title: Plasma HIV-1 RNA detection below 50 copies/ml and risk of virologic rebound in patients receiving highly active antiretroviral therapy.
abstract: BACKGROUND
  Plasma human immunodeficiency virus type 1 (HIV-1) RNA suppression <50 copies/mL is regarded as the optimal outcome of highly active antiretroviral therapy (HAART). Current viral load (VL) assays show increased sensitivity, but the significance of RNA detection <50 copies/mL is unclear.
  
  
  METHODS
  This study investigated the virologic outcomes of 1247 patients with VL <50 copies/mL at an arbitrary time point during HAART (= T0), according to whether the actual, unreported (T0)VL was 40-49 copies/mL, RNA detected <40 copies/mL (RNA(+)), or RNA not detected (RNA(-)), as measured by the Abbott Real Time assay. Predictors of rebound >50 and >400 copies/mL over 12 months following T0 were analyzed with Cox proportional hazards models incorporating the (T0)VL and demographic and clinical data.
  
  
  RESULTS
  Rebound rates >50 copies/mL were 34.2% for (T0)VL 40-49 copies/mL, 11.3% for RNA(+), and 4.0% for RNA(-); rebound rates >400 copies/mL were 13.0%, 3.8%, and 1.2%, respectively. The adjusted hazard ratios for rebound >50 copies/mL were 4.67 (95% confidence interval, 2.91-7.47; P < .0001) and 1.97 (1.25-3.11; P < .0001) with (T0)VL 40-49 copies/mL and RNA(+), respectively, relative to RNA(-), and 6.91 (2.90-16.47; P < .0001) and 2.88 (1.24-6.69; P < .0001), respectively, for rebound >400 copies/mL. The association was independent of adherence levels.
  
  
  CONCLUSIONS
  In treated patients monitored by RealTime, a VL of 40-49 copies/mL and, to a lesser extent, RNA detection <40 copies/mL predict rebound >50 and >400 copies/mL independently of other recognized determinants. The goal of HAART may need to be revised to a lower cutoff than 50 copies/mL.
authors.affiliation: Department of Virology, Royal Free Hampstead NHS Trust, and Department of Virology, UCL Medical School, London, United Kingdom.
authors.forename: Tomas
authors.initials: T
authors.lastname: Doyle
authors.forename: Colette
authors.initials: C
authors.lastname: Smith
authors.forename: Paola
authors.initials: P
authors.lastname: Vitiello
authors.forename: Valentina
authors.initials: V
authors.lastname: Cambiano
authors.forename: Margaret
authors.initials: M
authors.lastname: Johnson
authors.forename: Andrew
authors.initials: A
authors.lastname: Owen
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Phillips
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Geretti
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral