TY - JOUR
T1 - Tenofovir-Associated Nephrotoxicity Among a US National Historical Cohort of HIV-Infected Veterans
T2 - Risk Modification by Concomitant Antiretrovirals
AU - LaFleur, Joanne
AU - Bress, Adam P.
AU - Esker, Stephen
AU - Knippenberg, Kristin
AU - Crook, Jacob
AU - Nyman, Heather
AU - Bedimo, Roger
AU - Tebas, Pablo
AU - Rosenblatt, Lisa
N1 - Funding Information:
Supported by Bristol-Myers Squibb by a grant to the University of Utah; J.L., J.C., and K.K. received some salary support from this grant; and H.N. received travel support from this grant. Outside of the funded work, over the last 3 years, the following organizations provided research grants to the University of Utah and the following individuals worked on those projects and/or received salary or other types of support that were funded by those grants: Cubist (J.C.); Gilead Sciences, Inc. (J.L., A.P.B., J.C., and K.K.); Anolinx LLC (J.L., J.C., and K.K.); Skaggs Foundation (J.L., J.C., and K.K.); Agency for Healthcare Research and Quality (J.L., J.C., and K.K.); Utah Department of Health (J.C. and K.K.); and the National Heart, Lung, and Blood Institute (NHLBI) (A.P.B.). H.N. has received consultancy honoraria from Otsuka and Fresenius. R.B. 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. P.T. 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. S.E. and L.R. are employees of, and own stock in, Bristol-Myers Squibb. The remaining authors have no funding or conflicts of interest to disclose.
Funding Information:
Editorial assistance was provided by Julian Martins of inScience Communications, Springer Healthcare, which was funded by Bristol-Myers Squibb.
Publisher Copyright:
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - Background: Tenofovir disoproxil fumarate (TDF) has been associated with renal complications. The third agent in TDF-containing antiretroviral regimens may modify that risk. We compared renal adverse outcomes among treatment-naive HIV-infected patients initiating TDF-containing regimens including efavirenz (EFV) or other agents. Setting: This population-based historical cohort study used national Veterans Health Administration (VHA) clinical and administrative data sets to identify treatment-naive HIV-infected veterans initiating antiretroviral therapy with TDF/emtricitabine (FTC) + EFV, rilpivirine (RPV), elvitegravir/cobicistat (EVG/c), or ritonavir (RTV)boosted protease inhibitors (PIs) from 2003 to 2015. Methods: Unadjusted incidence rates (IRs) for each regimen and covariate-adjusted hazard ratios [ using Cox proportional hazards models and inverse probability of treatment weighting] for between-regimen comparisons were calculated for renal outcomes including confirmed proteinuria, defined as 2 consecutive protein-to-creatinine ratios >150 mg/g or albumin-to-creatinine ratios >30 mg/g occurring ≥90 days apart; chronic kidney disease (CKD), defined as 2 consecutive estimated glomerular filtration rate measurements <60 mL$min-1$1.73 m-2 occurring ≥90 days apart; and kidney dialysis. Results: Of 33,048 HIV-positive veterans, 4172 received EFV + TDF/FTC, 234 EVG/c/TDF/FTC, 173 RPV/TDF/FTC, and 2651 RTV-boosted PIs + TDF/FTC. Confirmed proteinuria and CKD IRs were numerically lower with EFV + TDF/FTC versus non-EFV + TDF/FTC (dialysis IRs were rare and comparable). After inverse probability of treatment weighting adjustment, EFV + TDF/FTC was associated with lower CKD risk versus non-EFV + TDF/FTC (hazard ratio, 0.62; 95% confidence interval, 0.53 to 0.72), EVG/c/ TDF/FTC (0.75; 0.59 to 0.95), RPV/TDF/FTC (0.20; 0.17 to 0.24), and RTV-boosted PIs + TDF/FTC (0.62; 0.53 to 0.72). Conclusions: EFV + TDF/FTC was associated with significantly lower risk of CKD versus other TDF-containing regimens in the Veterans Health Administration.
AB - Background: Tenofovir disoproxil fumarate (TDF) has been associated with renal complications. The third agent in TDF-containing antiretroviral regimens may modify that risk. We compared renal adverse outcomes among treatment-naive HIV-infected patients initiating TDF-containing regimens including efavirenz (EFV) or other agents. Setting: This population-based historical cohort study used national Veterans Health Administration (VHA) clinical and administrative data sets to identify treatment-naive HIV-infected veterans initiating antiretroviral therapy with TDF/emtricitabine (FTC) + EFV, rilpivirine (RPV), elvitegravir/cobicistat (EVG/c), or ritonavir (RTV)boosted protease inhibitors (PIs) from 2003 to 2015. Methods: Unadjusted incidence rates (IRs) for each regimen and covariate-adjusted hazard ratios [ using Cox proportional hazards models and inverse probability of treatment weighting] for between-regimen comparisons were calculated for renal outcomes including confirmed proteinuria, defined as 2 consecutive protein-to-creatinine ratios >150 mg/g or albumin-to-creatinine ratios >30 mg/g occurring ≥90 days apart; chronic kidney disease (CKD), defined as 2 consecutive estimated glomerular filtration rate measurements <60 mL$min-1$1.73 m-2 occurring ≥90 days apart; and kidney dialysis. Results: Of 33,048 HIV-positive veterans, 4172 received EFV + TDF/FTC, 234 EVG/c/TDF/FTC, 173 RPV/TDF/FTC, and 2651 RTV-boosted PIs + TDF/FTC. Confirmed proteinuria and CKD IRs were numerically lower with EFV + TDF/FTC versus non-EFV + TDF/FTC (dialysis IRs were rare and comparable). After inverse probability of treatment weighting adjustment, EFV + TDF/FTC was associated with lower CKD risk versus non-EFV + TDF/FTC (hazard ratio, 0.62; 95% confidence interval, 0.53 to 0.72), EVG/c/ TDF/FTC (0.75; 0.59 to 0.95), RPV/TDF/FTC (0.20; 0.17 to 0.24), and RTV-boosted PIs + TDF/FTC (0.62; 0.53 to 0.72). Conclusions: EFV + TDF/FTC was associated with significantly lower risk of CKD versus other TDF-containing regimens in the Veterans Health Administration.
KW - Chronic kidney disease
KW - Efavirenz
KW - HIV
KW - Tenofovir
KW - Veterans
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U2 - 10.1097/QAI.0000000000001608
DO - 10.1097/QAI.0000000000001608
M3 - Article
C2 - 29210830
AN - SCOPUS:85061846769
VL - 77
SP - 325
EP - 330
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
SN - 1525-4135
IS - 3
ER -