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

Introduction: Concomitant 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).

Methods: Observational 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.

Results: We 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.

Conclusion: We 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.

Keywords: Co-infection HIV/HCV; Drug-drug interactions; HCV treatment; Protease inhibitor; Renal toxicity; Sofosbuvir/ledipasvir; Tenofovir.

Conflict of interest statement

This study was approved by the Ethical Commission of Centro Hospitalar do Porto and by the Portuguese National Data Protection Commission. Written informed consent was obtained for all patients.

All authors agreed with the final manuscript and consented publication. Participants consented publication.

The authors declare that they have no competing interests.

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Figures

Fig. 1

Evolution of the eGFR during treatment and at SVR12 according to ARV regimen. (eGFR – estimated glomerular filtration rate; D1 – day 1, beginning of treatment; W2 – week 2 of treatment; W4 – week 4 of treatment; EOT – end of treatment; SVR12 – end of follow up; TDF – tenofovir; PI – protease inhibitor; Non TDF – regimens without TDF; Non-boosted TDF – regimens with TDF without boosted PI; TDF + Boosted PI – regimens with TDF and boosted PI)