODS: Systematic, analytical review of HIV prevention interventions targeting youth in South Africa since 2000. Critical assessment of interventions in 4 domains:
Abigail Harrison; Marie-Louise Newell; John Imrie; Graeme Hoddinott
We explore the pentapeptide overlapping between human immunodeficiency virus (HIV) proteins and the human proteome. Our intent was to define viral peptides to be used in vaccines effective against different HIV strains, vaccines that are able to overcome the difficulties posed by the tendency of HIV to mutate, and that are also exempt from harmful collateral cross-reactions, as well as being repeatedly administrable to the global population. Analysis of HIV-1 envelope glycoprotein 160 (Env gp160) sequences revealed a set of 15 pentapeptides highly conserved among a number of retroviral sequences, and absent in the human proteome, thus representing unique molecular retroviral signatures. Use of these short viral peptide modules may represent the first concrete step toward the goal of a universal, safe and effective anti-HIV vaccine.
Lucchese, Guglielmo; Stufano, Angela
For the development of human immunodeficiency virus type 1 (HIV-1) vaccines, traditional approaches inducing virus-neutralizing antibodies have so far failed. Thus the effort is now focused on elicitation of cellular immunity. We are currently testing in clinical trials in the United Kingdom and East Africa a T-cell vaccine consisting of HIV-1 clade A Gag-derived immunogen HIVA delivered in a prime-boost
J P Nkolola; EG-T Wee; E-J Im; C P Jewell; N Chen; X-N Xu; A J McMichael; T Hanke
Trial participation in the proposed HIV Vaccine Trials in South Africa is discussed in the context of the ethical tension that exists between international ethical research standards and local standards of care and cultural norms in the Third World. The important concepts of informed consent, risk-benefit ratio and fair treatment of trial participants are interpreted differently in traditional, rural African communities, where a moderate form of communitarianism referred to as "Ubuntu" or "communalism" is still prevalent. Research is an altruistic endeavor that benefits communities and societies as a result of risks taken by individuals. Universal ethical guidelines that are highly individualistic and fail to emphasize communalism may represent serious problems for the sort of research needed in Africa today. PMID:11961697
We used the simian immunodeficiency virus mac251 (SIVmac251) macaque model to study the effect of the dose of mucosal exposure on vaccine efficacy. We immunized macaques with a DNA prime followed by SIV gp120 protein immunization with ALVAC-SIV and gp120 in alum, and we challenged them with SIVmac251 at either a single high dose or at two repeated low-dose exposures to a 10-fold-lower dose. Infection was neither prevented nor modified following a single high-dose challenge of the immunized macaques. However, two exposures to a 10-fold-lower dose resulted in protection from SIVmac251 acquisition in 3 out of 12 macaques. The remaining animals that were infected had a modulated pathogenesis, significant downregulation of interferon responsive genes, and upregulation of genes involved in B- and T-cell responses. Thus, the choice of the experimental model greatly influences the vaccine efficacy of vaccines for human immunodeficiency virus (HIV).
Vaccari, Monica; Keele, Brandon F.; Bosinger, Steven E.; Doster, Melvin N.; Ma, Zhong-Min; Pollara, Justin; Hryniewicz, Anna; Ferrari, Guido; Guan, Yongjun; Forthal, Donald N.; Venzon, David; Fenizia, Claudio; Morgan, Tia; Montefiori, David; Lifson, Jeffrey D.; Miller, Chris J.; Silvestri, Guido; Rosati, Margherita; Felber, Barbara K.; Pavlakis, George N.; Tartaglia, James
Actively engaging communities in effective partnerships is considered critical for ethically robust and locally relevant HIV prevention research. This can be challenging in developing countries that have little prior experience in this area. This paper summarizes processes and lessons learnt while setting up the Community Involvement Plan of National AIDS Research Institute, Pune, India. Formal partnerships were established with voluntary agencies. The focus was on using strategies adapted from participatory learning and action techniques. The community program was implemented through peer educators specifically identified from the communities where partner non-governmental organizations function. At the grass root level, peer educators imparted education to the common people about research studies and helped to implement community based recruitment and retention activities. The focus was on facilitating periodic interaction between the outreach workers of the research team and the peers and modifying the strategies till they were found locally implementable and appropriate. Through adequate time investment, mutually beneficial and respectful partnerships with community based organizations and grass root level workers, the community became actively involved in clinical research. The program helped in developing a sense of partnership among the peers for the research conducted by the research organization, widening the net of community education and identification of research participants. By building trust in the community and implementing research within an ethical framework, culturally sensitive matters were appropriately addressed. The community involvement process is long, laborious and ever-evolving. Effective community engagement requires institutional leadership support, adequate funding and commitment by researchers. It is possible to sustain such a model in a resource limited setting.
Sahay, Seema; Mehendale, Sanjay
ObjectivesAs no single HIV prevention program has eliminated HIV transmission, there is growing interest in the effectiveness of “combined” prevention programming. To compare HIV infection among persons injecting in the initial programs environment (IPE) in New York City (self-initiated risk reduction, methadone, education\\/outreach, and HIV testing) to HIV infection among persons injecting in a combined programs environment (CPE) (above programs
Don C. Des Jarlais; Kamyar Arasteh; Courtney McKnight; Holly Hagan; David C. Perlman; Lucia V. Torian; Sara Beatice; Salaam Semaan; Samuel R. Friedman
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
OBJECTIVES:: For the last twenty years the idea of alternative prevention strategies based on the use of topical vaginally products to inhibit HIV-1 infection in women has been established. The concept of a "microbicide" product has been born out of the unavailability of a vaccine against HIV-1 and the problems of women to negotiate the use of preventive prophylaxis by their partners, especially in developing countries. DESIGN:: We have developed and evaluated polyanionic carbosilane dendrimers G3-S16 and G2-NF16 with sulphated and naphthylsulfonated end groups as non-specific microbicides. METHODS:: Cellular in vitro or in vivo models were used to evaluate the safety, biocompatibility and anti-HIV ability of two polyanionic carbosilane dendrimers. RESULTS:: Both dendrimers showed high biosafety in human epithelial cell lines derived from uterus and vagina and in primary blood human cells (PBMC). These dendrimers not only have a partial capacity to block the entry of different X4 and R5 HIV-1 isolates inside epithelial cells but protect the epithelial monolayer from cell disruption and also reduce HIV-1 infection of activated PBMC. Additionally, treatment of epithelial cells with G3-S16 or G2-NF16 dendrimers did not produce changes in proinflammatory cytokines profile, in proliferation of PBMC, on microbiota or sperm survival. Finally, no irritation or vaginal lesions were detected in female CD1(ICR) mice after dendrimers vaginal administration. CONCLUSIONS:: These interesting results suggest that G3-S16 or G2-NF16 could be effective to inhibit HIV infection and transmission within genital mucosa as well as spread of HIV transmission to human PBMC. PMID:23435291
Córdoba, Enrique Vacas; Arnaiz, Eduardo; Relloso, Miguel; Sánchez-Torres, Carlos; García, Federico; Pérez-Álvarez, Lucía; Gómez, Rafael; de la Mata, Francisco J; Pion, Marjorie; Muñoz-Fernández, M Angeles
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; São Paulo, Brazil; and Dakar, Senegal. Data were collected before and after campaign implementation through population-based household surveys. Using linear regression techniques, our evaluation examined the effects of campaign exposure on interpersonal communication about HIV and the effects of campaign exposure and interpersonal communication on beliefs about HIV prevention. We found a consistent positive effect of exposure on interpersonal communication across all sites, though there were differences among sites with regard to whom the respondent talked about HIV. We also found a consistent positive effect of exposure on HIV prevention beliefs across sites when interpersonal communication was simultaneously entered into the model. Finally, in two sites we found a relationship between interpersonal communication and HIV prevention beliefs, controlling for exposure, though again, the effects differed by the type of person the communication was with. These similar findings in three diverse sites provide ecological validity of the findings that "Staying Alive" promoted interpersonal communication and influenced young people's beliefs about HIV prevention in a positive way, evidence for the potential of a global media campaign to have an impact on social norms. PMID:17411389
Geary, Cynthia Waszak; Burke, Holly McClain; Castelnau, Laure; Neupane, Shailes; Sall, Yacine Ba; Wong, Emily; Tucker, Heidi Toms
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
In 1991, the Center for AIDS Prevention Studies (CAPS) at the University of California, San Francisco, set out to develop a model of community collaborative research that would bring the skills of science to the service of HIV prevention and the knowledge of service providers into the domain of research. Essential elements of the model were training for community-based organizations
Katherine Haynes Sanstad; Ron Stall; Ellen Goldstein; Wendy Everett; Ruth Brousseau
The essay reflects practically and pragmatically the discourse regarding HIV/AIDS prevention in the light of current challenges. The authors argue that the potential for future quality improvement of prevention activities lies within the principles of "best practice" developed and approved during recent years. These principles are presented in an overview and discussed in detail. PMID:17387441
