Abacavir alters the transcription of inflammatory cytokines in virologically suppressed, HIV-infected women

J Int AIDS Soc. 2012 Jul 10;15(2):17393. doi: 10.7448/IAS.15.2.17393.

Abstract

Background: Abacavir (ABC) may be associated with a small, increased risk of myocardial infarction in HIV-infected adults, possibly related to cytokine-mediated inflammation.

Methods: To evaluate the induction of inflammatory cytokine transcription by ABC, we used samples from women randomized to receive zidovudine/lamivudine/ABC (Trizivir) or lopinavir/ritonavir and zidovudine/lamividine (Kaletra/Combivir) from the third trimester through six-months postpartum for the prevention of mother-to-child transmission (PMTCT). Women were matched by CD4 count and baseline HIV RNA. All women attained viral suppression (<50 copies/ml) by the time of sampling.

Results: Four cytokines showed a difference in expression between the treatment arms, all in a proinflammatory direction for the ABC arm: CD40LG 1.82-fold, (p=.027); IL-8 3.16-fold (p=.020); LTA 2.82-fold, (p=.008); and CCL5 -1.67-fold, (p=.035). At 12-months postpartum, 6-months after antiretroviral discontinuation, cytokine expression was similar by treatment arm.

Conclusions: We conclude that ABC may upregulate proinflammatory cytokines at the transcriptional level in this population.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / adverse effects*
  • Antiretroviral Therapy, Highly Active / adverse effects*
  • Antiretroviral Therapy, Highly Active / methods
  • CD4 Lymphocyte Count
  • Cytokines / biosynthesis*
  • Dideoxynucleosides / administration & dosage
  • Dideoxynucleosides / adverse effects*
  • Female
  • HIV / isolation & purification
  • Humans
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / adverse effects
  • Transcription, Genetic / drug effects*
  • Viral Load

Substances

  • Anti-HIV Agents
  • Cytokines
  • Dideoxynucleosides
  • Immunologic Factors
  • abacavir