Glomerular filtration rate change during chronic hepatitis C treatment with Sofosbuvir/Ledipasvir in HCV/HIV Coinfected patients treated with Tenofovir and a boosted protease inhibitor: an observational prospective study

Abstract

IntroductionConcomitant use of ledipasvir and boosted protease inhibitors (PIs) may increase the risk of tenofovir (TDF) nephrotoxicity, since both these drugs increase TDF levels. Our aim was to evaluate glomerular filtration rate (eGFR) evolution during HCV treatment with sofosbuvir/ledipasvir (SOF/LDV) in HCV/HIV coinfected patients, according to their antiretroviral treatment (ARV).MethodsObservational prospective study of HCV/HIV coinfected patients treated with SOF/LDV. eGFR evolution was evaluated during and 12 weeks after HCV treatment. Patients were categorized in three groups based on ARV regimen: non TDF, non-boosted TDF and TDF + boosted PI.ResultsWe included 273 patients: 145 were receiving a non-TDF regimen, 78 a non-boosted TDF scheme and 50 were receiving TDF + boosted PI. We observed a statistically significant decrease in eGFR during treatment in all groups (non TDF p = 0.03, 95%CI [0.23–3.86], non-boosted TDF p < 0.01, 95%CI [3.36–7.44], TDF + PI p = 0.01, 95%CI [1.09–7.53]). The decrease was more pronounced in those receiving unboosted TDF (− 5.40 ml/min/1.73m2), but differences in eGFR decrease between the three groups were small and not statistically different (p = 0.06). eGFR decrease was greater in patients treated for 24 weeks (p = 0.009) and in cirrhotic patients (p = 0.036). At the end of follow up a recovery of eGFR was observed in all groups.ConclusionWe observed a significant decrease in eGFR during treatment in all study groups, that was small and reversible after SOF/LDV discontinuation. TDF was not associated with an increase in renal toxicity.

Real-World Experience with Coformulated Ledipasvir and Sofosbuvir for HIV-Positive Patients with HCV Genotype 2 Infection: A Multicenter, Retrospective Study

“…LDV, an inhibitor of P-glycoprotein and BCRP efflux transporters, may increase tenofovir concentration when given with TDF, which may increase the risk of TDF-related nephrotoxicity. In contrast, two studies showed that TDF was not associated with increased risk of nephrotoxicity in patients treated with LDV/SOF [38,39]. In our study, 6.1% (n = 7) patients had a switch of their cART regimens to avoid TDF, while 18.4% (n = 21) continued TDF.…”

Sofosbuvir and risk of estimated glomerular filtration rate decline or end‐stage renal disease in patients with renal impairment

“…Butt and colleagues examined a large cohort of HCV‐infected Veterans and demographically matched HCV uninfected controls (ERCHIVES) to evaluate the risk of worsening kidney function, defined as a decline in eGFR >30 ml/min/1.73 m 2 from baseline, and found a statistically significantly lower risk associated with SOF‐containing vs non‐SOF‐containing regimens 32 . Finally, recent studies that have confirmed the kidney safety of coadministration of SOF with tenofovir‐based treatments in HIV/HCV co‐infected patients further corroborate this study’s findings 33,34 …”

Evolution of estimated glomerular filtration rate in human immunodeficiency virus and hepatitis C virus‐coinfected patients receiving sofosbuvir‐based direct‐acting antivirals and antiretroviral therapy

“…Soeiro et al prospectively assessed the eGFR changes during SOF/LDV treatment in HIV/HCV‐coinfected patients on TDF‐based and TDF‐free ART. Although the eGFR decline between baseline and end of treatment of SOF/LDV was numerically higher in patients on TDF‐based ART (5.40 ml/min/1.73 m 2 for non‐boosted TDF regimen; 4.31 ml/min/1.73 m 2 for non‐boosted TDF regimen) than those on TDF‐free ART (2.02 ml/min/1.73 m 2 for non‐TDF regimen), the differences did not reach statistical significance by paired t ‐test 21 . By applying the GEE model for repeated eGFR measurements at 10 different time points with only 0.7% missing data, our study indicated that patients on TFV‐based ART had a slight but significant eGFR decline (adjusted slope difference: −0.82 ml/min/1.73 m 2 /month) compared to those on TFV‐free ART during SOF‐based DAAs.…”

“…Two case reports indicated that the use of SOF may increase the risk of acute kidney injury (AKI) in patients on TFV‐based ART 18,19 . However, other studies showed that the risks of AKI and estimated glomerular filtration rate (eGFR) decline during SOF‐based DAA therapy were comparable in HIV/HCV‐coinfected patients irrespectively of ART regimen 20–22 . Because most studies were retrospective and lacked protocol‐defined time point assessment for eGFR, or recruited limited numbers of patients, the link between SOF and TFV to nephrotoxicity in HIV/HCV‐coinfected patients remains controversial.…”