Purpose: With more than 400,000 annual new HIV infections in South Africa, scaling up prevention is an urgent priority. Many experts believe a portfolio of interventions is the best strategy for controlling the epidemic. We aimed to evaluate the cost-effectiveness of HIV intervention portfolios in South Africa, to maximize health benefits given limited resources.
Methods: We developed a dynamic HIV transmission model to evaluate combinations of HIV screening, antiretroviral therapy (2010 guidelines), male circumcision, vaccination, and vaginal microbicide use. The model includes disease transmission, progression, morbidity, and mortality among adults aged 15-49 in South Africa. Initial conditions were based on demographic, epidemiologic, and behavioral data, and parameters were adjusted using trial data on intervention efficacy. Three trials in sub-Saharan Africa indicated that male circumcision reduced transmission in heterosexual men by 48-60%; a 2009 Thailand trial found a vaccine regimen conferring 31% protection; a 2010 South Africa vaginal tenofovir microbicide trial indicated a 39% transmission reduction in women. Calculated outcomes include incidence, prevalence, quality-adjusted life years (QALYs), and cost-effectiveness. We extended our deterministic results to include a Monte Carlo simulation and probabilistic cost-effectiveness analysis to account for uncertainty in each intervention's efficacy. Results: Under the status quo, 1.43 million (men) and 1.64 million (women) new infections occur over 10 years. Increased male circumcision is cost-saving, reducing infections by 19% (men) and 7% (women). Broad use of a vaginal microbicide reduces incidence by 30% (women) and 11% (men) due to reduced secondary transmission, for $750/QALY assuming an annual microbicide cost of $100. Extensive vaccination reduces cases by 26%, for $880/QALY assuming $500 per vaccination series. A program offering circumcision, microbicides, and vaccination has diminishing returns, preventing 43% of cases. Alternatively, increased screening and antiretroviral therapy reduces incidence by 45%, for $800/QALY. A portfolio with all five interventions averts 69% of infections, and is cost-effective at $1,860/QALY. Monte Carlo simulation results suggest that such a strategy costs <$5,000/QALY in 87% of trials, and <$10,000/QALY in 94% of trials. Conclusions: A comprehensive portfolio of expanded HIV screening, antiretroviral therapy, male circumcision, vaccination, and microbicide use prevents the greatest number of infections and is cost-effective. Male circumcision is cost-saving, but differentially benefits men. Given resource constraints, the model can help identify the optimal portfolio of interventions. 