Recovery of renal function after switching from TDF

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For HIV-infected patients with declining renal function who are receiving a regimen containing tenofovir disoproxil fumarate (TDF), switching to other antiretroviral agents (ARVs) results in significant recovery of the estimated glomerular filtration rate (eGFR), according to results of a cohort study led by Drs Purim Janepiriyaprayoon and Somnuek Sungkanuparph at the faculty of medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand presented at IDWeek 2017.

The study included 141 HIV-infected patients with renal insufficiency who discontinued TDF and initiated other ARVs. The patients were placed into 2 groups based on their eGFR at the time of switching agents: the early-switch group (eGFR of ≥60mL/min; n=54) and the late-switch group (eGFR <60mL/min; n=87).

Baseline demographics showed that 48.9% of the patients included in the study received NNRTI-based therapy while 51.1% received a PI-based regimen. The median (IQR) length of TDF use was reported as 5.2 years (2.7, 6.9). Of the total patients in the study, 72.3% switched from TDF to abacavir, while the remaining switched to other ARVs.

Mean patient age differed between the two groups (48.6 years vs. 57.9 years for early- and late-switch groups, respectively; P=0.004), as did body weight (mean 59 vs. 55kg; P=0.004).

At the time of TDF switching, the average eGFR was 72.4±13.7mL/min for patients in the early-switch group and 47.0±14.8mL/min for patients in the late-switch group. The study authors reported, “After switching TDF, mean eGFR in early-switch group significantly increased to 84.2±13.5mL/min at 6 months (P=0.001) and 81.8±18.1mL/min at 12 months (P=0.044); mean eGFR in late-switching group significantly increased to 58.5±13.2mL/min (P<0.001) and 60.2±14.3mL/min (P<0.001) at 6 and 12 months, respectively.” One year after switching from TDF to other ARVs, eGFR recovery to ≥90mL/min occurred in 44.4% of patients in the early-switch group and 2.3% of patients in the late-switch group (P<0.001).

For HIV-infected patients with renal insufficiency, eGFR was found to recover when patients discontinued therapy containing TDF and initiated a regimen containing other ARVs. The authors added, “Patients in the early-switch group have a higher chance of renal function recovery to normal eGFR. This may encourage clinicians to switch TDF early before eGFR declining to <60mL/min.”

Abstract
Background: Tenofovir disoproxil fumarate (TDF) is currently a preferred agent for antiretroviral therapy (ART). TDF use is associated with a significant risk of renal insufficiency. Although many guidelines recommend switching TDF to other antiretroviral agents (ARVs) if there is a progressive decline in estimated glomerular filtration rate (eGFR) not explained by other causes, the definite cut-point of eGFR for switching TDF is not known.
Methods: A cohort study was conducted among HIV-infected patients who switched from TDF to other ARVs, as a component of ART regimen, with a reason of declined eGFR at a medical-school hospital. Patients were categorized into 2 groups according to eGFR at the time of switching TDF: early-switch group (eGFR ≥60 ml/min) and late-switch group (eGFR <60 ml/min).
Results: A total of 141 patients were studied. The mean age was 54.2±12.2 years and 74.5% of patients were males. Mean body weight was 59.9±13.3 kgs. Mean CD4 cell count was 459±244 cells/mm3 and all patients had undetectable HIV RNA (<50 copies/ml). For ART regimen, 48.9% and 51.1% received NNRTI- and PI-based regimen, respectively. Median (IQR) duration of TDF use was 5.2 (2.7-6.9) years. Of all, 72.3% of patients switched from TDF to abacavir; the rest switched to other ARVs. Fifty-four patients were in early-switch group and 87 patients were in late-switch group. Mean eGFR at the time of TDF switching was 72.4±13.7 ml/min in early-switch group and 47.0±14.8 ml/min in late-switch group. After switching TDF, mean eGFR in early-switch group significantly increased to 84.2±13.5 ml/min at 6 months (p=0.001) and 81.8±18.1 ml/min at 12 months (p=0.044); mean eGFR in late-switching group significantly increased to 58.5±13.2 ml/min (p <0.001) and 60.2±14.3 ml/min (p <0.001) at 6 and 12 months, respectively. At 12 months after switching TDF to other ARVs, 44.4% of patients in early-switch group and 2.3% of patients in late-switch group had eGFR recovery to ≥90 ml/min (p <0.001).
Conclusion: In HIV-infected patients who receive TDF-containing regimen and have renal insufficiency, eGFR significantly recovers after switching TDF to other ARVs in both early-switch and late-switch groups. However, patients in early-switch group have a higher chance of renal function recovery to normal eGFR. This may encourage clinicians to switch TDF early before eGFR declining to <60 ml/min.

Authors
Purim Janepiriyaprayoon, Somnuek Sungkanuparph

MPR material
IDWeek abstract


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