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We assessed risk behaviour in a heterosexual cohort undergoing prescreening for the first Phase I/II HIV vaccine trials in Soweto. We developed a survey and collected self-reported data from HIV-negative potential volunteers. Of 488 participants, most were single and approximately half were from households with incomes below the poverty level. Males reported higher rates of heavy alcohol use (P < 0.001), marijuana use (P < 0.001) and other recreational drug use (P < 0.01). Males reported more sex partners than females in the previous six months (P < 0.001), as well as more casual/anonymous partners (P < 0.001) and one-night stands (P < 0.001). Multivariate analyses revealed substance use and male gender predicted higher risk behaviours, including <100% condom use with known/suspected HIV-positive partners, having casual/anonymous partners and having more than two partners. For this population, male volunteers may need increased risk-reduction counselling during Phase I/II trials and additional recruitment methods may be necessary to identify high-risk female volunteers for Phase III efficacy trials.
A major concern regarding the conduct of HIV vaccine trials is that individuals may increase their risk-taking behaviour, assuming that they are protected from HIV infection when, in actuality, they might not be.1– 4 In addition to placing individual vaccine trial participants at greater risk for HIV infection, changes in risk-taking behaviour can also affect both the sample size and efficacy calculations that determine trial outcomes and, ultimately, whether a vaccine candidate is licensed for use.5– 8 For these reasons, appropriate and accurate assessment of risk behaviour during vaccine trials remains a priority.
Data on the sexual risk behaviours of African cohorts entering HIV vaccine trials are scarce, and no effective tools have been published that measure risk behaviour in low- and middle-income country populations. Eight countries – Rwanda, Kenya, Uganda, Tanzania, Zambia, Botswana, Malawi and South Africa – are enrolling volunteers and conducting HIV vaccine trials to date.9,10 As the first of these to initiate HIV vaccine trials, South Africa provides an important example for studying African risk behaviour in potential HIV vaccine trial participants. The baseline sexual risk behaviours of South Africans enrolling into HIV vaccine trials, both individually and in the communities from which they originate, have not been characterized to date. Although one study has characterized the risk behaviour of participants in an observational cohort group examining incidence and retention in preparation for vaccine trials,11 further study is needed for participants being actively enrolled into vaccine trials, characterizing different communities and examining sexual risk behaviours within specific partnerships.
In this study, we report the initial results of risk behaviour monitoring of a predominantly heterosexual cohort of potential vaccine trial participants undergoing screening and enrolment into Phase I and II HIV vaccine trials in Soweto, using a detailed risk behaviour assessment tool adapted to South African language and customs developed for this purpose.12–15 The results we report here provide one of the first characterizations of the risk behaviours in an African population participating in HIV vaccine trials.
We assessed sexual risk behaviour within the context of ongoing screening and enrolment into Phase I/II adult HIV vaccine trials at the HIV/AIDS Vaccine Division (HAVD) of the Perinatal HIV Research Unit, University of the Witwatersrand, located at the Chris Hani Baragwanath Hospital in Soweto. Soweto is the largest black urban township in South Africa with a population of approximately 1.1 million16 (and personal communication, Johannesburg City Council) and antenatal HIV prevalence of 30% (personal communication, Perinatal HIV Research Unit); it is situated southwest of Johannesburg in Gauteng province, which has an overall HIV prevalence of 16% in residents 15–49 years of age.17 Residents of Soweto are offered free access to HIV volunteer counselling and testing (VCT) at HAVD.
Potential HIV-seronegative vaccine trial volunteers are recruited from VCT into a generic ‘prescreening protocol’, which was designed to allow the accumulation of suitably informed, healthy, low-risk HIV-seronegative cohorts for Phase I/II HIV vaccine trials being conducted at HAVD.18,19 The pre-screening protocol provides information sessions about HIV vaccines, baseline and follow-up assessments of understanding, as well as risk behaviour assessment and clinical screening for physical health. HIV prevention services are offered to participants at each visit, including VCT, provision of free condoms, risk-reduction counselling and referral for treatment of sexually transmitted diseases (STDs). Following completion of the prescreening protocol, potential volunteers may be referred to one of several Phase I/II HIV vaccine trials being conducted at HAVD. This study represents a cross-sectional analysis of the initial risk behaviour assessment at the first clinical visit for each potential vaccine trial volunteer enrolled into the prescreening protocol.
Eligibility criteria for enrolment into the prescreening protocol include having a minimum of 12 years of schooling (irrespective of education level achieved), being a resident of Soweto, 18–60 years of age, HIV-seronegative, healthy, able to provide informed consent, and for women, not pregnant or planning to become pregnant. All participants gave written informed consent for the study and received nominal financial compensation for transportation costs at each study visit. This study was approved by the Committee for Research on Human Subjects at the University of the Witwatersrand in Johannesburg and the Human Investigations Committee at the Yale University School of Medicine in New Haven.
We developed the risk behaviour assessment tool for use in South Africa following six focus groups at HAVD conducted with experienced HIV counsellors and staff, concentrating on appropriate local language, specific practices and customs of the population, and question content and clarity. We pilot-tested preliminary versions of the survey with 20 participants for comprehension, feasibility and cultural appropriateness. We trained interviewers to accurately administer the survey in a non-judgemental manner using a combination of individual and group teaching sessions on interviewing techniques as well as practice survey administration with observation and feedback.
We administered the risk behaviour survey to participants in a structured, face-to-face private interview using trained, multilingual interviewers. The survey took approximately 45 minutes to complete per individual and was generally conducted in a mixture of Sotho, Zulu and English according to the language needs of the participant.
Basic sociodemographic and general risk behaviour information as well as partnership-specific data were collected. Partnership data collection involved a structured recall of sexual partners in the prior six months and specific risk behaviour data for each sexual partner identified. The full survey is contained in the Appendix.
We formatted and coded the risk behaviour questionnaire for use with DataFax software (Clinical DataFax Systems Inc, Hamilton, Canada). Following a manual clinic review and automated data entry, data were then subjected to automated edit-checking as well as manual review by three separate individuals trained in data validation. Clinic staff routinely resolved quality control reports listing incomplete or incorrect data entries.
We conducted all statistical analyses with SAS Version 9.1 software (SAS Institute Inc., Cary, NC, USA). For statistical comparisons, we used t-tests for continuous variables and either the chi-square or Fisher’s exact test for categorical variables. For bivariate and multivariate analyses, we employed logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) using covariates from the sociodemographic, sexual history and sexual risk data. We created four outcome variables and dichotomized them to reflect higher and lower-risk behaviour: (i) engaging in any unprotected vaginal or anal sex; (ii) engaging in any unprotected vaginal or anal sex with a known or suspected HIV-positive partner; (iii) reporting any casual or anonymous sexual partners; and (iv) reporting three or more sexual partners.
We dichotomized continuous covariates at the median and categorical covariates evenly to the extent possible. We first used the covariates in bivariate models to determine independent predictors of higher risk behaviour for each of the four outcomes. We included covariates that were associated with an outcome of P value <0.20 in multivariate models for each of the four outcomes. We then eliminated covariates not significantly associated with the outcome at P value <0.05 from the model one at a time, using a manual backwards selection procedure. The final multivariate model contained covariates with statistical significance of P value <0.05. All multivariate models retained age and gender covariates due to their potential role as confounders.
A total of 488 participants in the prescreening protocol were administered an initial risk behaviour survey between June 2003 and February 2006 and were included in this analysis. Sociodemographic data are presented in Table 1, with no significant gender differences except as noted.
Male participants reported higher levels of alcohol and drug use than female participants over the previous six months: Overall, 62% of men reported at least one day of heavy drinking defined as consumption of more than five alcoholic beverages, with one beverage defined as 6 oz. wine, 12 oz. beer or 1 oz. liquor, compared with 33% of women (P < 0.001). Men reported more days of heavy drinking than women overall (16.6 vs. 3.4 days; t = 5.8; P < 0.001). More men than women reported marijuana use (19% vs. 3%, P < 0.001) and other recreational drug use (4.1% vs. 0.4%, P < 0.01). Only two participants reported injection drug use.
Most participants (97%) reported prior sexual activity (defined as vaginal, anal or oral sex). Prior STD diagnoses were reported by 30% of participants overall, with 7% of participants reporting an STD diagnosis in the past six months. In addition, 35% of males and 24% of females (P < 0.01) reported having at least one partner within the past six months without sexual activity.
Although 13% of those ever sexually active reported abstinence during the preceding six months, males generally reported higher levels of risk behaviour (Table 2).
