Colfax, Grant MD*; Buchbinder, Susan MD*; Vamshidar, Goli MPH†; Celum, Connie MD, MPH‡; McKirnan, David PhD§; Neidig, Judith PhD, RN∥; Koblin, Beryl PhD¶; Gurwith, Marc MD, JD#; Bartholow, Brad PhD†
From the *San Francisco Department of Public Health, San Francisco, CA; †Centers for Disease Control and Prevention, Atlanta, GA; ‡Division of Infectious Diseases, Department of Medicine, and Department of Epidemiology, University of Washington, Seattle, WA; §Howard Brown Health Center, Chicago, IL; ∥Office of Responsible Practices, Ohio State University, Columbus, OH; ¶New York Blood Center, New York, NY; and #VaxGen, Inc., Brisbane, CA.
Received for publication August 16, 2004; accepted November 16, 2004.
Reprints: Grant Colfax, HIV/AIDS Biostatistics, Epidemiology, and Interventions Section, San Francisco Department of Public Health, 25 Van Ness Avenue, Suite 500, San Francisco, CA 94102-6033 (e-mail: Grant.Colfax@sfdph.org).
An HIV vaccine, even if only partially effective, could prevent thousands of HIV infections and save thousands of lives.1 The development of such a product is likely to be an iterative process, however, requiring multiple efficacy trials, with each involving thousands of volunteers at high risk for HIV infection. The purpose of this analysis is to describe participants' motivations for joining the first phase 3 HIV vaccine efficacy trial, the VAX004 trial, and to identify the demographic and behavioral correlates of study participation. Although the trial did not demonstrate protective efficacy, it did demonstrate that a large number of men who have sex with men (MSM) and a smaller number of women at risk for heterosexual transmission of HIV could be enrolled into an HIV vaccine efficacy trial.
Assessment of motivations for joining HIV vaccine trials provides important information that helps to focus future education and recruitment efforts for vaccine trials. Motivations that people give for actually joining a phase 3 HIV vaccine trial may differ from motivations given when asked hypothetically if they would join a phase 3 trial and for actually joining phase 1 or 2 trials, partially because participants may have high expectations that the product in a phase 3 trial is going to have a protective effect. In addition, the large numbers of participants required for a phase 3 trial may include persons joining for a variety of reasons.
Prior studies assessing participants' motivations when asked if they would enroll in phase 1, phase 2, and hypothetic HIV vaccine trials have found that altruism was the most common reason given, although potential vaccine protection was also the motivation for substantial proportions of participants.2-4 One study of attitudes toward hypothetically participating in phase 3 trials found that MSM at higher sexual risk rated themselves as more likely to join a trial than did MSM at lower sexual risk.5
The VAX004 trial was a randomized, double-blind, placebo-controlled efficacy trial of AIDSVAX B/B. The product was a bivalent gp-120 HIV-1 subtype B vaccine developed using the MN and GNE8 strains of the predominant virus clade circulating in North America. The trial was conducted at 61 sites in the United States (n = 57), Canada (n = 3), and the Netherlands (n = 1). Two thirds of participants were randomly assigned to receive the vaccine and one third to receive a placebo. Details of trial design, recruitment methods, and study procedures have been previously described.6
The participants, MSM and women at risk for heterosexual transmission, were enrolled from June 1998 until November 1999. To be eligible, participants must have been 18 to 60 years of age, HIV-seronegative, healthy, and able to provide informed consent. Those reporting current injection drug use or a history of injection drug use up to 3 years before the baseline visit were excluded from enrollment. Men must have engaged in anal sex with a male partner during the previous 12 months and were excluded from enrollment if they had been involved in a monogamous relationship with an HIV-seronegative partner for 12 months or longer. Women were eligible to enroll if they reported any of the following behaviors during the prior 12 months: smoking crack, engaging in sex for drugs or money, having more than 5 or more male sex partners, or having a sexual relationship with an HIV-seropositive male partner. One male-to-female transgender person was included in the group of women at risk for heterosexual transmission. Recruitment methods varied by site and included printed advertisements, street outreach, and referrals from participants (ie, snowball sampling).
