Editorial - Laurence

A recent editorial in The New York Times heralded the conclusion, from 2 large sub-Saharan African studies, that male circumcision dramatically suppresses HIV acquisition rates as the "most important development in AIDS research since the debut of antiretroviral drugs."¹ The editorial went on to state that while a "real [AIDS] vaccine is years away . . . we know its near equivalent [now] exists."¹But Anthony Fauci, director of the National Institute for Allergy and Infectious Disease, was more circumspect. "These results could be negated by a small decrease in condom use or the addition of more sexual partners," he cautioned.²

In fact, that is just what at least some Africans at risk for HIV infection who are now lining up to undergo circumcision said they had in mind when they were interviewed last year after results from the first controlled trial of male circumcision were released. That study, a randomized controlled intervention conducted in a general population of 3274 uncircumcised men aged 18 to 24 years in South Africa, found 20 HIV infections in the intervention group compared with 49 among controls, representing a protection rate of 60% after a mean 18.1-month follow-up.³

These data paralleled numerous observational studies, some published more than 17 years ago, showing that uncircumcised men have higher rates of HIV infection than their circumcised counterparts.^4,5 The data are also consistent with the fact that while cells with receptors for HIV are present in all penile epithelia, heavy keratinization of the glans penis makes this tissue an unlikely target for primary infection unless it has been compromised by lesions, inflammation, or trauma.⁶

However, superficial Langerhans cells on the inner aspect of the foreskin and frenulum are poorly keratinized and highly sensitive to HIV infection.⁶ These same cells may also be targets for other sexually transmitted viruses. For example, uncircumcised men infect women with human papillomavirus at a rate 3-fold higher than that of circumcised partners.⁷ Although formal trials have not yet addressed this issue, male circumcision may also help protect some women from HIV spread. This was suggested by a retrospective study of 300 Ugandan couples conducted last year: circumcised men were 30% less likely to transmit HIV to their female partners.⁸

The South African trial has now been replicated in Kenya and Uganda. The Kenyan study involved 2784 men aged 18 to 24 years, half of whom were randomly assigned to be circumcised. Forty-seven cases of HIV infection were found in the control group versus 22 among the circumcised men, a 53% reduction.^2,8 In Uganda, 4996 men aged 15 to 49 years were studied; 43 cases of HIV infection occurred among the controls versus 22 among the circumcised men, for a 48% reduction in HIV transmission.^2,8

Apart from concerns over a behavioral backlash that might ultimately increase the spread of HIV infection, as raised by Fauci, others have questioned the acceptability and safety of the procedure itself. Circumcision removes the "most erogenous tissue" of the male body, one nurse and anti-circumcision activist argued.² As such, she questioned whether this diminished sensitivity might be an additional disincentive to use condoms. Male circumcision also does not diminish the spread of HIV through anal intercourse.⁸ And, "if performed by folk healers using dirty blades, as often happens in rural Africa," circumcision could conceivably accelerate the spread of HIV infection.⁸

This latter issue has become increasingly prominent in efforts to focus HIV prevention programs in the resource-poor world. Both traditional healers and medical clinics have been investigated as potential central sources for HIV transmission through needles. According to a recent interview with Edward Mills from McMaster University, who has investigated this issue in South Africa, "there is no doubt that traditional practices are spreading HIV. . . . UNAIDS [The Joint United Nations Programme on AIDS] has been ignoring it. I think it's because people think it's culturally insensitive to talk about."⁹

In Africa, there is only 1 physician for every 40,000 persons, a factor leading to the reliance of many on alternative health care providers. An estimated 70% of adults use traditional healers as their primary source of health care.9 The very low prevalence of HIV infection in children aged 5 to 14 years would be difficult to explain if unsafe medical injections were an important part of the spread of HIV infection, because such injections are more common in children.¹⁰ In addition, according to one mathematical modeling study, iatrogenic transmission probabilities and numbers of unsafe injections that would be required to generate observed HIV prevalence rates in Africa are "unfeasibly high."¹¹

However, in one small survey, 50% of ritual healers were themselves infected with HIV, and they rarely use sterile equipment for injection, scarification, and such.⁹ If a program of male circumcision is to be disseminated rapidly, as recommended by several reports from federal and private funding agencies,² then use of such alternative venues must be discouraged or the practitioners must be assisted in employing safer techniques. In any event, this is a new area of HIV prevention that will be followed with great interest.

References:

References
1. Rare good news about AIDS [editorial]. New York Times. December 14, 2006:A40.
2. Russell S. Male circumcision shows promise as defense against HIV transmission. San Francisco Chronicle. December 14, 2006.
3. Auvert B, Taljaard D, Lagarde E, et al. Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: the ANRS 1265 trial [published correction appears in PLoS Med. 2006;3:e298]. PLoS Med. 2005;2:e298.
4. Cameron DW, Simonsen JN, DÕCosta LJ, et al. Female to male transmission of human immunodeficiency virus type 1: risk factors for seroconversion in men. Lancet. 1989;2:403-407.
5. Siegfried N, Muller M, Deeks J, et al. HIV and male circumcisionÑa systematic review with assessment of the quality of studies. Lancet Infect Dis. 2005;5:165-173.
6. McCoombe SG, Short RV. Potential HIV-1 target cells in the human penis. AIDS. 2006;20:1491-1495.
7. Castellsague X, Bosch FX, Munoz N, et al; International Agency for Research on Cancer Multicenter Cervical Cancer Study Group. Male circumcision, penile human papillomavirus infection, and cervical cancer in female partners. N Engl J Med. 2002;346:1105-1112.
8. McNeil DG Jr. HIV risk halved by circumcision, US agency finds. New York Times. December 14, 2006:A1.
9. Rosenthal E. Traditional ways spread AIDS in Africa, experts say. New York Times. November 21, 2006:A3.
10. Hayes RJ, White RG. How important are unsafe medical injections in the spread of HIV in Africa? Sex Transm Dis. 2006;33:135-136.
11. French K, Riley S, Garnett G. Simulations of the HIV epidemic in sub-Saharan Africa: sexual transmission versus transmission through unsafe medical injections. Sex Transm Dis. 2006;33:127-134.