title: Prevalence of genotypic and phenotypic resistance to anti-retroviral drugs in a cohort of therapy-naïve HIV-1 infected US military personnel.
abstract: OBJECTIVE
  While transmission of drug-resistant HIV-1 has been reported, estimates of prevalence of resistance in drug-naïve populations are incomplete. We investigated the prevalence of genotypic mutations and phenotypic antiretroviral resistance in a cohort of HIV-1 infected U.S. military personnel prior to the institution of antiretroviral therapy.
  
  
  METHODS
  Cross-sectional cohort study.
  
  
  METHODS
  Plasma was obtained from 114 recently HIV-1 infected subjects enrolled in an epidemiological study. Genotypic resistance was determined by consensus sequencing of a PCR product from the HIV-1 pol gene. Sequences were interpreted by a phenotypic-genotypic correlative database. Resistance phenotypes were determined by a recombinant virus cell culture assay.
  
  
  RESULTS
  Genotypic mutations and phenotypic resistance were found at a higher than expected frequency. Resistance to non-nucleoside reverse transcriptase inhibitors was most common, with a prevalence of 15% of 95 subjects by genotype and 26% of 91 subjects by phenotype. Genotypic and phenotypic resistance respectively were found in 4% and 8% of subjects for nucleoside reverse transcriptase inhibitors and in 10% and 1% for protease inhibitors. One subject harbored virus with resistance to all three drug classes.
  
  
  CONCLUSIONS
  A substantial frequency of resistance to antiretroviral drugs was identified in a therapy-naïve U.S. cohort. In most cases, the genotypic and phenotypic assays yielded similar results, although the genotypic assay could detect some protease inhibitor resistance-associated mutations in the absence of phenotypic resistance. These data suggest the need for optimization of treatment guidelines based on current estimates of the prevalence of drug resistance in HIV-1 seroconverters.
authors.affiliation: U.S. Military HIV Research Program, Rockville, MD, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Wegner
authors.forename: S K
authors.initials: SK
authors.lastname: Brodine
authors.forename: J R
authors.initials: JR
authors.lastname: Mascola
authors.forename: S A
authors.initials: SA
authors.lastname: Tasker
authors.forename: R A
authors.initials: RA
authors.lastname: Shaffer
authors.forename: M J
authors.initials: MJ
authors.lastname: Starkey
authors.forename: A
authors.initials: A
authors.lastname: Barile
authors.forename: G J
authors.initials: GJ
authors.lastname: Martin
authors.forename: N
authors.initials: N
authors.lastname: Aronson
authors.forename: W W
authors.initials: WW
authors.lastname: Emmons
authors.forename: K
authors.initials: K
authors.lastname: Stephan
authors.forename: S
authors.initials: S
authors.lastname: Bloor
authors.forename: J
authors.initials: J
authors.lastname: Vingerhoets
authors.forename: K
authors.initials: K
authors.lastname: Hertogs
authors.forename: B
authors.initials: B
authors.lastname: Larder
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004352:Drug Resistance, Microbial / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics; D005260:Female; D015751:Genes, pol; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D008875:Middle Aged; D008889:Military Personnel; D009154:Mutation; D010641:Phenotype; D012367:RNA, Viral / Q000032:analysis; D011995:Recombination, Genetic; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D014481:United States
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors