Association of Medical Male Circumcision and Sexually Transmitted Infections in a Population-Based Study: A Targeted Maximum Likelihood Estimation Approach

Abstract Background: Epidemiological theory and many empirical studies support the hypothesis that there is a protective effect of male circumcision against some sexually transmitted infections (STIs). However, there is a paucity of randomized control trials (RCTs) to test this hypothesis in the South African population. Due to the infeasibility of conducting RCTs, estimating marginal or average treatment effects with observational data, are of increasing interest. Using targeted maximum likelihood estimation (TMLE), a doubly robust estimation technique, we aim to provide evidence of association between medical male circumcision (MMC) and two STI outcomes.Methods: We investigated the associations between MMC and the two STI outcomes, HIV and HSV-2, using data from the HIV Incidence Provincial Surveillance System (HIPSS) study in KwaZulu-Natal, South Africa. We estimated marginal odds ratios using TMLE and compared estimates with those from propensity score full matching and inverse probability of treatment weighting (IPTW). Results: TMLE estimates suggest that MMC was associated with 46.9% lower odds of HIV (OR: 0.531; 95% CI: 0.455, 0.621) and 20.5% for HSV-2 (OR: 0.795; 95% CI: 0.694, 0.911). The propensity score analyses also provided evidence of association of MMC with lower odds of HIV and HSV-2. For full matching: HIV (OR: 0.546; 95% CI: 0.402, 0.741), and HSV-2 (OR: 0.705; 95% CI: 0.545, 0.910). For IPTW: HIV (OR: 0.541; 95% CI: 0.405, 0.722), and HSV-2 (OR: 0.694; 95% CI: 0.541, 0.889).Conclusion: Using a TMLE approach, we present further evidence of a protective effect of MMC against HIV and HSV-2 in this hyper-endemic South African setting. TMLE has the potential to enhance the evidence base for recommendations that embrace the effect of public health interventions on health or disease outcomes.