Combination antiretroviral therapy (ART) decreases the risk of sexual HIV transmission by suppressing blood and genital HIV RNA concentrations. We sought to determine HIV transmission risk prior to achieving complete viral suppression. Prospective cohort study. Using data from the Partners PrEP Study, a prospective study of 4747 heterosexual HIV-serodiscordant couples in Kenya and Uganda, we examined multiple markers of HIV transmission risk during the first months after ART initiation: time to viral suppression in blood, persistence of HIV RNA in genital specimens, sexual risk behavior, pregnancy incidence, and HIV transmission using survival analysis and generalized estimating equations logistic regression. The cumulative probabilities of achieving blood viral suppression (<80 copies per milliliter) 3, 6, and 9 months after ART initiation were 65.3%, 84.8%, and 89.1%, respectively. Endocervical and seminal HIV RNA were detectable in 12% and 21% of samples obtained within 6 months of ART. Pregnancy incidence was 8.8 per 100 person-years during the first 6 months of ART, and sex unprotected by condoms was reported at 10.5% of visits. Among initially uninfected partners, HIV incidence before ART was 2.08 per 100 person-years (55 infections; 2644 person-years), 1.79 for 0-6 months after ART initiation (3 infections; 168 person-years), and 0.00 with >6 months of ART (0 infections; 167 person-years). Residual HIV transmission risk persists during the first 6 months of ART, with incomplete viral suppression in blood and genital compartments. For HIV-serodiscordant couples in which the infected partner starts ART, other prevention options are needed, such as pre-exposure prophylaxis, until viral suppression is achieved.