Subgroup analyses of Maraviroc in previously treated R5 HIV-1 infection

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 & 1 others Elna Van Der Ryst

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: 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.)

Original languageEnglish
Pages (from-to)1442-1455
Number of pages14
JournalNew England Journal of Medicine
Volume359
Issue number14
DOIs
Publication statusPublished - Oct 2 2008

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HIV Infections
HIV-1
CD4 Lymphocyte Count
Therapeutics
Viral Load
Hepatitis B virus
Hepacivirus
maraviroc
Viral Tropism
Placebos
CCR5 Receptors
Pharmaceutical Preparations
CXCR4 Receptors
Virus Attachment
Tropism
Transaminases
Treatment Failure
Ethnic Groups
Cell Count
Genotype

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Fätkenheuer, G., Nelson, M., Lazzarin, A., Konourina, I., Hoepelman, A. I. M., Lampiris, H., ... Van Der Ryst, E. (2008). Subgroup analyses of Maraviroc in previously treated R5 HIV-1 infection. New England Journal of Medicine, 359(14), 1442-1455. https://doi.org/10.1056/NEJMoa0803154

Subgroup analyses of Maraviroc in previously treated R5 HIV-1 infection. / Fätkenheuer, Gerd; Nelson, Mark; Lazzarin, Adriano; Konourina, Irina; Hoepelman, Andy I M; Lampiris, Harry; Hirschel, Bernard; Tebas, Pablo; Raffi, François; Trottier, Benoit; Bellos, Nicholaos; Saag, Michael; Cooper, David A.; Westby, Mike; Tawadrous, Margaret; Sullivan, John F.; Ridgway, Caroline; Dunne, Michael W.; Felstead, Steve; Mayer, Howard; Van Der Ryst, Elna.

In: New England Journal of Medicine, Vol. 359, No. 14, 02.10.2008, p. 1442-1455.

Research output: Contribution to journalArticle

Fätkenheuer, G, Nelson, M, Lazzarin, A, Konourina, I, Hoepelman, AIM, Lampiris, H, Hirschel, B, Tebas, P, Raffi, F, Trottier, B, Bellos, N, Saag, M, Cooper, DA, Westby, M, Tawadrous, M, Sullivan, JF, Ridgway, C, Dunne, MW, Felstead, S, Mayer, H & Van Der Ryst, E 2008, 'Subgroup analyses of Maraviroc in previously treated R5 HIV-1 infection', New England Journal of Medicine, vol. 359, no. 14, pp. 1442-1455. https://doi.org/10.1056/NEJMoa0803154
Fätkenheuer G, Nelson M, Lazzarin A, Konourina I, Hoepelman AIM, Lampiris H et al. Subgroup analyses of Maraviroc in previously treated R5 HIV-1 infection. New England Journal of Medicine. 2008 Oct 2;359(14):1442-1455. https://doi.org/10.1056/NEJMoa0803154
Fätkenheuer, Gerd ; Nelson, Mark ; Lazzarin, Adriano ; Konourina, Irina ; Hoepelman, Andy I M ; Lampiris, Harry ; Hirschel, Bernard ; Tebas, Pablo ; Raffi, François ; Trottier, Benoit ; Bellos, Nicholaos ; Saag, Michael ; Cooper, David A. ; Westby, Mike ; Tawadrous, Margaret ; Sullivan, John F. ; Ridgway, Caroline ; Dunne, Michael W. ; Felstead, Steve ; Mayer, Howard ; Van Der Ryst, Elna. / Subgroup analyses of Maraviroc in previously treated R5 HIV-1 infection. In: New England Journal of Medicine. 2008 ; Vol. 359, No. 14. pp. 1442-1455.
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AU - Hoepelman, Andy I M

AU - Lampiris, Harry

AU - Hirschel, Bernard

AU - Tebas, Pablo

AU - Raffi, François

AU - Trottier, Benoit

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