Short-term in vivo modifications of platelet NADPH oxidase 2 (NOX2) and prostaglandin F in HIV-1 patients on abacavir-based therapies

HIV Med. 2016 Nov;17(10):774-777. doi: 10.1111/hiv.12383.

Abstract

Objectives: The aim of the study was to investigate the in vivo effect of abacavir (ABC) on platelet oxidative stress.

Methods: We performed a randomized pilot study including 39 HIV-1-infected patients, 17 on zidovudine/lamivudine (ZDV/3TC) and 22 on tenofovir/emtricitabine (TDF/FTC). Ten patients on ZDV/3TC and eight patients on TDF/FTC were randomly allocated to switching the nucleoside backbone to ABC/3TC. At baseline and after 6 months, platelet oxidative stress was assessed by platelet NADPH oxidase 2 (NOX2)-derived peptide (sNOX2-dp), a marker of NOX2 activation, and platelet prostaglandin F (8-iso-PGF ). Platelet activation was measured by soluble CD40L (sCD40L).

Results: At baseline, no differences between ZDV/3TC or TDF/FTC recipients were found. After 6 months, patients switching from ZDV/3TC showed a decrease of sNOX2-dp (from 20.9±5.7 to 12.5±3.8 pg/ml, p=0.002) and 8-iso-PGF (from 154.3±41.9 to 122.9±28.0 pmol/l, p=0.025). No effects on platelet oxidative stress biomarkers were observed in subjects from TDF/FTC, who showed a significant increase in blood glucose (p=0.043) and total cholesterol (p=0.027). ABC showed no effect on sCD40L levels in both groups.

Conclusions: ABC reduced platelet sNOX2-dp and 8-iso-PGF in HIV-1 subjects switching from ZDV/3TC but not in those from TDF/FTC after 6 months. No changes in platelet activation were found in both groups.

Keywords: HIV-1 infection; NADPH oxidase; abacavir; isoprostanes; platelet activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Blood Platelets / chemistry*
  • Blood Platelets / enzymology*
  • CD40 Ligand / blood
  • Dideoxynucleosides / therapeutic use*
  • Dinoprost / analysis*
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / pathology
  • Humans
  • Male
  • Membrane Glycoproteins / analysis*
  • Middle Aged
  • NADPH Oxidase 2
  • NADPH Oxidases / analysis*
  • Pilot Projects
  • Platelet Activation
  • Young Adult

Substances

  • Anti-HIV Agents
  • Dideoxynucleosides
  • Membrane Glycoproteins
  • CD40 Ligand
  • Dinoprost
  • CYBB protein, human
  • NADPH Oxidase 2
  • NADPH Oxidases
  • abacavir