Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance

J Infect Dis. 2009 May 1;199(9):1323-6. doi: 10.1086/597802.


Genotypic surveys suggest that human immunodeficiency virus type 1 (HIV-1) and HIV-2 evolve different sets of mutations in response to nucleoside reverse-transcriptase inhibitors (NRTIs). We used site-directed mutagenesis, culture-based phenotyping, and cell-free assays to determine the resistance profiles conferred by specific amino acid replacements in HIV-2 reverse transcriptase. Although thymidine analogue mutations had no effect on zidovudine sensitivity, the addition of Q151M together with K65R or M184V was sufficient for high-level resistance to both lamivudine and zidovudine in HIV-2, and the combination of K65R, Q151M, and M184V conferred classwide NRTI resistance. These data suggest that current NRTI-based regimens are suboptimal for treating HIV-2 infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / drug therapy*
  • Africa, Western / epidemiology
  • Amino Acid Substitution
  • Anti-HIV Agents / pharmacology
  • Antiviral Agents / pharmacology*
  • Drug Resistance, Viral / drug effects
  • Genetic Predisposition to Disease
  • HIV Infections / drug therapy*
  • HIV-1 / drug effects
  • HIV-1 / genetics
  • HIV-2 / drug effects
  • HIV-2 / enzymology
  • HIV-2 / genetics*
  • Humans
  • Mutagenesis, Site-Directed
  • Phenotype
  • RNA-Directed DNA Polymerase / drug effects
  • RNA-Directed DNA Polymerase / genetics*
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Zidovudine / pharmacology


  • Anti-HIV Agents
  • Antiviral Agents
  • Reverse Transcriptase Inhibitors
  • Zidovudine
  • RNA-Directed DNA Polymerase