title: European mitochondrial haplogroups are associated with CD4+ T cell recovery in HIV-infected patients on combination antiretroviral therapy.
abstract: BACKGROUND
  There is substantial interindividual variability in the rate and extent of CD4+ T cell recovery after starting combination antiretroviral therapy (cART). The aim of our study was to determine whether mitochondrial DNA (mtDNA) haplogroups are associated with recovery of CD4+ in HIV-infected patients on cART.
  
  
  METHODS
  We carried out a retrospective study on 275 cART-naive patients with CD4+ counts <350 cells/mm(3), who were followed-up during at least 24 months after initiating cART. mtDNA genotyping was performed by Sequenom's MassARRAY platform.
  
  
  RESULTS
  Patients within cluster JT and haplogroup J had a lower chance of achieving a CD4+ count ≥500 cells/mm(3) than patients within cluster HV and haplogroup H [hazard ratio (HR) = 0.68 (P = 0.058) and HR = 0.48 (P = 0.010), respectively]. The time of follow-up during which the CD4+ count was ≥500 cells/mm(3) was longer in haplogroups HV and H than in haplogroups JT and J [20 months versus 6.2 months (P = 0.029) and 20 months versus 0 months (P = 0.024), respectively]. Additionally, haplogroups HV and H had greater chances of achieving a CD4+ count ≥500 cells/mm(3) during at least 12, 36, 48 and 60 months post-cART initiation compared with patients within haplogroups JT and J. Patients within haplogroup T only had a lesser chance of achieving a CD4+ count ≥500 cells/mm(3) during at least 48 months and 60 months post-cART initiation.
  
  
  CONCLUSIONS
  European mitochondrial haplogroups might influence CD4+ recovery in HIV-infected patients following initiation with cART. Haplogroups J and T appear to be associated with a worse profile of CD4+ recovery, whereas haplogroup H was associated with a better CD4+ reconstitution.
authors.affiliation: Unit of HIV/Hepatitis Coinfection, National Centre of Microbiology. Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Guzmán-Fulgencio
authors.forename: Juan
authors.initials: J
authors.lastname: Berenguer
authors.forename: Dariela
authors.initials: D
authors.lastname: Micheloud
authors.forename: Amanda
authors.initials: A
authors.lastname: Fernández-Rodríguez
authors.forename: Mónica
authors.initials: M
authors.lastname: García-Álvarez
authors.forename: María Angeles
authors.initials: MA
authors.lastname: Jiménez-Sousa
authors.forename: José María
authors.initials: JM
authors.lastname: Bellón
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Campos
authors.forename: Jaime
authors.initials: J
authors.lastname: Cosín
authors.forename: Teresa
authors.initials: T
authors.lastname: Aldámiz-Echevarría
authors.forename: Pilar
authors.initials: P
authors.lastname: Catalán
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: López
authors.forename: Salvador
authors.initials: S
authors.lastname: Resino
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D044966:Anti-Retroviral Agents; D004272:DNA, Mitochondrial
keywords: AIDS; antiretroviral therapy; immune system reconstitution; mitochondria; polymorphisms