title: Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): a European multicohort study.
abstract: BACKGROUND
  The effect of transmitted drug resistance (TDR) on first-line combination antiretroviral therapy (cART) for HIV-1 needs further study to inform choice of optimum drug regimens. We investigated the effect of TDR on outcome in the first year of cART within a large European collaboration.
  
  
  METHODS
  HIV-infected patients of any age were included if they started cART (at least three antiretroviral drugs) for the first time after Jan 1, 1998, and were antiretroviral naive and had at least one sample for a genotypic test taken before the start of cART. We used the WHO drug resistance list and the Stanford algorithm to classify patients into three resistance categories: no TDR, at least one mutation and fully-active cART, or at least one mutation and resistant to at least one prescribed drug. Virological failure was defined as time to the first of two consecutive viral load measurements over 500 copies per mL after 6 months of therapy.
  
  
  RESULTS
  Of 10,056 patients from 25 cohorts, 9102 (90·5%) had HIV without TDR, 475 (4·7%) had at least one mutation but received fully-active cART, and 479 (4·8%) had at least one mutation and resistance to at least one drug. Cumulative Kaplan-Meier estimates for virological failure at 12 months were 4·2% (95% CI 3·8-4·7) for patients in the no TDR group, 4·7% (2·9-7·5) for those in the TDR and fully-active cART group, and 15·1% (11·9-19·0) for those in the TDR and resistant group (log-rank p<0·0001). The hazard ratio for the difference in virological failure between patients with TDR and resistance to at least one drug and those without TDR was 3·13 (95% CI 2·33-4·20, p<0·0001). The hazard ratio for the difference between patients with TDR receiving fully-active cART and patients without TDR was 1·47 (95% CI 0·19-2·38, p=0·12). In stratified analysis, the hazard ratio for the risk of virological failure in patients with TDR who received fully-active cART that included a non-nucleoside reverse transcriptase inhibitor (NNRTI) compared with those without TDR was 2·0 (95% CI 0·9-4·7, p=0·093).
  
  
  CONCLUSIONS
  These findings confirm present treatment guidelines for HIV, which state that the initial treatment choice should be based on resistance testing in treatment-naive patients.
  
  
  BACKGROUND
  European Community's Seventh Framework Programme FP7/2007-2013 and Gilead.
authors.affiliation: INSERM U897 Centre of Epidemiology and Biostatistics, ISPED Bordeaux School of Public Health, University Bordeaux Segalen, Bordeaux, France. linda.wittkop@isped.u-bordeaux2.fr
authors.forename: Linda
authors.initials: L
authors.lastname: Wittkop
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
authors.forename: Frank
authors.initials: F
authors.lastname: de Wolf
authors.forename: David
authors.initials: D
authors.lastname: Dunn
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cozzi-Lepri
authors.forename: Andrea
authors.initials: A
authors.lastname: de Luca
authors.forename: Claudia
authors.initials: C
authors.lastname: Kücherer
authors.forename: Niels
authors.initials: N
authors.lastname: Obel
authors.forename: Viktor
authors.initials: V
authors.lastname: von Wyl
authors.forename: Bernard
authors.initials: B
authors.lastname: Masquelier
authors.forename: Christoph
authors.initials: C
authors.lastname: Stephan
authors.forename: Carlo
authors.initials: C
authors.lastname: Torti
authors.forename: Andrea
authors.initials: A
authors.lastname: Antinori
authors.forename: Federico
authors.initials: F
authors.lastname: García
authors.forename: Ali
authors.initials: A
authors.lastname: Judd
authors.forename: Kholoud
authors.initials: K
authors.lastname: Porter
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Thiébaut
authors.forename: Hannah
authors.initials: H
authors.lastname: Castro
authors.forename: Ard I
authors.initials: AI
authors.lastname: van Sighem
authors.forename: Céline
authors.initials: C
authors.lastname: Colin
authors.forename: Jesper
authors.initials: J
authors.lastname: Kjaer
authors.forename: Jens D
authors.initials: JD
authors.lastname: Lundgren
authors.forename: Roger
authors.initials: R
authors.lastname: Paredes
authors.forename: Anton
authors.initials: A
authors.lastname: Pozniak
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Andrew
authors.initials: A
authors.lastname: Phillips
authors.forename: Deenan
authors.initials: D
authors.lastname: Pillay
authors.forename: Geneviève
authors.initials: G
authors.lastname: Chêne
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005060:Europe / Q000453:epidemiology; D005260:Female; D006678:HIV / Q000187:drug effects* / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019562:Viral Load; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents