HIV vaccine knowledge and beliefs among communities at elevated risk: conspiracies, questions and confusion

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.     

Current advances in HIV vaccines

Development of a safe and preventive HIV-1 vaccine is a high priority. Recent advances in HIV vaccine development include an improved understanding of HIV envelope structure, development of techniques that enable a detailed analysis of vaccine-induced immune responses in humans, expansion of the pipeline of promising candidate vaccines, and completion of the first vaccine efficacy trials. A common feature of several preventive vaccine strategies in early clinical trials is their ability to attenuate clinical disease rather than completely prevent HIV infection in nonhuman primates. One or more candidate vaccines will likely advance into efficacy trials within the next few years, while efforts to identify new designs that induce broadly neutralizing antibodies continue with incremental success.     

HIV vaccine trial participation among ethnic minority communities: barriers, motivators, and implications for recruitment

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 and 35% African American) were recruited using venue-based sampling in Los Angeles. Data were analyzed using narrative thematic analysis and Ethnograph qualitative software. RESULTS: Perceived barriers to HIV vaccine trial participation, in rank order, were (1) vaccine-induced HIV infection, (2) physical side effects, (3) uncertainty about vaccine efficacy, (4) uncertainty about other vaccine characteristics, (5) mistrust, (6) low perceived HIV risk, (7) study demands, (8) stigma, and (9) vaccine-induced HIV seropositivity. Motivators were (1) protection against HIV infection, (2) free insurance and/or medical care, (3) altruism, and (4) monetary incentives. CONCLUSIONS: Population-specific HIV vaccine trial recruitment and implementation strategies should address trial risks from a family perspective, cultural gender norms, mistrust, low perceived HIV risk, the importance of African-American and Latino/a community participation in HIV vaccine trials, and misconceptions about gaining protection against HIV infection. Increasing the cultural relevance of trial recruitment and implementation should facilitate the participation of Latinos/as and African Americans in HIV vaccine trials.     

Acceptance of a potential HIV/AIDS vaccine among minority women

PURPOSE: To explore the attitudes, opinions and concerns of minority women regarding acceptance of a potential HIV/ AIDS vaccine. METHODS: In-depth interviews were conducted with high-risk minority women (> or =18 years of age) attending an urban Atlanta health clinic specializing in sexually transmitted diseases, including HIV/AIDS prevention and treatment. Interviews were transcribed and content analyzed to identify common factors related to acceptance of an HIV/AIDS vaccine. RESULTS: Nine major themes were identified. These were general acceptance of an HIV/AIDS vaccine, concerns about the vaccine, vaccine knowledge, testing and research, provider recommendation, mistrust, alternative medicine, misperceptions and vaccine accessibility/availability. A strong theme emerged about the need for information from HIV/AIDS vaccine clinical trials, including the demographics of the studies' volunteer base, to inform decision-making about taking an HIV/AIDS vaccine in the future. CONCLUSIONS: Although fewer than half of the women indicated they would receive or recommend the vaccine, most agreed that development of a vaccine was an important endeavor. The findings of this study may assist in future efforts to determine how best to promote acceptance of an HIV/AIDS vaccine to minority women should one become available.     

Challenges to conducting HIV preventative vaccine trials with adolescents

It is estimated that 10.3 million people aged 15-24 are living with HIV infection/AIDS worldwide, with 7000 new infections occurring each day. Many of these infections occur during the adolescent years. These rates of infection make adolescents an important target for research in primary prevention. Currently, preparations are under way by the National Institutes of Health-supported HIV networks--the Adolescent Trials Network, the Pediatric AIDS Clinical Trials Group, and the HIV Vaccines Trials Network--for phase 1/2 HIV vaccine trials involving adolescents in the United States. Identifying the challenges to conducting HIV vaccine trials with this population is a crucial component of these preparations. Challenges to HIV vaccine trials with adolescents were identified by reviewing previous vaccine research for adolescents and HIV infection in adolescents and speaking with experts in HIV/AIDS and adolescent medicine. Adolescents (typically those younger than 18 years of age) are minors and fall under ethical and regulatory safeguards for their participation in clinical research including parental permission. Adolescents may not appropriately perceive personal risk, posing challenges for informed consent as well as prevention counseling during a trial. Safety and immunogenicity studies of adolescents are likely to be required by the US Food and Drug Administration before vaccine approval for this population. Early identification and subsequent follow-up of high-risk adolescents are problematic. Vaccine-induced seropositivity may present potential barriers to military service, employment, marriage, and acquiring health insurance. The age at optimal immunization, particularly for girls in some countries, may be during preadolescence. The successful completion of HIV vaccine trials with adolescents must address these challenges both in the United States and internationally. This report addresses relevant background information, identifies the issues surrounding HIV vaccine trials with adolescents, discusses what progress has been made, and addresses plans and implications for the implementation of these trials.     

