Abstract

Potent antiretroviral effect of MK-0518, a novel HIV-1 integrase inhibitor, as part of combination ART in treatment -naïve HIV-1 infected patients

M. Markowitz¹, B.-Y. Nguyen², F. Gotuzzo³, F. Mendo⁴, W. Ratanasuwan⁵, C. Kovacs⁶, J. Zhao⁷, L. Gilde², R. Isaacs², H. Teppler²

¹The Rockefeller University, Aaron Diamond AIDS Research Center, New York, United States, ²Merck Research Laboratories, Clinical Research, West Point, United States, ³Hospital Nacional Cayetano Heredia, Lima, Peru, ⁴Hospital Nacional Edgardo Rebagliati, Lima, Peru, ⁵Siriraj Hospital, Mahidol University, Bangkok, Thailand, ⁶Canadian Immunological Research Collaborative, Toronto, Canada, ⁷Merck Research Laboratories, Clinical Statistics, West Point, United States

Background: Phase II study evaluating MK-0518, a novel HIV integrase inhibitor, vs efavirenz, combined with tenofovir/lamivudine (TFV/3TC), in ART-naïve HIV-infected patients (pts) with HIV-1 RNA 5000 copies/mL and CD4 cells 100 /uL.

Methods: Multicenter, double-blind, randomized 2-part study evaluating MK-0518 (100, 200, 400, or 600mg p.o. b.i.d) vs efavirenz (600 mg qd) both with TFV/3TC. Pts entered this study (Part 2) after 10 days monotherapy (Part 1) or were newly enrolled, and monitored for safety, tolerability, and efficacy.

Results: 197 pts were enrolled and treated. At this preliminary analysis 85 had wK 16 data. Enrolled pts were of mean age 36 years, 80% male, 69% non-white, and 34% had AIDS. Mean baseline HIV RNA ranged from 4.6 - 4.8 log10 copies/mL per treatment group. Proportions of pts achieving HIV RNA <400 or <50 copies/mL (observed) at wk 16 are shown:
(† With TFV/3TC; *One pt pending UltraSensitive results excluded)

All groups showed 2.2 log10 decline in HIV RNA and similar increased CD4 cells (75-135/uL). Drug-related clinical adverse experiences (AEs) were generally similar in all groups; nausea, dizziness and headache were most common. Laboratory AEs were infrequent; one pt discontinued due to elevated AST in the MK-0518 600mg group. There were no drug related serious AEs. Full wk 24 data will be presented.

Conclusions: In this preliminary analysis, MK-0518 with TFV/3TC at all doses studied had potent antiretroviral activity and was generally well-tolerated in ART-naïve pts.

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