CD4+ T-cell restoration after 48 weeks in the maraviroc treatment-experienced trials MOTIVATE 1 and 2. 2010

David M Asmuth, and James Goodrich, and David A Cooper, and Richard Haubrich, and Natasa Rajicic, and Bernard Hirschel, and Howard Mayer, and Hernan Valdez
University of California Davis, Sacramento, CA, USA.

OBJECTIVE To determine factors associated with CD4 responses to maraviroc (MVC)-containing regimens in treatment-experienced patients. METHODS Forty-eight-week data from MOTIVATE 1 and 2 was used to assess MVC once or twice daily versus placebo (PBO), each with optimized background therapy (N = 1047). A repeated measures model evaluated longitudinal CD4 changes, multivariate linear regression evaluated predictors of week 48 increases, and Cox proportional hazard modeling evaluated time to category C events. RESULTS Median CD4 increases were greater on MVC once or twice daily than PBO (92, 103, and 24 cells/mm3, respectively; P < 0.05), and the difference remained significant among patients achieving less than 50 HIV-1 RNA copies/mL (126, 125, and 96 cells/mm3; P < 0.05) or when adjusted for other predictors of CD4 increase including change in HIV-1 RNA. Time to a category C event was longer on MVC; in multivariate models, higher on-treatment CD4 count, but not MVC treatment, was protective against new events (hazard ratio 0.8 per +25 cells/mm3; 95% confidence interval 0.78-0.87). CONCLUSIONS MOTIVATE patients receiving MVC had larger CD4+ T-cell increases than those receiving PBO, even after adjusting for the greater virologic potency of MVC-containing regimens. This additional CD4 response was associated with a longer time to the development of AIDS-defining events on MVC.

UI MeSH Term Description Entries
D009894 Opportunistic Infections An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. Infection, Opportunistic,Infections, Opportunistic,Opportunistic Infection
D002986 Clinical Trials as Topic Works about pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries. Clinical Trial as Topic
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
D013601 T-Lymphocytes Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor
D014230 Triazoles Heterocyclic compounds containing a five-membered ring with two carbon atoms and three nitrogen atoms with the molecular formula C2H3N3. Triazole
D015496 CD4-Positive T-Lymphocytes A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes. T4 Cells,T4 Lymphocytes,CD4-Positive Lymphocytes,CD4 Positive T Lymphocytes,CD4-Positive Lymphocyte,CD4-Positive T-Lymphocyte,Lymphocyte, CD4-Positive,Lymphocytes, CD4-Positive,T-Lymphocyte, CD4-Positive,T-Lymphocytes, CD4-Positive,T4 Cell,T4 Lymphocyte
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

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