Circumcision modestly reduces risk of male-to-female HIV transmission

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Male circumcision modestly reduces the risk of an HIV-positive man transmitting HIV to a female sex partner, an analysis of the Partners in Prevention study published in the journal AIDS suggests.

The risk of contracting HIV was 40% lower for the partners of circumcised men than uncircumcised men, but this reduction in risk was not statistically significant.

Randomised studies have shown that male circumcision reduces the risk of HIV acquisition for men by up to 60%.

Glossary

voluntary male medical circumcision (VMMC)

The surgical removal of the foreskin of the penis (the retractable fold of tissue that covers the head of the penis) to reduce the risk of HIV infection in men.

circumcision

The surgical removal of the foreskin of the penis (the retractable fold of tissue that covers the head of the penis) to reduce the risk of HIV infection in men.

statistical significance

Statistical tests are used to judge whether the results of a study could be due to chance and would not be confirmed if the study was repeated. If result is probably not due to chance, the results are ‘statistically significant’. 

p-value

The result of a statistical test which tells us whether the results of a study are likely to be due to chance and would not be confirmed if the study was repeated. All p-values are between 0 and 1; the most reliable studies have p-values very close to 0. A p-value of 0.001 means that there is a 1 in 1000 probability that the results are due to chance and do not reflect a real difference. A p-value of 0.05 means there is a 1 in 20 probability that the results are due to chance. When a p-value is 0.05 or below, the result is considered to be ‘statistically significant’. Confidence intervals give similar information to p-values but are easier to interpret. 

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.

Less is known about the effect of male circumcision on the incidence of male-to-female HIV transmission.

However, one recent study showed that HIV incidence was similar in the female partners of HIV-positive men who elected to be circumcised and the partners of men who remained uncircumcised. In addition, the study showed that the partners of recently circumcised HIV-positive men had a short-term increase in the risk of contracting HIV if sexual intercourse was resumed before wound healing.

To gain a better understanding of the impact of male circumcision on the risk of male-to-female HIV transmission, investigators from the Partners in Prevention HSV/HIV Transmission Study looked at the rate of new HIV infections that occurred during the study in women according to their male sexual partner’s circumcision status.

Importantly, the men in this study had undergone circumcision in childhood. Therefore it was able to determine the effects of circumcision on HIV transmission risk after full wound healing.

The study involved 1096 heterosexual couples where the man was HIV-positive and the woman HIV-negative. These couples were recruited in eastern and southern Africa between 2004 and 2007. The study’s primary aim was to see if prophylactic therapy with aciclovir reduced the risk of HIV transmission. No protective effect was found.

Median CD4 cell count amongst the men was 424 cells/mm3, with median viral load being 4.3 log10 copies/ml.

A total of 34% of men were circumcised. Men in eastern Africa (39%) were more likely than men in southern Africa (24%) to be circumcised.

The female partners were followed for a median period of 18 months. A median of four episodes of vaginal sex with their male partner was reported per month. Approximately 7% of these were unprotected. During follow-up, approximately 13% of men started antiretroviral therapy.

A total of 64 women contracted HIV during the study. The overall incidence rate was 3.8 per 100 person years.

The investigators were able to genetically link 50 of these seroconversions to the male study partner.

Analysis showed that HIV incidence was approximately 40% lower in these genetically linked transmissions amongst women whose partner was circumcised (hazard ratio 0.57; 95% CI, 0.29 to 1.11, p=0.10). However, this could have been down to chance as this reduction in risk was not statistically significant.

The investigators then excluded men who started antiretroviral therapy, and looked at transmission risk according to circumcision status and viral load.

They found the partners of men who were uncircumcised and had a viral load above 50,000 copies/ml had a 47% reduction in the risk of infection with HIV. This reduction in risk was of borderline significance (HR = 0.53; 95% CI, 0.26 to 1.07, p=0.07).

“We found a nonstatistically significant decreased risk of HIV-1 transmission from circumcised HIV-1 infected men to their female partners, compared with couples with uncircumcised HIV-1 infected men,” comment the investigators. They say that a larger sample size is probably necessary to determine if the apparent reduction in risk of transmission is statistically significant.

“This finding adds to a limited body of data relating circumcision status in HIV-1 infected men to the risk of male-to-female HIV-1 transmission, data which may be helpful for programs working to scale up male circumcision for HIV prevention,” they add.

Two possible biological reasons for the non-significant reduction in HIV transmission for the female partners of circumcised men are offered by the investigators. First, circumcision may reduce the risk of ulcerative sexually transmitted infections. However, the investigators note that the incidence of genital ulcers was comparable between the circumcised and uncircumcised men in their study. Alternatively, microtrauma or inflammation to the foreskin could facilitate transmission from uncircumcised men.

References

Baeten JM et al. Male circumcision and risk of male-to-female HIV-1 transmission: a multinational prospective study in African HIV-1-serodiscordant couples. AIDS 24: 737-44, 2010.