Concentrations of nevirapine, lamivudine and stavudine in semen of HIV-1-infected men

Objective: To determine the concentrations of nevirapine (NVP),lamivudine ( 3TC) and stavudine (D4T) in seminal and blood plasma in HIV-l-infected men. Methods: Twelve HIV-1-infected men on NVP-containing regimens including 3TC (n = 8) or D4T (n = 11) provided 23 blood plasma and 22 seminal plasma sam ples for drug concentration and viral load quantitation. Concentrations of all drugs were assessed by sensitive validated high performance liquid chro matography (HPLC) assays. Blood plasma and seminal plasma viral loads were measured using nucleic acid sequence-based amplification (NASBA). Samples w ere grouped according to time after drug ingestion, 0-2, 2-4, 4-8 and 8-12 h. For matched seminal and blood plasma samples, obtained within 1 h of eac h other, a seminal : blood plasma ratio was calculated. Results: The concentration of NVP in seminal plasma appeared to mirror the concentrations in blood plasma. Absolute median seminal plasma NVP concentr ations at 0-2, 2-4, 4-8 and 8-12 h were 3.1 mu g/ml (range 1.7-4.89), 2.68 mu g/ml (2.5-3.9), 2.5 mu g/ml (2.3-2.7) and 3.09 mu g/ml (1.3-9.1) The med ian seminal:blood plasma ratios for the four time periods were 0.54 (range 0.34-0.85), 0.83 (range 0.43-1.08), 0.53 (0.38-0.59), and 0.61 (0.59-0.78). 3TC and D4T appeared to reach concentrations in seminal plasma of a simila r magnitude or higher than concentrations in blood plasma. The median semin al plasma viral load for all patients was less than 800 copies/ml (range <8 00-11 000). The median blood plasma viral load was less than 400 copies/ml (< 400-1100). Conclusion: NVP reaches concentrations in the semen approximately 60% of th ose in the blood plasma throughout the 12 h dosing period. In a smaller dat aset 3TC and D4T concentrations in blood plasma and seminal plasma were sim ilar. These data may well have implications for the evolution of drug-resis tant virus within the genital (C) 2000 Lippincott Williams & Wilkins.