Vaccine approaches currently in development

The need for a vaccine against HIV/AIDS is becoming vital since the cost of treating the disease is making many poorer countries unable to provide widely-available therapies to their populations. Obstacles to vaccine development include lack of understanding by researchers on what constitutes immunity against HIV infection, the highly variable nature of HIV, and the lack of an ideal animal model to test HIV vaccines. The following vaccine approaches, which are currently in development, are discussed: subunit vaccines (gp120 vaccines), recombinant vector vaccines, prime boost regimens, DNA vaccines, whole-killed vaccines, live-attenuated vaccines, virus-like particle vaccines, and peptide vaccines. The progress being made in vaccine development is slow, but steady. However, none of the approaches appear ready for large-scale human trials. The growing realization that a vaccine is needed may lead to more substantial funding and greater progress in developing a vaccine.     

AIDS vaccines and adjuvant formulations

The AIDS epidemic is too large to continue ignoring prevention programs that appear to work. In this review the promising experimental immunogens and how close they are to the optimal requirements for a preventive vaccine are presented. Adjuvants and adjuvant formulations (mainly mixtures of adjuvants with suitable vehicles) can help in solving some specific problems of AIDS vaccines: overcome the variable nature of HIV subtypes, generate both antibody and T-cell response, induce mucosal immunity, avoid enhancing or autoimmune antibodies and distinguish vaccine-induced seropositivity from natural HIV infection. The following categories of adjuvants are discussed: alum, other mineral and bacterial cell-wall derived adjuvants, cytokines, carriers and vehicles. Although many specific mechanisms of the relative effectiveness of adjuvants have been clarified by recent advances in basic immunology the best adjuvant formulation remains largely empirical. A standardized protocol for preclinical testing of adjuvants for AIDS vaccines is a priority task.     

Human Papillomavirus Vaccines: Where Do They Fit in HIV-Infected Individuals?

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.     

Predicting the impact of a partially effective HIV vaccine and subsequent risk behavior change on the heterosexual HIV epidemic in low- and middle-income countries: A South African example

We developed a mathematical model to simulate the impact of various partially effective preventive HIV vaccination scenarios in a population at high risk for heterosexually transmitted HIV. We considered an adult population defined by gender (male/female), disease stage (HIV-negative, HIV-positive, AIDS, and death), and vaccination status (unvaccinated/vaccinated) in Soweto, South Africa. Input data included initial HIV prevalence of 20% (women) and 12% (men), vaccination coverage of 75%, and exclusive male negotiation of condom use. We explored how changes in vaccine efficacy and postvaccination condom use would affect HIV prevalence and total HIV infections prevented over a 10-year period. In the base-case scenario, a 40% effective HIV vaccine would avert 61,000 infections and reduce future HIV prevalence from 20% to 13%. A 25% increase (or decrease) in condom use among vaccinated individuals would instead avert 75,000 (or only 46,000) infections and reduce the HIV prevalence to 12% (or only 15%). Furthermore, certain combinations of increased risk behavior and vaccines with <43% efficacy could worsen the epidemic. Even modestly effective HIV vaccines can confer enormous benefits in terms of HIV infections averted and decreased HIV prevalence. However, programs to reduce risk behavior may be important components of successful vaccination campaigns.     

