Esther E. Freeman

Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies.

Objective:To estimate the sex-specific effect of herpes simplex virus type 2 (HSV-2) on the acquisition of HIV infection. Background:The increased number of longitudinal studies available since the last meta-analysis was published allows for the calculation of age- and sexual behaviour-adjusted relative risks (RR) separately for men and women. Design:Systematic review and meta-analysis of longitudinal studies. Methods:PubMed, Embase and relevant conference abstracts were systematically searched to identify longitudinal studies in which the relative timing of HSV-2 infection and HIV infection could be established. Where necessary, authors were contacted for separate estimates in men and women, adjusted for age and a measure of sexual behaviour. Summary adjusted RR were calculated using random-effects meta-analyses where appropriate. Studies on recent HSV-2 incidence as a risk factor for HIV acquisition were also collated. Results:Of 19 eligible studies identified, 18 adjusted for age and at least one measure of sexual behaviour after author contact. Among these, HSV-2 seropositivity was a statistically significant risk factor for HIV acquisition in general population studies of men [summary adjusted RR, 2.7; 95% confidence interval (CI), 1.9–3.9] and women (RR, 3.1; 95% CI, 1.7–5.6), and among men who have sex with men (RR, 1.7; 95% CI, 1.2–2.4). The effect in high-risk women showed significant heterogeneity, with no overall evidence of an association. Conclusions:Prevalent HSV-2 infection is associated with a three-fold increased risk of HIV acquisition among both men and women in the general population, suggesting that, in areas of high HSV-2 prevalence, a high proportion of HIV is attributable to HSV-2.

Proportion of new HIV infections attributable to herpes simplex 2 increases over time: simulations of the changing role of sexually transmitted infections in sub-Saharan African HIV epidemics

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 (PAFM)) increased with maturity of the HIV epidemic. In the different cities, the PAFM 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.

Male circumcision for HIV prevention in sub-Saharan Africa: Who what and when?

Background and objective:Male circumcision (circumcision) reduces HIV incidence in men by 50–60%. The United Nations Joint Programme on HIV/AIDS (UNAIDS) recommends the provision of safe circumcision services in countries with high HIV and low circumcision prevalence, prioritizing 12–30 years old HIV-uninfected men. We explore how the population-level impact of circumcision varies by target age group, coverage, time-to-scale-up, level of risk compensation and circumcision of HIV-infected men. Design and methods:An individual-based model was fitted to the characteristics of a typical high-HIV-prevalence population in sub-Saharan Africa and three scenarios of individual-level impact corresponding to the central and the 95% confidence level estimates from the Kenyan circumcision trial. The simulated intervention increased the prevalence of circumcision from 25 to 75% over 5 years in targeted age groups. The impact and cost-effectiveness of the intervention were calculated over 2–50 years. Future costs and effects were discounted and compared with the present value of lifetime HIV treatment costs (US

Understanding the differences between contrasting HIV epidemics in east and west Africa: Results from a simulation model of the Four Cities Study

4043). Results:Initially, targeting men older than the United Nations Joint Programme on HIV/AIDS recommended age group may be the most cost-effective strategy, but targeting any adult age group will be cost-saving. Substantial risk compensation could negate impact, particularly if already circumcised men compensate. If circumcision prevalence in HIV-uninfected men increases less because HIV-infected men are also circumcised, this will reduce impact in men but would have little effect on population-level impact in women. Conclusion:Circumcision is a cost-saving intervention in a wide range of scenarios of HIV and initial circumcision prevalence but the United Nations Joint Programme on HIV/AIDS/WHO recommended target age group should be widened to include older HIV-uninfected men and counselling should be targeted at both newly and already circumcised men to minimize risk compensation. To maximize infections-averted, circumcision must be scaled up rapidly while maintaining quality.

Treating Curable Sexually Transmitted Infections to Prevent HIV in Africa : Still an Effective Control Strategy?

