Tenofovir-Associated Bone Adverse Outcomes among a US National Historical Cohort of HIV-Infected Veterans

Risk Modification by Concomitant Antiretrovirals

Joanne LaFleur, Adam P. Bress, Joel Myers, Lisa Rosenblatt, Jacob Crook, Kristin Knippenberg, Roger Bedimo, Pablo Tebas, Heather Nyman, Stephen Esker

Research output: Contribution to journalArticle

Abstract

Introduction: Tenofovir disoproxil fumarate (TDF) has been associated with greater incidences of bone complications, which might be modified by some concomitantly administered antiretrovirals, possibly by their effect on tenofovir concentrations. We compared bone adverse outcomes among treatment-naïve HIV-infected US veterans initiating efavirenz (EFV)-containing TDF/emtricitabine (FTC) regimens versus those initiating non-EFV-containing TDF/FTC regimens. Methods: Using national Veterans Health Administration clinical and administrative data sets, we identified a cohort of treatment-naïve HIV-infected veterans without bone disease who initiated therapy with TDF/FTC plus EFV, rilpivirine, elvitegravir/cobicistat, or ritonavir-boosted protease inhibitors in 2003–2015. The primary composite adverse bone outcome was the unadjusted incidence rate (IR) of osteoporosis, osteopenia, or fragility fracture (any hip, wrist, or spine fracture). To account for selection bias and confounding, we used inverse probability of treatment-weighted Cox proportional hazards regression models to calculate adjusted hazard ratios (HRs) for each outcome associated with EFV + TDF/FTC versus each non-EFV-containing TDF/FTC regimen. Results: Of 33,048 HIV-positive veterans, 7161 initiated a TDF/FTC-containing regimen (mean age, 50 years; baseline CD4 < 200 cells/mm3, 33.3%; HIV-1 RNA > 100,000 copies/ml, 22.3%; mean follow-up, 13.0 months). Of these, 4137 initiated EFV- and 3024 non-EFV-containing regimens. Veterans initiating EFV- versus non-EFV-containing TDF/FTC regimens had a lower IR of the composite bone outcome (29.3 vs. 41.4 per 1000 patient-years), with significant risk reductions for this outcome [HR, 0.69; 95% confidence interval (CI), 0.58–0.83] and fragility fracture (HR, 0.59; 95% CI, 0.44–0.78). Conclusion: EFV + TDF/FTC is associated with a lower risk of adverse bone outcomes compared with other TDF-containing regimens in the VHA. Funding: Bristol-Myers Squibb.

Original languageEnglish (US)
Pages (from-to)293-308
Number of pages16
JournalInfectious Diseases and Therapy
Volume7
Issue number2
DOIs
StatePublished - Jun 1 2018

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Tenofovir
efavirenz
Veterans
HIV
Bone and Bones
Rilpivirine
Incidence
Confidence Intervals
Veterans Health

Keywords

  • Efavirenz
  • Fracture
  • Osteoporosis
  • Tenofovir disoproxil fumarate
  • Veterans

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Tenofovir-Associated Bone Adverse Outcomes among a US National Historical Cohort of HIV-Infected Veterans : Risk Modification by Concomitant Antiretrovirals. / LaFleur, Joanne; Bress, Adam P.; Myers, Joel; Rosenblatt, Lisa; Crook, Jacob; Knippenberg, Kristin; Bedimo, Roger; Tebas, Pablo; Nyman, Heather; Esker, Stephen.

In: Infectious Diseases and Therapy, Vol. 7, No. 2, 01.06.2018, p. 293-308.

