title: Triple-class virologic failure in HIV-infected patients undergoing antiretroviral therapy for up to 10 years.
abstract: BACKGROUND
  Life expectancy of people with human immunodeficiency virus (HIV) is now estimated to approach that of the general population in some successfully treated subgroups. However, to attain these life expectancies, viral suppression must be maintained for decades.
  
  
  METHODS
  We studied the rate of triple-class virologic failure (TCVF) in patients within the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) who started antiretroviral therapy (ART) that included a nonnucleoside reverse-transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI/r) from 1998 onwards. We also focused on TCVF in patients who started a PI/r-containing regimen after a first-line NNRTI-containing regimen failed.
  
  
  RESULTS
  Of 45 937 patients followed up for a median (interquartile range) of 3.0 (1.5-5.0) years, 980 developed TCVF (2.1%). By 5 and 9 years after starting ART, an estimated 3.4% (95% confidence interval [CI], 3.1%-3.6%) and 8.6% (95% CI, 7.5%-9.8%) of patients, respectively, had developed TCVF. The incidence of TCVF rose during the first 3 to 4 years on ART but plateaued thereafter. There was no significant difference in the risk of TCVF according to whether the initial regimen was NNRTI or PI/r based (P = .11). By 5 years after starting a PI/r regimen as second-line therapy, 46% of patients had developed TCVF.
  
  
  CONCLUSIONS
  The rate of virologic failure of the 3 original drug classes is low, but not negligible, and does not appear to diminish over time from starting ART. If this trend continues, many patients are likely to need newer drugs to maintain viral suppression. The rate of TCVF from the start of a PI/r regimen after NNRTI failure provides a comparator for studies of response to second-line regimens in resource-limited settings.
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authors.lastname: Lodwick
authors.forename: Dominique
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authors.lastname: Costagliola
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authors.forename: Federico
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authors.lastname: Castagna
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authors.lastname: Mussini
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authors.lastname: Duval
authors.forename: José
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authors.lastname: Ramos
authors.forename: Laurence
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authors.lastname: Meyer
authors.forename: Josiane
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authors.lastname: Warsawski
authors.forename: Claire
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authors.lastname: Thorne
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authors.lastname: Masip
authors.forename: Santiago
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authors.lastname: Pérez-Hoyos
authors.forename: Deenan
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authors.lastname: Pillay
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authors.lastname: van Sighem
authors.forename: Sergio
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authors.lastname: Lo Caputo
authors.forename: Huldrych
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authors.lastname: Günthard
authors.forename: Roger
authors.initials: R
authors.lastname: Paredes
authors.forename: Andrea
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authors.lastname: De Luca
authors.forename: Dimitrios
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authors.lastname: Paraskevis
authors.forename: Céline
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authors.lastname: Fabre-Colin
authors.forename: Jesper
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authors.lastname: Kjaer
authors.forename: Genèvieve
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authors.lastname: Chêne
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authors.lastname: Lundgren
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authors.lastname: Phillips
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D005060:Europe; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D006801:Humans; D053208:Kaplan-Meier Estimate; D008017:Life Expectancy; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D019438:Ritonavir / Q000627:therapeutic use; D017211:Treatment Failure; D019562:Viral Load / Q000187:drug effects*; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D019438:Ritonavir