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To evaluate the feasibility, fidelity, and effectiveness of a human immunodeficiency virus (HIV) prevention intervention delivered to HIV-infected patients by counselors during routine clinical care in KwaZulu-Natal, South Africa.A total of 152 HIV-infected patients, aged 18 years and older, receiving clinical care at an urban hospital in South Africa, were randomly assigned to intervention or standard-of-care control counselors. Intervention counselors implemented a brief risk reduction intervention at each clinical encounter to help patients reduce their unprotected sexual behavior. Self-report questionnaires were administered at baseline and 6 months to assess number of unprotected sex events in previous 3 months.Intervention was delivered in 99% of routine patient visits and included a modal 8 of 8 intervention steps. Although HIV-infected patients in both conditions reported more vaginal and anal sex events at 6-month follow-up than at baseline, patients who received the counselor-delivered intervention reported a significant decrease over time in number of unprotected sexual events. There was a marginally significant increase in these events among patients in the standard-of-care control condition.A counselor-delivered HIV prevention intervention targeting HIV-infected patients seems to be feasible to implement with fidelity in the South African clinical care setting and effective at reducing unprotected sexual behavior.