Objective: To determine if the differences in risk behaviours, the proportions of males circumcised and prevalences of sexually transmitted infections (STIs) observed in two African cities with low prevalence of HIV (Cotonou, Benin, and Yaoundé, Cameroon) and two cities with high prevalence (Kisumu, Kenya, and Ndola, Zambia) could explain the contrasting HIV epidemics in the four cities. Methods: An individual-based stochastic model, STDSIM, was fitted to the demographic, behavioural and epidemiological characteristics of the four urban study populations based on data from the Four Cities Study and other relevant sources. Model parameters pertaining to STI and HIV natural history and transmission were held constant across the four populations. The probabilities of HIV, syphilis and chancroid acquisition were assumed to be doubled among uncircumcised males. A priori plausible ranges for model inputs and outputs were defined and sexual behaviour characteristics, including those pertaining to commercial sex workers (CSWs) and their clients, which were allowed to vary across the sites, were identified based on comparisons of the empirical data from the four sites. The proportions of males circumcised in the model, 100% in Cotonou and Yaoundé, 25% in Kisumu and 10% in Ndola, were similar to those observed. A sensitivity analysis was conducted to assess how changes in critical parameters may affect the model fit. Results: Population characteristics observed from the study that were replicated in the model included younger ages at sexual debut and marriage in east Africa compared with west Africa and higher numbers of casual partners in the past 12 months in Yaoundé than in the other three sites. The patterns in prevalence of STIs in females in the general population and CSWs were well fitted. HIV prevalence by age and sex and time trends in prevalence in the model were consistent with study data with the highest simulated prevalences in Kisumu and Ndola, intermediate in Yaoundé and lowest in Cotonou. The sensitivity analysis suggested that the effect of circumcision on the development of the HIV epidemics may have been mediated indirectly by its effect on ulcerative STI. Conclusions: The contrasting HIV epidemics in east and west Africa could be replicated in our model by assuming that male circumcision reduced susceptibility to HIV, syphilis and chancroid. Varying rates of male circumcision may have played an important role in explaining the strikingly different HIV epidemics observed in different parts of sub-Saharan Africa.

Population-level effect of potential HSV2 prophylactic vaccines on HIV incidence in sub-Saharan Africa.

Background:Evidence regarding the effectiveness of sexually transmitted infection (STI) treatment for HIV prevention in Africa is equivocal, leading some policy makers to question whether it should continue to be promoted for HIV control. We explore whether treating curable STIs remains a cost-effective HIV control strategy in Africa. Methods:The model STDSIM was fitted to the characteristics of 4 populations in East and West Africa. Over the simulated HIV epidemics, the population-attributable fractions (PAFs) of incident HIV attributable to STIs, the impact of syndromic STI management on HIV incidence, and the cost per HIV infection averted were evaluated and compared with an estimate of lifetime HIV treatment costs (US

The Role of Systematic Reviews and Meta-analysis in Dermatology

3500). Results:Throughout the HIV epidemics in all cities, the total PAF for all STIs remained high, with ≥50% of HIV transmission attributed to STIs. The PAF for herpes simplex virus type 2 increased during the epidemics, whereas the PAF for curable STIs and the relative impact of syndromic management decreased. The models showed that the absolute impact of syndromic management remains high in generalized epidemics, and it remained cost-saving in 3 of the 4 populations in which the cost per HIV infection averted ranged between US

Population-level effect of HSV-2 therapy on the incidence of HIV in sub-Saharan Africa

321 and

A Seat at the Big Table: Expanding the Role of Dermatology at the World Health Organization and Beyond

1665. Conclusion:Curable STI interventions may remain cost-saving in populations with generalized HIV epidemics, particularly in populations with high-risk behaviors or low male circumcision rates.

Attempting to explain heterogeneous HIV epidemics in sub-Saharan Africa: potential role of historical changes in risk behaviour and male circumcision

Herpes simplex virus type-2 (HSV2) infection increases HIV transmission. We explore the impact of a potential prophylactic HSV2 vaccination on HIV incidence in Africa using STDSIM an individual-based model. A campaign that achieved 70% coverage over 5 years with a vaccine that reduced susceptibility to HSV2 acquisition and HSV2 reactivation by 75% for 10 years, reduced HIV incidence by 30–40% after 20 years (range 4–66%). Over 20 years, in most scenarios fewer than 100 vaccinations were required to avert one HIV infection. HSV2 vaccines could have a substantial impact on HIV incidence. Intensified efforts are needed to develop an effective HSV2 vaccine.