Competitive capacity of HIV-1 strains carrying M184I or Y181I drug-resistant mutations

Chin Med J (Engl). 2009 May 5;122(9):1081-6.

Abstract

Background: Virus with nucleoside reverse transcriptase inhibitors (NRTIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs) resistant mutations show different evolution tendencies when the anti-viral therapies are interrupted. Understanding the replication fitness of drug-resistant virus is important for the study of the prevalence of drug-resistance. For this purpose, we characterized the replication capacity of HIV-1 virus carrying lamivudine (3TC) or nevirapine (NVP) resistant mutations.

Methods: 3TC and NVP resistant variants were induced in vitro by selecting wild type virus in the presence of drugs. For the competitive replication assay, drug-resistant variants were cocultured with wild-type virus in the presence or absence of drugs. The ratios of the viral species were determined over time by using a real-time RT-PCR-based assay.

Results: 3TC-resistant (M184I mutation) and NVP-resistant (Y181I mutation) virus should be selected in vitro in two different ways. The competitive replication assay showed that the ratio of virus carrying a M184I mutation increased from 98.8%, while the wild type virus decreased to 1.2% after 4 passages in the presence of 3TC; the percentage of virus carrying the Y181I mutation increased to 90.5%, while wild type virus decreased to 9.5% in the presence of NVP. In the absence of drugs, the ratio of virus carrying the M184I mutation decreased to 5.3%, while wild type virus increased to 94.7%; the ratio of virus carrying Y181I increased to 75%, while wild type virus decreased to 25% after 4 passages.

Conclusions: The NVP-resistant virus is fitter than wild type virus even in the absence of NVP that may be the reason that NNRTIs-resistant virus is spreading quickly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Drug Resistance, Viral / genetics*
  • HIV-1 / drug effects
  • HIV-1 / genetics
  • HIV-1 / growth & development
  • HIV-1 / physiology*
  • Humans
  • Lamivudine / pharmacology
  • Mutation
  • Nevirapine / pharmacology
  • Reverse Transcriptase Inhibitors / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Virus Replication / genetics
  • Virus Replication / physiology

Substances

  • Reverse Transcriptase Inhibitors
  • Lamivudine
  • Nevirapine