title: Time trends in primary HIV-1 drug resistance among recently infected persons.
abstract: BACKGROUND
  Transmission of multiclass drug-resistant human immunodeficiency virus type 1 (HIV-1) may increase with wider use of antiretroviral therapy.
  
  
  OBJECTIVE
  To determine trends in prevalence of HIV-1 drug resistance among recently infected individuals in a geographic area with a high penetration of antiviral treatment.
  
  
  METHODS
  Consecutive case series of 225 patients referred to a San Francisco, Calif, hospital with recent HIV-1 infection from June 1996 through June 2001.
  
  
  METHODS
  Time trends in the prevalence of genotypic and phenotypic primary drug resistance.
  
  
  RESULTS
  Mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) steadily increased from 0% in 1996-1997 to 12 (13.2%) in 2000-2001 (P =.01). There was 1 mutation associated with protease inhibitor resistance in 1996-1997 (2.5%) and there were 7 (7.7%) in 2000-2001 (P =.25). Genotypic resistance to nucleoside reverse transcriptase inhibitors (NRTIs) initially decreased and then returned to prior levels (P =.007 for test of homogeneity). Genotypic resistance to 2 or more classes of drugs increased from 1 (2.5%) to 12 (13.2%) (P =.004), but only 1 infection (1.2%) in the latter period was resistant to all 3 classes of agents (P =.58). Primary phenotypic resistance decreased for NRTIs from 21% to 6.2% (P =.03) and increased for NNRTIs from 0 to 8 (9.9%) (P =.02). Phenotypic resistance increased for protease inhibitors from 2.6% to 6.2% (P =.32). Median time to virologic suppression (<500 copies/mL) during therapy was 12 weeks for patients with genotypic evidence of resistance compared with 5 weeks for patients with drug-sensitive infections (P =.02).
  
  
  CONCLUSIONS
  The frequency of primary resistance to NNRTIs is increasing, although resistance to all available classes of antiretroviral therapy remains rare. Genotypic resistance testing in recently infected persons predicts time to viral suppression during therapy.
authors.affiliation: Gladstone Institute of Virology and Immunology, PO Box 914100, San Francisco, CA 94141, USA. rgrant@itsa.ucsf.edu
authors.forename: Robert M
authors.initials: RM
authors.lastname: Grant
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Hecht
authors.forename: Maria
authors.initials: M
authors.lastname: Warmerdam
authors.forename: Lea
authors.initials: L
authors.lastname: Liu
authors.forename: Teri
authors.initials: T
authors.lastname: Liegler
authors.forename: Christos J
authors.initials: CJ
authors.lastname: Petropoulos
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Hellmann
authors.forename: Margaret
authors.initials: M
authors.lastname: Chesney
authors.forename: Michael P
authors.initials: MP
authors.lastname: Busch
authors.forename: James O
authors.initials: JO
authors.lastname: Kahn
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008297:Male; D009154:Mutation; D010641:Phenotype; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D012495:San Francisco / Q000453:epidemiology; D016019:Survival Analysis; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors