Durability of initial antiretroviral therapy in a resource-constrained setting and the potential need for zidovudine weight-based dosing
Authors
Willig, James H.Echevarria, Juan
Westfall, Andrew O.
Iglesias, David
Henostroza, German
Seas, Carlos
Mugavero, Michael J.
Allison, Jeroan J.
Paz, Jorge III
Hernandez, Fiorella
Tomatis, Cristina
Saag, Michael S.
Gotuzzo, Eduardo
UMass Chan Affiliations
Department of Quantitative Health SciencesDocument Type
Journal ArticlePublication Date
2010-01-28Keywords
AdultAnti-HIV Agents
Body Weight
Dose-Response Relationship, Drug
Drug Administration Schedule
Female
HIV Infections
Humans
Male
Middle Aged
Multivariate Analysis
Peru
Retrospective Studies
Zidovudine
Bioinformatics
Biostatistics
Epidemiology
Health Services Research
Metadata
Show full item recordAbstract
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.Source
J Acquir Immune Defic Syndr. 2010 Feb 1;53(2):215-21. Link to article on publisher's siteDOI
10.1097/QAI.0b013e3181bc0f10Permanent Link to this Item
http://hdl.handle.net/20.500.14038/47720PubMed ID
20104120Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1097/QAI.0b013e3181bc0f10