TY - JOUR
T1 - Tenofovir-Associated Bone Adverse Outcomes among a US National Historical Cohort of HIV-Infected Veterans
T2 - Risk Modification by Concomitant Antiretrovirals
AU - LaFleur, Joanne
AU - Bress, Adam P.
AU - Myers, Joel
AU - Rosenblatt, Lisa
AU - Crook, Jacob
AU - Knippenberg, Kristin
AU - Bedimo, Roger
AU - Tebas, Pablo
AU - Nyman, Heather
AU - Esker, Stephen
N1 - Funding Information:
Funding. This work was supported by Bristol-Myers Squibb by a grant to the University of Utah. The article processing charges were also funded by Bristol-Myers Squibb.
Funding Information:
Disclosures. This work was supported by Bristol-Myers Squibb by a grant to the University of Utah. Joanne LaFleur received some salary support from this grant and declares no intellectual property rights related to this research. Outside of the funded work, over the last 3 years, the following organizations provided research grants to the University of Utah and Joanne LaFleur worked on those projects and/or received salary or other types of support that were funded by those grants: Gilead Sciences, Inc., Anolinx LLC, Skaggs Foundation, and Agency for Healthcare Research and Quality. Adam P. Bress received some salary support from this grant and declares no intellectual property rights related to this research. Outside of the funded work, over the last 3 years, the following organizations provided research grants to the University of Utah, and Adam P. Bress worked on those projects and/or received salary or other types of support that were funded by those grants: Gilead Sciences, and National Heart, Lung, and Blood Institute (NHLBI). Joel Myers is an employee of, and owns stock in, Bristol-My-ers Squibb. Lisa Rosenblatt is an employee of, and owns stock in, Bristol-Myers Squibb. Jacob Crook received some salary support from this grant and declares no intellectual property rights related to this research. Outside of the funded work, over the last 3 years, the following organizations provided research grants to the University of Utah and Jacob Crook worked on those projects and/or received salary or other types of support that were funded by those grants: Cubist, Gilead Sciences, Inc., Anolinx LLC, Skaggs Foundation, Agency for Healthcare Research and Quality, and Utah Department of Health. Kristin Knippenberg received some salary support from this grant and declares no intellectual property rights related to this research. Outside of the funded work, over the last 3 years, the following organizations provided research grants to the University of Utah and Kristin Knippenberg worked on those projects and/or received salary or other types of support that were funded by those grants: Gilead Sciences, Inc., Anolinx LLC, Skaggs Foundation, Agency for Healthcare Research and Quality, and Utah Department of Health. Roger Bedimo has received grants and research support awarded to the Veterans Affairs North Texas Healthcare System from Merck & Co; he has served as a scientific advisor for Bristol-Myers Squibb, Merck & Co, Inc., and Theratechnologies, Inc. Pablo Tebas has served as a scientific advisor to Merck & Co, Inc., and is a member of an adjudication committee in a vaccine trial sponsored by Glaxo. Heather Nyman received some salary support and travel expenses from this grant and declares no intellectual property rights related to this research; she has also received consultancy honoraria from Otsuka and Fresenius. Stephen Esker is an employee of, and owns stock in, Bristol-Myers Squibb.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/6/1
Y1 - 2018/6/1
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.
AB - 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.
KW - Efavirenz
KW - Fracture
KW - Osteoporosis
KW - Tenofovir disoproxil fumarate
KW - Veterans
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U2 - 10.1007/s40121-018-0194-1
DO - 10.1007/s40121-018-0194-1
M3 - Article
C2 - 29492905
AN - SCOPUS:85048091831
SN - 2193-8229
VL - 7
SP - 293
EP - 308
JO - Infectious Diseases and Therapy
JF - Infectious Diseases and Therapy
IS - 2
ER -