This study documents the emergence of protease inhibitor (PI) resistance mutations in viral isolates obtained from seminal plasma. The nine individuals studied came from the ACTG 347 semen substudy evaluating the effects of amprenivir (APV) alone or in combination with AZT/3TC on HIV levels in semen. In that study 37 treatment-naïve men were enrolled, 23 in the APV arm and 14 in the APV/AZT/3TC arm, and were studied at baseline and later during therapy. In this analysis, nine men were studied, 7 on APV monotherapy and 2 on APV/AZT/3TC. While on therapy, four experienced viral load rebound in seminal plasma, and in these viral DNA was analyzed both for PI mutations and its similarity to virus obtained from blood plasma.

The first major PI resistance mutations were seen, not surprisingly, in 3 APV monotherapy patients. Two had APV-selected mutations and viral load rebound in both semen and blood, while the third had 90M mutation in and viral load rebound in semen but not in blood. To compare similarity of virus between semen and blood, an analysis of the envelope gene is undertaken and evaluated both at baseline (before therapy) and during therapy. Interestingly, prior to therapy in each of the four individuals, virus from semen was significantly different from blood plasma when comparing env gene in these isolates. During therapy however, the three who exhibited semen viral rebound and PI resistance demonstrated similarity with virus obtained from their blood at that time (using analysis of env gene). The fourth who demonstrated no viral rebound continued to show virus in blood that differed from virus obtained from semen.

From these data, the authors draw several conclusions. PI resistance can be seen in semen with rebound semen viral load during therapy, with or without a rebound in blood plasma viral load. Furthermore, selection of drug-resistant virus may involve trafficking between blood and the male genital tract because it seems as though semen and blood isolates become more related to each other (by env gene analysis) at the time of semen viral rebound during therapy.