Durability of initial antiretroviral therapy in a resource-constrained setting and the potential need for zidovudine weight-based dosing
Department of Quantitative Health Sciences
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
Bioinformatics | Biostatistics | Epidemiology | Health Services Research
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.
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Citation: J Acquir Immune Defic Syndr. 2010 Feb 1;53(2):215-21. Link to article on publisher's site