Amort, F M; Kuderna, C
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
Using insights from studies on social and cultural aspects of immunization in Africa and Asia the paper discusses the introduction of a HIV vaccine from three perspectives. Firstly, it shows how at the side of public health programs local differences will impact on the introduction of a new vaccine. Secondly, it elaborates how at the side of the users of
P. H. Streefland
The main research question in this article is how access to information about HIV/AIDS and level of HIV/AIDS prevention related knowledge are distributed among disabled people, and whether level of knowledge predicts access to HIV/AIDS related services. A survey was carried out among a sample of 285 disabled people from three provinces in South Africa. Analyses of the data revealed that gender and level of education, together with geographical differences, are key predictors for access to information and knowledge about HIV/AIDS among disabled people. For male respondents number of information sources predicts access to voluntary counselling and testing services and HIV testing, while knowledge about prevention predicts access to Voluntary Counselling and Testing centres. Significant gender differences with regards to information, knowledge and access to services highlight the need for gender specific prevention strategies among disabled people. PMID:21711179
Eide, Arne Henning; Schür, Clare; Ranchod, Chitra; Rohleder, Poul; Swartz, Leslie; Schneider, Marguerite
Staphylococcus aureus is a ubiquitous bacterial species that causes serious disease in a minority of carriers, particularly in hospital settings. S. aureus disease is difficult to treat, and antibiotic-resistant strains have become common. Prevention of S. aureus disease would therefore be the best way to limit the morbidity and mortality caused by this organism, but its virulence is determined by a number of different factors, making design of a widely effective vaccine difficult. Here, various S. aureus virulence factors and attempts to develop vaccines or other protective drugs based on these factors are reviewed. In particular, the results of a Phase III clinical study of a vaccine directed at capsular polysaccharides types 5 and 8 are discussed. PMID:16221068
Shinefield, Henry R; Black, Steven
Thirty five homosexual men (17 positive for antibody to the human immunodeficiency virus (HIV) and 18 consistently negative) were vaccinated against hepatitis B virus infection. Eight of the 17 seropositive patients failed to develop detectable hepatitis B surface antibody within three months of the third injection compared with only one of the 18 seronegative patients (p less than 0.01). HIV
C A Carne; I V Weller; J Waite; M Briggs; F Pearce; M W Adler; R S Tedder
The sustained effort towards developing an antibody vaccine against HIV\\/AIDS has provided much of our understanding of viral immunology. It is generally accepted that one of the main barriers to antibody neutralization of HIV is the array of protective structural carbohydrates that covers the antigens on the virus's surface. Intriguingly, however, recent findings suggest that these carbohydrates, which have evolved
Christopher N. Scanlan; John Offer; Nicole Zitzmann; Raymond A. Dwek
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,
P. A. Newman; M. R. Woodford; C. Logie
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,
P. A. Newman; M. R. Woodford; C. Logie
Genetic studies report the existence of a mutant allele ?32 of CCR5 chemokine receptor gene at high allele frequencies (?10%) in Caucasian populations. The presence of this allele is believed to provide partial or full resistance to HIV. In this study, we look at the impact of education, temporarily effective vaccines and therapies on the dynamics of HIV in homosexually
Sara Del Valle; Arlene Morales Evangelista; Maria Cristina Velasco; Christopher M. Kribs-Zaleta; Shu-Fang Hsu Schmitz
Since the discovery of AIDS in 1981, the global spread of HIV has reached pandemic proportions, representing a global developmental and public health threat. The development of a safe, globally effective and affordable HIV vaccine offers the best hope for the future control of the pandemic. Significant progress has been made over the past years in the areas of basic
Marc P. Girard; Saladin K. Osmanov; Marie Paule Kieny
Anecdotal information suggests many pediatricians are reluctant to immunize children who are infected with human immunodeficiency virus (HIV) because they fear the vaccines could cause severe reactions or accelerate HIV-related diseases. The study examine...
An understanding of men’s motivations to avoid risk behavior is needed to create efficacious HIV prevention programs for HIV-positive\\u000a men who have sex with men (MSM). This study investigates the relationship between sexual risk behavior and HIV prevention\\u000a altruism, which is defined as the values, motivations, and practices of caretaking towards one’s sexual partners to prevent\\u000a the transmission of HIV.
Brennan L. O’Dell; B. R. Simon Rosser; Michael H. Miner; Scott M. Jacoby
The first experimental immunization of humans against the AIDS retrovirus, HIV-1, was started in a series of HIV seronegative, healthy volunteers in November 19861. For the primary vaccination recombinant vaccinia virus (V25)2 expressing the complete gp160 env protein3 of the HTLV-IIIB strain4,5 of HIV-1 was introduced by scarification. This elicited a weak primary response which we subseqently attempted to enhance
Daniel Zagury; Jacky Bernard; Remi Cheynier; Isabelle Desportes; Regine Leonard; Michelle Fouchard; Brigitte Reveil; Daniele Ittele; Zirimwabagangabo Lurhuma; Kalumbu Mbayo; Justin Wane; Jean-Jacques Salaun; Bernard Goussard; Loic Dechazal; Arsene Burny; Peter Nara; Robert C. Gallo
BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) has infected more than 40 million people worldwide, mainly in sub-Saharan Africa. The high prevalence of HIV-1 subtype C in southern Africa necessitates the development of cheap, effective vaccines. One means of production is the use of plants, for which a number of different techniques have been successfully developed. HIV-1 Pr55Gag is a
Ann Meyers; Ereck Chakauya; Enid Shephard; Fiona L Tanzer; James Maclean; Alisson Lynch; Anna-Lise Williamson; Edward P Rybicki
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
...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...
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.
|Describes some developmental foundations for HIV counseling. Asserts that, in both formal sessions and moments of opportunity, educators, clinicians, and counselors can use the counseling relationship to promote healthy behavior change. This clinical process depends on careful self-appraisal, good counseling skills, and responsiveness to the…
Craig, Donald H.; And Others
Human papillomavirus (HPV) is a common sexually transmitted pathogen. Although most anogenital HPV infections resolve within several years, persistent infection may lead to neoplasia of the cervix, vagina, vulva, anus, and penis, and also genital warts. High-risk HPV types 16 and 18 are known to cause approximately 70% of all cervical cancers, and low-risk HPV types 6 and 11 are the main causes of genital warts. Prophylactic HPV vaccines have the potential to block the acquisition of HPV and hence subsequent development of anogenital neoplasia. Results from several clinical trials have demonstrated that the HPV L1 virus-like-particle vaccines are safe and highly immunogenic. These trials have documented a 100% vaccine efficacy in prevention of persistent HPV infection and, more important, of HPV-associated anogenital neoplasia in per-protocol analyses. Widespread vaccination of sexually naïve preadolescent children could substantially reduce the morbidity and mortality associated with anogenital malignancies. Furthermore, such a primary prevention program would also reduce healthcare costs. PMID:16729555
Ferris, Daron G
One of the fastest growing segments of the population infected with HIV is the nation's youths. Thus, prevention in this high-risk population is vital. The authors detail the process of adapting an evidence-based HIV\\/AIDS educational program (HIVEd) to the unique needs of high-risk youths in adjudicated and detained facilities and alternative high schools. The HIVEd program derives from St. Lawrence's
Georgia N. L. J. Polacek; Jennifer Coker; Kayan L. Lewis; Monica Minter; Verónica Villela-Perez; Anthony A. Scott
All too often in reviews of HIV prevention needs, the role of drugs is summarily dismissed, especially in contexts where the\\u000a heterosexual epidemic is the primary mode of transmission. Substance use and abuse, particularly injection drug use, play\\u000a a paramount role in maintaining the heterosexual spread of HIV, as well as in maintaining epidemics where heterosexual spread\\u000a of the infection
David D. Celentano
Global policy on HIV prevention among marginalised populations recommends a community-based approach with participation and mobilisation as central features. The overall aim is to empower individuals and groups to reduce their vulnerability to HIV. Community empowerment initiatives have had mixed results, however, in spite of utilising very similar peer-education based intervention strategies. This is particularly true of community-based interventions in
Catrin Evans; Helen Lambert
Each interpersonally delivered, evidence-based (EB) program for HIV prevention shares common features that aim to shift HIV\\u000a risk behaviors. We used qualitative research methods to examine manuals from five EB programs for adolescents and identified\\u000a 10 core principles embedded in each program’s activities. Principles reflect the stated goals and anticipated lessons in an activity. The principles were: Believe in your
Mary Jane Rotheram-Borus; Barbara L. Ingram; Dallas Swendeman; Diane Flannery
The success of antiretroviral therapies for prevention of mother-to-child transmission of HIV in the developed world has prompted\\u000a a wide array of research efforts, from improved implementation of voluntary counseling and testing programs to innovative\\u000a approaches for short-course peripartum prophylaxis to understanding the dynamics of HIV transmission via breastfeeding. Clinical\\u000a trials of modified short-course peripartum regimens which are applicable to
Mary A. Vogler
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.
