An HIV-preventive vaccine is urgently needed to control the HIV pandemic, particularly in developing countries where the prevalence and incidence of HIV are high, but resources for prevention and care are limited. 1–3 Given the genetic variability of HIV, the geographic differences in subtypes and negative results of the first phase 3 efficacy trial, 4 it is probable that multiple trials will be needed.
Knowledge of and attitudes toward HIV vaccines are among the factors that may influence participation in trials and the eventual acceptability of efficacious vaccines. 5–9 Most studies have been conducted in selected populations of gay men, injection drug users, commercial sex workers, and college students. 5–15 However, there is no information on willingness to participate (WTP) in HIV vaccine trials from general population studies particularly in developing countries, 16,17 which represent an important population for vaccine efficacy testing. To address this issue, we assessed knowledge and beliefs regarding HIV vaccines as well as WTP in vaccine trials in a rural population cohort in Rakai, Uganda, with an HIV prevalence of 15% and incidence of 1.4/100 person-years. Rakai district is a potential site for phase 3 HIV-preventive vaccine trials.
Between April 1999 and March 2002, we conducted the Community HIV Epidemiological Research study (CHER) to assess the suitability of Rakai district for future phase 3 HIV vaccine trials. The study was a continuation of a community cohort established in 1994 for the sexually transmitted diseases (STD) control study that ended in 1999. 18,19
Consenting adults aged 15–49 years, resident in 56 communities in Rakai, were enrolled and visited in the home every 10 months, during which a questionnaire was administered in privacy by same-sex interviewers, and venous blood was collected for HIV-1 testing. All questions were translated in the local language (Luganda) and pretested. Participants who provided blood were encouraged to receive free voluntary counseling and test (VCT) results provided by community-based counselors. Prebaseline health education was provided on study objectives and HIV/STD prevention strategies focusing mainly on safe sex behaviors including faithfulness (i.e., monogamy), abstinence, or condom use, and VCT.
At the baseline, CHER survey data were collected on knowledge and beliefs about vaccination, HIV/STD risk behaviors, and participants' perception of the severity of the AIDS epidemic in Rakai and methods for controlling it. For data collected on receipt of previous vaccination, reasons for use of vaccines, concerns about vaccine safety, eligibility for vaccination, and awareness of potential HIV vaccines, the questionnaire used unprompted questions and allowed for an “other” category for nonspecified responses, which were recorded verbatim.
Between baseline and follow-up surveys, education on potential HIV-preventive vaccines was provided. The topics included the need for an HIV-preventive vaccine, the research/testing processes (including use of placebo) that any potential vaccine would undergo, and the need to prepare populations for future HIV-preventive vaccine research. It was emphasized that CHER was neither a vaccine trial nor a preparatory phase for an available HIV vaccine construct.
During the CHER follow-up survey, we assessed WTP in HIV vaccine trials, eligibility for participation in trials, and knowledge of potential HIV vaccines. Additionally, we evaluated participants' awareness of the phase 1 ALVAC™-HIV trial in Kampala, Uganda. 9
We determined the frequencies of vaccine knowledge and attitudes by sociodemographic and behavioral characteristics, and differences were assessed by χ2 tests. Previous studies suggest that sociodemographic characteristics, risk behavior, and self-perception of HIV risk are associated with WTP. 5,7–9,16 We determined the rate of WTP and examined the association between WTP and sociodemographic characteristics, risk behaviors, self-perception of HIV risk, previous participation in VCT, and awareness of potential HIV vaccines. Log-binomial regression models were used to estimate the adjusted rate ratios (RRs) and 95% CIs of factors associated with WTP. 20 Models were adjusted for age, gender, and statistically significant covariates identified in univariate analyses. Statistical analysis was conducted using Stata 7.0 (Stata Corp.; College Station, TX).
Knowledge of and Attitudes Toward Vaccines at the Baseline Survey
Table 1 shows knowledge and attitudes toward vaccines at the baseline survey. Ninety-nine percent were aware of vaccination, 83% gave a history of previous vaccination, and 87% reported polio as a childhood immunizable disease. There were no gender or age differences in awareness of vaccination. However, adolescents and male participants were less likely to report receipt of previous vaccination (P < 0.001). Knowledge of the utility of vaccines was high (71%) but was notably higher in men than women (78.8 and 67.6%, respectively, P < 0.001). Vaccine knowledge increased with education levels (P < 0.001). Eighty-three percent of the participants expressed no concerns about vaccine safety, 7.8% thought vaccines might be lethal, and 2.6% reported that vaccines cause fever/illness. Concerns about vaccine safety were significantly higher among men and older participants (P < 0.001) and increased with higher levels of education (P < 0.001).
