title: Impact of transmitted drug-resistance on treatment selection and outcome of first-line Highly Active Antiretroviral Therapy (HAART).
abstract: OBJECTIVE
  The study aim was to determine how resistance testing influences outcome of first-line highly active antiretroviral therapy (HAART) in routine practice in the United Kingdom.
  
  
  METHODS
  The prevalence of transmitted drug resistance and the genotypic sensitivity score (GSS) of first-line HAART regimens were determined using data from the UK Collaborative HIV Cohort(CHIC) Study. Factors associated with starting a regimen with a reduced GSS and subsequent virological responses were analyzed by logistic and Cox regression.
  
  
  RESULTS
  Amongst patients tested in 1999–2006, 116 of 1175 (10%) had $1 resistance mutation; 64 patients (5.4%) had $1 mutation associated with resistance to drugs in the initial HAART regimen and 54 (4.6%) showed a GSS, 3. Factors independently associated with a GSS, 3 were starting HAART in 1999–2001 vs. 2004–2006 (odds ratio = 2.63; 95% confidence interval: 1.19 to 5.83) and use of ritonavir-boosted protease inhibitor (PI/r)–based vs. nonnucleoside reverse transcriptase inhibitor–based regimens (1.97; 1.06 to 3.64). AGSS .3 was independently associated with virological suppression(hazard ratio for GSS, 3 = 0.60; 95% confidence interval 0.41 to 0.87).
  
  
  CONCLUSIONS
  Most patients starting HAART after undergoing resistance testing received regimens with a GSS $3. PI/r-based therapy was often selected in patients with resistance to the nucleoside reverse transcriptase inhibitor backbone. Low GSS predicted poor virological suppression and the association persisted after adjusting for PI/r use.
authors.affiliation: HIV Epidemiology nad Biostatistics Group, Research Department of Infection and Population Health, Division of Population Health, Hampstead Campus, University College Medical School, University College London, Rowland Street, NW3 2PF, London, United Kingdom. l.bansi@pcps.ucl.ac.uk
authors.forename: Loveleen
authors.initials: L
authors.lastname: Bansi
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Geretti
authors.forename: David
authors.initials: D
authors.lastname: Dunn
authors.forename: Teresa
authors.initials: T
authors.lastname: Hill
authors.forename: Hannah
authors.initials: H
authors.lastname: Green
authors.forename: Esther
authors.initials: E
authors.lastname: Fearnhill
authors.forename: Brian
authors.initials: B
authors.lastname: Gazzard
authors.forename: Mark
authors.initials: M
authors.lastname: Nelson
authors.forename: Kholoud
authors.initials: K
authors.lastname: Porter
authors.forename: Andrew
authors.initials: A
authors.lastname: Phillips
authors.forename: Caroline
authors.initials: C
authors.lastname: Sabin
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D008297:Male; D015995:Prevalence; D012008:Recurrence; D016896:Treatment Outcome; D019562:Viral Load