We describe murine monoclonal antibodies (mAbs) raised by immunization with an electrophilic gp120 analog (E-gp120) expressing the rare ability to neutralize genetically heterologous human immunodeficiency virus (HIV) strains. Unlike gp120, E-gp120 formed covalent oligomers. The reactivity of gp120 and E-gp120 with mAbs to reference neutralizing epitopes was markedly different, indicating their divergent structures. Epitope mapping with synthetic peptides and electrophilic peptide analogs indicated binary recognition of two distinct gp120 regions by anti-E-gp120 mAbs, the 421-433 and 288-306 peptide regions. Univalent Fab and single chain Fv fragments expressed the ability to recognize both peptides. X-ray crystallography of an anti-E-gp120 Fab fragment revealed two neighboring cavities, the typical antigen-binding cavity formed by the complementarity determining regions (CDRs) and another cavity dominated by antibody heavy chain variable (VH) domain framework (FR) residues. Substitution of the FR cavity VH Lys-19 residue by an Ala residue resulted in attenuated binding of the 421-433 region peptide probe. The CDRs and VH FR replacement/silent mutation ratios exceeded the ratio for a random mutation process, suggesting adaptive development of both putative binding sites. All mAbs studied were derived from VH1 family genes, suggesting biased recruitment of the V gene germ line repertoire by E-gp120. The conserved 421-433 region of gp120 is essential for HIV binding to host CD4 receptors. This region is recognized weakly by the FR of antibodies produced without exposure to HIV, but it usually fails to induce adaptive synthesis of neutralizing antibodies. We present models accounting for improved CD4-binding site recognition and broad HIV neutralizing activity of the mAbs, long sought goals in HIV vaccine development.
Nishiyama, Yasuhiro; Planque, Stephanie; Mitsuda, Yukie; Nitti, Giovanni; Taguchi, Hiroaki; Jin, Lei; Symersky, Jindrich; Boivin, Stephane; Sienczyk, Marcin; Salas, Maria; Hanson, Carl V.; Paul, Sudhir; (Texas-MED); (Viral Rickettsial)
The HIV epidemic in the United States has affected at least two generations of gay men. Despite numerous efforts to intervene on this public health crisis, HIV infections continue to escalate, especially among young men. This condition is compounded by an ever-growing number of gay men who are aging and living with HIV. We must enact an innovative and proactive vision and framework for HIV prevention that moves us beyond the undertakings rooted in social-cognitive paradigms that have informed this work for the past 25 years. A new framework for HIV prevention must give voice to gay men; must consider the totality of their lives; must delineate the underlying logic, which directs their relation to sex and HIV; and must concurrently respect their diverse life experiences. This approach should be rooted in a biopsychosocial paradigm, should be informed by both theory and practice, and should be directed by three theoretical lenses--a theory of syndemics, developmental theories, and contextual understandings of HIV disease. Taken together, these elements are a call to action for research and practice psychologists who are working to improve the lives of gay men. PMID:21058777
Halkitis, Perry N
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
We evaluated the impact of a nurse program for hepatitis B virus vaccination in a center from the Swiss HIV Cohort Study. Immunity (anti-HBs >10 IU/mL) increased from 32% to 76% in the intervention center (n = 238) where vaccine management was endorsed by nurses, but only from 33% to 39% in control centers (n = 2712, P < 0.001) where management remained in charge of physicians. Immunity against HBV in the HIV population is insufficient in Switzerland. Specific nurse vaccination program may efficiently improve health care. PMID:21963937
Boillat Blanco, Noémie; Probst, Arnold; Da Costa, Vreneli Waelti; Giulieri, Stefano; Bernasconi, Enos; Calmy, Alexandra; Elzi, Luigia; Rauch, Andri; Weber, Rainer; Bertisch, Barbara; Cavassini, Matthias; Bochud, Pierre-Yves
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. PMID:23090677
Metch, Barbara; Frank, Ian; Novak, Richard; Swann, Edith; Metzger, David; Morgan, Cecilia; Lucy, Debbie; Dunbar, Debora; Graham, Parrie; Madenwald, Tamra; Escamilia, Gina; Koblin, Beryl
Human immunodeficiency virus (HIV)-infected patients often fail to produce protective antibodies to hepatitis B virus (HBV) vaccine. Some reports have suggested that increased-dose vaccination improves immune response to HBV vaccine in HIV-infected patients. To assess the efficacy of increased-dose HBV vaccination in HIV-infected patients, a systematic review of the literature and meta-analysis of clinical trials was conducted. We only included trials that compared the response rate at completion of HBV vaccine schedules in patients who had increased-dose HBV vaccine courses with controls (standard-dose HBV vaccine vaccination schedule). The fixed-effects model, with heterogeneity and sensitivity analyses, was used in this study. We identified five studies involving 883 HIV-positive vaccine recipients. Pooling of study results showed a significant increase in response rates among high-dose patients versus control patients; the pooled odds ratio (OR) was 1.96 (95% confidence interval [CI]: 1.47; 2.61). Four out of five identified studies included only vaccine-naive patients. The overall OR was 1.82 (95% CI: 1.35-2.47). No study heterogeneity was found. Our meta-analysis showed that increasing the dosage of vaccine may significantly improve immune responses in HIV-infected patients. PMID:23467291
Ni, J D; Xiong, Y Z; Wang, X J; Xiu, L C
Neutralizing antibody induction is a key feature of many effective vaccines and is the only immune response that has proven to be capable of completely blocking AIDS virus infection in animal models. Unfortunately, the extensive genetic variability and complex immune-evasion strategies of HIV-1 have thwarted all attempts to date at eliciting an effective neutralizing antibody response with candidate HIV-1 vaccine immunogens. Recent advances in our understanding of how these evasion strategies operate, coupled with growing progress in unravelling the structure and immunobiology of the viral envelope glycoproteins, are contributing to novel immunogen designs to overcome the many barriers to inducing protective antibodies against HIV-1.