Most participants thought children and women (99 and 88%, respectively) were eligible for vaccination, but only 28% thought that men were eligible. Moreover, 61% of male participants thought men should not receive vaccines. Only 12% considered HIV/AIDS a “very serious” problem in Rakai despite the high HIV prevalence and the HIV-attributable mortality in this population. 21 Regarding methods of controlling HIV, 41% reported faithfulness (monogamy), and only 20% reported use of an HIV vaccine. Men were more likely than women (23 vs. 17%, respectively, P < 0.001) and adolescents were less likely than adults (16.2 vs. 20.8%, P < 0.001) to report use of a vaccine as a means of preventing HIV. Sixty-eight percent were aware of potential HIV vaccines and 41% knew about Uganda's first HIV vaccine trial. 9
Knowledge and Attitudes Toward HIV Vaccines at Follow-up
Of the 14,177 participants interviewed at baseline, 10,312 (73%) were reinterviewed at the follow-up survey. We assessed the impact of a community-based education program on knowledge of potential HIV vaccines. Awareness of HIV vaccines increased from 68% at baseline to 81% at follow-up (P < 0.001), but knowledge of HIV vaccine testing in Uganda remained unchanged (41% at both interviews). Information on HIV vaccines came mainly from the Rakai project education program (74%); other sources included radio/television (15%) and hospitals/clinics/newspapers (~10%). It is noteworthy that participants believed that HIV-infected and HIV-uninfected subjects were appropriate for participation in trials (60.2 and 69.8%, respectively), despite the education program's emphasis on preventive vaccines.
Willingness to Participate in Future Vaccine Trials
At the follow-up survey, 77% of participants indicated willingness to participate in future HIV vaccine trials, and as shown in Table 2, WTP did not differ by sociodemographic characteristics. On univariate analysis, self-perception of HIV risk, previous receipt of VCT, awareness of potential HIV-preventive vaccines, and receipt of information on HIV vaccines were significantly associated with WTP. These covariates plus age and gender were incorporated in the multivariate regression model. After adjustment, only self-perception of HIV risk (adjusted RR = 1.12; 95% CI, 1.10–1.15) and receipt of education on vaccines (adjusted RR = 1.03; 95% CI, 1.01–1.06) were significantly associated with WTP.
Consistent with other studies, 9,13,16 we found a high level of knowledge of vaccination in this rural Ugandan population and this probably reflects the high childhood immunization coverage in the district 22 and nation-wide immunization campaigns. However, most participants, including more than half of the men, thought that vaccines were only useful for children and women. Many participants thought men were not eligible for vaccination, probably because vaccination in this population is mainly for children and pregnant women. If unchanged, this belief may affect participation of men in future HIV vaccine trials and the eventual acceptability of a successful vaccine. Vaccine trials will require comprehensive education, and our strategy of using village-based health education meetings resulted in a significant increase in the level of awareness of potential HIV vaccines from 68% at baseline to 81% at follow-up. However, fewer than half the participants were aware of the phase 1 ALVAC-HIV trial in Kampala. 23 In rural populations where illiteracy levels are high and access to media is low, education is probably best conducted via face-to-face village meetings.
With an HIV prevalence of 15% and almost 2 decades of experience with the AIDS epidemic in Rakai district, only 12% considered AIDS to be a “very serious problem,” and knowledge of the potential utility of an HIV-preventive vaccine was low (20%). This probably reflects the abatement of the HIV epidemic in Uganda, which has received considerable publicity that may be engendering growing complacency. There is need for more education on the persistence of the HIV/AIDS epidemic, the need to prevent transmission, and the potential role of HIV-preventive vaccines.
This population-based study showed a high level of WTP in HIV vaccine trials (77%), which is comparable to levels found in the Ugandan military (79%) but higher than levels in North American gay men/injection drug users (46%) and in commercial sex workers or STD clinic attendees in northern Thailand (~25%). 9,16,24 WTP did not vary substantially by sociodemographic characteristics, self-perceived risk of HIV, or knowledge of vaccines. Therefore, future vaccine trials may not require targeting of population subgroups.
The limitations of our data are that questions regarding WTP were hypothetical, and the Rakai cohort has been under surveillance for several years so attitudes toward participation in research activities may differ from those in other populations. Additionally, WTP was assessed after general community education rather than following an HIV vaccine trial-specific education program.
In conclusion, the Rakai population has a high level of knowledge of vaccination and WTP in HIV vaccine trials. However, there still is a need for more education, particularly on the severity of the HIV/AIDS epidemic and the potential utility of HIV-preventive vaccines.
The authors appreciate the contribution of study participants, project staff, and Dr. S.K. Sempala, Uganda Virus Research Institute.
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