Impact of improved treatment of sexually transmitted diseases on HIV infection in rural Tanzania: randomised controlled trial. Control of sexually transmitted diseases for AIDS prevention in Uganda: a randomised community trial. Rakai Project Study Group. Impact and process evaluation of integrated community and clinic-based HIV-1 control: a cluster-randomised trial in eastern Zimbabwe.
A randomised trial was done to evaluate the impact of improved sexually transmitted disease (STD) case management at primary health care level on the incidence of HIV infection in the rural Mwanza region of Tanzania. HIV incidence was compared in six intervention communities and six pair-matched comparison communities. A random cohort of about 1000 adults aged 15-54 years from each community was surveyed at baseline and at follow-up 2 years later. Intervention consisted of establishment of an STD reference clinic, staff training, regular supply of drugs, regular supervisory visits to health facilities, and health education about STDs. 12,537 individuals were recruited. Baseline HIV prevalences were 3.8% and 4.4% in the intervention and comparison communities, respectively. At follow-up, 8845 (71%) of the cohort were seen. Of those initially seronegative, the proportions seroconverting over 2 years were 48 of 4149 (1.2%) in the intervention communities and 82 of 4400 (1.9%) in the comparison communities. HIV incidence was consistently lower in the intervention communities in all six matched pairs. Allowing for the community-randomised design and the effects of confounding factors, the estimated risk ratio was 0.58 (95% CI 0.42-0.79, p = 0.007). No change in reported sexual behaviour was observed in either group. We conclude that improved STD treatment reduced HIV incidence by about 40% in this rural population. This is the first randomised trial to demonstrate an impact of a preventive intervention on HIV incidence in a general population. The study tested the hypothesis that community-level control of sexually transmitted disease (STD) would result in lower incidence of HIV-1 infection in comparison with control communities.
                This randomised, controlled, single-masked, community-based trial of intensive STD control, via home-based mass antibiotic treatment, took place in Rakai District, Uganda. Ten community clusters were randomly assigned to intervention or control groups. All consenting residents aged 15-59 years were enrolled; visited in the home every 10 months; interviewed; asked to provide biological samples for assessment of HIV-1 infection and STDs; and were provided with mass treatment (azithromycin, ciprofloxacin, metronidazole in the intervention group, vitamins/anthelmintic drug in the control). Intention-to-treat analyses used multivariate, paired, cluster-adjusted rate ratios.
                The baseline prevalence of HIV-1 infection was 15.9%. 6602 HIV-1-negative individuals were enrolled in the intervention group and 6124 in the control group. 75.0% of intervention-group and 72.6% of control-group participants provided at least one follow-up sample for HIV-1 testing. At enrolment, the two treatment groups were similar in STD prevalence rates. At 20-month follow-up, the prevalences of syphilis (352/6238 [5.6%]) vs 359/5284 [6.8%]; rate ratio 0.80 [95% CI 0.71-0.89]) and trichomoniasis (182/1968 [9.3%] vs 261/1815 [14.4%]; rate ratio 0.59 [0.38-0.91]) were significantly lower in the intervention group than in the control group. The incidence of HIV-1 infection was 1.5 per 100 person-years in both groups (rate ratio 0.97 [0.81-1.16]). In pregnant women, the follow-up prevalences of trichomoniasis, bacterial vaginosis, gonorrhoea, and chlamydia infection were significantly lower in the intervention group than in the control group. No effect of the intervention on incidence of HIV-1 infection was observed in pregnant women or in stratified analyses.
                We observed no effect of the STD intervention on the incidence of HIV-1 infection. In the Rakai population, a substantial proportion of HIV-1 acquisition appears to occur independently of treatable STD cofactors. HIV-1 control in sub-Saharan Africa requires cost-effective and sustainable programmes that promote behaviour change and reduce cofactor sexually transmitted infections (STIs) at the population and individual levels.
                We measured the feasibility of community-based peer education, free condom distribution, income-generating projects, and clinic-based STI treatment and counselling services and evaluated their impact on the incidence of HIV-1 measured over a 3-y period in a cluster-randomised controlled trial in eastern Zimbabwe. Analysis of primary outcomes was on an intention-to-treat basis. The income-generating projects proved impossible to implement in the prevailing economic climate. Despite greater programme activity and knowledge in the intervention communities, the incidence rate ratio of HIV-1 was 1.27 (95% confidence interval [CI] 0.92-1.75) compared to the control communities. No evidence was found for reduced incidence of self-reported STI symptoms or high-risk sexual behaviour in the intervention communities. Males who attended programme meetings had lower HIV-1 incidence (incidence rate ratio 0.48, 95% CI 0.24-0.98), and fewer men who attended programme meetings reported unprotected sex with casual partners (odds ratio 0.45, 95% CI 0.28-0.75). More male STI patients in the intervention communities reported cessation of symptoms (odds ratio 2.49, 95% CI 1.21-5.12).
                Integrated peer education, condom distribution, and syndromic STI management did not reduce population-level HIV-1 incidence in a declining epidemic, despite reducing HIV-1 incidence in the immediate male target group. Our results highlight the need to assess the community-level impact of interventions that are effective amongst targeted population sub-groups.
We failed to confirm the hypothesis that STI control is an effective HIV prevention strategy. Improved STI treatment services were shown in one study to reduce HIV incidence in an environment characterised by an emerging HIV epidemic (low and slowly rising prevalence), where STI treatment services were poor and where STIs were highly prevalent; Incidence was not reduced in two other settings. There is no evidence for substantial benefit from a presumptive treatment intervention for all community members. There are, however, other compelling reasons why STI treatment services should be strengthened, and the available evidence suggests that when an intervention is accepted it can substantially improve quality of services provided.