title: Effect of maraviroc on HIV disease progression-related biomarkers.
abstract: The potential effect of blocking the CCR5 receptor on HIV disease progression biomarkers is not well understood. We showed that an 8-day maraviroc (MVC) monotherapy clinical test (MCT) can be used in selecting patients to receive MVC-containing combined antiretroviral therapy (cART). Using this MCT model, we assessed the effect of MVC on several HIV disease progression biomarkers during the MCT (MVC-specific effect) and following short-term (12-week) cART. We compared 45 patients on MVC monotherapy with a control group of 25 patients on MVC-sparing cART. We found that MVC did not modify any biomarkers in patients that had no virological response after the MCT. MVC-specific effects in patients with virological responses included increased CD8(+) T-cell activation and senescence levels, preservation of an increase in soluble CD14 (sCD14), and a decrease in D dimer levels. After 12 weeks, MVC-containing cART increased CD8(+) T-cell counts and preserved CD4(+) T-cell senescence levels compared with MVC-sparing cART. Moreover, there was a decrease in sCD14 levels in patients that received MVC-containing cART. In conclusion, effects compatible with CD8(+) T-cell redistribution in peripheral blood were observed after MVC therapy. However, MVC was associated with a favorable profile in HIV disease progression biomarkers only in patients with a virological response. These results support a potential clinical benefit of a therapy which includes MVC in HIV-infected patients.
authors.affiliation: Laboratory of Immunovirology, Biomedicine Institute of Seville, Service of Infectious Diseases, Virgen del Rocío University Hospital (IBiS/CSIC/SAS/University of Seville), Seville, Spain.
authors.forename: M Concepción
authors.initials: MC
authors.lastname: Romero-Sánchez
authors.forename: Kawthar
authors.initials: K
authors.lastname: Machmach
authors.forename: Alejandro
authors.initials: A
authors.lastname: Gonzalez-Serna
authors.forename: Miguel
authors.initials: M
authors.lastname: Genebat
authors.forename: Ildefonso
authors.initials: I
authors.lastname: Pulido
authors.forename: María
authors.initials: M
authors.lastname: García-García
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Alvarez-Ríos
authors.forename: Sara
authors.initials: S
authors.lastname: Ferrando-Martinez
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Ruiz-Mateos
authors.forename: Manuel
authors.initials: M
authors.lastname: Leal
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers / Q000378:metabolism; D065100:CCR5 Receptor Antagonists; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000821:virology; D003510:Cyclohexanes / Q000494:pharmacology / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D023581:HIV Fusion Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D018655:Lymphocyte Count; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D012367:RNA, Viral / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D019713:Receptors, CCR5 / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use*; D019562:Viral Load / Q000187:drug effects
chemical_list: D015415:Biomarkers; D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes; D005338:Fibrin Fibrinogen Degradation Products; D023581:HIV Fusion Inhibitors; D018950:Lipopolysaccharide Receptors; D012367:RNA, Viral; D019713:Receptors, CCR5; D014230:Triazoles; C036309:fibrin fragment D; D000077592:Maraviroc