How does circumcision protect against hiv

Circumcision is "not a magic bullet, but a potentially important intervention," said Dr. Kevin M. To ensure safe and clean operations, male circumcision should only be performed by well-trained practitioners in sanitary settings under conditions of informed consent, confidentiality, proper counseling and safety. These considerations and others in relation to the AIDS response, including the fact that male circumcision has the potential to be an expensive intervention, that more research is needed to address whether male circumcision reduces risk of transmitting HIV-particularly for female partners, and the different ethical and human rights issues raised by male circumcision, will form discussions of the United Nations consultation on male circumcision that will take place in Geneva from 5 March.

Skip to main content. Recommended reads:. You might also be interested in one of the following sections:. Feature Story. If this hypothesis is true, then what causes the pro-inflammatory immune milieu that is seen in foreskin tissues adjacent to the sub-preputial space?

Emerging evidence suggests that both co-infections and the local polymicrobial community the penile microbiome play a key role. Circumcision reduces the incidence of viral co-infections, particularly human papilloma virus HPV and herpes simplex virus type 2 HSV-2 [ 1 ]. HPV is also associated with HIV acquisition, perhaps because host HPV clearance is associated with an increased density of dendritic cells in both the foreskin [ 36 ] and female genital tract [ 37 , 38 ]. However, the protective effect of circumcision against HIV infection is far greater than can be explained by a reduction in these viral co-infections alone [ 39 ]; another important mechanism by which circumcision may reduce penile inflammation is through the dramatic alterations that it induces in the penile microbiome [ 40 , 41 ].

Over 42 distinct bacterial families can be found in the sub-preputial space of uncircumcised men, and gram-negative anaerobic genera that are associated with bacterial vaginosis in women are common [ 41 ]. For instance, Prevotella spp. Furthermore, there was a strong association in uncircumcised Ugandan men between the presence of BV-associated anaerobes in the foreskin prepuce and subsequent HIV acquisition.

For instance, preputial Prevotella spp. However, while their causal role in driving genital inflammation in women has been demonstrated through the dramatic immune alterations induced by BV therapy [ 46 ], the direction of causality in men has not been defined, and may require clinical trials to assess the immune impact of microbiome-directed interventions. Circumcision reduces both the total bacterial load on the penis and also specifically reduces the relative abundance of these anaerobic genera associated with HIV acquisition [ 40 , 41 ].

Significant penile microbiome changes are apparent within 6 months of circumcision [ 40 ], and anaerobes continue to decline significantly for at least 2 years post-operatively, mirroring the progressive declines seen in IL-8 levels [ 24 ]. While vaginal bacterial dysbiosis is accepted as a driver of vaginal inflammation [ 47 , 48 ] and HIV acquisition [ 49 ], the concept that penile bacterial dysbiosis may also drive inflammation and HIV acquisition is new.

Coupled with the observation that the genital microbiome is shared between sexual partners, these observations have important implications for HIV prevention, but it remains to be shown whether they can be translated into prevention methods that extend beyond male circumcision.

Furthermore, it will important for preclinical and early phase clinical trials of novel HIV prevention methods, including HIV vaccines that aim to induce mucosal immune responses, to define intervention impacts on both genital inflammation and the genital microbiome. Male circumcision: a globally relevant but under-utilized method for the prevention of HIV and other sexually transmitted infections.

Annu Rev Med. PLoS Pathog. No difference in keratin thickness between inner and outer foreskins from elective male circumcisions in Rakai, Uganda. Keratinization of the adult male foreskin and implications for male circumcision. Int Urol Nephrol. Article PubMed Google Scholar. Potential HIV-1 target cells in the human penis. Setting the stage: host invasion by HIV. Nat Rev Immunol. Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection.

Haase AT. CCR5- and CXCR4-tropic subtype C human immunodeficiency virus type 1 isolates have a lower level of pathogenic fitness than other dominant group M subtypes: implications for the epidemic.

J Virol. Increased levels of inflammatory cytokines in the female reproductive tract are associated with altered expression of proteases, mucosal barrier proteins, and an influx of HIV-susceptible target cells. Mucosal Immunol. J Clin Invest. Activated CDderived Langerhans cells mediate trans infection with human immunodeficiency virus.

J Immunol. Th17 cells are preferentially infected very early after vaginal transmission of SIV in macaques. Cell Host Microbe. Foreskin T-cell subsets differ substantially from blood with respect to HIV co-receptor expression, inflammatory profile, and memory status. Chemokine levels in the penile coronal sulcus correlate with HIV-1 acquisition and are reduced by male circumcision in Rakai, Uganda. Evidence for a cross-talk between human neutrophils and Th17 cells. Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin immunity.

HIV acquisition is associated with increased antimicrobial peptides and reduced HIV neutralizing IgA in the foreskin prepuce of uncircumcised men. Cationic polypeptides are required for anti-HIV-1 activity of human vaginal fluid. Oral Dis. Within 1 h, HIV-1 uses viral synapses to enter efficiently the inner, but not outer, foreskin mucosa and engages langerhans—T cell conjugates.

Although researchers now agree that its removal is a proved method to reduce HIV spread in heterosexual men, the picture for homosexual men remains a bit foggy. In the late s observations of heterosexual men in Africa indicated that those who had been circumcised might be at less risk of contracting HIV than men who left their foreskins intact.

To definitely test the hypothesis, researchers initiated clinical trials in at-risk populations with low rates of circumcision. Two studies focused on young urban men ages 18 to 24 in Kenya and South Africa, whereas a third concentrated on a larger cross-section of rural men ages 15 to 49 in Uganda. Over 11, men volunteered for the trials with one group receiving circumcision on enrollment and a control group delaying surgery until the end of the study.

By tracking newly acquired infections in both groups, investigators discovered that circumcision cut HIV transmission rates by 55 to 65 percent. In fact, all three trials were stopped early due to the overwhelming evidence of circumcision's protective effect. But the question remained: Why? Microscopic examination of the foreskin yielded important clues for unraveling the benefits of circumcision. Normally, the skin provides a thick protective barrier stemming from keratin —a tough structural protein also found in hair and fingernails.

But on the inner surface of the foreskin, the keratin layer is much thinner, resembling the inner lining of the mouth or eyelid more than the palm of the hand. In uncircumcised men Langerhans cells—immune cells that are primary targets for HIV transmission—"are more richly concentrated near the surface of the foreskin," says Anthony Fauci , director of the U.

Without the keratin barrier, HIV can easily access these cells in the foreskin. Following infection, Langerhans cells not only serve as reservoirs for replicating virus, but also transport the virus to nearby lymph nodes where HIV spreads to other immune cells.

In fact, the foreskin's anatomical function actually amplifies the risks. In uncircumcised men the foreskin covers and protects the tip of the penis, paradoxically making the skin there more delicate and prone to microscopic abrasions. These tiny injuries promote inflammation, Fauci says, allowing the virus to come into closer contact with target immune cells.