title: Trends in virological and clinical outcomes in individuals with HIV-1 infection and virological failure of drugs from three antiretroviral drug classes: a cohort study.
abstract: BACKGROUND
  Limited treatment options have been available for people with HIV who have had virological failure of the three original classes of HIV antiretroviral drugs-so-called triple-class virological failure (TCVF). However, introduction of new drugs and drug classes might have improved outcomes. We aimed to assess trends in virological and clinical outcomes for individuals with TCVF in 2000-09.
  
  
  METHODS
  In our cohort study, we analysed data for adults starting antiretroviral therapy from 1998 in cohorts participating in the PLATO II project, which is part of COHERE, a collaboration of European cohorts. TCVF was defined as virological failure to at least two nucleoside reverse transcriptase inhibitors, one non-nucleoside reverse-transcriptase inhibitor, and one ritonavir-boosted protease inhibitor, with virological failure of a drug defined as one viral-load measurement of greater than 500 copies per mL after at least 4 months of continuous use. We used multivariable generalised estimating equation logistic models and Poisson regression models to study trends in virological suppression and incidence of AIDS or death after TCVF. We adjusted for sex, transmission group, age, AIDS status, CD4 cell count, plasma viral loads at TCVF, achievement of virological response (<50 copies per mL), and number of drug failures before TCVF.
  
  
  RESULTS
  28 of 33 cohorts in COHERE contributed data to the PLATO II project, of which four had no participants eligible for inclusion in this study. 2476 (3%) of 91 764 participants from the remaining 24 cohorts had TCVF and at least one viral load measurement in 2000-09. The proportion of patients with virological response after TCVF increased from 19·5% in 2000 to 57·9% in 2009 (adjusted p<0·0001). Incidence of AIDS decreased from 7·7 per 100 person-years in 2000-02 to 2·3 in 2008 and 1·2 in 2009 (adjusted p<0·0001). Mortality decreased from 4·0 per 100 person-years between 2000 and 2002 to 1·9 in 2007 and 1·4 in 2008 (unadjusted p=0·023), but the trend was not significant after adjustment (p=0·22).
  
  
  CONCLUSIONS
  A substantial improvement in viral load suppression and accompanying decrease in the rates of AIDS in people after extensive failure to drugs from the three original antiretroviral classes during 2000-09 was probably mainly driven by availability of newer drugs with better tolerability and ease of use and small cross-resistance profiles, suggesting the public health benefit of the introduction of new drugs.
authors: Dominique
authors: D
authors: Costagliola
authors: Rebecca
authors: R
authors: Lodwick
authors: Bruno
authors: B
authors: Ledergerber
authors: Carlo
authors: C
authors: Torti
authors: Ard
authors: A
authors: van Sighem
authors: Daniel
authors: D
authors: Podzamczer
authors: Amanda
authors: A
authors: Mocroft
authors: Maria
authors: M
authors: Dorrucci
authors: Bernard
authors: B
authors: Masquelier
authors: Andrea
authors: A
authors: de Luca
authors: Klaus
authors: K
authors: Jansen
authors: Stephane
authors: S
authors: De Wit
authors: Niels
authors: N
authors: Obel
authors: Gerd
authors: G
authors: Fätkenheuer
authors: Giota
authors: G
authors: Touoloumi
authors: Cristina
authors: C
authors: Mussini
authors: Antonella
authors: A
authors: Castagna
authors: Cristoph
authors: C
authors: Stephan
authors: Federico
authors: F
authors: García
authors: Robert
authors: R
authors: Zangerle
authors: Xavier
authors: X
authors: Duval
authors: Santiago
authors: S
authors: Pérez-Hoyos
authors: Laurence
authors: L
authors: Meyer
authors: Jade
authors: J
authors: Ghosn
authors: Céline
authors: C
authors: Fabre-Colin
authors: Jesper
authors: J
authors: Kjaer
authors: Genevieve
authors: G
authors: Chene
authors: Jesper
authors: J
authors: Grarup
authors: Andrew
authors: A
authors: Phillips
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D012044:Regression Analysis; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral