Impact of HIV-1 subtype and antiretroviral therapy on protease and reverse transcriptase genotype: results of a global collaboration

PLoS Med. 2005 Apr;2(4):e112. doi: 10.1371/journal.pmed.0020112. Epub 2005 Apr 26.

Abstract

Background: The genetic differences among HIV-1 subtypes may be critical to clinical management and drug resistance surveillance as antiretroviral treatment is expanded to regions of the world where diverse non-subtype-B viruses predominate.

Methods and findings: To assess the impact of HIV-1 subtype and antiretroviral treatment on the distribution of mutations in protease and reverse transcriptase, a binomial response model using subtype and treatment as explanatory variables was used to analyze a large compiled dataset of non-subtype-B HIV-1 sequences. Non-subtype-B sequences from 3,686 persons with well characterized antiretroviral treatment histories were analyzed in comparison to subtype B sequences from 4,769 persons. The non-subtype-B sequences included 461 with subtype A, 1,185 with C, 331 with D, 245 with F, 293 with G, 513 with CRF01_AE, and 618 with CRF02_AG. Each of the 55 known subtype B drug-resistance mutations occurred in at least one non-B isolate, and 44 (80%) of these mutations were significantly associated with antiretroviral treatment in at least one non-B subtype. Conversely, of 67 mutations found to be associated with antiretroviral therapy in at least one non-B subtype, 61 were also associated with antiretroviral therapy in subtype B isolates.

Conclusion: Global surveillance and genotypic assessment of drug resistance should focus primarily on the known subtype B drug-resistance mutations.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Anti-Retroviral Agents / pharmacology*
  • Anti-Retroviral Agents / therapeutic use
  • DNA Mutational Analysis
  • Drug Resistance, Viral
  • Global Health
  • HIV Infections / drug therapy*
  • HIV-1 / classification
  • HIV-1 / genetics
  • HIV-1 / pathogenicity*
  • Humans
  • Molecular Sequence Data
  • Peptide Hydrolases / genetics*
  • RNA-Directed DNA Polymerase / genetics*

Substances

  • Anti-Retroviral Agents
  • RNA-Directed DNA Polymerase
  • Peptide Hydrolases

Associated data

  • GENBANK/AF005494
  • GENBANK/AF005496
  • GENBANK/AF061642
  • GENBANK/AF082394
  • GENBANK/AJ006022
  • GENBANK/AJ249235
  • GENBANK/K03455
  • GENBANK/L20587
  • GENBANK/L39106
  • GENBANK/M27323
  • GENBANK/M62320
  • GENBANK/U46016
  • GENBANK/U54771