A Combination of Nucleoside Analogues and a Protease Inhibitor Reduces HIV-1 RNA Levels in Semen: Implications for Sexual Transmission of HIV Infection

Abstract

Direct contact with semen is the major route of sexual acquisition of human immunodeficiency virus (HIV) in homosexual and heterosexual partners of seropositive men. In this study, we show that concentrations of HIV-1 RNA molecules in plasma and semen of seropositive patients are related to the duration and type of anti-retroviral agents used in treatment. In patients treated with zidovudine alone, 1, 3 and 6 months after the start of therapy, the mean HIV-1 load in plasma was reduced by 0.57, 0.38 and 0.21 log₁₀ and in semen by 0.66, 0.50 and 0.15 log₁₀, respectively. In patients treated with zidovudine plus didanosine at months 1, 3 and 6, the mean decrease in plasma HIV-1 RNA was 1.40, 1.25 and 1.12 log₁₀ and in semen 1.10, 1.41 and 1.32 log₁₀, respectively. In patients treated with a combination of a protease inhibitor and two nucleoside analogues the mean log₁₀ decrease was 1.77, 1.83, 1.71 and 2.38 log₁₀ in plasma and 1.17, 1.74, 2.19 and 3.02 log₁₀ in semen at 1, 2, 3 and 4 months, respectively. Treatment with a combination of a protease inhibitor and two nucleoside analogues caused a dramatic decrease in cell-free HIV-1 RNA in semen, which is a reliable measure of viral load. These findings could have implications for the sexual transmission of HIV-1.