Upregulation of Apoptosis Pathway Genes in Peripheral Blood Mononuclear Cells of HIV-Infected Individuals with Antiretroviral Therapy-Associated Mitochondrial Toxicity

Antimicrob Agents Chemother. 2017 Jul 25;61(8):e00522-17. doi: 10.1128/AAC.00522-17. Print 2017 Aug.

Abstract

A case-control study of the effect of antiretroviral therapy (ART) on apoptosis pathway genes comprising 16 cases (HIV infected with mitochondrial toxicity) and 16 controls (HIV uninfected) was conducted. A total of 26 of 84 genes of the apoptosis pathway were differentially expressed. Two of the upregulated genes, DFFA and TNFRSF1A, classified 75% of study participants correctly as either a case or control. Thus, apoptosis may be in the causal pathway of ART-associated mitochondrial toxicity. These two genes could be markers for detecting and monitoring ART-induced mitochondrial toxicity.

Keywords: antiretroviral therapy; apoptosis; biomarker; mitochondrial toxicity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Anti-HIV Agents / adverse effects*
  • Anti-HIV Agents / pharmacology
  • Antiretroviral Therapy, Highly Active / adverse effects*
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / genetics
  • Case-Control Studies
  • Cytochromes c / blood
  • DNA, Mitochondrial / drug effects
  • Female
  • Gene Expression Regulation / drug effects*
  • HIV Infections / drug therapy*
  • Humans
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • Middle Aged
  • Mitochondria / drug effects
  • Mitochondria / pathology*
  • Principal Component Analysis
  • Receptors, Tumor Necrosis Factor, Type I / genetics

Substances

  • Anti-HIV Agents
  • Apoptosis Regulatory Proteins
  • DNA, Mitochondrial
  • Receptors, Tumor Necrosis Factor, Type I
  • caspase-activated DNase inhibitor
  • Cytochromes c