title: Increased regimen durability in the era of once-daily fixed-dose combination antiretroviral therapy.
abstract: BACKGROUND
  Data on initial antiretroviral regimen longevity predates the arrival of newer nucleoside reverse transcriptase inhibitor backbones and once-daily regimens. Modern regimens are thought to possess greater tolerability and convenience. We hypothesized this would translate into greater durability.
  
  
  METHODS
  Retrospective study of antiretroviral-naive patients starting treatment at the University of Alabama at Birmingham 1917 HIV/AIDS Clinic 1 January 2000-31 July 2007. Two periods of antiretroviral initiation were identified, prior and after August 2004 (arrival of once-daily fixed-dose regimens). Kaplan-Meier survival analyses of regimen durability by time period and regimen characteristics were performed. Staged Cox proportional hazards models evaluated the roles of dosing complexity and composition in explaining differences in regimen durability between study periods.
  
  
  RESULTS
  Overall 542 patients started antiretroviral drugs (n = 309, January 2000-July 2004; n = 233, August 2004-July 2007). Median durability was 263 days longer in after August 2004 regimens. Regimens started before August 2004 had increased hazards for discontinuation relative to after August 2004 regimens [hazard ratio (HR) = 1.44; 95% confidence interval (CI) = 1.03-2.02]. Time period of initiation lost statistical significance when the model included dosing frequency (HR = 1.92 for at least twice daily vs. daily; 95% CI = 1.29-2.88). As regimen composition variables were added, time period and dosing frequency lost significance. Increased hazards of discontinuation were observed with didanosine or stavudine relative to abacavir or tenofovir use (HR = 1.92; 95% CI = 1.29-2.88) and all third drugs compared with non-nucleoside reverse transcriptase inhibitor-based regimens (triple-nucleoside reverse transcriptase inhibitor HR = 1.76; 95% CI = 1.14-2.73; unboosted-protease inhibitor HR = 1.58; 95% CI = 1.02-2.46; boosted-protease inhibitor HR = 1.57; 95% CI = 1.02-2.41). Affective mental health disorders increased the hazard of discontinuation in all models.
  
  
  CONCLUSIONS
  Durability of contemporary once-daily fixed-dose antiretroviral regimens has significantly eclipsed the duration of earlier antiretroviral drug options. Our results indicate this is due to both more convenient dosing and improved tolerability of modern antiretroviral regimens.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA. jwillig@uab.edu
authors.forename: James H
authors.initials: JH
authors.lastname: Willig
authors.forename: Sarah
authors.initials: S
authors.lastname: Abroms
authors.forename: Andrew O
authors.initials: AO
authors.lastname: Westfall
authors.forename: Justin
authors.initials: J
authors.lastname: Routman
authors.forename: Sunil
authors.initials: S
authors.lastname: Adusumilli
authors.forename: Mohit
authors.initials: M
authors.lastname: Varshney
authors.forename: Jeroan
authors.initials: J
authors.lastname: Allison
authors.forename: Ashlee
authors.initials: A
authors.lastname: Chatham
authors.forename: James L
authors.initials: JL
authors.lastname: Raper
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kaslow
authors.forename: Michael S
authors.initials: MS
authors.lastname: Saag
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mugavero
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D004812:Epidemiologic Methods; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors
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