Utility of various commercially available human immunodeficiency virus (HIV) antibody diagnostic kits for use in conjunction with efficacy trials of HIV-1 vaccines.

There is a need for human immunodeficiency virus (HIV) screening assays which will distinguish uninfected HIV vaccine recipients from HIV-infected individuals. Commercial screening kits were used to test serum samples from low- and high-risk participants in clinical trials before and after immunization with various recombinant HIV type 1 (HIV-1) envelope glycoprotein 120 (gp120) candidate vaccines. All kits were 100% sensitive in detecting HIV infection. Both Murex Single Use Diagnostic System and United Biomedical, Inc., HIV type 1 or 2 (HIV-1/2) enzyme immunoassay (EIA) kits, which detect antibodies to HIV-1 gp41, were 98 to 100% specific when used to screen baseline or recombinant gp120-vaccinated populations as vaccine-induced antibodies to gp120 were nonreactive in these tests. The Abbott HIVAB HIV-1 EIA (lysate of whole infected cells, reactive with anti-gp120 antibodies) gave high levels of reactivity due to vaccine-induced antibodies and a high baseline rate of false positives (12 of 83) among nonvaccinated high-risk volunteers. Assays containing only gp41 and p24 solid-phase components are compatible with gp120-based vaccines but are unlikely to be useful in a similar role for vaccines containing gp160, gp41, or gp120 plus p24 antigens. Efficacy trials must be designed in concert with available diagnostic screening assays to avoid problems caused by vaccine-induced seroconversion in high-risk populations.     

139例HIV感染者P24抗原，HIV DNA，HIV RNA相关研究

目的探讨ＨＩＶＤＮＡ，ＨＩＶＲＮＡ，Ｐ２４Ａｇ与宿主的相互关系及三者间的内在联系。方法收集１３９例抗ＨＩＶ阳性血标本，用固相免疫酶法测Ｐ２４Ａｇ，定量逆转录聚合酶链生物酶法测定ＨＩＶＲＮＡ和巢式聚合酶链法测ＨＩＶＤＮＡ。结果ＨＩＶＲＮＡ阳性数１０８／１３９，ＨＩＶＤＮＡ阳性数１０９／１３９，Ｐ２４Ａｇ阳性数为３４／１３９。进一步分析，同一标本ＨＩＶＤＮＡ，ＨＩＶＲＮＡ均阳性的占８０％，单一阳性为２０％。结论三种ＨＩＶ检测方法的敏感性、一致性与ＨＩＶ毒株变异、个体宿主免疫应答及抗病毒治疗密切相关。多引物多区域同时测ＨＩＶＤＮＡ，ＨＩＶＲＮＡ和抗原，并结合临床进行综合分析，对加强ＨＩＶ感染机理的理解和疗效考核有实际意义     

Why blacks do not take part in HIV vaccine trials

BACKGROUND: AIDS is still a major cause of death. To combat this disease, researchers are developing a vaccine. Although blacks account for most new infections in the United States, they account for a low percent of experimental vaccine recipients. This study, conducted in a mid-sized U.S. city where vaccine trials are held, seeks to learn why. METHODS: We conducted 11 in-depth ethnographic interviews. Two groups were targeted: blacks who had not participated in HIV vaccine trials and blacks who had. RESULTS: Overall, three major causes of nonparticipation were identified: misinformation, fear/mistrust and stigma. Factors that favored participation included having close friends with HIV and being homosexual. CONCLUSIONS: HIV is considered by many blacks to be a gay, white disease. Steps to increase participation must include efforts to destigmatize the condition and disseminate accurate information. Efforts to address historical causes of mistrust through "education" alone are insufficient. Trust needs to be earned through long-term relationships with black communities.     