Volunteers were screened for HIV-1 antibodies using commercially available enzyme-linked immunoabsorbent assay (ELISA) kits approved by the US Food and Drug Administration (FDA). Positive test results were confirmed using commercially available immunoblot kits approved by the FDA. A face-to-face questionnaire with questions about participant demographics, medical history, sexually transmitted disease (STD) history, motivations for joining the trial, and sex- and drug-related risk behavior was administered at baseline. Questionnaires about HIV risk behavior and STDs were administered every 6 months throughout the trial.
Motivations for Participation
At baseline, participants were asked to report their motivations for joining the trial using a 5-point Likert-type scale (1 = agree strongly, 2 = agree, 3 = neither agree nor disagree, 4 = disagree, and 5 = disagree strongly). These motivations included altruism (ie, helping to find a vaccine or helping one's community); receiving money, care, or services (ie, HIV counseling and testing, medical care, information about HIV research); gaining protection from the vaccine; and being motivated to avoid risk behavior.
Multivariable linear and logistic regression methods were used to identify independent correlates of motivations for joining the VAX004 trial; outcomes of interest were motivations to join for protection, to reduce risk behavior, and composite benefits (to obtain free HIV testing and counseling, financial reimbursement or medical care, or current information on HIV). In these analyses, responses to motivation questions were collapsed into agree vs. disagree/undecided Predictor variables in all multivariate logistic regression models included sociodemographic and sexual risk variables and included adjustment for study site.
A total of 5417 participants were enrolled, with men enrolled at 98% (n = 60) of sites and women at 62% (n =38) of sites. Compared with men, the women were slightly older, were more ethnically diverse, had less education, had fewer median sex partners, and were more likely to report having had an STD in the past 6 months (Table 1). Substantial proportions of participants reported high-risk sexual behavior. Approximately 23% of the men and 21% of the women reported having had 13 or more sex partners in the 6 months before enrollment, and 39% of the men and 40% of the women reported having had unprotected anal or vaginal sex with a partner who was HIV-positive or of unknown serostatus.
Nearly all participants strongly agreed or agreed that they joined the trial for altruistic reasons, and three quarters reported having joined the trial to gain current information on HIV (Table 2). Approximately half of the participants agreed that they joined the trial to reduce their risk behavior or to get protection from HIV; 1 in 8 participants agreed strongly that he or she joined the trial to get protection. Approximately one third of participants reported having joined the trial to receive free HIV testing; relatively few participants reported having joined for financial reimbursement or to receive medical care. Women were more likely than men to provide multiple reasons for trial participation. The greatest differences between men and women were with regard to strong agreement or agreement with the following: to receive free HIV testing (31% of men strongly agreed or agreed vs. 71% of women; P < 0.001), to reduce risk behavior (54% vs. 83%; P < 0.001), for financial reimbursement (12% vs. 43%; P < 0.001), to obtain current information on HIV (74% vs. 97%; P < 0.0001), and to get protection from HIV (45% vs. 62%; P < 0.0001).
Multivariate analysis showed that women were nearly twice as likely as men to report having joined the trial for protection (Table 3). Univariate analysis showed the following high-risk sexual behaviors to be significantly associated with motivation for protection: having had any unprotected anal or vaginal sex in the prior 6 months, having an HIV-seropositive partner, and having had 13 or more sex partners. Having had 13 or more sex partners remained significantly associated with motivation for protection according to the multivariate model.
Women were also more likely than men to report having joined the trial to reduce their risk behavior, as were participants of race/ethnicity other than white compared with white persons, although these differences were of borderline statistical significance according to the multivariate model (see Table 3). Participants with less education were more likely than those with a graduate degree or greater to report joining the trial to reduce risk. Participants reporting any unprotected anal or vaginal intercourse during the prior 6 months were also more likely to be motivated to join the trial to reduce their risk, although those who reported having 13 or more sex partners were less likely to report having joined to reduce risk.
