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Long-term impact of antiretroviral therapy (ART) on sexual HIV-transmission risk in Africa is unknown. We assessed sexual behavior changes and estimated HIV transmission from HIV-infected adults on ART in Uganda.Between 2003 and 2007, we enrolled and followed ART-naive HIV-infected adults in a home-based AIDS program with annual counseling and testing for cohabitating partners, participant transmission risk-reduction plans, condom distribution and prevention support for cohabitating discordant couples. We assessed participants' HIV plasma viral load and partner-specific sexual behaviors. We defined risky sex as intercourse with inconsistent/no condom use with HIV-negative or unknown serostatus partners in previous 3 months. We compared rates using Poisson regression models, estimated transmission risk using established viral load-specific transmission estimates, and documented sero-conversion rates among HIV-discordant couples.Of 928 participants, 755 (81%) had 36 months data: 94 (10%) died and 79 (9%) missing data. Sexual activity increased from 28% (baseline) to 41% [36 months (P < 0.001)]. Of sexually active participants, 22% reported risky sex at baseline, 8% at 6 months (P < 0.001), and 14% at 36 months (P = 0.018). Median viral load among those reporting risky sex was 122 500 [interquartile range (IQR) 45 100–353 000] copies/ml pre-ART at baseline and undetectable at follow-up. One sero-conversion occurred among 62 cohabitating sero-discordant partners (0.5 sero-conversions/100 person-years). At 36 months, consistent condom use was 74% with discordant partners, 55% with unknown and 46% with concordant partners. Estimated HIV transmission risk reduced 91%, from 47.3 to 4.2/1000 person-years.Despite increased sexual activity among HIV-infected Ugandans over 3 years on ART, risky sex and estimated risk of HIV transmission remained lower than baseline levels. Integrated prevention programs could reduce HIV transmission in Africa.