title: Discordant responses to cART in HIV-1 patients in the era of high potency antiretroviral drugs: clinical evaluation, classification, management prospects.
abstract: The goal of antiretroviral treatment (ART) in HIV-1 patients is immune reconstitution following control of viral replication. CD4+ cell number/proportions are a crude but essential correlate of immune reconstitution. Despite suppression of HIV replication, a fraction of ART-treated patients still fails to fully reconstitute CD4+ T cell numbers (immunological nonresponders, INRs). New drugs, regimens and treatment strategies led to increased efficacy, lower side effects and higher virological success rates in clinical practice. The multitude of described immune defects and clinical events accompanying INR opposed to the marginal effect of antiretroviral intensification or immunotherapy trials underline the need for continuing efforts at understanding the mechanisms that underlie INR. Here, we reassess INR definition, frequency, and the achievements of active clinical and translational research suggesting a shared definition for insufficient, partial and complete CD4+ cell number recovery thus improving homogeneity in patient selection and mechanism identification.
authors.affiliation: a Ospedali Galliera , Genoa , Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cenderello
authors.affiliation: b Department of Health Sciences , University of Genova , Genoa 16132 , Italy.|c Clinica Malattie Infettive, IRCCS A.O.U. S. Martino - IST Genova , Istituto Nazionale per la Ricerca sul Cancro , Genoa , Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: De Maria
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers / Q000032:analysis; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology*; D002986:Clinical Trials as Topic; D019468:Disease Management; D024882:Drug Resistance, Viral / Q000187:drug effects; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D019562:Viral Load / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers
keywords: Antiretroviral treatment; CD4; HIV; cART; immune reconstitution; immunological nonresponder; immunotherapy