Proviral DNA as a Target for HIV-1 Resistance Analysis

Intervirology. 2015;58(3):184-9. doi: 10.1159/000431093. Epub 2015 Jun 27.

Abstract

Background: Resistance analysis from viral RNA is restricted to detectable viral load. Therefore, analysis from proviral DNA could help in cases with low-level or suppressed viremia.

Methods: Viral plasma RNA and the corresponding cellular proviral DNA of 78 EDTA samples from 48 therapy-naïve (TN) and 30 therapy-experienced (TE) HIV-1-infected patients were isolated and analyzed for their resistance profiles in the protease and reverse transcriptase genes.

Results: Overall, 175 drug-resistance mutations (DRMs) were detected in 25/30 TE (83.3%) and 5/48 TN (10.4%) samples. The TE patients displayed a mean number of 6.68 DRMs in RNA and 5.20 in DNA. In the TN patients, a mean of 0.8 DRMs was found in RNA and 1.0 in DNA; 75% of the DRMs were detected in RNA and DNA simultaneously. In the TE samples, 76% of the DRMs were detected simultaneously in RNA and DNA, 23% exclusively in RNA and 1% in DNA only. The TN samples revealed a significantly higher frequency of DRMs in DNA than in RNA.

Conclusions: Proviral DNA resistance testing provides additional resistance information for TN patients. It is also a reliable alternative for TE patients with unsuccessful RNA testing and can provide valuable information when no records are available.

MeSH terms

  • Anti-HIV Agents / pharmacology*
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active
  • DNA, Viral / genetics*
  • Drug Resistance, Viral / genetics*
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / virology*
  • HIV-1 / drug effects*
  • HIV-1 / genetics*
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Proviruses / drug effects
  • Proviruses / genetics*
  • Proviruses / isolation & purification
  • RNA, Viral / blood
  • RNA, Viral / isolation & purification
  • RNA-Directed DNA Polymerase / genetics
  • Viral Load
  • Viremia / drug therapy

Substances

  • Anti-HIV Agents
  • DNA, Viral
  • RNA, Viral
  • RNA-Directed DNA Polymerase