title: Second-line protease inhibitor-based antiretroviral therapy after non-nucleoside reverse transcriptase inhibitor failure: the effect of a nucleoside backbone.
abstract: BACKGROUND
  Virological failures on combined antiretroviral therapy still occur. Boosted protease inhibitor ( Pl/r)- based therapy is a commonly used option after non-nucleoside reverse transcriptase inhibitor ( NNRTI) failure, but whether two fully active nucleoside reverse transciptase inhibitors (NRTIs) are required is unknown. We investigated the effect of an NRTI backbone in individuals receiving Pl/r after failing NNRTI-based combined antiretroviral therapy.
  
  
  METHODS
  A longitudinal analysis of the UK Collaborative HIV Cohort (CHIC) and the UK HIV Drug Resistance Database to identify individuals who failed first-line NNRTI and two NRTIs, and switched to Pl/r-based therapy between January 1999 and December 2008 was conducted. We investigated the effect of NRTI on suppression.
  
  
  RESULTS
  In total, 470 individuals met study criteria: 19.6%, 34.5% and 46.0% started 0, 1 or ≥ 2 NRTIs, respectively. Median CD4+ T-cell count was 223 cells/mm3 and HIV-RNA was 4.3 log10 copies/ml; 246 (52.3%) underwent genotyping before switch. virological failure occurred in 10.9% and 13% after 48 and 96 weeks, respectively. In multivariable analysis, heterosexual risk group and HIV RNA were independently associated with virological failure; higher CD4+ T-cell count was protective (HR= 0.92). Number of new NRTIs or genotypic sensitivity score of backbone had no effect on treatment success rates when modelled as categorical or continuous variables.
  
  
  CONCLUSIONS
  Successful treatment with a second-line Pl/r may not require two active NRTIs. If replicated in clinincal trials, these findings could guide future recommendations.
authors: Department of GU/ HIV Medicine, Mortimer Market Centre, London, UK. lwaters@nhs.net
authors: Laura
authors: L
authors: Waters
authors: Loveleen
authors: L
authors: Bansi
authors: David
authors: D
authors: Asboe
authors: Anton
authors: A
authors: Pozniak
authors: Erasmus
authors: E
authors: Smit
authors: Chloe
authors: C
authors: Orkin
authors: Esther
authors: E
authors: Fearnhill
authors: David
authors: D
authors: Dunn
authors: Andrew
authors: A
authors: Phillips
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D012307:Risk Factors; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors