title: Comparative effectiveness of tenofovir in HIV-infected treatment-experienced patients: systematic review and meta-analysis.
abstract: Antiretroviral therapy (ART) regimens for HIV infection are frequently changed. We conducted a systematic review of randomized trials (RCTs) on the benefits and harms of switching to tenofovir disoproxil fumarate (TDF)-based regimens in ART-experienced patients.
  
  
  
  We included RCTs in HIV-infected adults comparing switching to a TDF-containing regimen with maintaining or switching to another regimen. We searched MEDLINE, EMBASE, CENTRAL, LILACS, SCI, and the WHO Global Health Library. We assessed bias with the Cochrane tool and synthesized data using random-effects meta-analyses and Peto's approach. For further analyses, we added data from a previous systematic review in treatment-naïve patients.
  
  
  
  17 RCTs with 2210 patients were included. All but one study had a high risk of bias. There was no significant association of switching to TDF-based regimens with mortality, fractures, CD4-cell count, body fat, virological failure, LDL-, and HDL-cholesterol. TDF-based regimens decreased total cholesterol (mean difference -12.05 mg/dL; 95% CI -20.76 to -3.34), trigylcerides (-14.33 mg/dL; -23.73 to -4.93), and bone mineral density (BMD; hip: -2.46%; -3.9 to -1.03; lumbar spine -1.52%; -2.69 to -0.34). Effects on estimated glomerular filtration (eGFR) were inconsistent and depended on the measurement. Adding 22 RCTs from 8297 treatment-naïve patients gave consistent results with then significant reductions of LDL (-7.57 mg/dL; -10.37 to -4.78), HDL (-2.38 mg/dL; -3.83 to -0.93), and eGFR (-3.49 ml/min; -5.56 to -1.43).
  
  
  
  Switching to TDF-based regimens is associated with reductions of BMD and lipid levels and possibly lowered kidney function. The evidence is limited by the high risk of bias.
authors.affiliation: a Basel Institute for Clinical Epidemiology & Biostatistics , University Hospital Basel , Basel , Switzerland.
authors.forename: Hannah
authors.initials: H
authors.lastname: Ewald
authors.affiliation: a Basel Institute for Clinical Epidemiology & Biostatistics , University Hospital Basel , Basel , Switzerland.|b Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation , Rio de Janeiro , Brazil.
authors.forename: Marilia
authors.initials: M
authors.lastname: Santini-Oliveira
authors.affiliation: a Basel Institute for Clinical Epidemiology & Biostatistics , University Hospital Basel , Basel , Switzerland.
authors.forename: Julian-Emanuel
authors.initials: JE
authors.lastname: Bühler
authors.affiliation: c Division of Infectious Diseases and Hospital Hygiene , University Hospital Basel , Basel , Switzerland.|d Department of Clinical Epidemiology and Biostatistics , McMaster University , Hamilton , Canada.
authors.forename: Danielle
authors.initials: D
authors.lastname: Vuichard
authors.affiliation: a Basel Institute for Clinical Epidemiology & Biostatistics , University Hospital Basel , Basel , Switzerland.|d Department of Clinical Epidemiology and Biostatistics , McMaster University , Hamilton , Canada.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schandelmaier
authors.affiliation: c Division of Infectious Diseases and Hospital Hygiene , University Hospital Basel , Basel , Switzerland.
authors.forename: Marcel
authors.initials: M
authors.lastname: Stöckle
authors.affiliation: a Basel Institute for Clinical Epidemiology & Biostatistics , University Hospital Basel , Basel , Switzerland.|d Department of Clinical Epidemiology and Biostatistics , McMaster University , Hamilton , Canada.|e Department of Clinical Research , University of Basel , Basel , Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Briel
authors.affiliation: a Basel Institute for Clinical Epidemiology & Biostatistics , University Hospital Basel , Basel , Switzerland.
authors.forename: Heiner C
authors.initials: HC
authors.lastname: Bucher
authors.affiliation: a Basel Institute for Clinical Epidemiology & Biostatistics , University Hospital Basel , Basel , Switzerland.
authors.forename: Lars G
authors.initials: LG
authors.lastname: Hemkens
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers; D015519:Bone Density / Q000187:drug effects; D018791:CD4 Lymphocyte Count; D050723:Fractures, Bone / Q000209:etiology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000097:blood; D017594:Publication Bias; D016032:Randomized Controlled Trials as Topic; D019233:Retreatment; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068698:Tenofovir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D015415:Biomarkers; D008055:Lipids; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir
keywords: Antiretroviral-experienced; HIV; Meta-analysis; Tenofovir