Haynes, Barton F; Montefiori, David C
Therapeutic immunization of HIV-1-infected individuals with or without anti-retroviral therapy is a new promising disease prevention. To induce a new cytotoxic T(CD8) lymphocyte (CTL) immunity during chronic HIV-1 infection 15 infrequently targeted but conserved HLA-supertype binding CTL epitopes from Gag, Pol, Nef, Env, Vpu and Vif were identified. The 15 T(CD8) and three T(CD4) helper peptides were GMP synthesised and formulated with a new adjuvant CAF01 which is a synthetic two-component liposomic adjuvant comprising the quaternary ammonium dimethyl-dioctadecyl-ammonium (DDA) and the immune modulator trehalose 6,6'-dibehenate (TDB). Using IFN-? ELISPOT assay, T-cell immune induction by the vaccine was found to both CD4 and CD8 T-cell restricted peptides in HLA-A2 transgenic mice. Comprehensive toxicity studies of the CAF01 adjuvant-alone and together with different vaccines showed that CAF01 when tested at human dose levels was safe and well tolerated with only local inflammation at the site of injection and no systemic reactions. No pharmacological safety issues were observed in Beagle dogs. The HIV-1 vaccine toxicity study in the Göttingen Minipig(®) showed no systemic toxicity from five repetitive i.m. injections, each with a 2-week interval, of either the 18 HIV-1 peptide antigen solution (AFO18) or the AFO18-CAF01, in which the 18 HIV-1 peptides were formulated with the CAF01 adjuvant. Distinct inflammatory responses were observed in the injected muscles of the AFO18-CAF01 vaccine treated animals as a result of the immune stimulating effect of the adjuvant on the vaccine. The results of the toxicity studies provide optimism for phase I clinical trials evaluating the therapeutic HIV-1 T-cell vaccination approach using multiple subdominant minimal epitope peptides applying the novel cationic adjuvant CAF01. PMID:21767590
Fomsgaard, Anders; Karlsson, Ingrid; Gram, Gregers; Schou, Christian; Tang, Sheila; Bang, Peter; Kromann, Ingrid; Andersen, Peter; Andreasen, Lars Vibe
Background We conducted a double-blind, randomized, placebo-controlled Phase I study of a recombinant replication-defective adenovirus type 5 (rAd5) vector expressing HIV-1 Gag and Pol from subtype B and Env from subtypes A, B and C, given alone or as boost following a DNA plasmid vaccine expressing the same HIV-1 proteins plus Nef, in 114 healthy HIV-uninfected African adults. Methodology/Principal Findings Volunteers were randomized to 4 groups receiving the rAd5 vaccine intramuscularly at dosage levels of 1×1010 or 1×1011 particle units (PU) either alone or as boost following 3 injections of the DNA vaccine given at 4 mg/dose intramuscularly by needle-free injection using Biojector® 2000. Safety and immunogenicity were evaluated for 12 months. Both vaccines were well-tolerated. Overall, 62% and 86% of vaccine recipients in the rAd5 alone and DNA prime - rAd5 boost groups, respectively, responded to the HIV-1 proteins by an interferon-gamma (IFN-?) ELISPOT. The frequency of immune responses was independent of rAd5 dosage levels. The highest frequency of responses after rAd5 alone was detected at 6 weeks; after DNA prime - rAd5 boost, at 6 months (end of study). At baseline, neutralizing antibodies against Ad5 were present in 81% of volunteers; the distribution was similar across the 4 groups. Pre-existing immunity to Ad5 did not appear to have a significant impact on reactogenicity or immune response rates to HIV antigens by IFN-? ELISPOT. Binding antibodies against Env were detected in up to 100% recipients of DNA prime - rAd5 boost. One volunteer acquired HIV infection after the study ended, two years after receipt of rAd5 alone. Conclusions/Significance The HIV-1 rAd5 vaccine, either alone or as a boost following HIV-1 DNA vaccine, was well-tolerated and immunogenic in African adults. DNA priming increased the frequency and magnitude of cellular and humoral immune responses, but there was no effect of rAd5 dosage on immunogenicity endpoints. Trial Registration ClinicalTrials.gov NCT00124007
Allen, Susan; Than, Soe; Adams, Elizabeth M.; Graham, Barney S.; Koup, Richard A.; Bailer, Robert T.; Smith, Carol; Dally, Len; Tarragona-Fiol, Tony; Bergin, Philip J.; Hayes, Peter; Ho, Martin; Loughran, Kelley; Komaroff, Wendy; Stevens, Gwynneth; Thomson, Helen; Boaz, Mark J.; Cox, Josephine H.; Schmidt, Claudia; Gilmour, Jill; Nabel, Gary J.; Fast, Patricia
Children and adolescents infected with HIV typically have a lower response to immunization than do those in the general population. In most developed countries, meningococcal serogroup C conjugate vaccine is one of the recommended vaccines for such individuals. However, there have been no studies evaluating the antibody response to this vaccine in HIV-infected children, adolescents or young adults. In this study, we evaluated that response using serum bactericidal antibody (SBA) and enzyme-linked immunosorbent assay, comparing HIV-infected with non-HIV-infected patients, as well as analysing the occurrence of side effects. In non-responders, we assessed the antibody response to revaccination. This clinical trial involved 92 patients between 10 and 20 years of age: 43 HIV-infected patients (HIV+ group) and 49 non-HIV-infected patients (HIV- group). After one dose of the vaccine, 72.1% of the HIV+ group patients and 100% of the HIV- group patients were considered protected. Of the HIV+ group patients who received a second dose of the vaccine, only 40% acquired protection. Overall, 81.4% of the HIV+ group patients acquired protection (after one or two doses of the vaccine). Side effects occurred in 16.3% and 44% of the HIV+ group and HIV- group patients, respectively. Therefore, the meningococcal serogroup C conjugate vaccine proved to be safe and effective for use in HIV-infected children, adolescents, and young adults, although their antibody response was weaker than that shown by non-HIV-infected patients. This indicates the need to discuss changes to the immunization schedule for children, adolescents, and young adults infected with HIV, in order to ensure more effective protection against meningococcal disease. PMID:22771509
Bertolini, Daniela Vinhas; Costa, Luciana Scarlazzari; van der Heijden, Inneke Marie; Sato, Helena Keiko; Marques, Heloísa Helena de Sousa
Human papillomavirus (HPV) is a significant source of morbidity and mortality throughout the world and is the most common\\u000a sexually transmitted infection in the United States. HPV is the primary etiologic agent of cervical cancer and dysplasia.\\u000a Thus, cervical cancer and other HPV-associated malignancies might be prevented or treated by HPV vaccines. Recent research\\u000a on the safety and efficacy of
Bradley J. Monk; Ali Mahdavi
The impetus for, and efforts in the past 20 years toward a women-initiated method for preventing sexual transmission of HIV has been previously well described. To date, four classes of topical agents categorized by mechanism of action as: surfactants, buffers, cell entry blockers and antiretroviral agents have undergone advanced clinical testing. Thus far, only coitally linked use of 1% tenofovir gel has demonstrated moderate effectiveness in preventing HIV and HSV-2 infection and has generated renewed hope for microbicide development. Studies of new antiviral agents, novel delivery mechanisms and combination/multipurpose products that address challenges of adherence and enhance the effectiveness of tenofovir gel are already underway to further enhance sexual and reproductive health needs of men and women and efforts to prevent HIV infection. PMID:23428099
Karim, Quarraisha Abdool; Baxter, Cheryl
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.
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.
Adolescents worldwide are at high risk for HIV, which makes them essential candidates for HIV vaccine trials. However, enrollment of adolescents into such trials has implications for trial sites. Adolescents are considered vulnerable subjects and require proxy consent in addition to their assent, which brings issues of confidentiality and access into play. HIV vaccine trial sites often do not have experience recruiting and retaining adolescents, and creating youth-friendly environments that are comfortable for guardians. This includes development of education materials that target both youth and their parents. Because these trials are of minimal individual benefit, sites will likely need to provide service in the form of health care and supportive structures to adolescents. Finally, a number of trial design options exist, and researchers will need to balance the risks and benefits of each, as for all issues surrounding the involvement of adolescents in HIV vaccine trials. PMID:16533798
Bekker, Linda-Gail; Jaspan, Heather; McIntyre, James; Wood, Robin; Gray, Glenda
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
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.
Biomedical research is critical to identifying effective and safe interventions, such as vaccines, microbicides, male circumcision and antiretrovirals, for prevention. Funding for clinical prevention trials is highly competitive and the benchmarks of success ultimately reduce to quickly enrolling a select group of people at risk, keeping them enrolled, and inducing them to be compliant with trial requirements - all at the lowest cost possible. Juxtaposed with this reality is the fact that HIV is situated with poverty, exploitation, assaults on human dignity, and human rights abuses. The result is a complex web of ethical challenges that are socially constructed along lines of wealth and power. While social science research methods are commonly employed to examine such topics, they have played a marginal role in biomedical HIV prevention research. Why? To answer this question, a core set of persistent interlocking social, behavioural and ethical challenges to biomedical HIV prevention research are described. A critique is offered on how the social has been framed relative to the behavioural, ethical and biomedical components. Examples of how this framing has devalued social knowledge are provided, including the conflation of qualitative research with anecdotal reporting, a bias toward brevity and accuracy over external validity, and difficulties in distinguishing between a moral understanding of social norms and achieving a moral outcome when confronted with ethical challenges in research. Lastly, opportunities are identified for enhancing the success of biomedical HIV prevention research through development of a coherent programme of social science research. Recommendations are offered for reframing the social as a valid domain of scientific inquiry in this highly applied and interdisciplinary context. PMID:21968079
MacQueen, Kathleen M
Biomedical research is critical to identifying effective and safe interventions, such as vaccines, microbicides, male circumcision and antiretrovirals, for prevention. Funding for clinical prevention trials is highly competitive and the benchmarks of success ultimately reduce to quickly enrolling a select group of people at risk, keeping them enrolled, and inducing them to be compliant with trial requirements - all at the lowest cost possible. Juxtaposed with this reality is the fact that HIV is situated with poverty, exploitation, assaults on human dignity, and human rights abuses. The result is a complex web of ethical challenges that are socially constructed along lines of wealth and power. While social science research methods are commonly employed to examine such topics, they have played a marginal role in biomedical HIV prevention research. Why? To answer this question, a core set of persistent interlocking social, behavioural and ethical challenges to biomedical HIV prevention research are described. A critique is offered on how the social has been framed relative to the behavioural, ethical and biomedical components. Examples of how this framing has devalued social knowledge are provided, including the conflation of qualitative research with anecdotal reporting, a bias toward brevity and accuracy over external validity, and difficulties in distinguishing between a moral understanding of social norms and achieving a moral outcome when confronted with ethical challenges in research. Lastly, opportunities are identified for enhancing the success of biomedical HIV prevention research through development of a coherent programme of social science research. Recommendations are offered for reframing the social as a valid domain of scientific inquiry in this highly applied and interdisciplinary context.
