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

• Published in: The Journal of infectious diseases Vol. 201; no. 6; pp. 803 - 813
• Main Authors: Cooper, David A., Heera, Jayvant, Goodrich, James, Tawadrous, Margaret, Saag, Michael, DeJesus, Edwin, Clumeck, Nathan, Walmsley, Sharon, Ting, Naitee, Coakley, Eoin, Reeves, Jacqueline D., Reyes-Teran, Gustavo, Westby, Mike, Van Der Ryst, Elna, Ive, Prudence, Mohapi, Lerato, Mingrone, Horacio, Horban, Andrzej, Hackman, Frances, Sullivan, John, Mayer, Howard
• Format: Journal Article
• Language: English
• Published: Oxford The University of Chicago Press 15.03.2010; University of Chicago Press; Oxford University Press
• Subjects: 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; Antiretroviral agent; Benzoxazine derivatives; RNA-directed DNA polymerase; Acetylenic compound; HIV-1 virus; Non nucleoside compound; Efavirenz; Maraviroc; Reverse transcriptase inhibitor; Nucleoside analog; Antiviral; Pyrimidine nucleoside; Immunopathology; Drug combination; Enzyme; Transferases; Enzyme inhibitor; Retroviridae; Lamivudine; AIDS; Immune deficiency; Lentivirus; Infection; Virus; CCR5 chemokine receptor; Allosteric inhibitor; Nucleotidyltransferases; Treatment; Dideoxynucleoside; Viral disease; Human immunodeficiency virus; Zidovudine
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1086/650697

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).