Transmission of antiretroviral-drug-resistant HIV-1 variants

Lancet. 1999 Aug 28;354(9180):729-33. doi: 10.1016/S0140-6736(98)12262-6.

Abstract

Background: Resistance of HIV-1 to antiretroviral drugs is the main cause of antiretroviral-treatment failure. We assessed the transmission of drug-resistant variants among individuals with primary HIV-1 infection.

Methods: Population-based sequencing of the viral reverse-transcriptase and protease genes derived from plasma viral RNA was done in 82 consecutive individuals with documented primary HIV-1 infection from January, 1996, to July, 1998. Phenotypic resistance to protease inhibitors was assessed by recombinant virus assay in individuals with two or more mutations associated with resistance to protease inhibitors.

Findings: Zidovudine-resistance mutations were detected in seven (9%) of 82 individuals. Mutations associated with resistance to other reverse-transcriptase inhibitors (RTIs) were detected in two individuals. Primary-resistance mutations associated with protease inhibitors (V82A, L90M) were detected in three (4%) of 70 individuals; two of these had also RTI-resistance mutations. Decreased sensitivity to three or four protease inhibitors was seen in three individuals, one of whom was infected with HIV-1 variants that harboured 12 mutations associated with resistance to multiple RTI and protease inhibitors.

Interpretation: To introduce the best antiretroviral treatment, resistance testing should be done in recently HIV-1-infected individuals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / therapeutic use*
  • DNA Mutational Analysis
  • Drug Resistance, Multiple* / genetics
  • Female
  • Genetic Variation
  • Genotype
  • HIV Infections / drug therapy
  • HIV Infections / transmission*
  • HIV Infections / virology
  • HIV Protease Inhibitors / adverse effects
  • HIV Protease Inhibitors / therapeutic use
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Switzerland
  • Zidovudine / adverse effects
  • Zidovudine / therapeutic use

Substances

  • Anti-HIV Agents
  • HIV Protease Inhibitors
  • Zidovudine