Trend of estimated glomerular filtration rate during ombistasvir/paritaprevir/ritonavir plus dasabuvir ± ribavirin in HIV/HCV co-infected patients

Abstract

The renal function is a key-issue in HIV/HCV co-infected patients, nevertheless, it has not established so far whether HCV treatment with new direct acting agents could impact on estimated glomerular filtration rate (eGFR) variations. In the present work, we examined the real-life data on renal function that have been prospectively collected in the SIMIT compassionate-use program of ombitasvir/paritaprevir/ritonavir plus dasabuvir (OBV/PTV/r + DSV) in 144 HIV/HCV genotype 1 co-infected patients. The population was 74% male, 30.5% in CDC stage C, with median age of 52 years (48.0–56.5) and median liver stiffness of 7.8 kPa (6.7–9.2). Median baseline eGFR was 102.0 (90.8–108.1), changing to 99.8 (83.5–104.8) at the end of treatment (EoT), and 100.0 (87.3–105.6) 12 weeks after the EoT (FU12), p<0.0001. No patient had grade 3–4 increase of creatinine. At EoT 60/144 (41.7%) patients had ≥ 5% reduction in their eGFR, confirmed at FU12 in 39/60 (65.0%) cases. Longer duration of HCV infection (cut-off 12.9 years), lower HCV-RNA viral load (cut-off 1,970,160 IU/ml) and lower platelet count (cut-off 167,000 x106/L) were significantly associated with eGFR decline at logistic analysis (adjOR 2.9, 95%CI 1.0–8.8, p = 0.05; adjOR 3.5, 95%CI 1.2–10.4, p = 0.02; adjOR 2.8, 95%CI 1.1–6.8, p = 0.03, respectively). After repeating the analysis throughout a mixed model, a higher eGFR decline was highlighted in patients concomitantly treated with tenofovir (p = 0.0001), ribavirin (p = 0.0001), or integrase inhibitors (p <0.0001), with longer duration of HIV (p = 0.0002) and HCV infection (p = 0.035), lower baseline HCV RNA (p <0.0001), previous HCV treatment (p<0.0001), and older age (p<0.0001). In conclusion, our study confirms a good renal safety profile of OBV/PTV/r + DSV treatment in HIV/HCV patients, and the median decline of 2 ml/min in eGFR, albeit statistically significant, is of doubtful clinical significance. The role of aging, concomitant therapies and duration of HIV/HCV infection needs to be further investigated.

Changes in renal function in patients with chronic hepatitis C treated with sofosbuvir‐velpatasvir

“…21 This corresponds to about 5% decline in patients with normal eGFR, and this 5% decline marker was also be used in previous study for HCV infected patients. 22 A longitudinal, observational study of chronic hepatitis C patients from multiple centers of North America and Europe (HCV-TARGET) by Saxena et al reported that patients with eGFR ≤ 45 mL/min/1.73m 2 more frequently experienced worsening renal function when they were treated with SOF-based regimen. 23 However, the major regimens of HCV-TARGET were SOF/simeprevir (SMV), SOF/RBV, SOF/pegylated interferon (PEG)/RBV, or SOF/SMV/RBV, and the rates of SVR12 were only 82%.…”

“…In human immunodeficiency virus infected patients, a rapid eGFR decline is generally defined by a reduction in eGFR > 5 mL/min/year in patients with baseline eGFR > 90 mL/min 21 . This corresponds to about 5% decline in patients with normal eGFR, and this 5% decline marker was also be used in previous study for HCV infected patients 22 …”

Viremia copy-years and risk of estimated glomerular filtration rate reduction in adults living with perinatal HIV infection

“…In the univariate analysis, we identified a relation between years of treatment with INI and eGFR reduction, while it was not observed in other ART regimens. Notably, both elvitegravir/cobicistat and dolutegravir have been associated with increased creatinine levels—though without a worsening of renal function—due to the inhibition of creatinine tubular secretion [ 20 , 27 – 29 ]. However, as shown in the multivariate analysis, higher VCY—and not years of exposure to INI—was retained as the predictor of eGFR reduction, thereby confirming the significant role of HIV replication in eGFR decline in the PHIV population studied.…”