ObjectiveTo determine the incidence of HIV-1 infection and associated risk factors among young, seronegative, and sexually active women in a mixed rural and urban population in southern Rwanda.DesignA prospective cohort study.MethodsBetween October 1991 and April 1993, we completed a 2-year follow-up survey among HIV-1-seronegative women aged ≤30 years at the time of their initial HIV-1 screening during pregnancy. All women aged ≤25 years and a randomly selected sample of 26–30-year olds were invited to participate from five prenatal clinics in the Butare region. The interview focused on potential risk factors for HIV-1 acquisition during the 2-year interval between blood collection.ResultsOut of 1524 women selected, 1150 (75%) participated in the follow-up survey. The 2-year incidence of HIV-1 infection was 2.7% [95% confidence interval (CD, 1.8–3.9]. Teenage women were at the highest risk (incidence, 10.5%; 95% Cl, 5.2–19.4), with incidence leveling off with increasing age (P<0.001). Women who began sexual activity recently were also at higher risk; the lowest risk category consisted of women aged 26–30 years with 5 or more years of sexual experience. The more urban the geographic residence of the woman, the more likely she was to have acquired HIV-1 infection (P<0.001). In the urban and peri-urban zones, the poorest women were at significantly higher risk of incident HIV-1 infection than women reporting higher household income. In a multivariate analysis, young maternal age, marital status (being single, divorced or widowed), multiple sexual partners, and a history of sexually transmitted diseases remained strongly associated with incident HIV-1 infection. Geographic residence, hormonal contraception, and receipt of injections were no longer significantly associated with incident HIV-1 infection when these other factors were accounted for simultaneously.ConclusionAmong young Rwandan women, the early years of sexual activity are particularly dangerous for acquisition of HIV-1 infection. Interventions should focus on young teenagers before they become sexually active.