Abstract and Introduction
The nephrotoxicity of sofosbuvir (SOF) on human immunodeficiency virus and hepatitis C virus (HIV/HCV)-coinfected patients receiving antiretroviral therapy (ART) remains controversial. We prospectively compared the estimated glomerular filtration rate (eGFR) changes in 167 patients receiving SOF-based direct-acting antivirals (DAAs) who also received tenofovir disoproxil fumarate (TFV)-based (n = 116) and TFV-free ART (n = 51). The eGFR was assessed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, and the eGFR changes between ART regimens were compared by the generalized estimated equation. During DAA treatment, participants on TFV-based ART had a higher eGFR decline than those on TFV-free ART (slope coefficient difference: −0.82 ml/min/1.73 m2/month [95% CI: −1.21 to −0.43]; p < 0.001), whereas the eGFR changes did not differ between groups (slope coefficient difference: 0.13 ml/min/1.73 m2/month [95% CI: −0.32 to 0.58]; p = 0.42) after discontinuing DAAs. Participants on TFV TDF-based ART had a higher eGFR decline than those on TFV alafenamide fumarate (TAF)-based ART (slope coefficient difference: −0.31 ml/min/1.73 m2/month [95% CI: −0.50 to −0.12]; p = 0.01). After discontinuing DAAs, the eGFR changes did not differ between groups (slope coefficient difference: 0.06 ml/min/1.73 m2/month [95% CI: −0.98 to 1.10]; p = 0.91). In conclusion, HIV/HCV-coinfected patients on TFV-based ART had a slight eGFR decline compared to those on TFV-free ART during SOF-based DAA therapy. A similar trend between TDF-based and TAF-based ART was also observed. Because the differences of eGFR changes are limited, the physicians should not discourage the use of SOF-based DAAs in HIV-positive patients on TFV-based ART.
Chronic hepatitis C virus (HCV) infection remains a health burden in people living with human immunodeficiency virus (HIV). Compared to the midpoint prevalence rate of HCV coinfection at 2.4% in the general HIV-positive population, the prevalence rates are higher among bisexual men (4.0%), gay men (6.4%) and people who inject drugs (PWIDs) (82.4%). Following the widespread use of antiretroviral therapy (ART) for HIV which improves the health outcome by reducing the acquired immunodeficiency syndrome (AIDS)-related deaths, the liver-related death has become a frequent cause of non-AIDS-related deaths in HIV-positive populations. If HCV is left untreated, the HIV/HCV-coinfected patients may have higher risk of developing hepatic decompensation or hepatocellular carcinoma (HCC) than HCV-monoinfected patients due to the accelerated progression of hepatic fibrosis.[3–5] Therefore, an effective and safe antiviral therapy for HCV is mandatory to halt the adverse outcome in HIV/HCV-coinfected patients.
In the era of interferon (IFN)-based therapies for HCV, the sustained virologic response (SVR) rates are far from satisfactory in HIV/HCV-coinfected patients. The long treatment duration, the need of subcutaneous drug administration, the pill burden for ribavirin (RBV) or 1st generation of protease inhibitors, and the high treatment–emergent adverse event rates further compromise the patients' tolerance and adherence.[7–9] The advent of IFN-free direct-acting antiviral (DAA) therapy has made a paradigm shift in the care of HCV by improving the antiviral response and tolerance.[10,11] Sofosbuvir (SOF), a pyrimidine nucleotide analogue, acts as the chain terminator for HCV ribonucleic acid (RNA) by inhibiting HCV non-structural protein 5B (NS5B) RNA-dependent RNA polymerase. Clinically, SOF is coformulated with an NS5A inhibitor such as ledipasvir (LDV) or velpatasvir (VEL), which can be administered once daily with excellent antiviral potency, tolerability and genetic barrier to viral resistance. Therefore, the fixed-dosed combination of SOF with NS5A inhibitor can serve as an ideal option for treating HCV among HIV/HCV-coinfected patients.[13,14]
Despite that the combination of ART and DAAs is considered safe for HIV/HCV-coinfected patients, several studies indicated that SOF may induce tubulointerstitial nephritis.[15,16] Due to the well-documented tenofovir (TFV)-associated nephrotoxicity, the renal safety is particularly relevant to HIV/HCV-coinfected patients on long-term TFV-based ART treatment before initiating DAA therapy for HCV. 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. Our study aimed to prospectively compare the eGFR evolution in HIV/HCV-coinfected patients receiving SOF-based DAAs for HCV, (1) who were on TFV-based or TFV-free ARTs and (2) who were on TFV disoproxil fumarate (TDF)-based or TFV alafenamide fumarate (TAF)-based ARTs.
J Viral Hepat. 2021;28(6):887-896. © 2021 Blackwell Publishing