HIV-1 proviral resistance mutations: usefulness in clinical practice

HIV Med. 2010 Sep;11(8):483-92. doi: 10.1111/j.1468-1293.2009.00814.x. Epub 2010 Feb 16.

Abstract

Objectives: Transmitted HIV strains may harbour drug resistance mutations. HIV-1 drug resistance mutations are currently detected in plasma viral RNA. HIV-1 proviral DNA could be an alternative marker, as it persists in infected cells.

Methods: This was a prospective study assessing the prevalence and persistence of HIV-1 drug resistance mutations in DNA from CD4 cells before and after protease inhibitor (PI)- or nonnucleoside reverse transcriptase inhibitor (NNRTI)-based therapy initiation in 69 drug-naïve patients.

Results: Before therapy, 90 and 66% of detected mutations were present in CD4 cells and plasma, respectively. We detected seven key mutations, and four of these (M184M/V, M184M/I, K103K/N and M46M/I) were only found in the cells. When treatment was started, 40 patients were followed; the mutations detected at the naïve stage remained present for at least 1 year. Under successful treatment, new key mutations emerged in CD4 cells (M184I, M184M/I and Y188Y/H).

Conclusions: The proportion of mutations detected in the DNA was statistically significantly higher than that detected in standard RNA genotyping, and these mutations persisted for at least 1 year irrespective of therapy. The pre-existence of resistance mutations did not jeopardise treatment outcome when the drug concerned was not included in the regimen. Analysis of HIV-1 DNA could be useful in chronic infections or when switching therapy in patients with undetectable viraemia.

MeSH terms

  • Adult
  • Aged
  • Amino Acid Sequence
  • Anti-Retroviral Agents / therapeutic use
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / virology
  • DNA Mutational Analysis
  • DNA, Viral / analysis*
  • DNA, Viral / genetics
  • Drug Resistance, Viral / genetics*
  • Drug Therapy, Combination
  • Female
  • Genotype
  • HIV Infections / blood
  • HIV Infections / drug therapy
  • HIV Infections / virology*
  • HIV-1 / drug effects
  • HIV-1 / genetics*
  • HIV-1 / isolation & purification
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Mutation / drug effects
  • Mutation / genetics
  • Prevalence
  • Prospective Studies
  • Proviruses / genetics*
  • RNA, Viral / analysis*
  • RNA, Viral / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Statistics, Nonparametric
  • Viral Load
  • Young Adult

Substances

  • Anti-Retroviral Agents
  • DNA, Viral
  • RNA, Viral