As shown in Table 3, associations of having joined for composite benefits were similar to having joined to reduce risk behavior. The multivariate analysis showed that women were nearly 3 times more likely than men to have joined the trial for composite benefits; participants of race/ethnicity other than white were also more likely than white participants to have joined for composite benefits. Participants with less education were more likely than those with more education to have joined for composite benefits. Participants reporting 13 or more sex partners were less likely than those reporting fewer sex partners to have joined for composite benefits.
We found that most participants were motivated to join this phase 3 vaccine trial for altruistic reasons, although substantial proportions also joined to gain protection from HIV and to reduce their risk behavior. Compared with findings from studies of willingness of participants to join non-HIV clinical trials, we found participants more likely to report altruistic reasons for participation and similar proportions reporting joining for personal health benefits.7 Our findings are similar to those from phase 1 and 2 HIV vaccine trials, in which altruistic reasons were the primary motivators for trial participation.4 They also reflect findings from the HIVNET Vaccine Preparedness Study, which found that participants gave primarily altruistic reasons when asked hypothetically whether they would join a phase 3 vaccine trial.8 These findings indicate that vaccine recruitment strategies appealing to the altruistic aspects of vaccine trial participation may be one of the most effective strategies for recruiting participants for future vaccine trials. Such strategies may include appealing to volunteerism, participating in research to help stop the HIV epidemic, and helping the community.
Nearly half of the participants reported having joined the trial to gain protection from HIV, despite having received vaccine education before trial enrollment as part of the informed consent process. The education emphasized that the efficacy of the product was unknown and that one third of participants would receive a placebo. Similar to prior studies of potential and actual participants in phase 1 and 2 vaccine trials,9,10 our study showed that the most sexually active participants were more motivated by protection than were those participants with fewer sex partners. Importantly, we also found that these participants were the least likely to join the trial to reduce their risk behavior. These findings suggest that HIV risk-reduction counseling within vaccine efficacy trials should emphasize the unknown efficacy of the experimental vaccine and the need for sexual risk reduction, especially for persons with high numbers of sex partners. Potentially, these persons should be targeted for additional counseling and education before trial enrollment. Continued risk reduction counseling after enrollment should also be emphasized: our finding that participants who reported unprotected anal intercourse were likely to join the trial to reduce their risk behavior indicates that some persons engaging in high-risk sexual behavior may be responsive to risk reduction counseling during vaccine trials.
Although altruistic reasons were commonly cited by MSM and women at risk for heterosexual transmission, we found clear differences in the motivations for joining the VAX004 trial between the 2 groups. Women were more likely than men to provide multiple reasons for study participation. The fact that women were more likely than men to join the trial to gain protection from HIV raises concern that female participants may have had unrealistic expectations about the benefits of trial participation. Many women provided additional personal reasons for trial participation, suggesting that compared with men, women had fewer options to receive HIV prevention services (eg, free testing, medical care, HIV prevention information) outside the trial. We found similar patterns for participants of race/ethnicity other than white compared with white participants, after adjusting for gender. To ensure that people do not feel compelled to join vaccine trials to receive services, additional public health efforts may be needed to ensure that women and persons of color have access to such services outside trials. Similarly, our finding that participants with less education were especially likely to join the VAX004 trial to reduce their risk behavior suggests that there may be a greater need for HIV prevention services, including risk reduction counseling, among less-educated populations.
Our results may be limited by data collection techniques. The data were collected using interviewer-based questionnaires, potentially leading to the underreporting of socially undesirable behaviors. Similarly, participants may have been less comfortable reporting joining the trial for nonaltruistic reasons. Data were not collected on a large number of potential confounding variables. For instance, although we were able to control for education level, our findings on gender-specific differences may be confounded by other unmeasured variables, such as income or other social class-related variables. Finally, it should be noted that no data were available on possible motivations for potential trial participation among persons who may have been screened for the study but were not enrolled.
In summary, most persons participating in this first phase 3 vaccine trial gave altruistic reasons for trial participation. The fact that many participants reported joining the trial, at least in part, for personal benefits reinforces the need to broaden HIV vaccine education and prevention efforts before and during future vaccine trials, especially for women and people of color.
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