Analysis of risk behaviours for participants sexually active during the previous six months revealed further gender differences (Table 3). More men reported at least one casual and/or anonymous sex partner, ‘one night stand’, known or suspected HIV-infected sex partner and a sex partner at least 15 years older or younger.
When comparing risk behaviours in the previous six months by partner type, mean condom use was higher and the number of unprotected sex acts was lower for casual/anonymous sex partners when compared with steady partners (Table 4).
For the outcomes used in logistic regression analyses, 55% reported <100% condom use, 4% reported <100% condom use with a known or suspected HIV-positive partner, 35% reported sex with a casual or anonymous partner and 13% reported having three or more sex partners. Individual factors from bivariate analyses were included in the multivariate regression models as indicated in Table 5.
Our study has described the sexual risk-taking behaviour profile of potential Phase I and II HIV vaccine trial volunteers undergoing prescreening in Soweto, South Africa for the first HIV vaccine trials being conducted in Southern Africa. We designed a survey appropriately adapted for local use, which is an important component of measuring risk behaviour in international HIV vaccine trials.2,20 We assessed risk behaviour by self-reported condom use and self-reported numbers and types of sex acts, which have been shown to be appropriate, reliable and accurate indicators for the risk of acquiring an STD.21,22 We administered this survey as a component of the prescreening protocol, a generic protocol applied to all HIV-negative potential volunteers expressing an interest in participating in various Phase I/II HIV vaccine trials at the vaccine trial site in Soweto.
South Africa is extraordinarily diverse, with 11 national languages and a variety of cultures. Although risk behaviours have been well-documented on a national level, little has been published on Soweto in particular, and even less is known about the residents of Soweto who actually volunteer for HIV prevention trials. In our study, we showed this to be a young, predominantly single and unemployed, multi-ethnic population, of whom half reside in households with incomes below the poverty line.
Our analyses demonstrate that men in this study reported higher levels of risk behaviour than females overall during the previous six months, as indicated by the higher numbers of total sex partners, casual or anonymous sex partners, sex partners known or suspected to be HIV-positive and ‘one night stands’, as well as the higher levels of heavy alcohol and recreational drug use. In adjusted models, men were five times more likely than women to have casual or anonymous sex partners and 12 times more likely to have three or more sex partners. While it is possible that men throughout Soweto have higher levels of risky sexual behaviour than women, it is also possible that men with higher risk behaviour or women with lower risk behaviour were more likely to attend VCT services and subsequently enrol in this screening protocol for future HIV vaccine trials. Regardless of the explanation for these findings, the trend for higher risk behaviours among male participants may indicate that they should be targeted for increased risk-reduction counselling during the course of future African HIV vaccine trials.
Male gender was not the only predictor of higher levels of reported risk behaviour. Reporting any incidence of heavy alcohol use, choosing a partner without regard to personal safety or HIV status, and reporting at least one partner who travelled away from home for employment were also significant predictors of having had sex with a casual or anonymous partner. Any incidence of heavy alcohol use, reporting one or more partners with an age difference of at least 15 years, and reporting at least one partner who travelled away from home for employment were additional significant predictors of having had three or more sex partners. These outcomes are consistent with research showing that South African youth with partners with an age difference of only five years were at increased risk of HIV infection23 and that rural South African migrant men and their partners were at an increased risk of contracting STDs compared with non-migrant men.24
In adjusted models, reporting any recreational drug use significantly predicted having had any incidence of unprotected vaginal or anal sex, as well as having had any unprotected sex with a known or suspected HIV-positive partner, in the previous six months. Female gender and age greater than 25 years were also significant predictors of having unprotected sex. However, female gender and older age are not necessarily associated with increased risk behaviour, because this relationship might indicate married older women having unprotected sex with monogamous HIV-negative partners. But this association may be an indication of a form of ‘passive’ high-risk behaviour, in which married older women, for example, are forced into having unprotected sex with husbands who subsequently infect them with HIV,25 a concept reinforced by studies showing that married older women are more likely to use condoms inconsistently.26 Refinement of the survey tool to gather information regarding whether participants engaged in unprotected sex of their own volition or by force would help to clarify this association further.