Assessing the attitudes, knowledge, and awareness of HIV vaccine research among adults in the United States

OBJECTIVES: To assess HIV vaccine research attitudes, awareness, and knowledge among adults in the general US population, African Americans, Hispanics, and men who have sex with men (MSM). METHODS: Applying results of focus groups and a media content analysis, a survey was designed and conducted to validate key HIV vaccine research themes and messages identified by focus groups and a media content analysis. Between December 2002 and February 2003, 3509 telephone interviews were conducted, including 2008 randomly selected from the general population, and 501 population-specific samples of African Americans and Hispanics, and 500 from MSM. RESULTS: Although the majority of each population believes that an HIV preventive vaccine is the best way to control and end the global AIDS epidemic, only 34.9% of African Americans and 28.8% of the general population are supportive of someone they know volunteering for an HIV vaccine trial. The study also found that 47.1% of African Americans, 26.5% of Hispanics, and 13.4% of MSM believed an HIV vaccine already exists and is being kept secret, and 78.0% of African Americans, 57.5% of Hispanics, and 68.0% of MSM did not know or incorrectly believed that the vaccines being tested could cause HIV infection. A subanalysis of the general population also found that women generally had less knowledge of or a decreased awareness about HIV vaccine research. CONCLUSIONS: Awareness, knowledge, and attitudes toward HIV vaccine research vary by population and these issues must be addressed to ensure an adequate number of volunteers for future domestic HIV preventive vaccine clinical trials. In some populations, barriers such as misinformation and distrust must be targeted to increase support for HIV vaccine research.     

Novel approach for differential diagnosis of HIV infections in the face of vaccine-generated antibodies: utility for detection of diverse HIV-1 subtypes

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 HIV-SELECTEST, 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 >3,000 infections with diverse HIV subtypes worldwide. The HIV-SELECTEST 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.     

Forecasting the future of HIV epidemics: the impact of antiretroviral therapies & imperfect vaccines

Mathematical models can be used as health policy tools and predictive tools. Here we review how mathematical models have been used both to predict the consequences of specific epidemic control strategies and to design epidemic control strategies. We review how models have been used to evaluate the potential impact on HIV epidemics of (i) combination antiretroviral therapies (ART) and (ii) imperfect vaccines. In particular, we discuss how models have been used to predict the potential effect of ART on incidence rates, and to predict the evolution of an epidemic of drug-resistant HIV. We also discuss, in detail, how mathematical models have been used to evaluate the potential impact of prophylactic, live-attenuated and therapeutic HIV vaccines. We show how HIV vaccine models can be used to evaluate the epidemic-level impact of vaccine efficacy, waning in vaccine-induced immunity, vaccination coverage level, and changes (increases or decreases) in risky behavior. We also discuss how mathematical models can be used to determine the levels of cross-immunity that vaccines will need to attain if they are to be used to control HIV epidemics in countries where more than one subtype is being transmitted.     

Randomized,controlled evaluation of a prototype informed consent process for HIV vaccine efficacy trials

Procedures must be developed to ensure that valid informed consent is obtained from participants in HIV vaccine efficacy trials. A prototype informed consent process was evaluated among 4,892 persons at high risk for HIV infection in the HIV Network for Prevention Trials Vaccine Preparedness Study (VPS), a prospective cohort study of HIV seroincidence in eight U.S. metropolitan areas. Twenty percent of VPS participants were selected at random to undergo the prototype informed consent process at VPS month 3. Participants' knowledge of 10 key HIV vaccine trial concepts and willingness to participate in HIV vaccine efficacy trials were assessed and compared at baseline and semiannually thereafter for 18 months. Knowledge of HIV vaccine trial concepts was low at baseline. Participation in the prototype process was associated with substantial and sustained increases in knowledge (relative risks for the 10 items, 1.04-2.26), which were of similar magnitude across HIV risk groups, race/ethnicity, and educational levels. It is recommended that the prototype informed consent process be adopted for future HIV vaccine efficacy trials as well as for clinical trials in other research areas.     

