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Durability of initial antiretroviral therapy in a resource-constrained setting and the potential need for zidovudine weight-based dosing
Quantitative Health Sciences Publications and Presentations
  • James H. Willig, University of Alabama
  • Juan Echevarria, Universidad Peruana Cayetano Heredia
  • Andrew O. Westfall, University of Alabama
  • David Iglesias, Universidad Peruana Cayetano Heredia
  • German Henostroza, University of Alabama
  • Carlos Seas, Universidad Peruana Cayetano Heredia
  • Michael J. Mugavero, University of Alabama
  • Jeroan J. Allison, University of Massachusetts Medical School
  • Jorge Paz, III, Universidad Peruana Cayetano Heredia
  • Fiorella Hernandez, Universidad Peruana Cayetano Heredia
  • Cristina Tomatis, Universidad Peruana Cayetano Heredia
  • Michael S. Saag, University of Alabama
  • Eduardo Gotuzzo, Hospital Cayetano Heredia
UMMS Affiliation
Department of Quantitative Health Sciences
Date
1-28-2010
Document Type
Article
Medical Subject Headings
Adult; Anti-HIV Agents; Body Weight; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; HIV Infections; Humans; Male; Middle Aged; Multivariate Analysis; Peru; Retrospective Studies; Zidovudine
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.
Rights and Permissions
Citation: J Acquir Immune Defic Syndr. 2010 Feb 1;53(2):215-21. Link to article on publisher's site
Related Resources
Link to Article in PubMed
Citation Information
James H. Willig, Juan Echevarria, Andrew O. Westfall, David Iglesias, et al.. "Durability of initial antiretroviral therapy in a resource-constrained setting and the potential need for zidovudine weight-based dosing" Vol. 53 Iss. 2 (2010) ISSN: 1525-4135 (Linking)
Available at: http://works.bepress.com/jeroan_allison/77/