Maraviroc: perspectives for use in antiretroviral-naive HIV-1-infected patients. 2009

Linos Vandekerckhove, and Chris Verhofstede, and Dirk Vogelaers
AIDS Reference Centre, Gent University Hospital, Belgium. linos.vandekerckhove@ugent.be

Maraviroc (Pfizer's UK-427857, Selzentry or Celsentri outside the USA) is the first agent in the new class of oral HIV-1 entry inhibitors to acquire approval by the US Food and Drug Administration and the European Medicine Agency. Considering the mechanism of action, it is expected that this drug will be effective only in a subpopulation of HIV-1-infected people, namely those harbouring the R5 virus. The favourable toxicity profile of the drug has been demonstrated in Phase III clinical trials in treatment-naive (MERIT) and treatment-experienced (MOTIVATE) patients. In the latter population, maraviroc showed a superior antiviral efficacy and immunological activity compared with optimized backbone therapy + placebo. However, in MERIT, a prospective double-blind, randomized trial in treatment-naive patients, maraviroc + zidovudine/lamivudine failed to prove non-inferiority to efavirenz + zidovudine/lamivudine as standard of care regimen in the 48 week intention-to-treat analysis. Using an assay with higher sensitivity for minority CXCR4-using (X4) HIV variants (the enhanced Trofile assay-Monogram), non-inferiority was reached for the maraviroc- versus efavirenz-based combination. These data indicate the important impact of the sensitivity of tropism testing on treatment outcome of maraviroc-containing regimens. This paper discusses both the prospective and retrospective analyses of the MERIT data and highlights the impact of these results on daily practice in HIV care.

UI MeSH Term Description Entries
D003510 Cyclohexanes Six-carbon alicyclic hydrocarbons.
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077592 Maraviroc A cyclohexane and triazole derivative that acts as an antagonist of the CCR5 RECEPTOR. It prevents infection by HIV-1 virus strains which use CCR5 as a co-receptor for membrane fusion and cellular entry. 4,4-Difluoro-N-((1S)-3-(exo-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo(3.2.1)oct-8-yl)-1-phenylpropyl)cyclohexanecarboxamide,Selzentry,UK-427,857,UK-427857,UK 427,857,UK 427857,UK427,857,UK427857
D014230 Triazoles Heterocyclic compounds containing a five-membered ring with two carbon atoms and three nitrogen atoms with the molecular formula C2H3N3. Triazole
D015497 HIV-1 The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte. Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
D015658 HIV Infections Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS). HTLV-III Infections,HTLV-III-LAV Infections,T-Lymphotropic Virus Type III Infections, Human,HIV Coinfection,Coinfection, HIV,Coinfections, HIV,HIV Coinfections,HIV Infection,HTLV III Infections,HTLV III LAV Infections,HTLV-III Infection,HTLV-III-LAV Infection,Infection, HIV,Infection, HTLV-III,Infection, HTLV-III-LAV,Infections, HIV,Infections, HTLV-III,Infections, HTLV-III-LAV,T Lymphotropic Virus Type III Infections, Human
D016032 Randomized Controlled Trials as Topic Works about clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Clinical Trials, Randomized,Controlled Clinical Trials, Randomized,Trials, Randomized Clinical
D016896 Treatment Outcome Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series. Rehabilitation Outcome,Treatment Effectiveness,Clinical Effectiveness,Clinical Efficacy,Patient-Relevant Outcome,Treatment Efficacy,Effectiveness, Clinical,Effectiveness, Treatment,Efficacy, Clinical,Efficacy, Treatment,Outcome, Patient-Relevant,Outcome, Rehabilitation,Outcome, Treatment,Outcomes, Patient-Relevant,Patient Relevant Outcome,Patient-Relevant Outcomes
D019380 Anti-HIV Agents Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS. AIDS Drug,AIDS Drugs,Anti-AIDS Agents,Anti-AIDS Drug,Anti-HIV Agent,Anti-HIV Drug,Anti-AIDS Drugs,Anti-HIV Drugs,Agent, Anti-HIV,Agents, Anti-AIDS,Agents, Anti-HIV,Anti AIDS Agents,Anti AIDS Drug,Anti AIDS Drugs,Anti HIV Agent,Anti HIV Agents,Anti HIV Drug,Anti HIV Drugs,Drug, AIDS,Drug, Anti-AIDS,Drug, Anti-HIV,Drugs, AIDS,Drugs, Anti-AIDS,Drugs, Anti-HIV

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