One in five volunteers in a multicenter HIV vaccine efficacy trial reported that their participation had at least one negative social impact in a three-year period.1 The overwhelming majority of negative experiences involved difficulties in interpersonal relationships; reports of problems with insurance or employment were rare. More than nine in 10 of the volunteers were men; for them, reports of negative events were associated with being 35 or younger, having more than one partner, participating at a study site that enrolled no more than 50 volunteers and participating at a site located in a city with a high AIDS prevalence.

The study, known as Vax004, was a randomized, placebo-controlled trial conducted at 57 sites in the United States, three in Canada and one in the Netherlands. Over a 17-month period beginning in 1998, a total of 5,417 individuals at risk of HIV infection—5,108 HIV-negative men who have sex with men and 309 women—enrolled. Participants were followed up for 36 months; every six months, they completed interviews that assessed the social impact of taking part in the trial. Interviewers asked about potential negative impacts involving personal relationships, unintentional disclosure of participation in the trial, employment, life and disability insurance, health insurance, housing, medical care, government agencies, travel and immigration, and unspecified other issues. Participants who acquired HIV infection during the trial had medical visits every four months for two years and were asked about social impacts at these visits as well.

Male participants were predominantly white (86%) and had at least a college education (64%); their average age was 36. Forty-four percent had had an HIV-infected partner in the six months before their baseline interview; the median number of partners in that interval was five. About half of male volunteers were enrolled at sites in cities with a medium-size population (more than 150,000 and less than 750,000), and about half were at sites located in cities with a medium prevalence of AIDS (more than 3,230 and fewer than 21,658 cumulative cases); six in 10 were enrolled at sites that had more than 100 trial participants.

Female volunteers were 37 years old, on average; most were black or Latino (69%) and had no more than a high school education (83%). Women’s median number of partners in the six months before enrollment was two; 42% had had an HIV-positive partner during that time. Close to six in 10 women were enrolled in sites in large cities, and a similar proportion were in cities where the cumulative number of AIDS cases was high (21,658 or more). Sixty-two percent were enrolled at sites with more than 100 volunteers.

Overall, 18% of volunteers experienced at least one negative social impact of trial participation; 3% experienced two or more. The most common problem was negative reaction from friends, family or partners (reported by 14% of participants), generally reflecting concern that the participant had or was at risk of acquiring HIV infection. The second most common event, reported by 3% of volunteers, was unintentional disclosure of participation in the trial. Each of the other potential problems was mentioned by fewer than 1% of participants.

During the trial, 368 volunteers became infected with HIV; 95% of this group provided information about negative social impacts after infection. Twelve reported a negative experience: Ten said that friends or relatives had blamed the vaccine for the infection or for increasing the participant’s susceptibility to infection, one had been denied life insurance by an insurer that attributed his HIV status to his participation in the trial and one had been told that his participation made him ineligible to enroll in an unrelated clinical trial.

Seventeen percent of participants who reported a negative event answered questions about the degree to which these events affected their quality of life. Overall, 87% said that the experiences had minimal or moderate impact; this proportion includes 93% of those reporting interpersonal problems. However, four of the five who had had problems with health insurance, six of the 22 who had had employment difficulties and one of the four reporting problems with medical or dental care said that these experiences had had a significant impact on their quality of life.

Because 94% of the volunteers were men, researchers assessed predictors of negative experiences separately by gender. For women, they conducted only univariate analyses, which indicated two significant relationships: The likelihood of reporting negative social impacts was elevated early in the trial and among women enrolled at sites with fewer than 50 participants.

For men, however, they assessed predictors in a model controlling for participants’ demographic characteristics and risk behaviors, characteristics of the enrollment site and timing of the interview. This analysis showed that the likelihood of reporting a negative experience was higher among men who were aged 18–25 or 26–35 at enrollment than among those aged 46 or older (odds ratios, 1.6 and 1.4, respectively), and higher among men who had had multiple partners shortly before entering the study than among those who had had none or one (1.3–1.4, depending on number). The odds of reporting a negative social impact were elevated for men at the sites with the fewest participants (2.3) and at sites in cities with the highest numbers of AIDS cases (1.4). Reports of negative experiences were less likely at the 12-month visit than at six months (0.5), and the differential increased at each successive visit (to 0.3 at 36 months).

The researchers find several important lessons in their results. One is the need for vaccine researchers to make clear to the public that HIV vaccines do not cause infection; another is the need for trial staff to discuss with volunteers whether and how to disclose their participation to family, friends and others. The unexpected finding that the likelihood of negative social events is elevated in AIDS epicenters suggests that “staff from these settings should not presume that living in a city heavily affected by HIV/AIDS translates to greater knowledge of HIV vaccines.” In conclusion, the researchers remark that “these and other steps should support culturally appropriate efforts to protect the well-being of future vaccine efficacy trial volunteers.”


1. Fuchs J et al., Negative social impacts among volunteers in an HIV vaccine efficacy trial, Journal of Acquired Immune Deficiency Syndromes, 2007, 46(3):362–368.