Journal Article

Maraviroc versus Efavirenz, Both in Combination with Zidovudine-Lamivudine, for the Treatment of Antiretroviral-Naive Subjects with CCR5-tropic HIV-1 Infection

Cooper, David A., Walmsley, Sharon, Coakley, Eoin, Mingrone, Horacio, Tawadrous, Margaret, Reeves, Jacqueline D., Sullivan, John, Mayer, Howard, Saag, Michael, Westby, Mike, Ive, Prudence, Ting, Naitee, DeJesus, Edwin, Mohapi, Lerato, Hackman, Frances, Clumeck, Nathan, Horban, Andrzej, Heera, Jayvant, Goodrich, James, Van Der Ryst, Elna, Reyes-Teran, Gustavo

2010

Overview

Background. The MERIT (Maraviroc versus Efavirenz in Treatment-Naive Patients) study compared maraviroc and efavirenz, both with zidovudine-lamivudine, in antiretroviral-naive patients with R5 human immunodeficiency virus type 1 (HIV-1) infection. Methods. Patients screened for R5 HIV-1 were randomized to receive efavirenz (600 mg once daily) or maraviroc (300 mg once or twice daily) with zidovudine-lamivudine. Coprimary end points were proportions of patients with a viral load <400 and <50 copies/mL at week 48; the noninferiority of maraviroc was assessed. Results. The once-daily maraviroc arm was discontinued for not meeting prespecified noninferiority criteria. In the primary 48-week analysis (n=721), maraviroc was noninferior for <400 copies/mL (70.6% for maraviroc vs 73.1% for efavirenz) but not for <50 copies/mL (65.3% vs 69.3%) at a threshold of −10%. More maraviroc patients discontinued for lack of efficacy (11.9% vs 4.2%), but fewer discontinued for adverse events (4.2% vs 13.6%). In a post hoc reanalysis excluding 107 patients (15%) with non-R5 screening virus by the current, more sensitive tropism assay, the lower bound of the 1-sided 97.5% confidence interval for the difference between treatment groups was above −10% for each end point. Conclusions. Twice-daily maraviroc was not noninferior to efavirenz at <50 copies/mL in the primary analysis. However, 15% of patients would have been ineligible for inclusion by a more sensitive screening assay. Their retrospective exclusion resulted in similar response rates in both arms Trial registration. ClinicalTrials.gov identifier: (NCT00098293).

• Publisher: The University of Chicago Press,University of Chicago Press,Oxford University Press
• Subject: Adolescent / Adult / Aged / Anti-HIV Agents - pharmacology / Anti-HIV Agents - standards / Anti-Retroviral Agents / Antiviral Agents - pharmacology / Benzoxazines - pharmacology / Benzoxazines - standards / Benzoxazines - therapeutic use / Biological and medical sciences / CCR5 Receptor Antagonists / Cyclohexanes - pharmacology / Cyclohexanes - standards / Cyclohexanes - therapeutic use / Double-Blind Method / Drug Combinations / Drug Resistance, Viral / Drug Therapy, Combination / Female / Fundamental and applied biological sciences. Psychology / HIV / HIV 1 / HIV Infections - drug therapy / HIV-1 - drug effects / HIV-1 - physiology / HIV/AIDS / Human immunodeficiency virus 1 / Human viral diseases / Humans / Infections / Infectious diseases / Lamivudine - administration & dosage / Male / Medical sciences / Microbiology / Middle Aged / Miscellaneous / Post hoc / Receptors, CCR5 - metabolism / Response rates / RNA / Stock options / Treatment Outcome / Triazoles - pharmacology / Triazoles - standards / Triazoles - therapeutic use / Tropisms / Viral diseases / Viral diseases of the lymphoid tissue and the blood. Aids / Viral Load / Viral Tropism / Virology / Viruses / Young Adult / Zidovudine - administration & dosage