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.     

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.     

Willingness of injection drug users to participate in an HIV vaccine efficacy trial in Bangkok, Thailand.

We assessed willingness to participate in an HIV recombinant gp120 bivalent subtypes B/E candidate vaccine efficacy trial among 193 injection drug users (IDUs) attending drug treatment clinics in Bangkok, Thailand. IDUs previously enrolled in a prospective cohort study were invited to group sessions describing a potential trial, then completed questionnaires assessing comprehension and willingness to participate. A week later, they completed a follow-up questionnaire that again assessed comprehension and willingness to participate, as well as barriers to and positive motives for participation, with whom (if anyone) they talked about the information, and whether others thought participation was a good, bad, or neutral idea. At baseline, 51% were definitely willing to participate, and at follow-up 54%; only 3% were not willing to participate at either time. Comprehension was high at baseline and improved at follow-up. Participants who viewed altruism, regular HIV tests, and family support for participation as important were more willing to volunteer. Frequency of incarceration and concerns about the length of the trial, possible vaccine-induced accelerated disease progression, and lack of family support were negatively associated with willingness. Overall, IDUs comprehended the information needed to make a fully informed decision about participating in an rgp120 vaccine efficacy trial and expressed a high level of willingness to participate in such a trial.     

Behavioral and social issues among volunteers in a preventive HIV vaccine trial in Thailand

Behavioral and social issues were investigated in 363 phase I/II preventive HIV-1 vaccine trial volunteers in Thailand. These issues included risk behavior, HIV knowledge, distress, and social consequences of vaccine trial participation. Data were collected at baseline and at 4-, 8-, and 12-month follow-up visits. Volunteers reported relatively low levels of risk behaviors at baseline and at follow-up. Overtly negative reactions from family or friends were reported by 5.9%. No experiences of discrimination in employment, health care, or insurance were reported. Mean levels of distress were low throughout the trial, and HIV-related knowledge was high, although it was common to consider the possibility of HIV transmission through casual contact. Findings add to the evidence that preventive HIV vaccine trials are feasible in Thailand.     

Determinants of enrollment in a preventive HIV vaccine trial: hypothetical versus actual willingness and barriers to participation

OBJECTIVE: To compare hypothetical and actual willingness to enroll in a preventive HIV vaccine trial and identify factors affecting enrollment. METHODS: Participants previously enrolled in an HIV vaccine preparedness study (VPS) in 8 US cities were invited to be screened for a phase 2 HIV vaccine trial. Demographic and risk characteristics of those enrolling, ineligible, and refusing enrollment were compared using the chi2 or Fisher exact test. Multivariable logistic models were used to identify independent predictors of refusal. RESULTS: Of 2531 high-risk HIV-uninfected former VPS participants contacted for the vaccine trial, 13% enrolled, 34% were ineligible, and 53% refused enrollment. Only 20% of those stating hypothetical willingness during the VPS actually enrolled in this vaccine trial. In multivariate analysis, refusal was higher among African Americans and lower in persons >40 years of age, those attending college, and those with > or =5 partners in the prior 6 months. All racial ethnic groups cited concerns about vaccine-induced seropositivity; African Americans also cited mistrust of government and safety concerns as barriers to enrollment. CONCLUSIONS: Steps can be taken to minimize potential social harms and to mobilize diverse communities to enroll in trials. Statements of hypothetical willingness to participate in future trials may overestimate true enrollment.     

Inclusion of adolescents in preventive HIV vaccine trials: public health policy and research design at a crossroads

The search for a safe effective HIV vaccine has been a centerpiece of HIV research for almost 2 decades. More than 60 clinical HIV vaccine trials have been conducted to date. Several promising candidate HIV vaccines are in advanced clinical development. To date, however, no trial has included adolescents, one of the most important target groups for any preventive HIV vaccine. To license a vaccine for use in this age group, efficacy data or, at a minimum, bridging safety and immunogenicity data in this population are needed. To accomplish this, several critical issues and special challenges in the development and implementation of HIV vaccine trials in adolescents must be addressed, including regulatory considerations, potential differentials in safety and immunogenicity, alternative trial design strategies, recruitment and retention challenges, community involvement models, and approaches to informed consent/assent. This article examines these issues and proposes specific next steps to facilitate the routine inclusion of this high-priority population in preventive HIV vaccine trials as early and seamlessly as possible.     

Knowledge about vaccines and willingness to participate in preventive HIV vaccine trials: a population-based study, Rakai, Uganda

The purpose of the study was to assess knowledge and beliefs regarding vaccines and willingness to participate in HIV vaccine trials. A baseline survey assessed knowledge and attitudes toward vaccination and potential HIV vaccines among 14,177 participants aged 15-49 years, in a population cohort. Willingness to participate in HIV-preventive vaccine trials was assessed during a follow-up survey 10 months later after providing community education on HIV vaccines. Knowledge of the preventive utility of vaccines was high (71%), but higher in men than women (P<0.001), and increased with education levels (P<0.001). Vaccines were considered appropriate for children and women (99 and 88%, respectively), but not for adult men (28%). Participants felt that adolescents were the most appropriate subjects for HIV preventive vaccine trials (93.7%) but also thought that HIV-positive persons were eligible for trials (60.2%), and only 20% thought a preventive vaccine could help control HIV. HIV vaccine awareness increased from 68% at baseline to 81% at follow-up (P<0.001). Willingness to participate in HIV-preventive vaccine trials was 77%. Vaccine knowledge and willingness to participate in trials are high in this population. However, there still is need for education on the potential role of preventive HIV vaccines in the control of the epidemic and the importance of vaccination for men, especially in the context of an HIV vaccine.     

Race and HIV Clinical Trial Participation

PurposeThis study was designed to examine at the role race/ethnicity plays in human immunodeficiency virus (HIV) clinical trial enrollment.BackgroundHIV clinical trials are vitally important for improving knowledge about medications and their impact on the pathogenesis of HIV/AIDS. African Americans are disproportionately underrepresented in HIV clinical trials.MethodsA 49-item survey was administered to 145 patients at an urban HIV clinic to explore race and HIV clinical trial participation.ResultsStudy participants were 56% Caucasian, 19% other, 16% African American, and 13% Hispanic. Fewer African Americans had been asked to participate in a trial compared to other groups (8% vs 24%) (p < .05). African Americans were less likely to volunteer for a trial compared to Hispanics and Caucasians, but African Americans did not differ significantly in their willingness participate in clinical trials vs other racial groups. In a regression model age, past trial participation, monetary gain, and comfort with the clinical setting predicted willingness to participate in a trial across racial groups (p < .05).DiscussionThere is a strong need to identify strategies to increase African American enrollment in trials. Such strategies need to begin with trial recruiters actively seeking out African Americans for clinical trial enrollment.     

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 interest to participate in a dengue vaccine efficacy trial among residents of Puerto Rico

Dengue, endemic in Puerto Rico, is a major public health problem. Vaccines are thought the best means to prevent dengue because vector control alone has been largely ineffective. We implemented qualitative studies in 2006 and 2010 to determine the acceptability of conducting placebo-controlled dengue vaccine efficacy trials in Puerto Rican children. Key informant interviews and focus groups with parents and children were conducted in municipalities with high dengue incidence. We used structured open-ended questions to determine motivators and attitudes regarding vaccine trial participation. Knowledge about dengue risk and prevention, and knowledge, attitudes, and beliefs regarding vaccines and vaccine trials were assessed. Using grounded theory, we conducted content analysis and established categories and sub-categories of participant responses. All participants were knowledgeable about dengue prevention and perceived children as most affected age groups. Participants were aware of vaccines benefits and they thought a vaccine could prevent dengue. However, most would not allow their children to participate in a placebo-controlled vaccine trial. Barriers included lack of trust in new vaccines and vaccine trial procedures; fear of developing dengue or side effects from the vaccine and lack of information about candidate dengue vaccines. Participants thought information, including results of previous trials might overcome barriers to participation. Motivators for participation were altruism, protection from dengue, free medical attention, and compensation for transportation and participation. Parents would consider children participation if accurate vaccine trial information is provided.     

Determinants of Participation in HIV Clinical Trials: The Importance of Patients’ Trust in Their Provider

Abstract

Purpose: To investigate the factors that contribute to willingness to participate in HIV clinical trials and to determine the impact of a brief intervention on willingness to participate. Methods: 115 consecutive outpatients receiving HIV primary care participated in this prospective study. Each patient completed a questionnaire about clinical trials and met with a research assistant who discussed the purpose of clinical trials. After the educational intervention, participants completed a second questionnaire and responses from the two surveys were compared. Results: 115 patients were enrolled (56% had previously enrolled in a clinical trial; 50% of whom were currently enrolled in a trial); 92% would consider participating in a future clinical trial. Increased patient trust in the provider was associated with increased willingness to participate in a trial. After the intervention, 94% indicated that they would be willing to be contacted about a clinical trial for which they may be eligible and 85% preferred to be contacted by their primary physician. Conclusions: Patients’ trust in their provider may predict willingness to participate in clinical trial. Providing HIV-infected patients and their providers with information about HIV clinical trials at the site where they receive care may increase participation rates in HIV clinical trials.     

The HVTN protocol 903 vaccine preparedness study: lessons learned in preparation for HIV vaccine efficacy trials

Successful recruitment and retention of HIV-uninfected at-risk participants are essential for HIV vaccine efficacy trials. A multicountry vaccine preparedness study was started in 2003 to assess enrollment and retention of HIV-negative high-risk participants and to assess their willingness to participate in future vaccine efficacy trials. HIV-negative high-risk adults were recruited in the Caribbean, in Southern Africa, and in Latin America, and were followed for 1 year. Participants included men who have sex with men, heterosexual men and women, and female sex workers. History of sexually transmitted infections and sexual risk behaviors were recorded with HIV testing at 0, 6, and 12 months, and willingness to participate in future vaccine trials was recorded at 0 and 12 months. Recruitment, retention, and willingness to participate in future trials were excellent at 3 of the 6 sites, with consistent declines in risk behaviors across cohorts over time. Although not powered to measure seroincidence, HIV seroincidence rates per 100 person-years (95% confidence interval [CI]) were as follows: 2.3 (95% CI: 0.3 to 8.2) in Botswana, 0.5 (95% CI: 0 to 2.9) in the Dominican Republic, and 3.1 (95% CI: 1.1 to 6.8) in Peru. The HIV Vaccine Trials Network 903 study helped to develop clinical trial site capacity, with a focus on recruitment and retention of high-risk women in the Americas, and improved network and site expertise about large-scale HIV vaccine efficacy trials.     

Impact of age on CD4 recovery and viral suppression over time among adults living with HIV who initiated antiretroviral therapy in the African Cohort Study

