title: Incidence of HIV-1 drug resistance among antiretroviral treatment-naive individuals starting modern therapy combinations.
abstract: BACKGROUND
  Estimates of drug resistance incidence to modern first-line combination antiretroviral therapies against human immunodeficiency virus (HIV) type 1 are complicated by limited availability of genotypic drug resistance tests (GRTs) and uncertain timing of resistance emergence.
  
  
  METHODS
  Five first-line combinations were studied (all paired with lamivudine or emtricitabine): efavirenz (EFV) plus zidovudine (AZT) (n = 524); EFV plus tenofovir (TDF) (n = 615); lopinavir (LPV) plus AZT (n = 573); LPV plus TDF (n = 301); and ritonavir-boosted atazanavir (ATZ/r) plus TDF (n = 250). Virological treatment outcomes were classified into 3 risk strata for emergence of resistance, based on whether undetectable HIV RNA levels were maintained during therapy and, if not, whether viral loads were >500 copies/mL during treatment. Probabilities for presence of resistance mutations were estimated from GRTs (n = 2876) according to risk stratum and therapy received at time of testing. On the basis of these data, events of resistance emergence were imputed for each individual and were assessed using survival analysis. Imputation was repeated 100 times, and results were summarized by median values (2.5th-97.5th percentile range).
  
  
  RESULTS
  Six years after treatment initiation, EFV plus AZT showed the highest cumulative resistance incidence (16%) of all regimens (<11%). Confounder-adjusted Cox regression confirmed that first-line EFV plus AZT (reference) was associated with a higher median hazard for resistance emergence, compared with other treatments: EFV plus TDF (hazard ratio [HR], 0.57; range, 0.42-0.76), LPV plus AZT (HR, 0.63; range, 0.45-0.89), LPV plus TDF (HR, 0.55; range, 0.33-0.83), ATZ/r plus TDF (HR, 0.43; range, 0.17-0.83). Two-thirds of resistance events were associated with detectable HIV RNA level ≤500 copies/mL during treatment, and only one-third with virological failure (HIV RNA level, >500 copies/mL).
  
  
  CONCLUSIONS
  The inclusion of TDF instead of AZT and ATZ/r was correlated with lower rates of resistance emergence, most likely because of improved tolerability and pharmacokinetics resulting from a once-daily dosage.
authors: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Switzerland. vowv@usz.uzh.ch
authors: Viktor
authors: V
authors: von Wyl
authors: Sabine
authors: S
authors: Yerly
authors: Jürg
authors: J
authors: Böni
authors: Cyril
authors: C
authors: Shah
authors: Cristina
authors: C
authors: Cellerai
authors: Thomas
authors: T
authors: Klimkait
authors: Manuel
authors: M
authors: Battegay
authors: Enos
authors: E
authors: Bernasconi
authors: Matthias
authors: M
authors: Cavassini
authors: Hansjakob
authors: H
authors: Furrer
authors: Bernard
authors: B
authors: Hirschel
authors: Pietro L
authors: PL
authors: Vernazza
authors: Bruno
authors: B
authors: Ledergerber
authors: Huldrych F
authors: HF
authors: Günthard
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents