Research: Male Circumcision and HIV Prevention

Under the United States President’s Emergency Plan for AIDS Relief, USAID has been supporting preliminary activities to investigate male circumcision as a potential tool to prevent transmission of HIV.

Global Interest in Male Circumcision

Source: Scientific American, 1996.

The effect of male circumcision (MC) on the risk of HIV infection – and the practice's impact on the spread of HIV across different populations – have for many years been subjects of interest to epidemiologists and other researchers. Numerous studies have noted a decreased risk of infection in circumcised men as well as continued low HIV prevalence rates in populations that traditionally practice MC. Especially now that a randomized controlled trial in South Africa has found a 60 – 75 percent reduction in HIV risk¹, international bodies such as the United Nations Programme on HIV/AIDS (UNAIDS), World Health Organization (WHO), and World Bank, along with growing numbers of HIV/AIDS and reproductive health program professionals, have become interested in MC. Under the United States President’s Emergency Plan for AIDS Relief, the U.S. Agency for International Development (USAID) has also been supporting preliminary activities to investigate male circumcision as a potential tool to prevent transmission of HIV.

Background

Male circumcision (removal of the foreskin of the penis) is a common practice in many cultures. It may be a birth ritual or, as in many parts of sub-Saharan Africa, a rite of passage performed around adolescence. In clinical settings, it is normally done as a quick outpatient procedure using local anesthesia.

Researchers have noted links between MC and HIV prevalence rates since the 1980s. The body of research now includes:

• A review that analyzed the findings of 38 studies, mostly in Africa, and found that circumcised men appear to be less than half as likely to be infected by HIV as uncircumcised men. A sub-analysis of 16 of these studies found an estimated 70 percent reduction in HIV infection among higher-risk men (see table: Geographic Variation of HIV and Estimated MC Prevalence).²
  
  
• A two-year cohort study of male partners of HIV-positive women in Rakai, Uganda, in which 40 of 137 uncircumcised men became infected, compared with 0 of 50 circumcised men.³
  
  
• Mapping of the HIV epidemic that has demonstrated a strong correlation between regions with higher levels of HIV infection and those with lower MC rates.⁴
  
  
• A Joint United Nations Programme on HIV/AIDS(UNAIDS) multisite study that found MC to be the principal factor in the large and pervasive disparities in HIV prevalence across different African regions.⁵ Similar patterns have been observed in South and Southeast Asia (see table: Geographic Variation of HIV and Estimated MC Prevalence).⁶
  
  
• Most recently and most importantly, in April 2005 a randomized clinical trial of over 3,000 young men in Orange Farm, South Africa, was halted prematurely by the study’s ethics board, because the protective effect of MC was found to be so strong.¹
  
  
• New data from Rakai, Uganda, presented at the the 13th Conference on Retroviruses and Opportunistic Infections (CROI) in February 2006, suggests that MC may also directly reduce the risk of HIV (and of some STIs) to the female partners of HIV+ men.⁷

Geographic Variation of HIV and Estimated MC Prevalence

* Countries within each region have similar risk factors for HIV (e.g., number of sexual partners, condom use, etc.) ** June 1998 UNAIDS/WHO percent estimates. *** Excluding the predominately non-circumcised region around Kisumu, western Kenya, where prevalence is 34.9 percent, national prevalence would be around 8 percent.

Male Circumcision and HIV Infection: 10 Years and Counting. D. Halpern, R. Bailey. Lancet 1999, 354: 1813-15.

Other Health Benefits

Circumcision is already known to greatly reduce a man's risk of penile cancer (still a major killer in some developing countries), and it also reduces risk of some other sexually transmitted diseases (STDs), including chancroid, herpes, and syphilis. It eliminates problems such as phimosis (narrow foreskin opening) and balanitis (infected foreskin), and has also been shown to significantly reduce the risk of cervical cancer among female partners of circumcised men.

Research has identified plausible biological explanations for a connection between HIV infection and lack of circumcision. The tissue of the internal foreskin absorbs HIV up to nine times more efficiently than other genital tissue, mainly because it contains Langerhans and other HIV "target cells" in much greater quantities than tissues such as the cervix (including other parts of the penis). In addition, the internal foreskin has a mucosal surface, as opposed to the more hardened skinlike surface of the external foreskin. This mucosal surface is particularly susceptible to tears and abrasions, and, consequently, infection by HIV and other STDs.^{8 9}

Continuing Research

Risk Reduction in High-Risk Circumcised Males, Various Studies

Source: H. Weiss, M. Quigley, R. Hayes

These epidemiological, geographic, and biological findings provide very strong – though not entirely conclusive – evidence that MC significantly lowers the risk of HIV infection. Two other large clinical trials to confirm an association between MC and HIV risk are now underway. Qualitative research, surveys and field studies to assess the acceptability and feasibility of expanding safe, voluntary MC services, conducted in many African countries and Haiti, have also helped identify the possible role of MC in HIV prevention.

Clinical trials. Randomized controlled trials funded by the National Institutes of Health (NIH), the Bill & Melinda Gates Foundation, and the Canadian International Development Agency (CIDA) are being conducted in Kenya and Uganda to definitively confirm whether circumcision of adult men protects them against HIV. The Uganda trial will also test observational findings suggesting MC may additionally protect the female partners of HIV-infected men. Combined, these studies involve about 9,000 men. Results from the studies will be available by mid-2007, and could be known as early as mid-2006 (when the NIH ethics board will review the interim data).

