326   Comparative Antiviral Activity and Toxicity of Nevirapine (NVP) versus Lamivudine (3TC), in Combination with Stavudine (d4T) and Indinavir (IDV), for the Treatment of HIV-1-Infected Patients.

O. Launay*¹, L. Gerard², L. Morand-Joubert³, P. Flandre², S. Guiramand³, V. Joly¹, G. Peytavin¹, A. Certain¹, C. Jacomet¹, S. Rivet², J. P. Aboulker², and P. Yeni¹for the ANRS 081 Study Group.
¹Bichat Hosp., Paris;³Saint-Antoine Hosp., Paris; and²INSERM SC10, Villejuif, France.

Background:A triple "divergent" combination therapy including one drug of each class (nucleoside reverse transcriptase inhibitor/non-nucleoside reverse transcriptase inhibitor (NNRTI)/protease inhibitor (PI)) in PI- and NNRTI-naive patients (pts) has not been investigated in a randomized trial. We compared the efficacy and the tolerance of NVP versus 3TC, in combination with IDV and d4T, using an intent-to-treat analysis.

Methods:145 pts, naive (n = 115) or pretreated with AZT and/or ddX (n = 30), were randomized in a 1:1 ratio to either 3TC (n = 72) or NVP (n = 73), in combination with d4T and IDV, and followed for 72 wks. In the NVP arm, the daily dosage of IDV was increased to 1 g tid.

Results:At baseline, median CD4⁺was 359 cells/mm³and median plasma HIV RNA was 4.62 log copies/ml. The median decrease in plasma HIV-1 RNA was similar in both arms at 72 wks (-3.20 vs. -3.15 log in the 3TC and NVP arms, respectively). Suppression of plasma HIV-1 RNA below 20 copies/ml was more frequent in the 3TC arm (81%) than in the NVP arm (62%, p = 0.02). Median increase in CD4⁺cell count was similar in both arms (+239 and +199 cells/mm³in the 3TC and d4T arms, respectively). More pts discontinued treatment because of adverse events in the NVP arm (44%) than in the 3TC arm (25%, p = 0.008). In the NVP arm, grade >2 rash and hepatitis were observed in 10 and 7 pts, respectively. Median IDV plasma trough concentration (C_min) after 16 weeks of therapy was in the therapeutic range in both arms, but was higher in the 3TC arm than in the NVP arm (96 vs. 71 ng/mL, p = 0.04), in spite of the increased daily dosage of IDV in the NVP arm.

Conclusions:In combination with d4T and IDV, NVP did not demonstrate a superior antiviral activity compared to 3TC and was associated with an increased number of adverse events.