title: Effect of baseline renal function on tenofovir-containing antiretroviral therapy outcomes in Zambia.
abstract: BACKGROUND
  Although tenofovir disoproxil fumarate (TDF) use has increased as part of first-line antiretroviral therapy (ART) across sub-Saharan Africa, renal outcomes among patients receiving TDF remain poorly understood. We assessed changes in renal function and mortality in patients starting TDF- or non-TDF-containing ART in Lusaka, Zambia.
  
  
  METHODS
  We included patients aged ≥16 years who started ART from 2007 onward, with documented baseline weight and serum creatinine. Renal dysfunction was categorized as mild (estimated glomerular filtration rate [eGFR], 60-89 mL/min), moderate (30-59 mL/min), or severe (<30 mL/min) according to the chronic kidney disease-epidemiology (CKD-EPI) formula. Differences in eGFR during ART were analyzed using linear mixed-effect models. The odds of developing moderate or severe eGFR decrease and mortality were assessed using logistic and competing risk regression, respectively.
  
  
  RESULTS
  We included 62 230 adults, of which 38 716 (62.2%) initiated a TDF-based regimen. The proportion with moderate or severe renal dysfunction at baseline was lower in the TDF than in the non-TDF group (1.9% vs 4.0%). Among patients with no or mild renal dysfunction, those receiving TDF were more likely to develop moderate (adjusted odds ratio, 3.11; 95% confidence interval, 2.52-3.87) or severe (2.43; 1.80-3.28) eGFR decrease, although the incidence in such episodes was low. Among patients with moderate or severe renal dysfunction at baseline, renal function improved independently of ART regimen, and mortality rates were similar in both treatment groups.
  
  
  CONCLUSIONS
  TDF use did not attenuate renal function recovery or increase the mortality rate in patients with renal dysfunction. Further studies are needed to determine the role of routine renal function monitoring before and during ART use in Africa.
authors.affiliation: Centre for Infectious Disease Research in Zambia.
authors.forename: Lloyd
authors.initials: L
authors.lastname: Mulenga
authors.forename: Patrick
authors.initials: P
authors.lastname: Musonda
authors.forename: Albert
authors.initials: A
authors.lastname: Mwango
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Vinikoor
authors.forename: Mary-Ann
authors.initials: MA
authors.lastname: Davies
authors.forename: Aggrey
authors.initials: A
authors.lastname: Mweemba
authors.forename: Alexandra
authors.initials: A
authors.lastname: Calmy
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Stringer
authors.forename: Olivia
authors.initials: O
authors.lastname: Keiser
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: Chi
authors.forename: Gilles
authors.initials: G
authors.lastname: Wandeler
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D003404:Creatinine / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D015658:HIV Infections / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D051437:Renal Insufficiency / Q000139:chemically induced* / Q000401:mortality; D000068698:Tenofovir; D015024:Zambia
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D000068698:Tenofovir; D003404:Creatinine; D000225:Adenine
keywords: Zambia; renal function; tenofovir