Outcomes of tenofovir discontinuation among human immunodeficiency virus (HIV)-infected patients with suspected tenofovir-associated nephrotoxicity

Background: Tenofovir-associated nephrotoxicity (TAN) has been approximated at a yearly incidence of 1%. Limited data exist regarding the reversibility of TAN. The aim of this study is to describe outcomes of tenofovir discontinuation (d/c) among HIV-infected patients with suspected TAN.

Methods: This retrospective, single-center, observational, cohort study enrolled HIV-infected patients who discontinued tenofovir disoproxil fumarate (TDF) due to suspected TAN from 2005 to 2015. Patients must have had serum creatinine ≥ 1.3 mg/dL to be included. Patients with pre-existing renal dysfunction were excluded. Renal function was estimated pre-TDF, at time of suspected TAN, and at pre-specified time periods up to 5 years after TDF d/c. Estimated glomerular filtration rate (eGFR) was calculated using Modification of Diet in Renal Disease (MDRD) equation. Improvement was defined as eGFR increase ≥7 mL/min/m². Recovery was defined as return to pre-TDF renal function. Time-to-event analysis was performed to assess speed of improvement and recovery. Logistic regression was performed to assess factors associated with recovery.

Results: Sixty patients met study criteria. Median eGFR pre-TDF, at TDF d/c, and after TDF d/c were 78.3, 51.7, and 73.5 mL/min/m², respectively (eGFR at TDF d/c vs after TDF d/c; p<0.001). The majority of patients (80%) had improvement, but only half of these (40%) had recovery. Time-to-event analysis revealed a median time to improvement and recovery of 5 and 52 months, respectively. No factors were found to be associated with recovery in the multivariate logistic regression.

Variable	Univariate Analysis OR (95% CI);p-value
Male	8.8 (1.5, 168.7);0.045
Pre-treatment HIV RNA (log)	0.5 (0.21, 1.1);0.095
Pre-treatment CD4 (per every 50 cells/mm3)	1.1 (0.97, 1.2);0.16
Pre-treatment CD4 <200 cells/mm3	0.4 (0.1, 1.1);0.091
Receipt of thiazide at time of recovery	3 (0.98, 9.42);0.058
Number of prior antiretroviral regimens	1.5 (1.04, 2.1);0.033
Number of prior antiretrovirals	1.2 (1.03, 1.5);0.029

Conclusion: Among patients with suspected TAN, renal function improves for most patients after TDF d/c, but not all patients fully recover. A patient’s greatest improvement may not occur until many months after TDF d/c.

Disclosures: All authors: No reported disclosures.