Acceptability of HIV vaccine trials in high-risk heterosexual cohorts in Mombasa, Kenya.

OBJECTIVES: To ascertain the level of acceptance of a prophylactic HIV vaccine trial in high-risk HIV-seronegative heterosexual cohorts of men and women in Mombasa, Kenya, and to assess the anticipated effects of participation on risk behavior. METHODS: Standardized questionnaire administered to a convenience sample of commercial sex workers and trucking company employees enrolled in prospective cohort studies. RESULTS: Ninety-six per cent of respondents believed that HIV was a major problem in Kenya and 86% of men and 94% of women perceived themselves at risk. One hundred per cent of women and 84% of men expressed interest in participation in an HIV vaccine trial, after explanation of the experimental nature of the vaccine, double-blind placebo-controlled design, prolonged follow-up and potential change in serostatus. Seventeen per cent of men and 9% of women anticipated an increase in risk behavior as a result of participation. CONCLUSION: The majority of individuals in two high-risk cohorts were interested in participating in Phase III efficacy trials of HIV vaccines. A significant minority anticipated an increase in risk behavior, which emphasizes the need for intensive counseling and education throughout a vaccine trial.

PIP: The acceptability of a theoretical human immunodeficiency virus (HIV) vaccine trial was investigated in HIV-negative commercial sex workers and trucking company employees in Mombasa, Kenya. The 206 women and 201 men who completed questionnaires were already enrolled in a prospective cohort study of high-risk heterosexuals. 95% of men and 98% of women surveyed agreed that acquired immunodeficiency syndrome (AIDS) is a major problem in Kenya; however, only 14% and 6%, respectively, considered themselves at personal risk of infection. Only 4% of male and 1% of female respondents stated they would refuse an HIV vaccine of proven safety and efficacy. However, 91% of women but only 67% of men indicated they would participate in a double-blind, placebo-controlled vaccine trial that involved vaccine-induced HIV seropositivity and prolonged follow-up. The main concerns about participation in such a trial were the positive HIV blood test result and fear of acquiring HIV from the vaccine. 9% of men and 6% of women anticipated they would decrease their condom use as a result of participation in such a trial, and 9% of men and 3% of women thought they would increase their number of sexual partners. Anticipated higher risk behavior was significantly associated with male gender, but not with age, education, history of prostitution or of sex with prostitutes, or current condom use. If and when vaccine trials become possible, this high-risk cohort would comprise an ideal target population; however, concurrent counseling about the need to continue preventive behavioral measures would be a necessity.

Hormonal contraception, sexually transmitted diseases, and risk of heterosexual transmission of human immunodeficiency virus type 1.

To examine associations between method of contraception, sexually transmitted diseases (STDs), and incident human immunodeficiency virus type 1 (HIV-1) infection, a prospective observational cohort study was done among female sex workers attending a municipal STD clinic in Mombasa, Kenya. Demographic and behavioral factors significantly associated with HIV-1 infection included type of workplace, condom use, and parity. In multivariate models, vulvitis, genital ulcer disease, vaginal discharge, and Candida vaginitis were significantly associated with HIV-1 seroconversion. Women who used depo medroxyprogesterone acetate (DMPA) had an increased incidence of HIV-1 infection (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.4-3.4). In a multivariate model controlling for demographic and exposure variables and biologic covariates, the adjusted HR for HIV-1 infection among DMPA users was 2.0 (CI, 1.3-3.1). There was a trend for an association between use of high-dose oral contraceptive pills and HIV-1 acquisition (HR, 2.6; CI, 0.8-8.5).

Safety of a nonoxynol-9 vaginal gel in Kenyan prostitutes. A randomized clinical trial.

OBJECTIVE: To evaluate the safety and toxicity of once-daily administration of Advantage-24 (Columbia Research Laboratories, Inc., Rockville Centre, NY), a vaginal gel containing 52.5 mg of nonoxynol-9 (N-9), including the effects of this gel on the vaginal and cervical epithelium. STUDY DESIGN: Randomized, placebo-controlled, double-blind crossover trial, with a 2-week product application period and a 2-week washout period. METHODS: Female sex workers in Mombasa, Kenya were randomized to one of two sequences, N-9 followed by placebo, or vice versa. Women were instructed to apply one applicator of N-9 or placebo gel vaginally once each day. During each of the two product periods, subjects were evaluated by questionnaire and physical examination, including colposcopy, after 7 and 14 days of product use. The primary outcome was genital epithelial disruption. RESULTS: Sixty subjects were randomized, of whom 52 (87%) had complete follow-up. There were four episodes of epithelial disruption, three of which occurred during the placebo period and one during the N-9 period. The estimated risk of epithelial disruption associated with N-9 use was 0.33 (95% confidence interval, 0.03-3.26). There was no increased frequency of other, nondisruptive epithelial lesions during N-9 use. CONCLUSIONS: No genital epithelial toxicity of N-9 vaginal gel was observed. This safety profile suggests that this N-9 product is appropriate for evaluation for human immunodeficiency virus type 1 prevention in a phase III efficacy trial.

Use of nonoxynol-9 and changes in vaginal lactobacilli.

