Abstract: We included four trials. One trial evaluated mass treatment of all individuals in a particular community. The other three trials evaluated various combinations of improved syndromic STI management in clinics, STI counselling, and STI treatment. In the mass treatment trial in rural southwestern Uganda, after three rounds of treatment of all community members for STIs, the adjusted rate ratio (aRR) of incident HIV infection was 0.97 (95% CI 0.81 - 1.2), indicating no effect of the intervention. The three STI management intervention studies were all conducted in rural parts of Africa. One study, in northern Tanzania, showed that the incidence of HIV infection in the intervention groups (strengthened syndromic management of STIs in primary care clinics) was 1.2% compared with 1.9% in the control groups (aRR = 0.58, 95% CI 0.42 - 0.79), corresponding to a 42% reduction (95% CI 21.0% - 58.0%) in HIV incidence in the intervention group. Another study, conducted in rural southwestern Uganda, showed that the aRR of behavioural intervention and STI management compared to control on HIV incidence was 1.00 (95% CI 0.63 - 1.58). In the third STI management trial, in eastern Zimbabwe, there was no effect of the intervention on HIV incidence (aRR = 1.3, 95% CI 0.92 - 1.8). These are consistent with data from the mass treatment trial showing no intervention effect. Overall, pooling the data of the four studies showed no significant effect of any intervention (rate ratio [RR] = 0.97, 95% CI 0.78 - 1.2). Combining the mass treatment trial and one of the STI management trials, we find that there is a significant 12.0% reduction in the prevalence of syphilis for those receiving a biomedical STI intervention (RR 0.88, 95% CI 0.80 - 0.96). For gonorrhoea, we find a statistically significant 51.0% reduction in its prevalence in those receiving any of these interventions (RR 0.49, 95% CI 0.31 - 0.77). Finally, for chlamydia, we found no significant difference between any biomedical intervention and control (RR 1.03, 95% CI 0.77 - 1.4). 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.

Plain-language summary: Subsequent trials, however, failed to confirm these findings and also failed to show a substantial benefit for community-wide presumptive treatment for STIs. This is likely due to the endemic nature of HIV and relatively low incidence of STIs in these populations. There are, however, other good reasons as to why STI treatment services should be strengthened and the available evidence suggests that when an intervention is applied and accepted in a community, it can improve the quality of services provided. The trial in Masaka District, Uganda showed an increase in the use of condoms, a marker for less risky sexual behaviours, although a newer study by Gregson conducted in Zimbabwe suggested no effect. With the last three trials having shown disappointing results with respect to HIV prevention, it is unlikely that further community trials will be conducted, let alone yield different results. Future trials of biomedical interventions that involve individual randomisation, however, may represent an opportunity to reexamine presumptive treatment of STIs. Such trials should also aim to measure a range of factors that include health-seeking behaviour and quality of treatment, as well as HIV, STI and other biological endpoints.