title: Long term probability of detection of HIV-1 drug resistance after starting antiretroviral therapy in routine clinical practice.
abstract: BACKGROUND
  Little is known about the long term risk of development of HIV-1 drug resistance for patients starting antiretroviral therapy (ART) with three or four drug regimens in routine clinical practice.
  
  
  METHODS
  We analysed a large cohort study of patients seen in one of six large HIV clinics in and around London, UK. The focus of this analysis was on patients who started ART with two nucleosides plus either a single protease inhibitor (PI), a PI with ritonavir, abacavir or a non-nucleoside reverse transcriptase inhibitor (NNRTI).
  
  
  RESULTS
  4306 patients were followed; 1436 (33%) started with a single PI, 279 (6%) with a PI plus ritonavir, 156 (4%) with triple nucleosides and 2435 (57%) with an NNRTI. The overall cumulative risk of viral load failure was 38% by 6 years. Risk of > or =1 major IAS-USA mutation was 27% by 6 years; risk of mutations from at least two of the three main drug classes was 20% over the same period. These are lower limit estimates as test results were not available for many with viral load failure. Risk of PI mutations being detected in people who started ART with regimens containing a PI with ritonavir was significantly lower than the risk of NNRTI mutations being detected in those starting with NNRTI-containing regimens (relative hazard 0.3195% CI 0.15-0.61; p = 0.0008).
  
  
  CONCLUSIONS
  In routine practice, rates of viral load failure and of resistance detection in patients who started ART with three or four drugs are appreciable.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Phillips
authors.forename: David
authors.initials: D
authors.lastname: Dunn
authors.forename: Caroline
authors.initials: C
authors.lastname: Sabin
authors.forename: Anton
authors.initials: A
authors.lastname: Pozniak
authors.forename: Ryanne
authors.initials: R
authors.lastname: Matthias
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Geretti
authors.forename: John
authors.initials: J
authors.lastname: Clarke
authors.forename: Duncan
authors.initials: D
authors.lastname: Churchill
authors.forename: Ian
authors.initials: I
authors.lastname: Williams
authors.forename: Teresa
authors.initials: T
authors.lastname: Hill
authors.forename: Hannah
authors.initials: H
authors.lastname: Green
authors.forename: Kholoud
authors.initials: K
authors.lastname: Porter
authors.forename: George
authors.initials: G
authors.lastname: Scullard
authors.forename: Margaret
authors.initials: M
authors.lastname: Johnson
authors.forename: Philippa
authors.initials: P
authors.lastname: Easterbrook
authors.forename: Richard
authors.initials: R
authors.lastname: Gilson
authors.forename: Martin
authors.initials: M
authors.lastname: Fisher
authors.forename: Clive
authors.initials: C
authors.lastname: Loveday
authors.forename: Brian
authors.initials: B
authors.lastname: Gazzard
authors.forename: Deenan
authors.initials: D
authors.lastname: Pillay
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D015224:Dideoxynucleosides / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D012307:Risk Factors; D019438:Ritonavir / Q000627:therapeutic use; D013997:Time Factors; D019562:Viral Load; D000099227:Abacavir
chemical_list: D044966:Anti-Retroviral Agents; D015224:Dideoxynucleosides; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D019438:Ritonavir; D000099227:Abacavir