title: Impact of HIV-1 subtype and antiretroviral therapy on protease and reverse transcriptase genotype: results of a global collaboration.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Global surveillance and genotypic assessment of drug resistance should focus primarily on the known subtype B drug-resistance mutations.
authors.affiliation: Division of Infectious Disease and Center for AIDS Research, Stanford University, Stanford, California, USA. rkantor@brown.edu
authors.forename: Rami
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authors.lastname: Kantor
authors.forename: David A
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authors.forename: Ana Patricia
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authors.lastname: Cane
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authors.forename: Marcelo A
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authors.lastname: Snoeck
authors.forename: Candice
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authors.forename: Hagit
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authors.lastname: Rudich
authors.forename: Rosangela
authors.initials: R
authors.lastname: Rodrigues
authors.forename: Africa
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authors.lastname: Holguin
authors.forename: Koya
authors.initials: K
authors.lastname: Ariyoshi
authors.forename: Maria Belen
authors.initials: MB
authors.lastname: Bouzas
authors.forename: Pedro
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authors.lastname: Cahn
authors.forename: Wataru
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authors.lastname: Sugiura
authors.forename: Vincent
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authors.lastname: Soriano
authors.forename: Luis F
authors.initials: LF
authors.lastname: Brigido
authors.forename: Zehava
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authors.lastname: Grossman
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authors.lastname: Morris
authors.forename: Anne-Mieke
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authors.lastname: Vandamme
authors.forename: Amilcar
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authors.lastname: Tanuri
authors.forename: Praphan
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authors.lastname: Phanuphak
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Weber
authors.forename: Deenan
authors.initials: D
authors.lastname: Pillay
authors.forename: P Richard
authors.initials: PR
authors.lastname: Harrigan
authors.forename: Ricardo
authors.initials: R
authors.lastname: Camacho
authors.forename: Jonathan M
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authors.lastname: Schapiro
authors.forename: Robert W
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mesh_terms: D000595:Amino Acid Sequence; D044966:Anti-Retroviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D024882:Drug Resistance, Viral; D014943:Global Health; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000235:genetics*; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*
chemical_list: D044966:Anti-Retroviral Agents; D012194:RNA-Directed DNA Polymerase; D010447:Peptide Hydrolases