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For trials of user-dependent HIV prevention products, accurate adherence measurements are essential to interpret and compare results across trials. We used pill count data from two recent HIV prevention trials of herpes simplex virus type 2 (HSV-2) suppression, to show that estimates of adherence vary substantially depending on assumptions that are made in analysing pill count data. We associate calculated adherence with biological markers of anti-HSV-2 activity. In both trials, calculated adherence varied considerably, depending on the summary measure used, and the handling of intervals with apparent 'over-adherence' (fewer pills returned than expected), and unreturned pills. Intervals of apparent over-adherence were associated with reduced antiviral effects on biological markers of herpes reactivation, indicating these are likely to represent periods of non-adherence. Our results demonstrate the clear need for standardisation in reporting of adherence data that are based on pill counts.

Objective: To understand the changing impact of herpes simplex 2 (HSV-2) and other sexually transmitted infections (STIs) on HIV incidence over time in four sub-Saharan African cities, using simulation models., Methods: An individual-based stochastic model was fitted to demographic, behavioural and epidemiological data from cross-sectional population-based surveys in four African cities (Kisumu, Kenya; Ndola, Zambia; Yaoundé, Cameroon; and Cotonou, Benin) in 1997. To estimate the proportion of new HIV infections attributable to HSV-2 and other STIs over time, HIV incidence in the fitted model was compared with that in model scenarios in which the cofactor effect of the STIs on HIV susceptibility and infectivity were removed 5, 10, 15, 20 and 25 years into the simulated HIV epidemics., Results: The proportion of incident HIV attributable to HSV-2 infection (the model estimated population attributable fraction (PAF(M))) increased with maturity of the HIV epidemic. In the different cities, the PAF(M) was 8-31% 5 years into the epidemic, but rose to 35-48% 15 years after the introduction of HIV. In contrast, the proportion of incident HIV attributable to chancroid decreased over time with strongest effects five years after HIV introduction, falling to no effect 15 years after. Sensitivity analyses showed that, in the model, recurrent HSV-2 ulcers had more of an impact on HIV incidence than did primary HSV-2 ulcers, and that the effect of HSV-2 on HIV infectivity may be more important for HIV spread than the effect on HIV susceptibility, assuming that HSV-2 has similar cofactor effects on HIV susceptibility and infectivity. The overall impact of other curable STIs on HIV spread (syphilis, gonorrhoea and chlamydia) remained relatively constant over time., Conclusions: Although HSV-2 appears to have a limited impact on HIV incidence in the early stages of sub-Saharan African HIV epidemics when the epidemic is concentrated in core groups, it has an increasingly large impact as the epidemic progresses. In generalised HIV epidemics where control programmes for curable STIs are already in place, interventions against HSV-2 may have a key role in HIV prevention.

Objectives: Syphilis is an important cause of morbidity in sub-Saharan Africa, and a cofactor for the sexual transmission of HIV. A better understanding of the prevalence and risk factors of syphilis in African populations would help to formulate effective interventions for its prevention and treatment., Methods: The prevalence and incidence of syphilis were obtained from a cohort recruited in Mwanza, Tanzania. Two unmatched case-control studies nested within the cohort provide information on potential risk factors., Results: The prevalence of active syphilis (TPHA positive and RPR positive any titre) was 7.5% in men and 9.1% in women, but in youths (aged 15-19 years) the prevalence was higher in women (6.6%) than in men (2.0%). The incidence of TPHA seroconversion was highest in women aged 15-19 at 3.4% per year, and around 2% per year at all ages among men. A higher prevalence of syphilis was found in those currently divorced or widowed (men: OR=1.61, women: OR=2.78), and those previously divorced or widowed (men: OR=1.51, women: OR=1.85). Among men, prevalence was associated with lack of circumcision (OR=1.89), traditional religion (OR=1.55), and reporting five or more partners during the past year (OR=1.81) while incidence was associated with no primary education (OR=2.17), farming (OR=3.85), and a self perceived high risk of STD (OR=3.56). In women, prevalence was associated with no primary education (OR=2.13), early sexual debut (OR=1.59), and a self perceived high risk of STD (OR=3.57), while incidence was associated with living away from the community (OR=2.72)., Conclusion: The prevalence and incidence of syphilis remain high in this rural African population. More effort is needed to promote safer sexual behaviour, and to provide effective, accessible treatment. The high incidence of syphilis in young women calls for sexual health interventions targeted at adolescents.