Building collaborative networks for HIV/AIDS vaccine development: the AVIP experience

The need for an effective HIV/AIDS vaccine is imperative to halt a pandemic that involves more than 40 million individuals worldwide as of 2005 and is causing enormous socio-economic losses, especially in developing countries (DC). The overall failure of more than two decades of HIV vaccine research justifies the demands for a concerted effort for the rapid development of new and efficacious vaccines against HIV/AIDS. In this context, building international collaborative networks is a must for speeding up scientific research and optimizing the use of funding in a synergistic fashion, as resources for HIV/AIDS are limited and do not involve most of the biggest Pharmas that are more interested in drug discovery. The AIDS Vaccine Integrated Project (AVIP) consortium is an example of synergistic partnership of international European Union and DC experts with a common research goal. AVIP is a European Commission-funded (FP-6), consortium-based, 5-year program directed to the fast development of new HIV/AIDS vaccine candidates to be tested in phase I clinical trials in Europe for future advancement to phase II/III testing in DC. To ensure their rapid development, AVIP novel combined vaccines include both regulatory and structural HIV antigens, which have already been tested, as single components, in phase I clinical trials. In particular, such combination vaccines may be superior to earlier vaccine candidates, the vast majority of which are based only on either structural or regulatory HIV products. In fact, the generation of immune responses to both types of viral antigens expressed either early (regulatory products) or late (structural products) during the viral life cycle can maximize immune targeting of both primary or chronic viral infection. Further, the rational design of combined vaccines allows exploitation of immunomodulatory functions of HIV regulatory proteins, which can improve immunity against structural vaccine components. The building of the AVIP consortium and its scientific strategy will be reviewed in this paper as an example of the establishment of a consortium regulated by a specific intellectual property agreement.     

Endpoints and regulatory issues in HIV vaccine clinical trials: lessons from a workshop

A successful HIV vaccine would have a substantial impact on acquisition of infection, progression of disease among the infected, or infectiousness of the infected. Current vaccine candidates are anticipated to have their major effect on viremia, however, with the expectation that this would induce or be concordant with a reduced rate of AIDS, death, or infectiousness. Although direct assessment of disease progression or infectiousness may be impractical, available potential surrogates for these endpoints may be misleading. This article summarizes the proceedings of a National Institute of Allergy and Infectious Disease-sponsored workshop to explore the use of surrogate endpoints for licensure of an HIV vaccine. Early, medium, and late endpoints were discussed, along with challenges such as surrogate validity, the confounding effect of antiretroviral therapy initiation, and potential selection bias in the vaccine and placebo recipients who become infected. Results from 5 hypothetic HIV vaccine clinical trials with ambiguously successful results were presented to an expert panel for interpretation and discussion of next steps. Key recommendations included assessing magnitude and durability of surrogate effects, generalization across populations, and directed improvement of vaccines. Use of acquisition and a postinfection surrogate as coprimary endpoints was supported, along with use of composite endpoints and exploration of heterogeneity in vaccine efficacy by characteristics of the host and virus.     

An overview of vaccinations in HIV

Prevention is an important aspect of HIV care in the era of highly active antiretroviral therapy. Vaccines provide an excellent opportunity to avert certain infectious diseases for which patients with HIV infection are at increased risk due to immunosuppression. However, the state of immunosuppression reduces the efficacy of vaccines and increases the risk associated with certain vaccines. The study of vaccine responses in patients with HIV infection has greatly advanced the understanding of the underlying immune deficits, particularly with regards to reduced CD4 cell number and function and the level of immune activation associated with chronic viremia. This research has also solidified the safety and utility of vaccines for this population. Continued research of vaccine responses will further our understanding of the immune system and optimize the utilization of routine immunizations.     

Injecting drugs of abuse and immunity: implications for HIV vaccine testing and efficacy

The recreational use of legal and illegal drugs has significant effects on immune responses and can potentially modulate susceptibility to infection by a number of pathogens. A number of agents including cannabinoids (marijuana), cocaine opiates, amphetamines, nicotine and alcohol were demonstrated to have potentially adverse effects on the susceptibility to infections, mediated most likely, by adverse effects on immunity. As such, these drugs of abuse could have significant and potentially adverse effects on the vaccination efficacy of a number of vaccines currently on the market and on potential experimental vaccines currently in the pipeline. This review will present an overview on how drugs of abuse potentially impacts immune responses and vaccination efficacy. The emphasis of this review will be the effects of opiate abuse, as exemplified by injecting/intravenous drug users (IDU), on HIV/AIDS and its potential impact on vaccine efficacy trials against this devastating infection/syndrome.