Male circumcision and human immunodeficiency virus infection: An update on randomized controlled trials and molecular evidences

Male circumcision is one of the common and oldest surgical modalities performed worldwide for social, cultural, and medicals reasons. It is now well documented that 37-39% of men globally are circumcised.[1] The frequency of male circumcision was markedly increased in all over the world since three consecutive randomized controlled trials (RCTs) have concluded that male circumcision decreases the risk of acquiring human immunodeficiency virus-1 (HIV-1 or HIV) infection by 50–60% in men.[2-4] These trails findings were fully supported by a large number of survey-based studies in United States and Africa.[5,6] In agreement with these views, the World Health Organization (WHO) and Joint United Program on HIV/AIDS (UNAIDS) together have issued a formal recommendation on voluntary implementation of male circumcision for HIV prevention.[7] In support of these, the American Academy of Pediatrics (AAP) took a similar step in favor of male circumcision for newborns,[8] and moreover, this has also been supported by the American College of Obstetricians and Gynecologists.[6,8] Male circumcision has now become a valuable component for HIV prevention policy in Sub-Saharan Africa, with almost 15 million circumcisions performed from 2007 to 2016.[9,10] Furthermore, UNAIDS has already set a target that 90% of men aged between 15 and 29 years should be circumcised in Africa by 2021 with a total of 27 million more circumcision on a voluntary basis.[9,11] Although the WHO and UNAIDS proposed reaching 80% of male circumcision coverage in HIV widespread countries, but in developed countries, current rates declined far behind the target and circumcision remains continues to be a controversial topic. [6,12-14] In spite of these, AAP has recognized the importance of male circumcision and has fully supported the procedure for insurance coverage.[6,8] According to the data published so far on RCTs, it is quite clear that male circumcision decreases femaleto-male HIV-1 risk but data on circumcised male-to-female HIV-1 transmission are still conflicting.[15] One randomized trial performed in Rakai, Uganda, in 2011 on male-to-female HIV transmission showed that male circumcision does not reduce the HIV infection in female partners, and female partners are more prone when intercourse with HIV-infected circumcised men.[15] Grung et al. have recently reviewed this aspect closely and they pointed out that the increased risk of HIV in females could be due to early sex after male circumcision.[9] In addition, Baeten et al. performed a welldesigned study on male-to-female HIV-1 transmission on 1096 HIV-1-serodiscordant couples, in which 34% were circumcised men and were HIV-1 infected. They observed that male circumcision decreases transmission in their female partners.[16] This was also observed by many other investigators that female partners with circumcised men were found to have a much lower risk of HIV transmission as compared to those females with uncircumcised men.[17-20] Thus, there are substantial RCT-based evidence that male circumcision reduces female-to-male or male-to-female HIV transmission.[5,6,17] However, the role of male circumcision for the reduction of HIV transmission among homosexual men is still not clear and highly controversial.[4,5,17] A study by Buchbinder et al. performed in six cities of the United States and found that the uncircumcised men who have sex with men were associated with twice the risk of HIV infection as compared to those with circumcised men.[21] Similar observations have also been previously reported by Kreiss and Hopkins.[22] However, Grulich et al., in Australia, found no correlation between circumcision and HIV acquisition among homosexual men.[23] Similar results have also been reported by Templeton et al.[24] Furthermore, a meta-analysis by Millett et al. also showed no association between circumcision and HIV acquisition in homosexual men.[25] These data indicate that male circumcision may work as a safeguard against vaginal insertion but not against anal intercourse,[6] and therefore, circumcised men involving sexual intercourse in both forms may have partial protection. Editorial