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

Autor: Fätkenheuer, G, Nelson, M, Lazzarin, A, Konourina, I, Hoepelman, Ai, 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, Vullo, Vincenzo, VAN DER RYST, E, MOTIVATE AND MOTIVATE STUDY TEAMS
Přispěvatelé: Amsterdam institute for Infection and Immunity, Infectious diseases, Surgery
Rok vydání: 2008
Předmět:
Oncology
Male
Enfuvirtide
HIV Infections
medicine.disease_cause
HIV Envelope Protein gp41/therapeutic use
Maraviroc
chemistry.chemical_compound
Transaminases/blood
HIV Fusion Inhibitors
Ethnicity
Odds Ratio
Medicine
ddc:616
HIV Infections/drug therapy/immunology/virology
Receptors
CCR5/antagonists & inhibitors/genetics
General Medicine
Middle Aged
Viral Load
Hepatitis B
Hepatitis C
HIV-1/chemistry/genetics
HIV Envelope Protein gp41
Treatment Outcome
Anti-Retroviral Agents
HIV Fusion Inhibitors/adverse effects/therapeutic use
CCR5 Receptor Antagonists
RNA
Viral
Drug Therapy
Combination
Female
Viral disease
Viral load
Cyclohexanes/adverse effects/therapeutic use
medicine.drug
Adult
medicine.medical_specialty
Genotype
Receptors
CCR5
Hepatitis C virus
Triazoles/adverse effects/therapeutic use
Ethnic Groups
SDG 3 - Good Health and Well-being
Double-Blind Method
Cyclohexanes
Internal medicine
HIV tropism
Humans
RNA
Viral/blood
Transaminases
Aged
Hepatitis B virus
Hepatitis B/blood/complications
Peptide Fragments/therapeutic use
business.industry
Triazoles
Anti-Retroviral Agents/adverse effects/therapeutic use
Peptide Fragments
CD4 Lymphocyte Count
chemistry
Immunology
HIV-1
Hepatitis C/blood/complications
Vicriviroc
business
Zdroj: New England journal of medicine, 359(14), 1442-1455. Massachussetts Medical Society
New England Journal of Medicine, Vol. 359, No 14 (2008) pp. 1442-1455
New England Journal of Medicine, 359(14), 1442-U46. Massachussetts Medical Society
ISSN: 1533-4406
0028-4793
Popis: 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.)
Databáze: OpenAIRE
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