European mitochondrial haplogroups are associated with CD4+ T cell recovery in HIV-infected patients on combination antiretroviral therapy

J Antimicrob Chemother. 2013 Oct;68(10):2349-57. doi: 10.1093/jac/dkt206. Epub 2013 Jun 7.

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.

Conclusion: 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.

Keywords: AIDS; antiretroviral therapy; immune system reconstitution; mitochondria; polymorphisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Retroviral Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active*
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology*
  • DNA, Mitochondrial / genetics*
  • Female
  • Follow-Up Studies
  • HIV Infections / drug therapy*
  • HIV Infections / immunology*
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies

Substances

  • Anti-Retroviral Agents
  • DNA, Mitochondrial