Research output: Contribution to journalArticle

LaFleur, Joanne ; Bress, Adam P. ; Myers, Joel ; Rosenblatt, Lisa ; Crook, Jacob ; Knippenberg, Kristin ; Bedimo, Roger ; Tebas, Pablo ; Nyman, Heather ; Esker, Stephen. / Tenofovir-Associated Bone Adverse Outcomes among a US National Historical Cohort of HIV-Infected Veterans : Risk Modification by Concomitant Antiretrovirals. In: Infectious Diseases and Therapy. 2018 ; Vol. 7, No. 2. pp. 293-308.
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abstract = "Introduction: Tenofovir disoproxil fumarate (TDF) has been associated with greater incidences of bone complications, which might be modified by some concomitantly administered antiretrovirals, possibly by their effect on tenofovir concentrations. We compared bone adverse outcomes among treatment-na{\"i}ve HIV-infected US veterans initiating efavirenz (EFV)-containing TDF/emtricitabine (FTC) regimens versus those initiating non-EFV-containing TDF/FTC regimens. Methods: Using national Veterans Health Administration clinical and administrative data sets, we identified a cohort of treatment-na{\"i}ve HIV-infected veterans without bone disease who initiated therapy with TDF/FTC plus EFV, rilpivirine, elvitegravir/cobicistat, or ritonavir-boosted protease inhibitors in 2003–2015. The primary composite adverse bone outcome was the unadjusted incidence rate (IR) of osteoporosis, osteopenia, or fragility fracture (any hip, wrist, or spine fracture). To account for selection bias and confounding, we used inverse probability of treatment-weighted Cox proportional hazards regression models to calculate adjusted hazard ratios (HRs) for each outcome associated with EFV + TDF/FTC versus each non-EFV-containing TDF/FTC regimen. Results: Of 33,048 HIV-positive veterans, 7161 initiated a TDF/FTC-containing regimen (mean age, 50 years; baseline CD4 < 200 cells/mm3, 33.3{\%}; HIV-1 RNA > 100,000 copies/ml, 22.3{\%}; mean follow-up, 13.0 months). Of these, 4137 initiated EFV- and 3024 non-EFV-containing regimens. Veterans initiating EFV- versus non-EFV-containing TDF/FTC regimens had a lower IR of the composite bone outcome (29.3 vs. 41.4 per 1000 patient-years), with significant risk reductions for this outcome [HR, 0.69; 95{\%} confidence interval (CI), 0.58–0.83] and fragility fracture (HR, 0.59; 95{\%} CI, 0.44–0.78). Conclusion: EFV + TDF/FTC is associated with a lower risk of adverse bone outcomes compared with other TDF-containing regimens in the VHA. Funding: Bristol-Myers Squibb.",
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AU - Myers, Joel

AU - Rosenblatt, Lisa

AU - Crook, Jacob

AU - Knippenberg, Kristin

AU - Bedimo, Roger

AU - Tebas, Pablo

AU - Nyman, Heather

AU - Esker, Stephen

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N2 - Introduction: Tenofovir disoproxil fumarate (TDF) has been associated with greater incidences of bone complications, which might be modified by some concomitantly administered antiretrovirals, possibly by their effect on tenofovir concentrations. We compared bone adverse outcomes among treatment-naïve HIV-infected US veterans initiating efavirenz (EFV)-containing TDF/emtricitabine (FTC) regimens versus those initiating non-EFV-containing TDF/FTC regimens. Methods: Using national Veterans Health Administration clinical and administrative data sets, we identified a cohort of treatment-naïve HIV-infected veterans without bone disease who initiated therapy with TDF/FTC plus EFV, rilpivirine, elvitegravir/cobicistat, or ritonavir-boosted protease inhibitors in 2003–2015. The primary composite adverse bone outcome was the unadjusted incidence rate (IR) of osteoporosis, osteopenia, or fragility fracture (any hip, wrist, or spine fracture). To account for selection bias and confounding, we used inverse probability of treatment-weighted Cox proportional hazards regression models to calculate adjusted hazard ratios (HRs) for each outcome associated with EFV + TDF/FTC versus each non-EFV-containing TDF/FTC regimen. Results: Of 33,048 HIV-positive veterans, 7161 initiated a TDF/FTC-containing regimen (mean age, 50 years; baseline CD4 < 200 cells/mm3, 33.3%; HIV-1 RNA > 100,000 copies/ml, 22.3%; mean follow-up, 13.0 months). Of these, 4137 initiated EFV- and 3024 non-EFV-containing regimens. Veterans initiating EFV- versus non-EFV-containing TDF/FTC regimens had a lower IR of the composite bone outcome (29.3 vs. 41.4 per 1000 patient-years), with significant risk reductions for this outcome [HR, 0.69; 95% confidence interval (CI), 0.58–0.83] and fragility fracture (HR, 0.59; 95% CI, 0.44–0.78). Conclusion: EFV + TDF/FTC is associated with a lower risk of adverse bone outcomes compared with other TDF-containing regimens in the VHA. Funding: Bristol-Myers Squibb.

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