for HIV prevention purposes is undetermined. It is not known whether the effect of male circumcision differs by HIV-1 variant. The predominant subtype of HIV-1 in the United States is subtype B, and in Africa, the predominant subtypes are A, C, and D. Recommendations The most recent WHO review of the evidence reiterates prior estimates of the impact of male circumcision on HIV incidence rates. In 2020, WHO again concluded that male circumcision is an efficacious intervention for HIV prevention and that the promotion of male circumcision is an essential strategy, in addition to other preventive measures, for the prevention of heterosexually acquired HIV infection in men. Eastern and southern Africa had a particularly low prevalence of circumcised males. This region has a disproportionately high HIV infection rate, with a significant number of those infections stemming from heterosexual transmission. The WHO has made voluntary medical male circumcision (VMMC) a priority intervention in that region since their 2007 recommendations. In the United States, the American Academy of Pediatrics (AAP) led a 2012 task force which included the American Academy of Family Physicians (AAFP), the American College of Obstetricians and Gynecologists (ACOG), and the Centers for Disease Control (CDC). The task force concluded that circumcision may be helpful for the prevention of HIV in the United States. The CDC 2018 position on circumcision and HIV recommended that circumcision should continue to be offered to parents who are informed of the benefits and risks, including a potential reduction in risk of HIV transmission. The position asserts that circumcision conducted after sexual debut can result in missed opportunities for HIV prevention. Because the evidence that circumcision prevents HIV mainly comes from studies conducted in Africa, the Royal Dutch Medical Association (KNMG) in 2010 questioned the applicability of those studies to developed countries. Circumcision has not been included in their HIV prevention recommendations. The KNMG circumcision policy statement was endorsed by several Dutch medical associations. Mechanism of action While the biological mechanism of action is not known, a 2020 meta-analysis stated "the consistent protective effect suggests that the reasons for the heterogeneity lie in concomitant individual social and medical factors, such as presence of STIs, rather than a different biological impact of circumcision." The inner foreskin harbours an increased density of CD4 T-cells and releases increased levels of pro-inflammatory cytokines. Hence the sub-preputial space displays a pro-inflammatory environment, conducive to HIV infection. Langerhans cells (part