Results from several observational studies of HIV-discordant couples and a randomized controlled trial (HIV Prevention Trials Network 052) show that antiretroviral therapy (ART) can greatly reduce heterosexual HIV transmission in stable HIV-discordant couples. However, such data do not prove that ART will reduce HIV incidence at the population level. Observational investigations using ecological measures have been used to support the
M. Kumi Smith; Kimberly A. Powers; Kathryn E. Muessig; William C. Miller; Myron S. Cohen
Summary The promise of combination HIV prevention—the application of multiple HIV prevention interventions to maximize population-level impact—has never been greater. However, to succeed in achieving significant reductions in HIV incidence, an additional concept needs to be considered—combination implementation. Combination implementation for HIV prevention is defined here as the pragmatic, localized application of evidence-based strategies to realize high sustained uptake and quality of HIV prevention interventions. This review explores diverse implementation strategies including HIV testing and counseling models, task shifting, linkage to and retention in care, antiretroviral therapy support, behavior change, demand creation, and structural interventions and discusses how they could be used in the provision of HIV prevention interventions such as medical male circumcision and treatment as prevention. Only through careful consideration of how to implement and operationalize HIV prevention interventions will the HIV community be able to move from clinical trial evidence to population-level impact.
Chang, Larry W; Serwadda, David; Quinn, Thomas C; Wawer, Maria J; Gray, Ronald H; Reynolds, Steven J
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 anti-retroviral drug discovery and development, Vol 85, issue 1, 2010. PMID:19874851
Buckheit, Robert W; Watson, Karen M; Morrow, Kathleen M; Ham, Anthony S
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.
Objective Controversy surrounds the linkage of prevention counseling with emergency department (ED)–based HIV testing. Further, the effectiveness and feasibility of prevention counseling in the ED setting is unknown. We investigate these issues by conducting a preliminarily exploration of several related aspects of our ED's HIV prevention counseling and testing program. Methods Our urban, academic ED provides formal client-centered prevention counseling in conjunction with HIV testing. Five descriptive, exploratory observations were conducted, involving surveys and analysis of electronic medical records and programmatic data focused on (1) patient perception and feasibility of prevention counseling in the ED, (2) patient perceptions of the need to link prevention counseling with testing, and (3) potential effectiveness of providing prevention counseling in conjunction with ED-based HIV testing. Results Of 110 ED patients surveyed after prevention counseling and testing, 98% believed privacy was adequate, and 97% reported that their questions were answered. Patients stated that counseling would lead to improved health (80%), behavioral changes (72%), follow-up testing (77%), and discussion with partners (74%). However, 89% would accept testing without counseling, 32% were willing to seek counseling elsewhere, and 26% preferred not to receive the counseling. Correct responses to a 16-question knowledge quiz increased by 1.6 after counseling (95% confidence interval 1.3 to 12.0). The program completed counseling for 97% of patients tested; however, 6% of patients had difficulty recalling the encounter and 13% denied received testing. Among patients undergoing repeated testing, there was no consistent change in self-reported risk behaviors. Conclusion Participants in the ED prevention counseling and testing program considered counseling acceptable and useful, though not required. Given adequate resources, prevention counseling can be provided in the ED, but it is unlikely that all patients benefit.
Sitlinger, Andrea P.; Lindsell, Christopher J.; Ruffner, Andrew H.; Wayne, D. Beth; Hart, Kimberly W.; Trott, Alexander T.; Fichtenbaum, Carl J.; Lyons, Michael S.
Background HIV-infected youth are at risk of hepatitis B (HBV) infection and should be vaccinated. Previous reports suggest reduced response to standard HBV vaccine regimens. Methods HIV-infected youth, age 12 to <25 years, were randomly assigned to one of three treatment arms: Arm 1: Engerix B®, 20 mcg HBsAg; Arm 2: Engerix B®, 40 mcg; and Arm 3: Twinrix®, 20mcg HBsAg combined with 720 ELU hepatitis A antigen. Vaccines were administered at weeks 0, 4 and 24. Results Characteristics of evaluable patients (n=336) at entry were similar in the study arms. At enrollment, median CD4+ T-cell count was 460 cells/mm3 (IQR: 305 to 668); 13% were < 200 cells/mm3. Among Engerix B®, 20 mcg recipients, 60.4% responded to vaccine (HBsAb ? 10 IU/mL at week 28). Improved vaccine response was seen in recipients of Engerix B®, 40 mcg, (73.2%, vs. Arm 1, p=0.04) and Twinrix® (75.4%, vs. Arm 1, p=0.02). In multivariate analysis, only baseline CD4+ T-cell count and study arm were independent predictors of vaccine response. Conclusions In HIV-infected youth, a three dose vaccination regimen with Engerix B®, 40 mcg, or Twinrix® and higher baseline CD4+ T-cell counts were independently associated with improved vaccine response.
Flynn, Patricia M.; Cunningham, Coleen K.; Rudy, Bret; Wilson, Craig M.; Kapogiannis, Bill; Worrell, Carol; Bethel, James; Monte, Dina; Bojan, Kelly
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 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 Centers for Disease Control and Prevention (CDC) purchases childhood and adult vaccines through contracts with pharmaceutical manufacturers and suppliers (vendors). The vendors distribute the vaccines to such recipients as States, territories, and maj...
This study was a pilot investigation of the feasibility, acceptability, and effects of TRAIN (Transit to Russia AIDS Intervention with Newcomers) a three-session HIV preventive intervention for Tajik male labor migrants performed in transit. Sixty adult Tajik male labor migrants on the 5-day train ride from Dushanbe to Moscow were randomly assigned to either the intervention or a control condition. Each initially completed an in-person survey then another 3 days later (immediately postintervention), and participated in a cell phone survey three months later. All participants came to all intervention sessions, were satisfied with the program, and completed all postassessments. In comparison with the controls, the TRAIN group reported significant increases in condom use with sex workers and non-sex workers, condom knowledge, worry about HIV/AIDS, talking with persons about HIV/AIDS, talking with wife about HIV/AIDS, community activities, and religious activities. HIV/AIDS prevention performed in transit is feasible, accceptable, and potentially efficacious in diminishing HIV risk behaviors in labor migrants. PMID:21696244
Bahromov, Mahbat; Weine, Stevan
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.
We treated a cohort of 38 HIV-infected individuals with a therapeutic vaccine (Remune, HIV-1 Immunogen) in an open label study. We then determined whether baseline parameters, such as CD4 cell count, viral load and IgG levels, were predictive of the magnitude of the HIV-specific lymphocyte proliferative responses (LPRs). We demonstrate herein that there is a significant enhancement from baseline for both HIV and p24 antigen-stimulated LPRs after immunization. Using a responder definition of a stimulation index of >5 on at least two post-immunization time-points, 29/38 (76%) responded to HIV-1 antigen while 27/38 (71%) responded to native p24 antigen. Viral load and total IgG were negatively correlated, while CD4 cell counts were positively associated with the magnitude of the HIV antigen LPR. In a multivariable analysis, baseline CD4 was the best predictor of HIV antigen LPR post-immunization.
MOSS, R B; WALLACE, M R; STEIGBIGEL, R T; MORRISON, S A; GIERMAKOWSKA, W K; NARDO, C J; DIVELEY, J P; CARLO, D J
Strategies to protect against sexual transmission of HIV include the development of products formulated for topical application, which limit the toxicities associated with systemic oral pre-exposure prophylaxis. Following several clinical trial failures, attention is now focused on antiretroviral (ARV) agents. Highly potent ARV topical formulations provide a female-controlled, targeted, and feasible option for HIV prevention. A recently completed tenofovir gel trial was the first to demonstrate significant protection against HIV acquisition. Topical ARVs have the advantage of delivering high concentration of drug at the site of transmission of HIV, with low systemic absorption. Sustained-release formulations, such as intravaginal rings, will likely improve adherence and can be designed to provide controlled and continuous delivery of ARV combinations. Further studies to test alternative dosing strategies and pharmacokinetic/pharmacodynamic relationships in the genital tract will provide valuable information as the field strives to improve upon the promising tenofovir gel trial results.
Verma, Natasha A.; Lee, Anna C.; Herold, Betsy C.
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. PMID:23584060
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”.
BACKGROUND: Results from HIV vaccine trials on potential volunteers will contribute to global efforts to develop an HIV vaccine. The purpose of this study among police officers in Dar es Salaam, Tanzania, was to explore the underlying reasons that induce people to enrol in an HIV vaccine trial. METHODS: We conducted discussions with eight focus groups, containing a total of
Edith A. M. Tarimo; Anna Thorson; Thecla W. Kohi; Joachim Mwami; Muhammad Bakari; Eric Sandström; Asli Kulane
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
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
Insulin-dependent or type 1 diabetes (T1D) is a paradigm for prevention of autoimmune disease: Pancreatic ?-cell autoantigens are defined, at-risk individuals can be identified before the onset of symptoms, and autoimmune diabetes is preventable in rodent models. Intervention in asymptomatic individuals before or after the onset of subclinical islet autoimmunity places a premium on safety, a requirement met only by lifestyle-dietary approaches or autoantigen-based vaccination to induce protective immune tolerance. Insulin is the key driver of autoimmune ?-cell destruction in the nonobese diabetic (NOD) mouse model of T1D and is an early autoimmune target in children at risk for T1D. In the NOD mouse, mucosal administration of insulin induces regulatory T cells that protect against diabetes. The promise of autoantigen-specific vaccination in humans has yet to be realized, but recent trials of oral and nasal insulin vaccination in at-risk humans provide grounds for cautious optimism. PMID:23888323
Harrison, Leonard C; Wentworth, John M; Zhang, Yuxia; Bandala-Sanchez, Esther; Böhmer, Ralph M; Neale, Alana M; Stone, Natalie L; Naselli, Gaetano; Bosco, Julian J; Auyeung, Priscilla; Rashidi, Maryam; Augstein, Petra; Morahan, Grant
Summary Background Chinese injection drug users (IDUs) may be a proper candidate population for HIV vaccine trials. Objective To evaluate willingness to participate (WTP) in HIV vaccine trials among Chinese IDUs. Methods Questionnaire interviews were completed among 401 IDUs in Urumqi City in northwestern China in 2005. Results Overall 74.3% of participants said that they would be definitely willing to participate in HIV vaccine trials, 17.7% were probably willing, 6.2% were probably not willing, and remaining 1.8% were definitely not willing to join. Multivariate logistic regression analysis demonstrated that WTP was positively associated with having ever had sex with a drug use partner (adjusted odds ratio [AOR]: 1.8; 95% confidence interval [CI]: 1.04, 3.2), sharing needle and syringe with a new drug use partner in the past 3 months (AOR: 3.8; 95% CI: 1.2, 11.7), perceived family support for participation (AOR: 7.4; 95% CI: 4.3, 12.7), and perceived vaccine protection against HIV infection (AOR: 16.1; 95% CI: 3.7, 70.8), and was negatively associated with perceived risk of social stigma and isolation for participation (AOR: 0.3; 95% CI: 0.2, 0.5). Conclusions The stated WTP in hypothetical HIV vaccine trials was high among Chinese IDUs. Further studies are needed to evaluate actual enrollment into the trials.
Yin, Lu; Zhang, Yuanzhi; Qian, Han-Zhu; Rui, Baoling; Zhang, Lijiang; Zhu, Junling; Guan, Yongsheng; Wang, Yunxia; Li, Qingchun; Ruan, Yuhua; Shao, Yiming
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
People living with HIV are at an increased risk of acquiring HPV and of developing evolutive cervical cancers (women) and penile and anal cancers (men). Low-cost screening-visual inspection with acetic acid, HPV DNA diagnostics and primary care level treatment, cryotherapy for cervical intraepithelial neoplasia (CIN 2), and primary prevention through HPV vaccination of girls aged 9-13 years-makes the goal of eliminating cervical cancer possible in the long term. Integration of cervical cancer screening and treatment into a sexual and reproductive health service package raises programmatic questions and calls for a continuum of care. The latter is only possible when adequate cytopathology skills and treatment for advanced cancer conditions are available. The present paper highlights the role of member societies of the International Federation of Gynecology and Obstetrics (FIGO) in developing the base for an integrated package that responds to women's sexual and reproductive health needs. PMID:23477703
Belhadj, Hedia; Rasanathan, Jennifer J K; Denny, Lynette; Broutet, Nathalie
HIV and hepatitis C virus infection are serious and prevalent health conditions among many women who inject drugs. Qualitative interviews with 20 injection drug using women at a short term drug treatment center in Rhode Island revealed six primary barriers and facilitators for testing and receiving results and treatment for hepatitis and HIV, as well as for hepatitis vaccination. The primary barriers were prioritization of drug use; low level of diseases-pecific knowledge; stigmatization; accessibility of testing, results and treatment; and psychological factors. The primary facilitator was interest in promoting one’s health. Our findings indicate that injection drug using women experience multiple barriers to HIV and hepatitis testing, results, treatment and vaccination. Methods for improving the motivators for health, facilitating infectious disease prevention, and decreasing unnecessary disease complications of injection drug using women need to be utilized. These methods should include strategies that minimize stigma and facilitate accessibility of health care.
LALLY, MICHELLE A.; MONTSTREAM-QUAS, SYDNEY A.; TANAKA, SARA; TEDESCHI, SARA K.; MORROW, KATHLEEN M.
The purpose of this survey is to generate baseline data on the level of HIV infection awareness and willingness to participate (WTP) in hypothetical vaccine trials, ahead of any trial conduct in Nigeria. In a cross-sectional survey, 500 respondents were interviewed, including sex workers, male motorcycle taxi drivers, students, and the general public. About 153 (30.6%) of the respondents did
Gambo Aliyu; Mukhtar Mohammad; Ahmed Saidu; Prosanta Mondal; Man Charurat; Alash'le Abimiku; Abdulsalami Nasidi; William Blattner
Summary To test the efficacy of a sustainable community-level HIV intervention among sex workers, the Sonagachi Project was replicated, including community organizing and advocacy, peer education, condom social marketing, and establishment of a health clinic. Sex workers were randomly selected in 2 small urban communities in northeastern India (n = 100 each) and assessed every 5–6 months over 15 months (85% retention). Overall condom use increased significantly in the intervention community (39%) compared with the control community (11%), and the proportion of consistent condom users increased 25% in the intervention community compared with a 16% decrease in the control community. This study supports the efficacy of the Sonagachi model intervention in increasing condom use and maintaining low HIV prevalence among sex workers.
Basu, Ishika; Jana, Smarajit; Rotheram-Borus, Mary Jane; Swendeman, Dallas; Lee, Sung-Jae; Newman, Peter; Weiss, Robert
Charged with the task of reviewing the research outcome literature on HIV prevention with Mexican migrants in the United States, the following broad observations and conclusion were made: (1) there is little research on this specialized topic of concern; (2) the research that exists reflects an overly individualistic behavioral science approach designed to reduce individual risk factors, with little regard for structural and environmental factors that influence HIV risk; and (3) there is a compelling need to develop better theoretic frameworks for understanding the complex and dynamic social and cultural processes influencing sexual behavior among Mexican migrants so as to better inform HIV prevention efforts with this unique and diverse Latino(a) population. PMID:15722865
Organista, Kurt C; Carrillo, Héctor; Ayala, George
The Centers for Disease Control and Prevention (CDC) hosted its first National HIV Prevention Conference. CDC data presented at the conference shows that while the decline in U.S. AIDS deaths is not as steep as it had been, numbers of deaths are continuing to drop. The CDC attributes the decline to the introduction of widespread use of combination therapy. The data suggests that current anti-HIV drugs may not be as effective in the long term. HIV/AIDS infection rates among specific groups were presented. Researchers at the conference noted that AIDS rates are higher among prisoner populations than in the general population. Prisoners also have a high prevalence of tuberculosis, hepatitis C, and other sexually transmitted diseases. PMID:11367258
A current debate in the HIV-1 vaccine field concerns the ability of an immunodeficiency virus to elicit a protective response. One argument is that HIV-1 superinfections are frequent in healthy individuals, because virus evades conventional immune surveillance, a serious obstacle to vaccine design. The opposing argument is that protection from superinfection is significant, reflecting a robust immune response that might
Robert Sealy; Xiaoyan Zhan; Timothy D. Lockey; Louis Martin; James Blanchard; Vicki Traina-Dorge; Julia L. Hurwitz
More than half a million Americans became newly infected with HIV in the first decade of the new millennium. The domestic epidemic has had the heaviest impact on men who have sex with men (MSM) and people from racial and ethnic minority populations, particularly African-Americans. For example, Black MSM represent <1% of the U.S. population but 25% of the new HIV cases, as per CDC estimates published in 2008. While Black and Hispanic women constitute 24% of all U.S. women, they accounted for 82% of HIV cases in women in 2005, based on data from 33 states with confidential name-based reporting. There is a nearly 23-fold higher rate of AIDS diagnoses for Black women (45.5/100,000 women) and nearly 6-fold higher rate for Hispanic women (11.2/100,000) compared to the rate for white women (2.0/100,000). Investigators from the HIV Prevention Trials Network (HPTN), an NIH-sponsored collaborative clinical trials group, have crafted a domestic research agenda with community input. Two new domestic studies are in progress (2009) and a community-based clinical trial feasibility effort is in development (2010 start date). These studies focus on outreach, testing, and treatment of infected persons as a backbone for HIV prevention. Reaching persons not receiving health message and service with novel approaches to both prevention and care/treatment is an essential priority for HIV control in the U.S.; our research is designed to guide the best approaches and assess the impact of bridging treatment and prevention.
