Correspondence
A Study in Rural Uganda of Heterosexual Transmission of Human Immunodeficiency Virus
N Engl J Med 2000; 343:364-365August 3, 2000
- Article
To the Editor:
Largely ignored in the report by Quinn et al. of their study of the heterosexual transmission of human immunodeficiency virus type 1 (HIV-1) in Uganda (March 30 issue)1 is the finding that of 137 uncircumcised men who were negative for HIV-1, 40 seroconverted, whereas 0 of 50 circumcised men seroconverted. This finding suggests that male circumcision is at least as protective against female-to-male transmission of HIV-1 as low viral load in the female partner. Yet the authors do not consider male circumcision among their list of possible strategies for the prevention of HIV-1 infection.
There are now more than 30 epidemiologic studies from sub-Saharan Africa dating back to 1987 that report a significant protective effect of male circumcision against HIV-1 infection.2 Is it not time for those in Rakai, Uganda (where Quinn et al. conducted their study), as well as others, to benefit from these studies? The feasibility of offering information on voluntary male circumcision and circumcision services to this community with a high prevalence of HIV-1 infection could at least be investigated. Justice and scientific evidence demand it.
2 ReferencesRobert C. Bailey, Ph.D., M.P.H.
University of Illinois School of Public Health, Chicago, IL 603021
Quinn TC ,Wawer MJ ,Sewankambo N , et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. N Engl J Med 2000;342:921-929
Full Text | Web of Science | Medline2
Halperin DT ,Bailey RC . Male circumcision and HIV infection: 10 years and counting. Lancet 1999;354:1813-1815
CrossRef | Web of Science | Medline
To the Editor:
Quinn et al. state that 51 of the 415 untreated HIV-1–positive subjects in their study had undetectable serum levels of HIV-1 RNA (<400 copies per milliliter). Such a large number of untreated subjects with viral loads of less than 400 copies per milliliter (12 percent of untreated subjects) is surprising. In the large Multicenter AIDS Cohort Study, use of the same methods indicated that only about 3 percent of untreated HIV-positive persons had plasma levels of less than 400 copies per milliliter.1 According to the editorial accompanying the article by Quinn et al.,2 plasma HIV-1 RNA levels tend to be higher, not lower, in sub-Saharan Africa than in more developed countries, and the incidence of host mutations that might lead to low viral levels is lower. It is possible, therefore, that the serum specimens from these 51 subjects had degraded or become denatured during the one to three years of storage before laboratory measurement. Are the “undetectable” values erroneous? If so, this may cast doubt on the other viral RNA measurements and thus on the conclusion that the plasma HIV-1 RNA level is the chief predictor of heterosexual transmission of HIV-1.
2 ReferencesKenneth Fremont-Smith, M.D.
1550 Trotting Horse Ln., Missoula, MT 598041
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;181:872-880
CrossRef | Web of Science | Medline2
Cohen MS . Preventing sexual transmission of HIV: new ideas from sub-Saharan Africa. N Engl J Med 2000;342:970-972
Full Text | Web of Science | Medline
Author/Editor Response
The authors reply:
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 Study2 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 transmission5 and in a study of heterosexual transmission in Zambia6; this consistency further supports the validity of our measurements of viral levels.
6 ReferencesThomas C. Quinn, M.D.
National Institute of Allergy and Infectious Diseases, Bethesda, MD 21205Maria J. Wawer, M.D.
Columbia University, New York, NY 10032Nelson K. Sewankambo, M.B., Ch.B.
Makerere University, Kampala, Uganda1
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;181:872-880
CrossRef | Web of Science | Medline3
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;177:1742-1746
CrossRef | Web of Science | Medline4
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;36:1471-1479
Web of Science | Medline5
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;341:385-393
Full Text | Web of Science | Medline6
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.
- Citing Articles (2)
Citing Articles
1
Yoram Vardi, Hossein Sadeghi-Nejad, Shimon Pollack, Oseremen I. Aisuodionoe-Shadrach, Ira D. Sharlip. (2007) Male Circumcision and HIV Prevention. The Journal of Sexual Medicine 4:4i, 838-843
CrossRef2
Robert C Bailey, Stephen Moses, Corette B Parker, Kawango Agot, Ian Maclean, John N Krieger, Carolyn FM Williams, Richard T Campbell, Jeckoniah O Ndinya-Achola. (2007) Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial. The Lancet 369:9562, 643-656
CrossRef
