Maraviroc versus efavirenz, both in combination with zidovudine-lamivudine, for the treatment of antiretroviral-naive subjects with CCR5-tropic HIV-1 infection.
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) .
Cooper
David A
DA
University of New South Wales, Sydney, Australia.
Heera
Jayvant
J
Goodrich
James
J
Tawadrous
Margaret
M
Saag
Michael
M
Dejesus
Edwin
E
Clumeck
Nathan
N
Walmsley
Sharon
S
Ting
Naitee
N
Coakley
Eoin
E
Reeves
Jacqueline D
JD
Reyes-Teran
Gustavo
G
Westby
Mike
M
Van Der Ryst
Elna
E
Ive
Prudence
P
Mohapi
Lerato
L
Mingrone
Horacio
H
Horban
Andrzej
A
Hackman
Frances
F
Sullivan
John
J
Mayer
Howard
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000480:Alkynes; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000592:standards; D044966:Anti-Retroviral Agents; D000998:Antiviral Agents / Q000494:pharmacology; D048588:Benzoxazines / Q000494:pharmacology / Q000592:standards / Q000627:therapeutic use*; D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes / Q000494:pharmacology / Q000592:standards / Q000627:therapeutic use*; D003521:Cyclopropanes; D004311:Double-Blind Method; D004338:Drug Combinations; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000378:metabolism; D016896:Treatment Outcome; D014230:Triazoles / Q000494:pharmacology / Q000592:standards / Q000627:therapeutic use*; D019562:Viral Load; D056189:Viral Tropism; D055815:Young Adult; D015215:Zidovudine / Q000008:administration & dosage
D000480:Alkynes; D019380:Anti-HIV Agents; D044966:Anti-Retroviral Agents; D000998:Antiviral Agents; D048588:Benzoxazines; D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes; D003521:Cyclopropanes; D004338:Drug Combinations; D019713:Receptors, CCR5; D014230:Triazoles; D019259:Lamivudine; D015215:Zidovudine; C098320:efavirenz; D000077592:Maraviroc