Vermund, Sten H.; Hodder, Sally L.; Justman, Jessica E.; Koblin, Beryl A.; Mastro, Timothy D.; Mayer, Kenneth H.; Wheeler, Darrell P.; El-Sadr, Wafaa M.
|This study compared two groups of adolescents seeking help at HIV prevention drop-in agencies. The first group attended agencies in low-income Hispanic neighborhoods which recruited within the locale. The second group of youth attended agencies that recruited based upon a specific population--they targeted homeless and LGBQ youth. We explored the…
Hohman, Melinda; Shillington, Audrey M.; Min, Jong Won; Clapp, John D.; Mueller, Kristin; Hovell, Melbourne
|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.
Purpose To explore the feasibility of engaging community businesses in HIV prevention. Design Randomly selected business owners/managers were asked to display discreetly wrapped condoms and brochures provided free-of-charge for 3 months. Assessments were conducted at baseline, mid-, and post-program. Customer feedback was obtained through an online survey. Setting San Diego, California neighborhood with a high rate of AIDS. Subjects Fifty-one business owners/managers representing 10 retail categories, and 52 customers. Measures Participation rates, descriptive characteristics, number of condoms and brochures distributed, customer feedback, business owners'/managers' program satisfaction and willingness to provide future support for HIV prevention. Analysis Kruskal-Wallis, Mann-Whitney U, Fisher's exact, and McNemar's tests were used to analyze data. Results The 20 business owners/managers (39%) who agreed to distribute condoms and brochures reported fewer years in business and more employees than those who agreed only to distribute brochures (20%) or refused to participate (41%), p <.05. Bars were the easiest of ten retail categories to recruit. Businesses with more employees and customers distributed more condoms and brochures, p < .05. More than 90% of customers supported distributing condoms and brochures in businesses and 96% of business owners/managers described their program experience as “positive.” Conclusion Businesses are willing to distribute condoms and brochures to prevent HIV. Policies to increase business participation in HIV prevention should be developed and tested.
Rovniak, Liza S.; Hovell, Melbourne F.; Hofstetter, C. Richard; Blumberg, Elaine J.; Sipan, Carol L.; Batista, Marcia F.; Martinez-Donate, Ana P.; Mulvihill, Mary M.; Ayala, Guadalupe X.
|This 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…
In the absence of pharmacological, immunological, and medical interventions, the change in behavior and attitude of the public may only be considered a possible way for the prevention and cure for HIV\\/AIDS. The basic purpose of this study is to analyze the various communication models and steps that play a pivotal role in making successful communication campaigns for shaping public
Mian Ahmad Hanan
This study compared two groups of adolescents seeking help at HIV prevention drop-in agencies. The first group attended agencies in low-income Hispanic neighborhoods which recruited within the locale. The second group of youth attended agencies that recruited based upon a specific population--they targeted homeless and LGBQ youth. We explored the…
Hohman, Melinda; Shillington, Audrey M.; Min, Jong Won; Clapp, John D.; Mueller, Kristin; Hovell, Melbourne
Recent advances in the development of humanized mice hold great promise to advance our understanding of protective immunity to human immunodeficiency virus (HIV) infection and to aid in the design of an effective HIV vaccine. This supplement of the Journal of Infectious Diseases summarizes work in the humanized mouse model presented at an HIV Humanized Mouse workshop in Boston, Massachusetts, in November 2012, including recent advances in the development of humanized mice, the trafficking of human immune cells following mucosal HIV transmission, the role of immune activation and Toll-like receptor agonists in the control of HIV, the induction and efficacy of HIV-specific cellular and humoral immune responses, and the preclinical modeling of novel anti-HIV therapeutics. Many gaps remain in our understanding of how to design an effective HIV vaccine and novel therapeutics to eliminate the viral reservoir. Promising early results from studies in humanized mice suggest great potential and enthusiasm for this model to accelerate these critical areas of HIV research. PMID:24151317
Tager, Andrew M; Pensiero, Michael; Allen, Todd M
We evaluated the efficacy and tolerability of a single dose of the split virion AS03-adjuvanted pandemic H1N1 influenza vaccine (A/California/7/2009) in 84 HIV-1 infected individuals. Antibody titers were determined by hemagglutination inhibition assay and by microneutralization. Vaccine was well tolerated. At 21 days post vaccination, 56 (67%) patients had seroconverted. There was no correlation between baseline CD4 cell count (p=0.539) or HIV viral load (p=0.381) and immune response. Other vaccine strategies should be evaluated in this HIV population, to improve response rates. PMID:21185423
Tremblay, Cécile L; Rouleau, Danielle; Fortin, Claude; Toma, Emil; Sylla, Mohamed; Cyr, Lise; Cote, Serge; Baz, Mariana; Sampalis, John; Trautman, Lydie; Sékaly, Rafick-Pierre; Boivin, Guy
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
Background Recruitment of low- and middle-income country volunteers from most-at-risk populations in HIV vaccine trials is essential to vaccine development. In India, men who have sex with men (MSM) are at disproportionately high risk for HIV infection and an important population for trial recruitment. Investigations of willingness to participate (WTP) in HIV vaccine trials have focused predominantly on individual-level determinants. We explored multi-level factors associated with WTP among MSM in India. Methods We conducted 12 focus groups (n?=?68) with low socioeconomic MSM in Chennai and Mumbai, and 14 key informant interviews with MSM community leaders and service providers. Focus groups/interviews were recorded, transcribed and translated into English. Two bilingual investigators conducted thematic analysis using line-by-line coding and a constant comparative method, with member-checking by community representatives. Results Factors associated with WTP were evidenced across the social ecology of MSM–social-structural: poverty, HIV-, sexual- and gender non-conformity stigma, institutionalized discrimination and government sponsorship of trials; community-level: endorsement by MSM community leaders and organizations, and fear of within-group discrimination; interpersonal: anticipated family discord, partner rejection, having financially-dependent family members and disclosure of same-sex sexuality; and individual-level: HIV vaccine trial knowledge and misconceptions, safety concerns, altruism and preventive misconception. Conclusion Pervasive familial, community and social-structural factors characteristic of the Indian sociocultural context may complicate individual-focused approaches to WTP and thereby constrain the effectiveness of interventions to support recruitment and retention in HIV vaccine trials. Interventions to reduce stigma and discrimination against MSM and people living with HIV, capacity-building of MSM community organizations and transparent communications tailored to the knowledge and educational level of local communities may support meaningful engagement of MSM in HIV vaccine trials. Vigilance in providing fair but not excessive compensation and healthcare benefits and in mitigating preventive misconception are warranted to support ethical conduct of trials among MSM in India.
Chakrapani, Venkatesan; Newman, Peter A.; Singhal, Neeti; Jerajani, Jhalak; Shunmugam, Murali
Drug use continues to be a major factor fueling the global epidemic of HIV infection. This paper provides an updated review of the research literature assessing the ability of drug treatment programs to reduce HIV transmission among injection and non-injection drug users. Most data come from opiate dependence treatments and continue to provide strong support for the effectiveness of medication assisted treatments in reducing the frequency of drug use, risk behaviors, and infections. This finding has remained consistent over time and across diverse cultural settings. Data on the ability of medications other than methadone (buprenorphine/naloxone and naltrexone) have emerged in recent years and shown promise as effective prevention interventions and in providing more treatment options to communities most heavily affected by drug use and HIV infection. Still, only a few treatment interventions for stimulant use have shown efficacy in reducing HIV risk. The literature of the past 10 years provides strong support for the importance of drug treatment programs in improving access and adherence to antiretroviral treatment and suggests that drug users in substance abuse treatment are significantly more likely to achieve sustained viral suppression making viral transmission less likely. While important challenges remain in maximizing its impact, the scientific literature provides strong evidence for the efficacy of drug treatment as an HIV prevention strategy.
Woody, George E.; O'Brien, Charles P.
OBJECTIVES: HIV transmission behaviors and health practices of HIV-infected youths were examined over a period of 15 months after they received a preventive intervention. METHODS: HIV-infected youths aged 13 to 24 years (n = 310; 27% African American, 37% Latino) were assigned by small cohort to (1) a 2-module ("Stay Healthy" and "Act Safe") intervention totaling 23 sessions or (2) a control condition. Among those in the intervention condition, 73% attended at least 1 session. RESULTS: Subsequent to the "Stay Healthy" module, number of positive lifestyle changes and active coping styles increased more often among females who attended the intervention condition than among those in the control condition. Social support coping also increased significantly among males and females attending the intervention condition compared with those attending the control condition. Following the "Act Safe" module, youths who attended the intervention condition reported 82% fewer unprotected sexual acts, 45% fewer sexual partners, 50% fewer HIV-negative sexual partners, and 31% less substance use, on a weighted index, than those in the control condition. CONCLUSIONS: Prevention programs can effectively reduce risk acts among HIV-infected youths. Alternative formats need to be identified for delivering interventions (e.g., telephone groups, individual sessions).
Rotheram-Borus, M J; Lee, M B; Murphy, D A; Futterman, D; Duan, N; Birnbaum, J M; Lightfoot, M
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.