Several in vitro studies have shown nonoxynol-9 (N-9) to be toxic to lactobacilli, especially to strains that produce H2O2. Data from a randomized, double-blind, placebo-controlled crossover trial that investigated the safety and toxicity of 2 weeks of daily vaginal application of an N-9 gel were analyzed, to examine the effect of N-9 use on vaginal lactobacilli and bacterial vaginosis. In vivo, N-9 promoted sustained colonization by H2O2-producing lactobacilli among women already colonized (relative risk [RR], 1.8; 95% confidence interval [CI], 1.2-2.7). In addition, use of N-9 for 2 weeks reduced the likelihood of bacterial vaginosis (RR, 0.5; 95% CI, 0.3-1.0). In contrast, N-9 use by women initially colonized only by non-H2O2-producing lactobacilli resulted in loss of vaginal lactobacilli (RR, 2.5; 95% CI, 1.2-5.3). These data suggest that daily use of N-9 does not adversely affect vaginal colonization by H2O2-producing lactobacilli but that such use may promote loss of non-H2O2-producing strains.

Hormonal contraception and risk of sexually transmitted disease acquisition: results from a prospective study.

OBJECTIVES: To examine the relationship between use of oral contraceptive pills or depot medroxyprogesterone acetate and sexually transmitted disease acquisition. STUDY DESIGN: Prospective cohort included 948 Kenyan prostitutes. Multivariate Andersen-Gill proportional hazards models were constructed, adjusting for sexual behavioral and demographic variables. RESULTS: When compared with women who were using no contraception, users of oral contraceptive pills were at increased risk for acquisition of chlamydia (hazard ratio, 1.8; 95% confidence interval, 1.1-2.9) and vaginal candidiasis (hazard ratio, 1.5; 95% confidence interval, 1.2-1.9) and at decreased risk for bacterial vaginosis (hazard ratio, 0.8; 95% confidence interval, 0.7-1.0). Women using depot medroxyprogesterone acetate had significantly increased risk of chlamydia infection (hazard ratio, 1.6; 95% confidence interval, 1.1-2.4) and significantly decreased risk of bacterial vaginosis (hazard ratio, 0.7; 95% confidence interval, 0.5-0.8), trichomoniasis (hazard ratio, 0.6; 95% confidence interval, 0.4-1.0), and pelvic inflammatory disease (hazard ratio, 0.4; 95% confidence interval, 0.2-0.7). Consistent condom use was associated with significantly decreased risk of gonorrhea, chlamydia, genital ulcer disease, bacterial vaginosis, and pelvic inflammatory disease. CONCLUSIONS: The use of oral or injectable hormonal contraception altered susceptibility to sexually transmitted diseases, which may in turn influence transmission of human immunodeficiency virus type 1. Consistent condom use was protective with regards to sexually transmitted disease and should be encouraged for the prevention of sexually transmitted disease and human immunodeficiency virus type 1 among women who use hormonal contraception.

Vaginal lactobacilli, microbial flora, and risk of human immunodeficiency virus type 1 and sexually transmitted disease acquisition.

A prospective cohort study was conducted to examine the relationship between vaginal colonization with lactobacilli, bacterial vaginosis (BV), and acquisition of human immunodeficiency virus type 1 (HIV-1) and sexually transmitted diseases in a population of sex workers in Mombasa, Kenya. In total, 657 HIV-1-seronegative women were enrolled and followed at monthly intervals. At baseline, only 26% of women were colonized with Lactobacillus species. During follow-up, absence of vaginal lactobacilli on culture was associated with an increased risk of acquiring HIV-1 infection (hazard ratio [HR], 2.0; 95% confidence interval [CI], 1.2-3.5) and gonorrhea (HR, 1.7; 95% CI, 1.1-2.6), after controlling for other identified risk factors in separate multivariate models. Presence of abnormal vaginal flora on Gram's stain was associated with increased risk of both HIV-1 acquisition (HR, 1.9; 95% CI, 1.1-3.1) and Trichomonas infection (HR, 1.8; 95% CI, 1.3-2.4). Treatment of BV and promotion of vaginal colonization with lactobacilli should be evaluated as potential interventions to reduce a woman's risk of acquiring HIV-1, gonorrhea, and trichomoniasis.

Trends in HIV-1 incidence in a cohort of prostitutes in Kenya: implications for HIV-1 vaccine efficacy trials.

BACKGROUND: Accurate predictions of HIV-1 incidence in potential study populations are essential for designing HIV-1 vaccine efficacy trials. Little information is available on the estimated incidence of HIV-1 in such populations, especially information on incidence over time and incidence while participating in risk-reduction programs. OBJECTIVES: To examine time trends in HIV-1 incidence in a vaccine preparedness cohort. DESIGN: Prospective cohort study of female prostitutes in Mombasa, Kenya. METHODS: HIV-1 incidence was determined using open and closed cohort designs. Generalized estimating equations were used to model HIV-1 and sexually transmitted disease (STD) incidence and sexual risk behaviors over time. RESULTS: When analyzed as a closed cohort, HIV-1 incidence declined 10-fold during 3 years of follow-up (from 17.4 to 1.7 cases/100 person-years; p <.001). More than 50% of the cases of HIV-1 occurred during the first 6 months after enrollment, and 73% during the first 12 months. When analyzed as an open cohort, HIV-1 incidence density fell during the first 4 calendar years, influenced by accumulation of lower risk participants and variations in study recruitment. Significant declines occurred in both STD incidence and high-risk sexual behaviors during follow-up. CONCLUSIONS: This study documents a dramatic decline in the risk of HIV-1 infection while participating in a prospective cohort, with most seroconversions occurring within 1 year of enrollment. Variations in HIV-1 incidence within high-risk populations should be anticipated during the design of vaccine trials.