title: Immunodiscordant responses to HAART--mechanisms and consequences.
abstract: A relevant fraction of HIV-1-infected individuals (ranging from 15 to 30%) presenting virologically successful highly active antiretroviral therapy fail to recover CD4 T-cell counts. These individuals, called immunodiscordant or immunological nonresponders, are at increased risk of clinical progression and death. Although older age, lower nadir CD4 T-cell count and HCV co-infection are some of clinical predictive factors, immunological mechanisms rely on impaired thymic production and accumulation of apoptosis-prone CD4 T cells. Indeed, immunodiscordant individuals may show increased tissue fibrosis and damage of gut-associated lymphoid tissue that results in higher hyperactivation, inflammation and immunosenescence, altered Treg/Th17 ratio and increased T-cell death. A better knowledge of the final pathogenic mechanism and factors influencing CD4 T-cell recovery will help to select the optimal therapeutic strategies for them.
authors.affiliation: Department of Pathology, University of California San Diego, La Jolla, CA, USA.
authors.forename: Marta
authors.initials: M
authors.lastname: Massanella
authors.forename: Eugènia
authors.initials: E
authors.lastname: Negredo
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Julià
authors.initials: J
authors.lastname: Blanco
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D016922:Cellular Senescence; D004351:Drug Resistance; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D012307:Risk Factors; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology / Q000821:virology
chemical_list: D019380:Anti-HIV Agents