title: Real-World Assessment of Renal and Bone Safety among Patients with HIV Infection Exposed to Tenofovir Disoproxil Fumarate-Containing Single-Tablet Regimens.
abstract: OBJECTIVE
  Tenofovir disoproxil fumarate (TDF)-containing antiretroviral regimens have been associated with an increased incidence of renal and bone adverse outcomes. Here, we estimated the real-world incidence of renal and bone adverse outcomes among patients with HIV infection receiving different TDF-containing single-tablet regimens (STRs).
  
  
  METHODS
  This cohort study used US health insurance data spanning the years 2008-2014. We identified HIV-infected patients aged ≥18 years (all HIV patients) and those with ≥6 months of continuous enrollment prior to initiating efavirenz/emtricitabine/TDF (EFV/FTC/TDF), rilpivirine/FTC/TDF (RPV/FTC/TDF) or elvitegravir/cobicistat/FTC/TDF (EVG/COBI/FTC/TDF). Renal adverse outcomes were identified using renal International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes. Bone adverse outcomes were identified using ICD-9-CM diagnosis codes for fracture. Incidence rates (IRs) and associated 95% confidence intervals (CIs) were estimated assuming a Poisson distribution, and outcomes between STRs were compared using IR ratios (IRRs) and IR differences (IRDs).
  
  
  RESULTS
  We identified 9876 and 10,383 eligible patients for the renal and fracture analyses, respectively. Observed IRs for renal adverse outcomes were 9.7, 10.5, 13.6, and 18.0 per 1000 person-years among those receiving EFV/FTC/TDF, RPV/FTC/TDF, or EVG/COBI/FTC/TDF, or all HIV patients, respectively. Corresponding values for IRs of fracture were 3.4, 3.6, 7.2, and 4.4 per 1000 person-years, respectively. Renal adverse outcomes with EFV/FTC/TDF were significantly less frequent than with EVG/COBI/FTC/TDF (IRD -3.96; 95% CI: -7.31, -1.06). No IRR differences were identified for the renal analysis. Fractures with EFV/FTC/TDF were significantly less frequent than with EVG/COBI/FTC/TDF (IRR 0.47; 95% CI: 0.27, 0.81 and IRD -3.85; 95% CI: -5.02, -2.78).
  
  
  CONCLUSIONS
  In this large real-world database, observed IRs for renal adverse outcomes with TDF-containing STRs were lower or similar to those for all HIV patients, with the lowest IRs observed among patients receiving EFV/FTC/TDF. Compared with all HIV patients, the observed IR for fracture was higher with EVG/COBI/FTC/TDF, comparable with RPV/FTC/TDF, and lower with EFV/FTC/TDF.
authors.affiliation: Global Pharmacovigilance and Epidemiology, Bristol-Myers Squibb, Pennington, New Jersey, United States of America.
authors.forename: Ella T
authors.initials: ET
authors.lastname: Nkhoma
authors.affiliation: US Health Economics and Outcomes Research, Bristol-Myers Squibb, Plainsboro, New Jersey, United States of America.
authors.forename: Lisa
authors.initials: L
authors.lastname: Rosenblatt
authors.affiliation: Research and Development, Bristol-Myers Squibb, Plainsboro, New Jersey, United States of America.
authors.forename: Joel
authors.initials: J
authors.lastname: Myers
authors.affiliation: Research and Development, Bristol-Myers Squibb, Plainsboro, New Jersey, United States of America.
authors.forename: Angelina
authors.initials: A
authors.lastname: Villasis-Keever
authors.affiliation: Global Pharmacovigilance and Epidemiology, Bristol-Myers Squibb, Hopewell, New Jersey, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Coumbis
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D001847:Bone Diseases / Q000453:epidemiology* / Q000209:etiology*; D015897:Comorbidity; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D007674:Kidney Diseases / Q000453:epidemiology* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D012307:Risk Factors; D013607:Tablets; D000068698:Tenofovir / Q000009:adverse effects* / Q000627:therapeutic use; D014481:United States / Q000453:epidemiology
chemical_list: D018894:Reverse Transcriptase Inhibitors; D013607:Tablets; D000068698:Tenofovir