Although some of these predictors occurred more frequently in male participants, they were independently associated with higher risk behaviour and might also be used to target vaccine trial participants for increased risk-reduction counselling. In particular, the substance use predictors were associated with all four classifications for increased risk behaviour and may be particularly useful in risk stratification of vaccine trial volunteers: participants reporting any history of recreational drug use were twice as likely to have had unprotected sex and five times as likely to have had unprotected sex with a known or suspected HIV-positive partner, while participants reporting any history of heavy alcohol use were three times as likely to have had sex with casual or anonymous partners and three times as likely to have had more than two partners in the previous six months.
A study of the risk behaviour patterns in another South African cohort of participants, observed for evaluating HIV incidence and study retention rates in preparation for HIV vaccine trials, showed that the cohort engaged in higher levels of sexual risk behaviour than similar participants from the same community.11 It is difficult to ascertain how closely our sample represents the sexual risk-taking behaviour of the general population of Soweto. There may be a potential bias in participant enrolment, as participants in our study were initially recruited because they had sought HIV VCT and were subsequently found to be HIV-negative. Compared with the general population, our methods may have selected a group of participants who practice riskier sex, because individuals at greater risk for HIV infection sought VCT services, or a group of participants who practice safer sex, because individuals at lower risk for HIV infection sought assurance that they were not infected. Regardless, it underscores the need to characterize the baseline characteristics of the actual populations that are participating in HIV vaccine trials, which was the intent of this study, as well as to understand how this population differs from the potential target population for an eventual vaccine.
There are several limitations that are inherent to the survey procedures used in this study. Both the assessment of personal information in a face-to-face interview and the risk-reduction counselling offered with VCT services prior to risk behaviour survey administration may have influenced the social desirability bias of reported behaviours. In addition, although the counsellors administering the survey were periodically trained and monitored, the administration of the survey by multiple interviewers over time and in a mixture of languages (English, Sotho, Zulu) might have varied between participants. These problems could be resolved with the future use of audio computer-assisted self-interviewing (ACASI) technology. ACASI has been shown in a longitudinal randomized trial within an HIV risk behaviour study to improve behaviour data collection, likely by decreasing social desirability bias, removing interviewer bias and error, and standardizing the interview questions.27 Another limitation is that participant recall bias might prevent accurate risk assessment, although studies have shown that structured interviews to recall information for the previous three to six months are preferable to recalling shorter or longer time periods.28 A further limitation is that behaviour may be accurately reported by the participant, but may not completely represent true risk. For example, a person might report 100% condom use but not have used condoms correctly during that time, which would under-represent risky sexual behaviour.
Suitable methods for assessing risk are particularly important in communities where baseline sexual practices and customs are not well-known. Research on risk behaviour and HIV vaccines must proceed together, and risk behaviour education must be an integral part of any future HIV prevention programme that includes an HIV vaccine.3,4 Our study provides the first sexual risk behaviour data for an African population participating in HIV vaccine trials to date as well as a baseline reference for determining whether sexual risk behaviour might change in response to participation in South African HIV vaccine trials. In addition to increased risk-reduction counselling for the prevention of HIV transmission in targeted groups, the predictors of higher risk behaviour described in this study might also be used to differentiate between participants more suitable for Phase I and II safety and immunogenicity studies, which require volunteers at relatively low risk for HIV infection, or Phase III efficacy studies, which require volunteers at relatively high risk for HIV infection.
The authors wish to thank the participants at the HIV Vaccine Clinic at the Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital in Soweto for taking part in this study. In addition, the authors thank the counsellors and other staff at the Perinatal HIV Research Unit for their coordination and technical assistance with implementing this study. Support for this work was provided by the National Institute of Allergy and Infectious Diseases HIV Vaccine Trials Network, the International AIDS Vaccine Initiative, the South African AIDS Vaccine Initiative, the Yale Center for the Study of Globalization, the Yale Center for International and Area Studies and the AIDS Vaccine Integrated Project Consortium. KMA was supported (under the maiden name Kyeen Mesesan) by the National Institute on Drug Abuse (RO1DA015612), and the National Institute of General Medical Sciences MD/PhD Medical Scientist Training Programme (GM07205). This research was undertaken in South Africa as part of graduate studies in the MD/PhD programme at Yale University and under the maiden name Kyeen Mesesan.
The risk behaviour assessment survey developed for use in this study can be seen in full in the on-line version of this paper at www.ijsa.rsmjournals.com/cgi/content/full/20/2/95/DC1.