title: CCR5 antagonism impacts vaccination response and immune profile in HIV-1 infection.
abstract: Maraviroc (MVC) is the first licensed antiretroviral therapeutic agent to target a host cell surface molecule, and successful HIV-1 entry blockade by this C-C chemokine receptor type 5 (CCR5)-antagonist potentiates immunomodulation. We hypothesized that MVC intensification impacts immunization responses, T-cell phenotype, function and delayed type hypersensitivity (DTH) in HIV-1(+) subjects. A 24-wk, double-blinded, placebo-controlled study of the addition of MVC to suppressive antiretroviral therapy in HIV-1(+) persons was performed. Subjects received DTH tests, intramuscular tetanus, meningococcal and oral cholera immunizations. Antibody titers, T-cell function and phenotype were assessed. Of 157 patients referred, 47 were randomized 1:1; MVC:placebo. MVC enhanced meningococcal neo-immunization, blunted cholera response and expedited lymphoproliferation to tetanus boost, without affecting recall humoral response. Anti-HIV-1 group-specific antigen (Gag) and tetanus toxoid (TTox) function improved significantly, HIV-1-associated CD8 T-cell skewing normalized, and the percentage of late-stage and major histocompatibility complex (MHC) class II expressing CD4 T-cells increased. Activated CD4(+) CD38(+) human leukocyte antigen (HLA)-DR(+) T-cells declined, and costimulation shifted to coinhibition. DTH was unchanged. Maraviroc intensification, through antagonism of the cell surface molecule CCR5, favorably influences immune profiles of HIV-1(+) patients, supporting its immunomodulatory use in HIV-1 infection and potentially in other immunologically relevant settings.
authors.affiliation: Department of Medicine, Imperial College London, London, UK.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Westrop
authors.forename: Graeme
authors.initials: G
authors.lastname: Moyle
authors.forename: Akil
authors.initials: A
authors.lastname: Jackson
authors.forename: Mark
authors.initials: M
authors.lastname: Nelson
authors.forename: Sundhiya
authors.initials: S
authors.lastname: Mandalia
authors.forename: Nesrina
authors.initials: N
authors.lastname: Imami
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes / Q000009:adverse effects / Q000494:pharmacology; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control*; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007109:Immunity / Q000187:drug effects / Q000276:immunology*; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D056724:Immunity, Humoral / Q000187:drug effects / Q000276:immunology; D016130:Immunophenotyping; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects / Q000494:pharmacology; D014611:Vaccination / Q000009:adverse effects
chemical_list: D016915:AIDS Vaccines; D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes; D019713:Receptors, CCR5; D014230:Triazoles; D000077592:Maraviroc