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

Abstract

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.

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

“…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 Our results complement recent findings of clinical trials evaluating LDV/SOF and SOF/VEL in patients with ESRD which concluded these regimens were safe and effective and led to an expanded FDA label for SOF-containing regimens in patients with all levels of kidney function in 2019, 16,17 and data demonstrating that the GS-331007 metabolite is efficiently removed by haemodialysis (53% extraction ratio) resulting in markedly reduced exposure after dialysis. 35 SOF-based treatment, eGFR remained stable after treatment.…”

“…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 …”

Sofosbuvir/velpatasvir or glecaprevir/pibrentasvir for treating patients with hepatitis C virus reinfection following direct‐acting antiviral‐induced sustained virologic response

“…36 Our study also confirmed that no patients experienced ≥ grade 2 renal function declines, irrespective of the HIV status or types of DAAs. 24,25 Due to the concomitant use of TAF-based ART for HIV that was also active against HBV, no HBV reactivation or HBV-associated hepatitis was observed in our HBV-coinfected patients.…”

“…23,24 In HIV-positive patients, the CD4 count and serum HIV RNA (Cobas Taqman HIV-1 Test v2.0, Roche Diagnostics GmbH, lower limit of quantification [LLOQ]: 20 copies/mL), and information about antiretroviral therapy (ART) were assessed. 25 The stage of hepatic fibrosis was graded by transient elastography (FibroScan, Echosens, Paris, France) with a liver stiffness measurement (LSM) cutoff of ≤7.0 kilopascal (kPa) to be F0 to F1, 7.1 to 9.4 kPa to be F2, 9.5 to 12.3 kPa to be F3, and ≥12.4 kPa to be F4, respectively. 26,27 Patients received SOF/VEL (Epclusa, FDC 400/100 mg per tablet, Gilead Sciences, Carrigtohill, Co. Cork, Ireland) one tablet once daily for 12 weeks or GLE/PIB (Maviret, FDC 100/40 mg per tablet, AbbVie Deutschland GmbH & Co. KG, Germany) three tablets once daily orally for 8 to 12 weeks according to manufacturer's instructions.…”

“…Among the reinfected patients who received SOF/VEL or GLE/PIB, patient demographics, hemogram, serum albumin, total bilirubin (upper limit of normal [ULN]: 1.0 mg/dL), direct bilirubin, aspartate aminotransferase (AST) (ULN: 30 U/L for males and 19 U/L for females), alanine aminotransferase (ALT) (ULN: 30 U/L for males and 19 U/L for females), estimated glomerular filtration rate (eGFR) which was calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) equation, alpha‐fetoprotein (AFP), anti‐HCV (Abbott HCV EIA 2.0, Abbott Laboratories, Abbott Park, Illinois), hepatitis B virus (HBV) surface antigen (HBsAg) (Abbott Architect HBsAg qualitative assay, Abbott Laboratories), anti‐HIV (Abbott Architect HIV Ag/Ab Combo, Abbott Laboratories), HCV RNA, HCV genotype were assessed 23,24 . In HIV‐positive patients, the CD4 count and serum HIV RNA (Cobas Taqman HIV‐1 Test v2.0, Roche Diagnostics GmbH, lower limit of quantification [LLOQ]: 20 copies/mL), and information about antiretroviral therapy (ART) were assessed 25 . The stage of hepatic fibrosis was graded by transient elastography (FibroScan, Echosens, Paris, France) with a liver stiffness measurement (LSM) cutoff of ≤7.0 kilopascal (kPa) to be F0 to F1, 7.1 to 9.4 kPa to be F2, 9.5 to 12.3 kPa to be F3, and ≥12.4 kPa to be F4, respectively 26,27 …”