title: Durability of initial antiretroviral therapy in a resource-constrained setting and the potential need for zidovudine weight-based dosing.
abstract: BACKGROUND
  Whereas access to antiretroviral therapy (ART) for HIV-infected individuals in the developing world is increasing, data on factors impacting initial regimen durability are lacking.
  
  
  METHODS
  Retrospective review patients starting initial ART at Instituto de Medicine Tropical (Lima, Peru) April 1, 2004 to December 30, 2007. Survival methods (Kaplan-Meier, Cox proportional hazard) assessed factors associated with regimen durability including an interaction term between nucleoside reverse transcriptase inhibitor backbone and time.
  
  
  RESULTS
  Decreased initial regimen durability was observed with weight <60 kg [hazards ratio (HR) = 1.77; 95% confidence interval (CI) = 1.25-2.51], CD4 <200 (HR = 1.73; 95% CI = 1.03-2.91), and zidovudine (AZT) use at <120 days (HR = 2.09; 95% CI = 1.22-3.57). In contrast, after 120 days, AZT use decreased risk of discontinuation (HR = 0.52; 95% CI = 0.28-0.95). Early (<120 days) toxicity-related discontinuation of AZT containing regimens was observed in 44% of patients <50 kg at baseline vs. 14% of those >70 kg. An increased risk of early toxicity-related discontinuation of AZT-containing regimens was observed for baseline weight <60 kg (HR = 2.52; 95% CI = 1.46-4.35).
  
  
  CONCLUSIONS
  Lower baseline weight and lower CD4 values at ART initiation were associated with decreased regimen durability. Compared with didanosine/stavudine, AZT use initially increased, then subsequently (>120 days) lowered hazards for regimen discontinuation. Weight <60 kg was associated with an increased risk of toxicity-related AZT discontinuation. As ART use expands globally, further study into maximally durable, least toxic regimens, and the role of weight-based AZT dosing is imperative.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, AL, USA. jwillig@uab.edu
authors.forename: James H
authors.initials: JH
authors.lastname: Willig
authors.forename: Juan
authors.initials: J
authors.lastname: Echevarria
authors.forename: Andrew O
authors.initials: AO
authors.lastname: Westfall
authors.forename: David
authors.initials: D
authors.lastname: Iglesias
authors.forename: German
authors.initials: G
authors.lastname: Henostroza
authors.forename: Carlos
authors.initials: C
authors.lastname: Seas
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mugavero
authors.forename: Jeroan
authors.initials: J
authors.lastname: Allison
authors.forename: Jorge
authors.initials: J
authors.lastname: Paz
authors.forename: Fiorella
authors.initials: F
authors.lastname: Hernandez
authors.forename: Cristina
authors.initials: C
authors.lastname: Tomatis
authors.forename: Michael S
authors.initials: MS
authors.lastname: Saag
authors.forename: Eduardo
authors.initials: E
authors.lastname: Gotuzzo
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000494:pharmacology*; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010568:Peru / Q000453:epidemiology; D012189:Retrospective Studies; D015215:Zidovudine / Q000191:economics / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D015215:Zidovudine