August 3, 2000.

A Study in Rural Uganda of Heterosexual Transmission of Human Immunodeficiency Virus

To the Editor:

Bailey comments on the association between circumcision and reduced rate of acquisition of HIV-1 in male subjects in our study of couples discordant for HIV-1 status. Although circumcision was strongly associated with reduced acquisition of HIV-1 in these highly exposed couples, additional analyses suggest that generalization to the whole population is complicated by confounding. (1) In our representative population in Rakai, we found that circumcision was associated with a reduced rate of HIV-1 acquisition; this was particularly true for circumcision performed before puberty. However, this effect was mainly due to the lower incidence of HIV-1 among Muslims, who constitute the largest group of circumcised males. Circumcision was not significantly protective among non-Muslim men or in couples in which both partners were HIV-1-negative. (1) The 30 African epidemiologic studies mentioned by Bailey are mainly cross-sectional investigations with inconsistent findings and inadequate control for potential confounding. These observational data are difficult to interpret, and clinical trials are needed before circumcision can be promoted as a means of preventing HIV infection.

Fremont-Smith questions the proportion of subjects with undetectable viral loads in our study on the basis of a comparison with a subgroup analysis from the Multicenter AIDS Cohort Study (2) and a previous report that plasma HIV-1 RNA levels tend to be higher in sub-Saharan Africa. (3) Unfortunately, these studies cannot be directly compared with ours. Both studies referred to by Fremont-Smith used plasma, whereas we used serum. HIV-1 RNA levels in plasma are 30 to 80 percent higher than those in serum, (4) so specimens with low levels of HIV-1 RNA in plasma may have undetectable levels in serum. Prolonged periods between collection, processing, and storage in our study may also have lowered viral detection, since the greatest decrease in RNA levels occurs within the first six hours after collection. However, the overall results remain internally valid, since the methods of sample preparation and assay were consistent throughout the study. Our estimate of the risk of transmission per log (base 10) increment in viral load is nearly identical to the risk observed in a study of mother-to-infant transmission (5) and in a study of heterosexual transmission in Zambia (6); this consistency further supports the validity of our measurements of viral levels.

Thomas C. Quinn, M.D.
National Institute of Allergy and Infectious Diseases
Bethesda, MD 21205

Maria J. Wawer, M.D.
Columbia University
New York, NY 10032

Nelson K. Sewankambo, M.B., Ch.B.
Makerere University
Kampala, Uganda


  1. Gray RH, Kiwanuka N, Quinn TC, et al. Male circumcision and HIV acquisition and transmission: cohort studies in Rakai, Uganda. AIDS (in press).
  2. Lyles RH, Munoz A, Yamashita TE, et al. Natural history of human immunodeficiency virus type 1 viremia after seroconversion and proximal to AIDS in a large cohort of homosexual men. J Infect Dis 2000;181:872-80.
  3. Dyer JR, Kazembe P, Vernazza PL, et al. High levels of human immunodeficiency virus type 1 in blood and semen of seropositive men in sub-Saharan Africa. J Infect Dis 1998;177:1742-6.
  4. Lew J, Reichelderfer P, Fowler M, et al. Determinations of levels of human immunodeficiency virus type 1 RNA in plasma: reassessment of parameters affecting assay outcome. J Clin Microbiol 1998;36:1471-9.
  5. Mofenson LM, Lambert JS, Stiehm ER, et al. Risk factors for perinatal transmission of human immunodeficiency virus type 1 in women treated with zidovudine. N Engl J Med 1999;341:385-93.
  6. Fideli U, Allen S, Musonda R, et al. Virologic determinants of heterosexual transmission in Africa. Presented at the 7th Conference on Retroviruses and Opportunistic Infections, San Francisco, January 30-February 2, 2000.

(File revised 3 September 2003)

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