The Effects of Protease Inhibitor Therapy on Human Immunodeficiency Virus Type 1 Levels in Semen (AIDS Clinical Trials Group Protocol 850) [JJ Eron, et al. J Infect Dis 2000; 181: 1622]: This is a substudy of an ACTG trial comparing amprenavir plus AZT plus 3TC versus amprenavir monotherapy. Men participating in the substudy were asked to donate semen at baseline and at week 8 and 24 of treatment. There were 30 participants, 19 in the amprenavir monotherapy group and 11 that received triple therapy. The median baseline plasma RNA level was 4.4 log₁₀ c/mL; the median baseline seminal HIV RNA level was 3.45 log₁₀ c/mL. There was weak correlation between blood and seminal fluid levels. Treatment was associated with a substantial reduction in seminal fluid HIV RNA levels for both arms of the study. Levels below 400 copies/mL were achieved in seminal fluid in all 11 men receiving triple therapy and in 14 of 19 in the amprenavir monotherapy group. In the second visit, there were 8 (27%) with detectable HIV in seminal fluid including 4 with increasing levels compared to the earlier sample. The authors concluded that antiretroviral therapy effectively reduces HIV in genital tract samples in men, but there are individual patient variations which suggests that this treatment might be expected to reduce HIV transmission in a population of patients, but cannot be relied on for individual patients.
Comment: The assumption is that the genital tract represents a unique compartment for HIV replication. The authors point out that this separation of compartments is supported by differences in HIV envelope genotypes, differences in phenotype, different rates of HIV replication, and differences in antiviral agent resistance patterns. This study shows for the first time that protease inhibitors effectively reduce HIV replication within this compartment. This was previously a concern because high protein binding suggested that there might not be penetration into the genital compartment. Nevertheless, the "bottom line" is clear: HAART might be expected to reduce HIV transmission in most patients, but not necessarily all, and the individual variations cannot clearly be selected on the basis of plasma HIV RNA levels. posted 6/16/2000