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OBJECTIVES: To describe awareness and use of antiretroviral treatments, viral load monitoring, and post-exposure prevention; to assess changing concerns about HIV transmission; and to examine the effect of these advances on sexual behavior in HIV-serodiscordant heterosexual couples. METHODS: Cross-sectional analysis of a baseline sample of 104 couples (n = 208 individuals) from the California Partners Study II, an intervention trial for HIV-serodiscordant couples in California. Questions on sexual practices, viral load testing, HIV treatment, post-exposure prevention, and their effect on sexual behaviors, risk taking and transmission concerns were measured at intake. RESULTS: Over two-thirds of couple members surveyed reported unprotected sex with their partner in the past 6 months. Among seropositive respondents, 37% were taking protease inhibitor therapy, 92% had undergone viral load testing, and of those, 40% said it had ben undetectable at their most recent test. Most respondents, regardless of serostatus, said that viral load testing and awareness of post-exposure prevention had no effect on their condom use. In addition, perceiving that their partner had an undetectable viral load was associated with having protected sex among seronegative subjects (P < 0.05). Seropositive respondent taking protease inhibitors were 2.4 times less likely to report unprotected sex compared with those not taking protease inhibitors (P = 0.05). However, up to 33% of seropositive and 40% of seronegative respondents acknowledged decreased transmission concerns in the light of the new HIV treatments. In comparison with their seropositive partners, seronegative individuals were more likely to acknowledge increased risk taking and decreased HIV transmission concerns (P < 0.05). CONCLUSIONS: New medical advances were not associated with unprotected sex in HIV-serodiscordant couples. However, new treatment options may decrease concerns about HIV transmission, particularly among seronegative partners. Providers should discuss the effect of antiretroviral treatments on sexual transmission risk with their patients. The inclusion of seronegative partners in counseling interventions may decrease risk taking in serodiscordant couples