The viral load of an HIV-positive sexual partner is the most important factor affecting heterosexual transmission of the virus in rural Uganda.1 Among 415 serodiscordant couples identified in a population-based study in Rakai, transmission rates increased with the number of copies of HIV ribonucleic acid (RNA) in the blood, from two seroconversions per 100 person-years when the infected partner had fewer than 3,500 copies per milliliter to 23 per 100 person-years when the partner had at least 50,000 copies per milliliter. No seroconversions occurred when the HIV-positive partner's viral load was less than 1,500 copies per milliliter.

The data for analysis came from a community-based study conducted in Rakai to determine whether treatment of sexually transmitted diseases (STDs) would lower the rate of HIV transmission. All participants were offered HIV testing, were counseled on how to prevent HIV transmission and were provided with free condoms.

To determine behavioral and biological risk factors for heterosexual transmission of HIV, researchers conducted individual interviews with participants at baseline and at follow-up visits occurring every 10 months over a period of up to 30 months. Each partner provided information on demographic characteristics; sexual history, including number of partners and use of condoms; and health history, including past and current symptoms of STDs and symptoms of AIDS. Biological samples for HIV and STD testing were taken at every visit.

Following the study, data from couples (either married or in a long-term consensual union) in which one partner had been HIV-positive at baseline and the other had not were analyzed. Couples in which the HIV-negative partner seroconverted were matched with couples in which no seroconversion occurred by sex of the positive and negative partner, by five-year age-group and by the timing of the biological sampling.

At baseline, the male partner was infected in 55% of the 415 couples and the female partner in 45%. During follow-up, 22% (90) of the seronegative partners seroconverted; of these, 56% were women and 44% were men. Among men, seroconversion occurred only among those who had not been circumcised (29%). Transmission was more likely if the seropositive partners had genital discharge (34%) or symptoms of AIDS (43%) than if they did not (21% each). No significant differences were found according to number of sexual partners or use of condoms (only 12% of couples used them). The rate of transmission from men to women was equal to the rate from women to men.

Blood levels of HIV RNA were highly associated with transmission. Among couples in which the HIV-positive partner had a viral load of up to 1,500 copies per milliliter, no uninfected partner seroconverted. Transmission rates progressed from 2.2 per 100 person-years when the infected partner's viral load was no more than 3,499 copies per milliliter to 23.0 per 100 person-years when the viral load was at least 50,000 copies per milliliter. The mean viral load of the infected partner in couples who experienced seroconversion was 90,254 copies per milliliter, compared with 38,029 copies per milliliter in couples who did not.

According to a multivariate analysis, the infected partner's viral load was the most important factor predicting transmission. Compared with men and women whose partner had a viral load of less than 3,500 copies of HIV RNA per milliliter, those whose partner had a viral load of 3,500-9,999 were 5.8 times as likely to seroconvert, those whose partner had a viral load of 10,000-49,999 were 6.9 times as likely and those whose partner had a viral load of 50,000 or more were 11.9 times as likely. Transmission rates declined with advancing age: Men and women in their 20s were 68% as likely to seroconvert as those aged 15-19, while those in their 30s were 32% as likely and those in their 40s and 50s were 27% as likely.

The investigators caution that the study data could not specify the viral load at the time of seroconversion because of the 10-month interval between follow-up visits. The length of the interval, they add, may also have obscured the role of STDs in HIV transmission. The investigators conclude, nevertheless, that the use of antiretroviral drugs or vaccines could lower transmission rates by reducing the levels of viral RNA in blood and in genital secretions. The author of an accompanying editorial comments that although programs treating seropositive individuals to reduce their infectiousness may be just as important as those focused on seronegative persons in high-risk populations, "antiretroviral therapy is currently too expensive and the treatment regimen is too complex for routine use in developing countries."2--L. Ninger


1. Quinn TC et al., Viral load and heterosexual transmission of human immunodeficiency virus type 1, New England Journal of Medicine, 2000, 342(13):921-929.

2. Cohen MS, Preventing sexual transmission of HIV: new ideas from sub-Saharan Africa, New England Journal of Medicine, 2000, 342(13):970-972.