File(s) under permanent embargo
Subgroup analyses of maraviroc in previously treated R5 HIV-1 infection
journal contribution
posted on 2023-06-08, 15:21 authored by Gerd Fätkenheuer, Mark Nelson, Adriano Lazzarin, Irina Konourina, Andy I M Hoepelman, Harry Lampiris, Bernard Hirschel, Pablo Tebas, François Raffi, Benoit Trottier, Nicholaos Bellos, Michael Saag, David A Cooper, Mike Westby, Margaret Tawadrous, John F Sullivan, Caroline Ridgway, Michael W Dunne, Steve Felstead, Howard Mayer, Elna van der Ryst, Martin Fisher, for the MOTIVATE 1 and MOTIVATE 2 Study TeamsBACKGROUND We conducted subanalyses of the combined results of the Maraviroc versus Optimized Therapy in Viremic Antiretroviral Treatment-Experienced Patients (MOTIVATE) 1 and MOTIVATE 2 studies to better characterize the efficacy and safety of maraviroc in key subgroups of patients. METHODS We analyzed pooled data from week 48 from the two studies according to sex, race or ethnic group, clade, CC chemokine receptor 5 (CCR5) delta32 genotype, viral load at the time of screening, the use or nonuse of enfuvirtide in optimized background therapy (OBT), the baseline CD4 cell count, the number of active antiretroviral drugs coadministered, the first use of selected background agents, and tropism at baseline. Changes in viral tropism and the CD4 count at treatment failure were evaluated. Data on aminotransferase levels in patients coinfected with hepatitis B virus (HBV) or hepatitis C virus (HCV) were also analyzed. RESULTS A treatment benefit of maraviroc plus OBT over placebo plus OBT was shown in all subgroups, including patients with a low CD4 cell count at baseline, those with a high viral load at screening, and those who had not received active agents in OBT. Analyses of the virologic response according to the first use of selected background drugs showed the additional benefit of adding a potent new drug to maraviroc at the initiation of maraviroc therapy. More patients in whom maraviroc failed had a virus binding to the CXC chemokine receptor 4 (CXCR4) at failure, but there was no evidence of a decrease in the CD4 cell count at failure in such patients as compared with those in whom placebo failed. Subanalyses involving patients coinfected with HBV or HCV revealed no evidence of excess hepatotoxic effects as compared with baseline. CONCLUSIONS Subanalyses of pooled data from week 48 indicate that maraviroc provides a valuable treatment option for a wide spectrum of patients with R5 HIV-1 infection who have been treated previously. (ClinicalTrials.gov numbers, NCT00098306 and NCT00098722.)
History
Publication status
- Published
File Version
- Published version
Journal
New England Journal of MedicineISSN
0028-4793Publisher
Massachusetts Medical SocietyExternal DOI
Issue
14Volume
359Page range
1442-1455Department affiliated with
- BSMS Publications
Notes
Martin Fisher is part of the Motivate 2 Study Group and is not in the list of main authorsFull text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2013-07-09First Compliant Deposit (FCD) Date
2013-07-09Usage metrics
Categories
No categories selectedKeywords
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC