750   Efavirenz (EFV)- Containing Antiretroviral (ARV) Therapy (T) Effectively Reduces HIV RNA in the Seminal Plasma (SP) of HIV-1-Infected Men (M).

S. Reddy*, J. Kim, J. Eron, S. Fiscus, K. Gotzkowsky, D. Manion, W. Fiske, M. Cohen, and A. Kashuba.
Univ. of North Carolina, Chapel Hill and DuPont Pharmaceuticals Co., Wilmington, DE.

Background:Therapeutic (TH) concentrations (C) of ARV in SP may reduce viral replication and influence selection and transmission of resistant HIV-1. We have previously reported that EFV achieves TH C in the SP of HIV-infected M (40th ICAAC, abstr.1171). We now compare the effects of EFV-containing ARV T on HIV RNA in SP and blood plasma (BP).

Methods:16 M with no active genital tract infection were recruited. Multiple EFV 1st-dose and steady-state SP and BP samples were obtained over 40 d in 4 EFV-naive and 12 EFV-experienced subjects. HIV RNA was measured in SP and BP by Organon Teknika Nuclisens (BLQ <400 c/mL) and Roche Amplicor Monitor (BLQ <50 c/mL) kits, respectively. HIV RNA is reported as log₁₀c/ml.

Results:In the 4 1th-dose subjects, 32 BP and 31 SP samples (~8 samples/subject) were collected over 40 d. Baseline (BL) SP and BP RNA ranged from 3.8—6.6 and from 4.3—5.7, respectively. By day 40, 3/4 were BLQ in SP. In BP, 2 were <2.6 and 1 had RNA = 2.6 (a decline of 3.1). The 4th man had only a transient decline in BP and a 1.3 decline in SP to BLQ. In 12 EFV-experienced subjects [median time on EFV 11 (5.75—17) months], 52 SP samples and 53 BP samples (~5 samples/subject) were collected over 30 d. At BL, all M were BLQ in the SP. 2/12 (17%) had detectable SP RNA on study; one with a single value of 2.7, the other with a reproducible increase to 3.3. 5/12 had detectable BP RNA at BL. 3/5 had low-level viremia (<2.6), which fluctuated between BLQ-2.9. 2/5 had BL BP RNA of 3.9 and 3.3, and these levels remained in this range. In both of these M, HIV RNA in SP was BLQ. One man with low-level BP HIV RNA (BLQ-2.3) had the 3.3 rise in SP RNA. Generally, EFV exposure in SP was lower in M with detectable SP RNA.

Conclusions:EFV-containing ART effectively decreases HIV RNA in SP in concert with BP changes. Low levels of replication were detected in BP in 25% of M chronically on EFV-containing ART which were not detected in SP. Discordance between BP and SP was observed in 25%. In one subject, SP harbored substantial viral replication, raising the possibility of resistance first developing in this compartment.