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Title The impact of tenofovir disoproxil fumarate on estimated glomerular filtration rate change and progression to end-stage renal disease among HIV-infected adults in North America
Publication Date
Date Available
Date Accessioned
University/Publisher Johns Hopkins University
Abstract Background: Tenofovir disoproxil fumarate (TDF) was associated with an increased risk of renal toxicity, resulting in proximal tubular dysfunction, proteinuria, and chronic kidney disease (CKD). However, TDF-related nephrotoxicity has not been studied in the context of end-state renal disease (ESRD). We hypothesized that TDF-induced toxicity mainly affected a subset of susceptible HIV-infected patients that led to faster progression to ESRD. Methods: Data was extracted from 12 clinical cohorts under the North American AIDS Cohort Collaboration for Research and Design study that carried out systematic ESRD validation from January 2000 to December 2009. Piece-wise log-linear mixed effects models were used to compare and contrast estimated glomerular filtration rate (eGFR) trajectories in TDF and other nucleoside reverse transcriptase inhibitor (NRTI) therapy groups. A nested design was employed to identify risk factors associated with increased ESRD risk after TDF exposure. Results: Among the 19,653 patients, over 20% of high-risk individuals received less than two serum creatinine-based assessments of kidney function per year. For TDF users with baseline eGFR≥90, 60-89.9 and 45-59.9 mL/min/1.73m2, the annualized eGFR change decreased at -10.1% (p<-0.001), -9.9% (p<-0.001) and -27.2% (p<-0.001), respectively during the first 6 months after therapy initiation. In contrast, eGFR decreased at a slower rate or stabilized among alternative NRTI initiators during this period at rates of -5.9% (p<0.001), 0.7% (p=0.596) and 9.8% (p=0.027) for the same eGFR categories. For patients with baseline eGFR in ranges of 30-44.9 and <30 mL/min/1.73m2, eGFR change was non-significant at -14.0% (p=0.068) and -9.3% (p=0.617) per year, respectively among TDF initiators, whereas among alternative NRTI users, eGFR declined at -27.7% (p<0.001) and -31.2% (p<0.001) per year. Among TDF-exposed patients, black race was independently associated with 3.4 [95% CI: 1.2-9.6] times higher ESRD risk. Conclusion: Insufficient screening and monitoring of kidney function remains as an issue for clinical care of kidney diseases among HIV-infected patients. TDF-based therapies are associated with higher ESRD risks. TDF-induced toxicity mainly affects a small subset of susceptible individuals.
Subjects/Keywords HIV-infection; Tenofovir disoproxil fumarate (TDF); Nucleoside reverse transcriptase inhibitor (NRTI); End-stage renal Disease (ESRD); Glomerular filtration rate (GFR)
Contributors Abraham, Alison G (advisor)
Country of Publication us
Format application/pdf
Record ID oai:jscholarship.library.jhu.edu:1774.2/38064
Repository jhu
Date Retrieved
Date Indexed 2016-10-05
Issued Date 2015-05-04 00:00:00

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…research. Tenofovir disoproxil fumartate (TDF) is a member of the NRTI class of antiretroviral drug (ARV). TDF-containing regimens are the first-line therapy recommended by the US Department of Health and Human Services (DHHS)…

…patterns, we stratified this analysis by risk groups determined based on different eGFR thresholds at the time of TDF or alternative NRTI therapy initiation. In addition, to assess the impact of TDF exposure leading to a terminal renal outcome, we examined…

…x28;42) Our study included HIVinfected adults (≥18 years old) who received routine HIV care in these 12 cohorts and initiated a TDF or alternative NRTI-containing therapy between study enrollment on or after January 1, 2000 and study exit…

…on or before December 31, 2009. An alternative NRTI-containing therapy was defined as any HAART regimen containing one or more of the following antiretroviral drugs (ARV): abacavir (ABC), zidovudine (AZT), stavudine (…

…initiation of TDF or alternative NRTI-containing therapy (defined as baseline) to the onset of ESRD, death, cohort-specific end date for ESRD verification, or administrative censoring (December 31, 2009). Negative times from study…

…enrollment to the initiation of TDF or alternative NRTI-containing therapy contributed to the pre-initiation eGFR trajectory estimates. The eGFR trajectories were compared between the two therapy groups without regard for subsequent therapy changes prior to…

…containing regimen without concomitant use of ABC, AZT, d4T or ddI during observation. Initiation of an alternative NRTI-based therapy was defined as starting a TDFsparing regimen that contains at least one of following NRTIs: ABC, AZT, d4T and ddI…

…Individuals who had TDF exposure prior to study enrollment or at any point during observation (between study enrollment and endpoint) were excluded from the alternative NRTI-base therapy group to prevent potential residual TDF exposure effects from…