A combination of nucleoside analogues and a protease inhibitor reduces HIV-1 RNA levels in semen: implications for sexual transmission of HIV infection

Direct contact with semen is the major route of sexual acquisition of human immunodeficiency virus (HIV) in homosexual and heterosexual partners of se ropositive men. In this study, we show that concentrations of HIV-1 RNA mol ecules in plasma and semen of seropositive patients are related to the dura tion and type of antiretroviral agents used in treatment. In patients treat ed 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 log(10) and in semen by 0.66, 0.50 and 0.15 log(10), respectively. In patients treated wi th zidovudine plus didanosine at months 1, 3 and 6, the mean decrease in pl asma HIV-1 RNA was 1.40, 1.25 and 1.12 log(10) and in semen 1.10, 1.41 and 1.32 log(10), respectively. In patients treated with a combination of a pro tease inhibitor and two nucleoside analogues the mean log(10) decrease was 1.77, 1.83, 1.71 and 2.38 log(10) in plasma and 1.17, 1.74, 2.19 and 3.02 l og(10) in semen at 1, 2, 3 and 4 months, respectively. Treatment with a com bination of a protease inhibitor and two nucleoside analogues caused a dram atic 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 transm ission of HIV-1.