HIGH VIRAL LOAD IN SEMEN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE 1-INFECTED MEN AT ALL STAGES OF DISEASE AND ITS REDUCTION BY THERAPY WITH PROTEASE AND NONNUCLEOSIDE REVERSE-TRANSCRIPTASE INHIBITORS

Seminal viral load is likely to be directly related to the sexual tran smissibility of human immunodeficiency virus type 1 (HIV-1). However, it is not clear whether the level of HIV-1 in semen varies with the st age of infection and whether antiretroviral therapy reduces seminal vi ral load. A nucleic acid sequence-based amplification (NASBA) techniqu e was used to quantify HIV-1 RNA as an indicator of infectious viral l oad in semen and blood plasma of homosexual men with different stages and durations of HIV-1 infection. The median viral load in a cross sec tion of 34 men was 11,000 HIV-1 RNA copies/ml (range, < 400 to 1.3 x 1 0(7) copies/ml) in whole semen and 5,238 HIV-1 RNA copies/ml (range, < 400 to 2.8 x 10(5) copies/ml) in seminal plasma, which is 10- to 1,00 0-fold higher than previous estimates. Viral loads in whole semen and seminal plasma were strongly correlated with blood plasma viral load ( P < 0.001) but not with blood CD4+ T-cell count (P = 0.420). Longitudi nal analysis of eight subjects who progressed to AIDS showed that semi nal viral load increased in most cases, with viral load consistently h igher in blood plasma than in semen. Viral loads in semen and blood pl asma decreased markedly in six other patients following initiation of potent combination therapy with a protease inhibitor (indinavir) and a nonnucleoside reverse transcriptase inhibitor (DMP-266). These findin gs have important implications for the biology of sexual transmission of HIV-1 and its potential reduction by antiretroviral therapy.