title: Shorter telomere length predicts poorer immunological recovery in virologically suppressed HIV-1-infected patients treated with combined antiretroviral therapy.
abstract: BACKGROUND
  Successful combined antiretroviral therapy (cART) does not always result in complete CD4 T-cell recovery despite the effective control of HIV replication. Because telomere dysregulation can lead to an abnormal cell proliferation, we hypothesized that the lack of CD4 recovery may be related to telomere defects; We thus evaluated the association between telomere length (TL) and CD4 T-cell recovery 48 weeks after cART initiation in virologically suppressed patients, and its possible relationship to oxidative stress (OS) and nitrosative stress (NOx) markers.
  
  
  METHODS
  We studied HIV-infected patients on stable cART who achieved a viral load <50 copies per milliliter after 48 weeks of their first cART. Leukocyte TL was measured and categorized into tertiles. We calculated mean increases in CD4 T-cell at 48 weeks from cART initiation and used multivariate linear regression models to estimate differences in mean increases according to tertiles of TL.
  
  
  RESULTS
  One hundred thirty-two patients, 86% male, 81% <50 years at cART initiation were studied. Mean increases in CD4 were greater in patients with long TL than in those with medium and short TLs (P = 0.007). After adjustment for sex, age, CD4 T-cell counts, viral load, and hepatitis C infection at cART initiation, differences in mean CD4 T-cell count increases according to TL remained statistically significant (P = 0.02). Additional adjustment for NOx and OS did not change the results.
  
  
  CONCLUSIONS
  A lower immunological response despite a successful virological response is associated with a shorter TL. The effect is not related to NOx or OS.
authors.affiliation: *Department of Infectious Diseases, Hospital San Pedro-CIBIR, Logroño, Spain; †Centro Nacional de Epidemiología, Instituto de Salud Carlos III, Madrid, Spain; ‡Oncologia-CIBIR, Logroño, Spain; §Biología Experimental Universidad de Jaén, Jaén, Spain; ‖Hospital General del Elche and University Miguel Hernández, Alicante, Spain; ¶Hospital de La Paz, Madrid, Spain; #Hospital Universitari de Tarragona Joan XXIII, Tarragona, Spain; and **Hospital Ramón y Cajal, IRYCIS, Madrid, Spain.
authors.forename: José-Ramón
authors.initials: JR
authors.lastname: Blanco
authors.forename: Inma
authors.initials: I
authors.lastname: Jarrin
authors.forename: Alfredo
authors.initials: A
authors.lastname: Martinez
authors.forename: Eva
authors.initials: E
authors.lastname: Siles
authors.forename: Ignacio M
authors.initials: IM
authors.lastname: Larrayoz
authors.forename: Ana
authors.initials: A
authors.lastname: Cañuelo
authors.forename: Félix
authors.initials: F
authors.lastname: Gutierrez
authors.forename: Juan
authors.initials: J
authors.lastname: Gonzalez-Garcia
authors.forename: Francesc
authors.initials: F
authors.lastname: Vidal
authors.forename: Santiago
authors.initials: S
authors.lastname: Moreno
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001483:Base Sequence; D017931:DNA Primers; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D015497:HIV-1; D016133:Polymerase Chain Reaction; D016615:Telomere
chemical_list: D019380:Anti-HIV Agents; D017931:DNA Primers