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Background  Countries in sub-Saharan Africa are scaling-up voluntary male medical circumcision (VMMC) as an HIV intervention. Emerging challenges in these programs call for increased focus on program efficiency (optimizing program impact while minimizing cost). A novel analytic approach was developed to determine how subpopulation prioritization can increase program efficiency using an illustrative application for Zambia.    Methods and Findings  A population-level mathematical model was constructed describing the heterosexual HIV epidemic and impact of VMMC programs (age-structured mathematical (ASM) model). The model stratified the population according to sex, circumcision status, age group, sexual-risk behavior, HIV status, and stage of infection. A three-level conceptual framework was also developed to determine maximum epidemic impact and program efficiency through subpopulation prioritization, based on age, geography, and risk profile. In the baseline scenario, achieving 80% VMMC coverage by 2017 among males 15–49 year old, 12 VMMCs were needed per HIV infection averted (effectiveness). The cost per infection averted (cost-effectiveness) was USD $1,089 and 306,000 infections were averted. Through age-group prioritization, effectiveness ranged from 11 (20–24 age-group) to 36 (45–49 age-group); cost-effectiveness ranged from $888 (20–24 age-group) to $3,300 (45–49 age-group). Circumcising 10–14, 15–19, or 20–24 year old achieved the largest incidence rate reduction; prioritizing 15–24, 15–29, or 15–34 year old achieved the greatest program efficiency. Through geographic prioritization, effectiveness ranged from 9–12. Prioritizing Lusaka achieved the highest effectiveness. Through risk-group prioritization, prioritizing the highest risk group achieved the highest effectiveness, with only one VMMC needed per infection averted; the lowest risk group required 80 times more VMMCs.    Conclusion  Epidemic impact and efficiency of VMMC programs can be improved by prioritizing young males (sexually active or just before sexual debut), geographic areas with higher HIV prevalence than the national, and high sexual-risk groups.

Investigating Voluntary Medical Male Circumcision Program Efficiency Gains through Subpopulation Prioritization: Insights from Application to Zambia