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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.