Effect of the substitution of one nucleoside analogue by one non-nucleoside reverse transcriptase inhibitor over mitochondrial DNA levels

Infection. 2008 Jun;36(3):266-70. doi: 10.1007/s15010-008-7312-z. Epub 2008 May 3.

Abstract

Background: Long-term antiretroviral therapy is associated with several side effects, like mitochondrial toxicity related to nucleoside reverse transcriptase inhibitors (NRTIs). Our objective was to analyze the effect of the substitution of one NRTI by one non-nucleoside reverse transcriptase inhibitor (NNRTI) in the antiretroviral regime of HIV-1-infected patients who were on a regime containing either two NRTIs and one NNRTI, or one NRTI, one NNRTI and one protease inhibitor (PI), over mtDNA level. Decreasing NRTIs could increase mtDNA level.

Methods: Fifteen HIV-1-infected patients were included in the study. As controls, 17 healthy individuals and 15 HIV-1-infected patients naïve for antiretroviral treatment were also analyzed. mtDNA level was quantified at baseline and after 48 weeks of treatment.

Results: Control groups showed higher levels of mtDNA than the study group (p<0.001). Among this latter group, no statistical differences between baseline and after 48 weeks were found. Naïve HIV-infected patients had lower mtDNA than healthy volunteers (p<0.001). Two patients had two consecutive blips (low viral load increases) but they did not show NNRTI-related resistance mutations.

Conclusions: This study shows that although this treatment was immunovirologically effective, mtDNA level did not increase at least after 48 weeks.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents* / administration & dosage
  • Anti-HIV Agents* / adverse effects
  • Anti-HIV Agents* / chemistry
  • Anti-HIV Agents* / therapeutic use
  • CD4 Lymphocyte Count
  • DNA, Mitochondrial / metabolism*
  • Drug Resistance, Viral
  • Drug Therapy, Combination
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-1 / drug effects
  • Humans
  • Male
  • Middle Aged
  • Nucleosides / chemistry
  • Reverse Transcriptase Inhibitors* / administration & dosage
  • Reverse Transcriptase Inhibitors* / adverse effects
  • Reverse Transcriptase Inhibitors* / chemistry
  • Reverse Transcriptase Inhibitors* / therapeutic use
  • Treatment Outcome

Substances

  • Anti-HIV Agents
  • DNA, Mitochondrial
  • Nucleosides
  • Reverse Transcriptase Inhibitors