Immunologic Effects of Maraviroc in HIV-Infected Patients with Severe CD4 Lymphopenia Starting Antiretroviral Therapy: A Sub-Study of the CADIRIS Trial.

Autor:	Belaunzarán-Zamudio PF; Departamento de Infectología, Instituto Nacional de Ciencias Médicas y Nutrición 'Salvador Zubirán', Mexico City, Mexico.; División de Investigación de la Facultad de Medicina, Universidad Nacional Autónoma de México', Mexico City, Mexico., Azzoni L; The WISTAR Institute, Philadelphia, Pennsylvania., Canaday DH; Center for AIDS Research (CFAR) Case Western Reserve University, Cleveland, Ohio., Caro-Vega YN; Departamento de Infectología, Instituto Nacional de Ciencias Médicas y Nutrición 'Salvador Zubirán', Mexico City, Mexico., Clagett B; Center for AIDS Research (CFAR) Case Western Reserve University, Cleveland, Ohio., Rassool MS; Clinical HIV Research Unit, Department of Internal Medicine, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa., Rodriguez B; Center for AIDS Research (CFAR) Case Western Reserve University, Cleveland, Ohio., Sanne I; Clinical HIV Research Unit, Department of Internal Medicine, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa., Sereti I; HIV Pathogenesis Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases/National Institutes of Health, Bethesda, Maryland., Sierra-Madero JG; Departamento de Infectología, Instituto Nacional de Ciencias Médicas y Nutrición 'Salvador Zubirán', Mexico City, Mexico., Lederman MM; Center for AIDS Research (CFAR) Case Western Reserve University, Cleveland, Ohio.
Jazyk:	angličtina
Zdroj:	Pathogens & immunity [Pathog Immun] 2017; Vol. 2 (2), pp. 151-177. Date of Electronic Publication: 2017 May 09.
DOI:	10.20411/pai.v2i2.181
Abstrakt:	Background: We aimed to describe the mechanisms of immunological recovery and the effects of blocking CCR5 in patients starting ART with advanced HIV-infection. Methods: This was a sub-study of a 48 week double-blind, clinical trial where patients starting ART with CD4+ cell counts <100 cells/uL were randomized to receive maraviroc or a placebo. CD4+ and CD8+ cell maturation phenotypes, expression of PD-1 and CCR5, and activation indices were measured at weeks 0, 4, 12, 24, and 48. The reactivity of CD4+ and CD8+cells with peptides of CMV and MTb, and with Staphylococcal enterotoxin B (SEB) was assessed by intracellular expression of IFNγ, TNFα, and CD40 ligand at weeks 0, 4, and 12 of ART. Results: Forty patients were included in the study (Maraviroc = 22; placebo = 18). Sustained increases in CD8+ cells and in proportions of CCR5+ CD4+ and CD8+ cells were observed in the maraviroc arm. Early increases in the proportions of activated (CD38+, HLA-DR+), PD-1+ CD4+, and CD8+ cells and more matured CD8+ cells, were observed in the maraviroc arm. T cell responses to CMV, MTb, and SEB did not differ by treatment arms. Conclusions: During antiretroviral therapy in advanced HIV infection, maraviroc retains mature, activated CCR5+ cells in circulation without impact on CD4+ T cell recovery or T cell reactivity to antigen or superantigen. Competing Interests: POTENTIAL CONFLICTS OF INTEREST Yanink Caro-Vega, David Canaday, and Irini Sereti declare no competing interests. Pablo F Belaunzaran-Zamudio reports travel support from Sanofi-Pasteur Mexico in the last year, unconnected with the submitted work. Livio Azzoni reports a data management contract from Pfizer during the conduct of the clinical trial main study, but no support during this study. Benigno Rodríguez reports grants from the NIH and personal fees from Gilead, both unconnected with the submitted work. Juan G Sierra-Madero reports grants from Pfizer during the course of the study; personal fees from Stendhal and Pfizer for consultancy and speakership and non-financial support for travel and accommodations; grants and personal fees from MSD for consultancy and non-financial support for travel and accommodations unconnected with the study; grants unrelated to the study from BMS and GSK; and personal fees from Janssen Pharmaceutical all unconnected with the submitted work. Michael M. Lederman has served as a consultant and has received grant support for this work from Pfizer.
Databáze:	MEDLINE
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