title: Comparison of tenofovir, zidovudine, or stavudine as part of first-line antiretroviral therapy in a resource-limited-setting: a cohort study.
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 naïve 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Aurum Institute, Johannesburg, South Africa.
authors.forename: Kavindhran
authors.initials: K
authors.lastname: Velen
authors.forename: James J
authors.initials: JJ
authors.lastname: Lewis
authors.forename: Salome
authors.initials: S
authors.lastname: Charalambous
authors.forename: Alison D
authors.initials: AD
authors.lastname: Grant
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Churchyard
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Hoffmann
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D006678:HIV / Q000187:drug effects / Q000502:physiology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D006295:Health Resources / Q000600:supply & distribution*; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000494:pharmacology / Q000627:therapeutic use; D012367:RNA, Viral / Q000378:metabolism; D012111:Residence Characteristics; D018119:Stavudine / Q000494:pharmacology / Q000627:therapeutic use; D000068698:Tenofovir; D055815:Young Adult; D015215:Zidovudine / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D012367:RNA, Viral; D015215:Zidovudine; D000068698:Tenofovir; D018119:Stavudine; D000225:Adenine