Patients With Chronic Kidney Disease Infected With HCV Have Low Resistance to Direct-Acting Antivirals

To better understand the characteristics of patients with chronic kidney disease (CKD) who require hemodialysis or renal transplant, researchers in Brazil evaluated the prevalence of resistance-associated substitutions (RASs) to direct-acting antivirals (DAAs) in this population who also carry the hepatitis C virus (HCV).

Patients with CKD receiving hemodialysis are highly susceptible to HCV,¹ primarily a result of the high levels of exposure to blood and blood-based products, longer time on dialysis, and the transmission of HCV in hemodialysis units. Further, chronic HCV infection has been shown to increase the mortality risk in patients with CKD, in addition to being associated with cirrhosis, development of hepatocellular carcinoma, and death from cardiovascular diseases.

While DAAs—namely inhibitors of NS3A, NS5A, and NS5B—have permitted the use of interferon-free treatment regimens, and have led to high sustained virologic response rates, concerns with RAS have emerged. RASs, which can be naturally occurring or treatment-induced, can lead to treatment failure. While the general population has been studied over the years for the development of RASs, there remains a gap in the knowledge on HCV treatment and RASs for patients with CKD who undergo hemodialysis or have received a kidney transplant.

The current study² sequenced the NS3, NS5A, and NS5B regions in the genome of this specific subgroup of patients who were infected with HCV-genotype 1 (GT1). Of the 76 patients included in the study, a majority (60.5%) were male, 37 (48.7%) were undergoing hemodialysis, and 39 (51.3%) were kidney transplant recipients. The analysis found that while slightly more than 38% of patients had prevalence of RASs, only 5.3% had mutations in more than a single region. Substitutions were detected in NS3A (17.8%), NS5A (21.9%), and NS5B (8.4%), and a Q80K mutation was detected in just 1 patient; this patient had received a transplant and had been treated with pegylated interferon and ribavirin and had not been treated with protease inhibitors.

The duration of HCV infection was not influenced by the presence of mutations.

Additional analysis showed that RASs were more common in HCV-GT1a (42.9%) than in HCV-GT1b (32.4%) and were detected in a little more than 52% of treatment-naïve patients versus nearly 28% of patients previously treated with interferon/ribavirin (P = .12). While there was no significant difference (P = .6) in RASs between patients undergoing hemodialysis (35.1%) and those who had received a renal transplant (59%), a significant association was observed between the time after transplant and the presence of RASs (P = .01).

The fact that the study found RASs that only confer a low-level resistance to DAAs resulted in the authors concluding that this subset of patients could respond favorably to their HCV treatment with DAAs.

References

1. Kidney Disease: Improving Global Outcomes. KDIGO clinical practice guideline on the prevention, diagnosis, evaluation and treatment of hepatitis C in CKD. KDIGO website. https://kdigo.org/clinical_practice_guidelines/Hep%20C/KDIGO%202017%20Hep%20C%20GL%20Public%20Review%20Draft%20FINAL.pdf. Published February 2017. Accessed November 26, 2018.
2. Tavares RCF, de Castro Amaral Feldner AC, Pinho JRR, et al. Prevalence of resistance-associated substitutions to direct-acting antiviral agents in hemodialysis and renal transplant patients infected with hepatitis C virus. Infect Drug Resist. 2018;11:1993-2000. doi: 10.2147/IDR.S169512. eCollection 2018.