The pressing need to expand the biomedical HIV prevention evidence base during pregnancy is now increasingly recognized. Women’s views regarding participation in such trials and initiating PrEP while pregnant are critical to inform evolving policy and best practices aimed at responsibly expanding evidence-based access for this population. We conducted 35 semi-structured interviews with reproductive-aged women in Malawi in the local language, Chichewa. Participants were HIV-negative and purposively sampled to capture a range of experience with research during pregnancy. Women’s perspectives on enrolling in three hypothetical HIV prevention trial vignettes while pregnant were explored, testing: (1) oral PrEP (Truvada) (2) a vaginal ring (dapivirine), and (3) a randomized trial comparing the two. The vignettes were read aloud to participants and a simple visual was provided. Interviews were audio-recorded, transcribed, translated, and coded using NVivo 11. Thematic analysis informed the analytic approach. A majority of women accepted participation in all trials. Women’s views on research participation varied largely based on their assessment of whether participation or nonparticipation would best protect their own health and that of their offspring. Women interested in participating described power dynamics with their partner as fueling their HIV exposure concerns and highlighted health benefits of participation—principally, HIV protection and access to testing/treatment and ancillary care, and perceived potential risks of the vignettes as low. Women who were uninterested in participating highlighted potential maternal and fetal health risks of the trial, challenges of justifying prevention use to their partner, and raised some modality-specific concerns. Women also described ways their social networks, sense of altruism and adherence requirements would influence participation decisions. The majority of participants conveyed strong interest in participating in biomedical HIV prevention research during pregnancy, largely motivated by a desire to protect themselves and their offspring. Our results are consistent with other studies that found high acceptance of HIV prevention products during pregnancy, and support the current direction of HIV research policies and practices that are increasingly aimed at protecting the health of pregnant women and their offspring through responsible research, rather than defaulting to their exclusion.     

Belief of vaccine receipt in HIV vaccine trials: further cautions.

The purpose of this cross-sectional study was to examine relationships between belief in vaccine receipt, motivations for trial participation, and side effects in phase 1 vaccine trials. Anonymous questionnaires were completed by 125 active vaccine volunteers at two vaccine evaluation sites. Participants believing they had received the vaccine reported more side effects (p < .01), were less likely to report knowing someone with HIV/AIDS as a motivation for trial participation (p < .01), and endorsed greater concern about becoming HIV-infected as motivation for participation (p < .05). Results indicate that inferences made by trial participants in vaccine trials should be identified and addressed, and that greater efforts for maintaining the blinded nature of vaccine trials and educating trial participants about the meaning of side effects are warranted.     

Partner-specific sexual behavioral differences between phase 3 HIV vaccine efficacy trial participants and controls: Project VISION

OBJECTIVE: To assess and compare sexual behaviors using partner-specific data between HIV-negative men who have sex with men (MSM) recruited for an HIV vaccine efficacy trial and a control group. METHODS: HIV-negative MSM from an HIV vaccine trial (n = 525) and controls (n = 732) were recruited by similar strategies and interviewed about behaviors with the 3 most recent partners in the past 6 months, obtained by audio computer-assisted self-interview (A-CASI). RESULTS: Vaccine trial participants were more likely than controls to report an HIV-positive partner (24.7% and 14.1%, respectively) or an HIV-positive primary partner (16.1% and 6.8%, respectively) and were less likely to report occasional or single-time partners of unknown HIV status (51.6% and 63.2%, respectively; P < 0.05 for each comparison). Vaccine trial participants more often reported receptive unprotected anal intercourse (UAI) during their last sexual encounter with an HIV-positive partner (adjusted odds ratio [OR] = 2.7, 95% confidence interval [CI]: 1.0 to 7.9). Most believed their HIV-positive partners were receiving antiretroviral treatment (ART), however, and after adjustment for perceived ART use, the association between vaccine study participation and receptive UAI with an HIV-positive partner was not significant. CONCLUSIONS: High-risk sexual behavior was reported by many VAX004 participants and controls. Differences between vaccine trial and control participants in the highest risk per contact behavior, receptive UAI with HIV-positive partners, was partly accounted for by perceived ART use. Partner level data are useful in refining risk assessment, which is important in the evaluation of HIV vaccine and other prevention trials.     

Readiness for HIV vaccine trials: changes in willingness and knowledge among high-risk populations in the HIV network for prevention trials. The HIVNET Vaccine Preparedness Study Protocol Team

Longitudinal data were analyzed to determine changes in willingness to participate in HIV vaccine efficacy trials and knowledge of vaccine trial concepts among populations at high risk of HIV-1 infection. Gay men (MSM), male and female injection drug users, and non-injecting women at heterosexual risk were recruited (n = 4892). Follow-up visits occurred every 6 months up to 18 months. Willingness was significantly lower at follow-up visits compared with at baseline. Knowledge levels increased for all study populations. Problematic concepts were possible effects of the vaccine on the immune system and lack of knowledge about efficacy of a vaccine before the start of a trial. For concepts concerning safety, blinding, and guarantees of future participation in trials, MSM men had significant increases in knowledge, but little to no change occurred for the other populations. An increase in knowledge was associated with becoming not willing, particularly among MSM with low knowledge levels. At least half of high-risk participants were consistently willing to participate in future vaccine efficacy trials and with basic vaccine education, knowledge levels increased. Continued educational efforts at the community and individual level are needed to address certain vaccine trial concepts and to increase knowledge levels in all potential study populations.     

Willingness to participate in HIV vaccine trials among men who have sex with men in Rio de Janeiro, Brazil. Projeto Praça Onze Study Group

Evaluation of HIV vaccines requires high-risk individuals willing to participate in a vaccine trial. We investigated the willingness to participate in HIV vaccine trials of initially HIV-seronegative homosexual men enrolled in an HIV seroincidence cohort study. Of 815 initially HIV-seronegative participants, 569 (69.8%) reported willingness to participate in an HIV vaccine trial. Altruism was the primary reason given for wanting to participate. Fear of HIV infection from the study's immunizations and a vaccine-induced positive HIV test result were the main reasons for not wanting to participate. Of the 34 study subjects who eventually had HIV seroconversion, 29 (85%) had indicated a willingness to participate. In a univariate analysis, factors associated with willingness to participate included HIV seroconversion during follow-up (odds ratio [OR]. 2.6; p =.04), low educational level (OR, 1.6; p =.005), low family income (p =.02), and exchanging sex for housing, food, or clothing (OR 6.1; p =.005). Students were less likely to be willing to participate in a trial (OR, 0.7; p = .03), as well as those who reported sex at the first encounter (OR, 0.7; p = .05). In a multivariate analysis, low education level, infection with Condyloma, and exchanging sex for housing, food, or clothing were positively associated with willingness to participate, whereas being a student and reporting sex at first encounter were negatively associated. In general, factors indicative of high-risk of HIV infection were associated with a higher willingness. These data demonstrate that this high-risk homosexual male cohort has a high willingness to participate in HIV vaccine trials.     

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.     

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.     

Negative social impacts among volunteers in an HIV vaccine efficacy trial

OBJECTIVE: Describe the negative social impacts (NSIs) and their predictors in an HIV vaccine efficacy trial. METHODS: Volunteers in the North American phase 3 trial of AIDSVAX B/B vaccine were questioned semiannually about NSIs. Multivariable logistic models identified independent predictors of NSI reporting. RESULTS: Of 5417 volunteers (94% male), 18% reported at least 1 NSI. Most events occurred early during trial participation and involved concerns by family and friends that the volunteer was HIV-infected or at risk for infection. Problems with disability/life insurance and employment occurred less frequently (<1%). Individuals who became HIV-infected reported NSIs similar to HIV-negative volunteers. In multipredictor analysis of male volunteers, NSI reporters were younger (adjusted odds ratio [OR(Adj)] = 1.6, 95% confidence interval [CI]: 1.2 to 2.1 and OR(Adj) = 1.4, 95% CI: 1.1 to 1.8 for ages 18 to 25 years and 26 to 35 years vs. > or =46 years, respectively), enrolled at sites with 50 or fewer volunteers (OR(Adj) = 2.3, 95% CI: 1.7 to 3.1), or lived in cities with high AIDS case rates (OR(Adj) = 1.4, 95% CI: 1.1 to 1.8). CONCLUSIONS: A modest proportion of vaccine efficacy trial volunteers reported problems in interpersonal relationships from trial participation. Serious harms involving insurance and employment were rare. Strategies to prevent harm from disclosure, particularly for younger volunteers and those from high seroincidence sites, may reduce NSIs in future trials.