Late Breaker Oral Presentation: PS1 - Initiation of Antiretroviral Therapy LBPS1/6 - Antiretroviral effect of MK-0518, a novel HIV-1 integrase inhibitor, in ART-naïve HIV-1 infected patients

Morales-Ramirez J.O.1, Teppler H.2, Kovacs C.3, Steigbigel R.T.4, Cooper D.5, Liporace R.L.6, Schwartz R.7, Wenning L.2, Zhao J.2, Gilde L.2, Isaacs R.D.2, Nguyen B.-Y.2, Protocol 004 Team

1Clinical Research Puerto Rico, Inc., San Juan, PR, United States of America, 2Merck Research Laboratories, West Point, PA, United States of America, 3Canadian Immunodeficiency Research Collaborative, Inc., Toronto, Canada, 4State University of New York at Stony Brook, Stony Brook, NY, United States of America, 5St. Vincent's Hospital, Darlinghurst, Australia, 6Albany Medical College, Albany, NY, United States of America, 7Associates In Research, Fort Myers, FL, United States of America

Introduction: MK-0518 is a novel HIV-1 integrase strand transfer inhibitor with potent in vitro activity against HIV-1 (IC95=33nM in 50% human serum) and good bioavailability in uninfected subjects. This study explored the antiretroviral activity and safety of MK-0518 vs. placebo for 10 days as monotherapy in ART-naïve HIV-1 infected patients with HIV RNA at least 5000 copies/mL and CD4 count at least 100 cells/uL. Methods: Multicenter, double blind, randomized controlled 2-part study, the first part using MK-0518 in one of 4 doses (100mg, 200 mg, 400 mg, and 600mg) vs. placebo (randomized 1:1:1:1:1) given BID for 10 days monotherapy. Patients were closely monitored for safety, pharmacokinetic parameters, and antiretroviral effect. Results: Thirty-five patients were enrolled (6-8 per treatment group) and completed 10 days of therapy; mean baseline log10 HIV RNA ranged from 4.5-5.0 in each group. On Day 10, the mean decrease from baseline in log10 HIV RNA was -0.2 for the placebo group and -1.9, -2.0, -1.7 and -2.2 log10 copies/mL for MK-0518 100, 200, 400, and 600mg treatment groups, respectively. All dose groups had superior antiviral activity compared to placebo (p<.001 for comparison of each dose to placebo). At least 50% of patients in each MK-0518 dose group achieved HIV RNA <400 copies/mL by Day 10. Mean trough MK-0518 concentrations at each dose exceeded the IC95 of 33nM. Study therapy was generally well tolerated. The most common adverse experiences (AEs) were headache and dizziness; these were similar between active and control groups. There were no discontinuations due to AEs and no serious AEs. Conclusion: MK-0518 showed potent antiretroviral activity as short term monotherapy and was generally well-tolerated at all doses. Based on these results, part 2 of the study, a dose-ranging 48 week trial of MK-0518 vs. efavirenz in a combination regimen, has been initiated. Contact: Dr. Javier O. Morales-Ramirez, Clinical Research Puerto Rico, Inc., 359 De Diego Avenue, Suite 501, 00909-1711 San Juan, PR, United States of America, Email: crpr@coqui.net