Comparison of Tenofovir, Zidovudine, or Stavudine as Part of First-Line Antiretroviral Therapy in a ResourceLimited- Setting: A Cohort Study


Velen, K; Lewis, JJ; Charalambous, S; Grant, AD; Churchyard, GJ; Hoffmann, CJ; (2013) Comparison of Tenofovir, Zidovudine, or Stavudine as Part of First-Line Antiretroviral Therapy in a ResourceLimited- Setting: A Cohort Study. PLoS One, 8 (5). ISSN 1932-6203 DOI: https://doi.org/10.1371/journal.pone.0064459

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Abstract

Background: Tenofovir (TDF) is part of the WHO recommended first-line antiretroviral therapy (ART); however, there are limited data comparing TDF to other nucleoside reverse transcriptase inhibitors in resource-limited-settings. Using a routine workplace and community-based ART cohort in South Africa, we assessed single drug substitution, HIV RNA suppression, CD4 count increase, loss-from-care, and mortality between TDF, stavudine (d4T) 30 mg dose, and zidovudine (AZT). Methods: In a prospective cohort study we included ART naive patients aged >= 17 years-old who initiated ART containing TDF, d4T, or AZT between 2007 and 2009. For analysis of single drug substitutions we used a competing-risks time-to-event analysis; for loss-from-care, mixed-effect Poisson modeling; for HIV RNA suppression, competing-risks logistic regression; for CD4 count slope, mixed-effects linear regression; and for mortality, proportional hazards modeling. Results: Of 6,196 patients, the initial drug was TDF for 665 (11%), d4T for 4,179 (68%), and AZT for 1,352 (22%). During the first 6 months of ART, the adjusted hazard ratio for a single drug substitution was 2.3 for d4T (95% confidence interval [CI]: 0.27, 19) and 5.2 for AZT (95% CI: 1.1, 23), compared to TDF; whereas, after 6 months, it was 10 (95% CI: 5.8, 18) and 4.4 (95% CI: 2.5, 7.8) for d4T and AZT, respectively. Virologic suppression was similar by agent; however, CD4 count rise was lowest for AZT. The adjusted hazard ratio for loss-from-care, when compared to TDF, was 1.5 (95% CI: 1.1, 1.9) for d4T and 1.2 (95% CI: 1.1, 1.4) for AZT. The adjusted hazard ratio for mortality, when compared to TDF, was 2.7 (95% CI: 2.0, 3.5) and 1.4 (95% CI: 1.3, 1.5) and for d4T and AZT, respectively. Discussion: In routine care, TDF appeared to perform better than either d4T or AZT, most notably with less drug substitution and mortality than for either other agent.

Item Type: Article
Keywords: south-africa, patients lost, follow-up, hiv, lamivudine, mortality, programs, individuals, combination, didanosine
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Research Centre: Centre for Evaluation
Tropical Epidemiology Group
PubMed ID: 23691224
Web of Science ID: 319107400128
URI: http://researchonline.lshtm.ac.uk/id/eprint/1105241

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