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Session 61 Poster Session Antiretroviral Chemotherapy in Previously Treated Individuals Session Time: 4:30-6:30 pm Room 4E-F

426-W. Virologic Activity of Efavirenz in Subjects who Experienced Virological Failure with Emivirine (EMV, MKC-442) K. Borroto-Esoda*1, I. Sanne2, S. Andrews3, C. Kelbe4, P. Naiker5, T. Sole6, J. Anderson1, J. Harris1, D. Kargl1, G. Painter1, F. Rousseau1, and C. Moxham1 1Triangle Pharmaceuticals Inc., Durham, NC; 2Witts Hlth. Consortium, Johannesburg, South Africa; 3Cape Town, South Africa; 4Richards Bay, South Africa; 5St. Augustine's Hosp., Durban, South Africa; and 6Frere Hosp. East London, South Africa Background: In vitro resistance studies have shown that HIV containing non-nucleoside reverse transcriptase (NNRTI) mutations other than K103N are sensitive to inhibition by efavirenz (EFV). Emivirine is a potent NNRTI that has a low incidence of K103N mutation when given in combination with lamivudine. Methods: Therapy-naïve subjects were enrolled in a randomized, open label study (MKC-401) to compare EMV vs abacavir (ABC) in the background of stavudine/emtricitabine (d4T/FTC). HIV RNA viral load (VL) was measured at baseline and every 12 weeks thereafter. Subjects who experienced virologic failure (VF) in the emivirine arm were allowed to switch to EFV and ABC + d4T. To determine if antiviral drug resistance was associated with therapy failure, genotypic analysis was performed at the time of a protocol-defined VF. Results: To date, 45 subjects in MKC-401 have switched to EFV + ABC + d4T. Genotypic analysis was available for 36 of the 45 subjects. NNRTI mutations were observed in 14/36 (39%) of these subjects, with 8/14 having single NNRTI mutations and 6/14 with multiple NNRTI mutations. The NNRTI mutations observed were: E138K (7/36), K103N (6/36), V108I (4/36), K101E/Q (2/36), K103T (2/36), and Y188C (1/36). 21 of the 36 (58%) subjects remained wild type at time of failure, and one subject developed NRTI associated mutations only. VL analysis of the subjects by week 12 following switch to EFV indicated that 25/34 (74%) of the subjects had <400 copies/mL and 50% of these subjects had <50 copies/mL. The patients with wild type virus at failure had VL measurements post switch. 18 of the 20 subjects achieved a VL <400 copies/mL and 15/20 subjects (75%) achieved <50 copies/mL. For subjects who failed with a NNRTI mutation but did not have a K103N, 7/8 (87.5%) had VL <50 copies/mL following 4-84 weeks on efavirenz. Data available for 5 of the 6 subjects with the K103N showed that 40% were able to achieve a transient decrease in VL to <50 copies/mL prior to discontinuing therapy. Of the 16 subjects who have discontinued alternate therapy, 3 discontinued due to VF, 4 due to AE, 2 lost to follow-up, and 7 due to other reasons (withdrew consent, pregnancy, etc.). Conclusions: These results show that subjects who fail an EMV-containing regimen subsequently achieved suppression of viral load to <50 copies/mL following rollover to an EFV-containing regimen.

©2002 9th Conference on Retroviruses and Opportunistic Infections