title: Relationship of injection drug use, antiretroviral therapy resistance, and genetic diversity in the HIV-1 pol gene.
abstract: OBJECTIVE
  To determine if a history of injection drug use influences genotypic protease inhibitor (PI) resistance to antiretroviral agents.
  
  
  METHODS
  We assessed the presence of resistance mutations in PI-naive injection drug users (IDUs) and non-IDUs participating in the Women's Interagency HIV Study. Eighteen HIV-infected participants who reported injection drug use before study enrollment and 32 HIV-infected non-IDUs contributed a total of 34 and 65 person-visits, respectively, to analyses.
  
  
  RESULTS
  Based on data from multiple clones obtained from different time points from each individual, we determined that primary PI resistance mutations were more frequent among person visits contributed by IDUs (24%) than non-IDUs (8%, P = 0.05). Although neither reached statistical significance, diversity was higher within the protease region among study visits carrying PI-resistant clones at both the nucleotide level (2.66 vs. 2.35; P = 0.08) and at the amino acid level (1.60 vs. 1.32; P = 0.23). Most of the primary resistance mutations could not be detected using the standard population sequencing employed in the clinical setting. Five of 6 individuals in whom clones encoding PI resistance mutations were identified failed PI-containing highly active antiretroviral therapy within 12 months of therapy initiation.
  
  
  CONCLUSIONS
  Our findings indicate that more aggressive sampling for resistance mutations among viral clones before highly active antiretroviral therapy initiation might permit selection of more effective treatment, particularly in IDUs.
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Kowalski
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Gange
authors.forename: Michael F
authors.initials: MF
authors.lastname: Schneider
authors.forename: Hua-Ling
authors.initials: HL
authors.lastname: Tsai
authors.forename: Alan
authors.initials: A
authors.lastname: Templeton
authors.forename: Qiujia
authors.initials: Q
authors.lastname: Shao
authors.forename: Guang Wen
authors.initials: GW
authors.lastname: Zhang
authors.forename: Mei-Fen
authors.initials: MF
authors.lastname: Yeh
authors.forename: Mary
authors.initials: M
authors.lastname: Young
authors.forename: Richard B
authors.initials: RB
authors.lastname: Markham
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D015751:Genes, pol; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D015819:Substance Abuse, Intravenous / Q000150:complications*
chemical_list: D019380:Anti-HIV Agents