Field studies. A reproductive health program in central Kenya, where MC is traditionally performed on adolescents, has built upon cultural values and integrated preventive health education with clinical circumcision. This hospital-based program for adolescent boys is an adaptation of the traditional one- to two-week period of seclusion following MC. A second project in western Kenya has suggested that with appropriate training, supplies, counseling, and informed consent procedures (and affordable pricing structures), effective clinical services can be introduced in areas where circumcision has not been traditionally practiced.

Program Issues

In September 2002, USAID and some of its partner organizations hosted a conference of 145 international researchers and HIV/AIDS program staff to review the epidemiological, clinical, and field data related to MC and to discuss policy and program considerations for building possible future MC services.² These include:

Program context. Both traditional and clinic-based MC programs will need to take into account cultural norms, religious traditions, and national and local laws.

Clinical management. To ensure quality services, standardized guidelines and clinical training will be needed in areas such as surgical procedures and techniques, patient counseling and education, and postoperative needs. WHO and UNAIDS are carrying out a comprehensive work plan (funded by NIH, the Bill & Melinda Gates Foundation, and USAID) in 2006, including development of clinical guidelines.

Accurate information. Ethical considerations must be carefully addressed to ensure informed choice and consent. Information materials for diverse groups such as adolescents, adult men and their spouses, and the parents of infants should be age- and culturally appropriate and give balanced information about both advantages and possible complications of MC.

MC will not be a "magic bullet." As will likely be true for future microbicides or AIDS vaccines, circumcision will not provide full protection against HIV. It will provide little or no protection against urethral STDs such as gonorrhea and chlamydia and obviously will not prevent unwanted pregnancies. Effective behavior change programs will therefore still be needed to address these risks. There will also be an urgent need to address possible behavioral "disinhibition" among circumcised men who may continue or return to high-risk behaviors if they feel they are protected by MC, when in fact such protection is partial, not 100 percent. Counseling that addresses informed choice and consent; the HIV prevention "ABC" behaviors of abstinence/delay of sexual debut, being faithful/partner reduction, and correct and consistent condom use; and other male reproductive health needs (such as HIV testing, family planning, and addressing gender-based violence) would therefore need to be part of any future MC services.

Looking to the future...

Other activities that will help determine male circumcision’s possible role in future HIV prevention include:

• Further feasibility studies (including cost-effectiveness analyses) to assess the addition of MC to male reproductive health services in high HIV-prevalence countries where most men are not circumcised.
  
  
• Quality and safety studies to gather more data on the safety of MC and complication rates in both traditional and clinical settings.
  
  
• Technical consultations to develop consensus on optimal medical and counseling procedures, standards of practice and care, and issues such as integration of reproductive health and HIV prevention messages into traditional rites of passage.

Download a Printer-Friendly version of meeting report, Male Circumcision: Current Epidemiological and Field Evidence [PDF, 471KB]

Footnotes

¹Auvert B. Taljaard D, Lagarde E, Sobngwi-Tambekou J, Sitta R, Puren A. Randomized, controlled intervention trial of male circumcision for reducion of HIV infection risk: the ANRS 1265 Trial, PloS Med. November 2005.

²Weiss H, Quigley M, Hayes R. Male circumcision and risk of HIV infection in sub-Saharan Africa: A systematic review and meta-analysis. AIDS 2000; 14:22361-2370.

³Quinn TC, Wawer MJ, Sweankambo N, et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. N Engl J Med 2000; 342:921-929.

⁴ Caldwell JC, Caldwell P. The African AIDS Epidemic, Scientific American, 1996. 62-68.

⁵ Auvert B, Buvé A, Khindo M, Chege J, RUtenberg N, Musonda R, Laourou M, Akam, Weiss HA. Male Circumcision and HIV infection in four cities in sub-Saharan Africa. AIDS 2001, 15 (suppl 4): S31-S40.

⁶ Halperin DT, Bailey, RC. Male circumcision and HIV infection: 10 years and counting. The Lancet, Nov. 20, 1999. 1813-1815.

⁷ Gray R, Wawer M, Thoma M, Swerwadda D, Nalugoda F, Li X, Kigozi G, Kiwamuka N, Laeyendecker O, Quinn T. Male Circumcision and the Risks of Female HIV and Sexually Transmitted Infections Acquisition in Rakai, Uganda. Oral presentation, 13th Conference on Retroviruses and Opportunistic Infections, Feb 508, 2006.

⁸ Halperin DT, Bailey RC. Male circumcision and HIV infection : 10 years and counting. Lancet 1999; 354:1813-1815

⁹ Patterson BK, Landay A, Siegel JN, et al. Susceptibility to human immunodeficiency virus-1 infection of human foreskin and cervical tissue grown in explant culture. Am J Pathol 2002; 161:867-873.

^6-10 6)Bailey RC, Muga R, Poulussen R, Abicht H. The acceptability of male circumcision to reduce HIV infections in Nyanza province, Kenya. AIDS Care 2002; 14:27-40. 7)Lagarde E, Taljaard D, Puren A, Taljaard R, Auvert B. Acceptability of male circumcision as a tool for preventing HIV infection in a highly infected community in South Africa. AIDS 2003; 17:89-95. 8)Nnko S, Wshija R, Urassa M, Boerma T. Dynamics of male circumcision practices in northwest Tanzania. Sex Transm Dis 2001; 28:214-218. 9)Kebaabetswe P, Lockman S, Mogwe S, et al. Male circumcision: An acceptable strategy for HIV prevention in Botswana and South Africa. 11)Halperin DT. Cut and dry: Feasibility and acceptability of reviving male circumcision and introducing dry sex prevention in Botswana and South Africa. Abstracts of the American Anthropological Association 99th Annual Meeting; San Francisco; November 18, 2000.

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