This paper presents a qualitative investigation of peer mentoring among HIV seropositive injection drug users in a randomized controlled trial, the INSPIRE study. Qualitative analyses of 68 in-depth open-ended interviews conducted in 2005 in Baltimore, New York, Miami, and San Francisco revealed that these individuals conceptualized themselves as change agents through the identity of peer mentor at the three related domains of individual, interpersonal, and community-level change. Implications for program development and future research of peer mentoring as a mechanism for HIV prevention are discussed. This study was funded by the Centers for Disease Control and Prevention and Health Resources and Services Administration (HRSA). PMID:22428820
Mackenzie, Sonja; Pearson, Charles; Frye, Victoria; Gómez, Cynthia A; Latka, Mary H; Purcell, David W; Knowlton, Amy R; Metsch, Lisa R; Tobin, Karin E; Valverde, Eduardo E; Knight, Kelly R
Reliable and effective induction of cytotoxic T-lymphocytes (CTL) is one of the prime objectives of vaccine research. Previously, novel HIV vaccine candidates were constructed as a string of CTL epitopes (20 human, 3 macaque and 1 mouse) delivered using a DNA vector [Hanke T, Schneider J, Gilbert SG, Hill AVS, McMichael A. DNA multi-CTL epitope vaccines for HIV and Plasmodium
Tomáš Hanke; Veronica C Neumann; Tom J Blanchard; Paul Sweeney; Adrian V. S Hill; Geoffrey L Smith; Andrew McMichael
BackgroundWe conducted a novel pilot study comparing different delivery routes of ALVAC-HIV (vCP205), a canarypox vaccine containing HIV gene inserts: env, gag and pol. We explored the concept that direct ex vivo targeting of human dendritic cells (DC) would enhance the immune response compared to either conventional intramuscular or intradermal injections of the vaccine alone.Methodology\\/Principal FindingsHealthy HIV-1 uninfected volunteers were
Michael A. Eller; Bonnie M. Slike; Josephine H. Cox; Emil Lesho; Zhining Wang; Jeffrey R. Currier; Janice M. Darden; Victoria R. Polonis; Maryanne T. Vahey; Sheila Peel; Merlin L. Robb; Nelson L. Michael; Mary A. Marovich; Mario A. Ostrowski
DNA vaccine against human immunodeficiency virus type-1 (HIV-1) can induce substantial levels of HIV-1-specific humoral and cell-mediated immunity. To develop more potent HIV-1 DNA vaccine formulations, we used a murine model to explore the immunomodulatory effects of an interleukin-2 (IL-2) expression plasmid on an HIV-1 DNA vaccine following intranasal administration of the combination. When the vaccine and expression plasmid were incorporated into cationic liposomes and administered to mice, the HIV-1-specific delayed-type hypersensitivity response and cytotoxic T lymphocyte activity were significantly increased. Restimulated immune lymphoid cells showed enhanced production of both IL-2 and interferon-gamma and reduced secretion of IL-4. The level of total antibody to HIV-1 antigen was not greatly changed by coadministration of the DNA vaccine and IL-2 expression plasmid. An analysis of serum HIV-1-specific IgG subclasses showed a significant drop in the IgG1/IgG2a ratio in the group that received the plasmid-vaccine combination. These results demonstrate that the IL-2 expression plasmid strongly enhances the HIV-1-specific immune response via activation of T helper type-1 cells. Images Figure 1 Figure 2
Xin, K Q; Hamajima, K; Sasaki, S; Honsho, A; Tsuji, T; Ishii, N; Cao, X R; Lu, Y; Fukushima, J; Shapshak, P; Kawamoto, S; Okuda, K
While DNA vaccines have been shown to prime cellular immune responses, levels are often low in nonhuman primates or humans. Hence, efforts have been directed toward boosting responses by combining DNA with different vaccination modalities. To this end, a polyvalent DNA prime\\/protein boost vaccine, consisting of codon optimized HIV-1 env (A, B, C, E) and gag (C) and homologous gp120
Anthony D. Cristillo; Shixia Wang; Michael S. Caskey; Tami Unangst; Lindsey Hocker; Leilei He; Lauren Hudacik; Stephen Whitney; Tim Keen; Te-hui W. Chou; Siyuan Shen; Swati Joshi; Vaniambadi S. Kalyanaraman; Balachandran Nair; Phillip Markham; Shan Lu; Ranajit Pal
Objective To evaluate the T-SPOT.TB interferon-? releasing assay and the tuberculin skin test (TST), for the diagnosis of latent tuberculosis infection(LTBI) and the development of subsequent active tuberculosis, in BCG-vaccinated HIV-infected individuals. Methods HIV-infected individuals without clinical suspicion of active TB or a past history of TB were enrolled from 1 January 2008 to 30 November 2010. Both T-SPOT.TB test and TST were offered to the participants whom were followed up prospectively until April 30, 2012 for development of TB. Results Among the 909 participants, 25% had positive TST reactions with cut-off point of 5 mm and 15% had positive T-SPOT.TB results. After a median follow-up of 2.97 years, there were 5 cases developed culture-confirmed active TB (all had dual positive TST and T-SPOT.TB results), and the incidence was 0.17 per 100 person-years. The relative risks (RRs) for subsequent active TB in HIV-infected individuals with positive TST results, positive T-SPOT.TB results and dual positive results compared with the risk for individuals with negative results were 40.6 (95% CI 2.1–767.9), 73.9 (95% CI 3.9–1397.7) and 226.5 (95% CI 12.0–4284), respectively. The number needed to treat to prevent one subsequent TB case among patients with a positive TST, a positive T-SPOT.TB and dual positive results was 35, 22 and 8 respectively. Conclusions Adopting positive results of the TST and T-SPOT.TB to screen LTBI among BCG-vaccinated HIV-infected individuals might be feasible. Number needed to treat for isoniazid preventive therapy could be reduced significantly by using dual positive strategy.
Yang, Chin-Hui; Chan, Pei-Chun; Liao, Say-Tsung; Cheng, Shu-Hsing; Wong, Wing-Wai; Huang, Li-Min; Hsueh, Po-Ren; Chiou, Hung-Yi
HIV vaccine clinical research occurs within a context where biomedical science and social issues are interlinked. Previous HIV vaccine research has considered behavioral and social issues, but often treated them as independent of clinical research processes. Systematic attention to the intersection of behavioral and social issues within a defined clinical research framework is needed to address gaps, such as those related to participation in trials, completion of trials, and the overall research experience. Rigorous attention to these issues at project inception can inform trial design and conduct by matching research approaches to the context in which trials are to be conducted. Conducting behavioral and social sciences research concurrent with vaccine clinical research is important because it can help identify potential barriers to trial implementation, as well as ultimate acceptance and dissemination of trial results. We therefore propose a conceptual framework for behavioral and social science in HIV vaccine clinical research and use examples from the behavioral and social science literature to demonstrate how the model can facilitate identification of significant areas meriting additional exploration. Standardized use of the conceptual framework could improve HIV vaccine clinical research efficiency and relevance.
Lau, Chuen-Yen; Swann, Edith M.; Singh, Sagri; Kafaar, Zuhayr; Meissner, Helen I.; Stansbury, James P.
Europrise is a Network of Excellence supported by the European Commission within the 6th Framework programme from 2007 to 2012. The Network has involved over 50 institutions from 13 European countries together with 3 industrial partners and 6 African countries. The Network encompasses an integrated program of research, training, dissemination and advocacy within the field of HIV vaccines and microbicides. A central and timely theme of the Network is the development of the unique concept of co-usage of vaccines and microbicides. Training of PhD students has been a major task, and some of these post-graduate students have here summarized novel ideas emanating from presentations at the last annual Europrise meeting in Prague. The latest data and ideas concerning HIV vaccine and microbicide studies are included in this review; these studies are so recent that the majority have yet to be published. Data were presented and discussed concerning novel immunisation strategies; microbicides and PrEP (alone and in combination with vaccines); mucosal transmission of HIV/SIV; mucosal vaccination; novel adjuvants; neutralizing antibodies; innate immune responses; HIV/SIV pathogenesis and disease progression; new methods and reagents. These - necessarily overlapping topics - are comprehensively summarised by the Europrise students in the context of other recent exciting data. PMID:22784600
Ruffin, Nicolas; Borggren, Marie; Euler, Zelda; Fiorino, Fabio; Grupping, Katrijn; Hallengärd, David; Javed, Aneele; Mendonca, Kevin; Pollard, Charlotte; Reinhart, David; Saba, Elisa; Sheik-Khalil, Enas; Sköld, Annette; Ziglio, Serena; Scarlatti, Gabriella; Gotch, Frances; Wahren, Britta; Shattock, Robin J
The absence of adequate and regular prevention counseling during routine clinical encounters translates in