8th Conference on Retroviruses and Opportunistic Infections Chicago, IL - February 4 - 8, 2001

Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:271 (abstract no. 749)

Pereira A, Gerber J, Smeaton L, Acosta E, Gulick R, Murphy R, Eron J; Univ of North Carolina, Chapel Hill.

BACKGROUND: Penetration of antiretroviral drugs into the male genital tract may be important for optimal HIV suppression in that compartment. Because drugs may distribute differently into the seminal and systemic compartments, a better understanding of the seminal PK of antiretrovirals is needed.

METHODS: 31 men enrolled in ACTG 850, a substudy of a 24-wk, randomized, placebo- controlled study. Men received either APV (n=19) or APV/3TC/ZDV (n=12) and donated blood (BP) and semen (SP) at known times following an observed medication dose at wks 8 and 24. Timed SP concentrations of APV, 3TC, and ZDV were plotted against the described population BP PK of these drugs. The first paired SP and BP collected from study subjects within 1 hr of each other were used to calculate SP: BP ratios (n=19, 8, and 7 for APV, 3TC, and ZDV; respectively). These data were then used to examine the correlation between the two compartments.

RESULTS: The 3 drugs demonstrated distinct SP PK compared to population BP PK. APV SP were < BP population PK concentrations; 3TC SP were > BP; and SP of ZDV approximated BP early in the dosing interval but was > BP during later time points. This was also true for the paired SP and BP study samples (p=0.0005, APV SP<BP; p=0.002, 3TC SP>BP, Wilcoxon signed rank test). In addition, median APV SP: BP ratios from 0-2 hr and 2-12 hr post dose were both less than 1. The ratios for 3TC and ZDV respectively were 1.8 and 1.0 (0-2 hr), and 5.3 and 12.9 (2-12 hr). Spearman's ranked correlation test revealed no correlation between paired SP and BP of 3TC (r = 0.36). ZDV and APV SP and BP were weakly correlated (r = 0.7 for both).

CONCLUSIONS: Both APV alone and APV/3TC/ZDV in combination reduce seminal shedding of HIV-1. All 3 drugs enter the seminal compartment; however, only ZDV and 3TC achieve SP > BP. The 3 drugs seem to have distinct SP PK. 3TC has a flat SP PK, suggesting active accumulation or inhibition of elimination; ZDV appears to be concentrated at later time points, suggesting slowed elimination; and APV SP follows the BP PK but at lower concentrations.

Keywords: AEGIS, Lamivudine, Zidovudine, HIV-1, Anti-HIV Agents, Sulfonamides, HIV Infections, Reverse Transcriptase Inhibitors, HIV Protease Inhibitors, HIV, HIV Protease, VX 478, Human, Male, pharmacokinetics, AIDS

2001-02-04
749

Copyright © 2001 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.