title: Determinants of virological failure after successful viral load suppression in first-line highly active antiretroviral therapy.
abstract: BACKGROUND
  We aimed to investigate the long-term virological outcomes of a cohort initially showing good responses to first-line highly active antiretroviral therapy (HAART) with no evidence ofvirological failure during the first year after achieving viral load (VL) undetectability (<50 copies/ml).
  
  
  METHODS
  Virological failure was defined as a confirmed VL >400 copies/ml or a single VL >400 copies/ml followed by a treatment change or end of follow-up. Risk factors for low-level VL rebound (50-400 copies/ml) in the first year after achieving undetectability and for virological failure during subsequent follow-up were investigated by logistic and Poisson regression.
  
  
  RESULTS
  In the first year after achieving VL undetectability, 354/1386 (25.5%) patients experienced low-level VL rebound, the remaining patients maintained consistent undetectability. Low-level rebound occurred less commonly with non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART than with other regimens (P = 0.01). Over median 2.2 (range 0.0-7.4) years of subsequent follow-up, 86 (6.2%) patients experienced virological failure, corresponding to 2.30 failures per 100 person-years (95% confidence interval [CI] 1.82-2.79). Independent predictors of virological failure included low-level rebound during the first year after achieving undetectability relative to consistent undetectability (rate ratio [RR] 2.18, 95%0 CI 1.15-4.10), female gender (RR 1.79, 95% CI 1.12-2.85) and receiving a ritonavir-boosted protease inhibitor (Pl/r) relative to NNRTI-based HAART (RR 1.88, 95% CI 1.02-3.46).
  
  
  CONCLUSIONS
  Patients on first-line HAART who maintain consistent VL undetectability for 1 year have a low risk of subsequent virological failure. A subset might benefit from targeted interventions, including women and patients on Pl/r-based HAART.
authors.affiliation: Royal Free and University College Medical School, London, UK. a.geretti@medsch.ucl.ac.uk
authors.forename: Anna M
authors.initials: AM
authors.lastname: Geretti
authors.forename: Colette
authors.initials: C
authors.lastname: Smith
authors.forename: Annette
authors.initials: A
authors.lastname: Haberl
authors.forename: Ana
authors.initials: A
authors.lastname: Garcia-Diaz
authors.forename: Gaia
authors.initials: G
authors.lastname: Nebbia
authors.forename: Margaret
authors.initials: M
authors.lastname: Johnson
authors.forename: Andrew
authors.initials: A
authors.lastname: Phillips
authors.forename: Schlomo
authors.initials: S
authors.lastname: Staszewski
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D008297:Male; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D012307:Risk Factors; D012737:Sex Factors; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors