Global Real-World Evidence of Sofosbuvir/Velpatasvir as a Highly Effective Treatment and Elimination Tool in People with Hepatitis C Infection Experiencing Mental Health Disorders

Abstract

Hepatitis C virus (HCV) is prevalent in people with mental health disorders, a priority population to diagnose and cure in order to achieve HCV elimination. This integrated analysis pooled data from 20 cohorts in seven countries to evaluate the real-world effectiveness of the pangenotypic direct-acting antiviral (DAA) sofosbuvir/velpatasvir (SOF/VEL) in people with mental health disorders. HCV-infected patients diagnosed with mental health disorders who were treated with SOF/VEL for 12 weeks without ribavirin as part of routine clinical practice were included. The primary outcome was sustained virological response (SVR) in the effectiveness population (EP), defined as patients with an available SVR assessment. Secondary outcomes were reasons for not achieving SVR, characteristics of patients with non-virological failures, adherence, and time from HCV RNA diagnosis to SOF/VEL treatment initiation. A total of 1209 patients were included; 142 did not achieve an SVR for non-virological reasons (n = 112; 83 lost to follow-up, 20 early treatment discontinuations) or unknown reasons (n = 30). Of the 1067 patients in the EP, 97.4% achieved SVR. SVR rates in the EP were ≥95% when stratified by type of mental health disorder and other complicating baseline characteristics, including active injection drug use and antipsychotic drug use. Of 461 patients with data available in the EP, only 2% had an adherence level < 90% and 1% had an adherence level < 80%; all achieved SVR. Patients with mental health disorders can be cured of HCV using a well-tolerated, pangenotypic, protease inhibitor-free SOF/VEL regimen. This DAA allows the implementation of a simple treatment algorithm, with minimal monitoring requirements and fewer interactions with central nervous system drugs compared with protease-inhibitor DAA regimens.

Real-world effectiveness and safety of direct-acting antivirals in hepatitis C virus patients with mental disorders

“…A 96.9% cure rate was achieved in the mentally affected group compared to 97.7% in the patients without psychiatric disorders, despite a higher proportion of men, those with liver cirrhosis, and a higher prevalence of GT3 infection in this population, which are considered negative predictors of SVR in HCV-infected patients treated with DAA[ 21 ]. Significantly lower SVR rates have been documented in patients with bipolar disorder, which is consistent with the results of the analysis by Wedemeyer et al [ 18 ]. However, this multicenter study did not control for potential confounders, while in our research, the multivariate analysis clearly excluded bipolar disorder as an independent predictor of non-response to treatment.…”

“…By documenting the high rate of SVR in patients with mental diseases, our study proves that this patient population does not differ in their response to DAA treatment from those with CHC not affected by psychiatric conditions supporting the findings of a recently published multicenter analysis[ 18 ]. Thus, there is no rationale for considering these patients as a difficult-to-treat population in terms of virologic response to therapy, as they were previously recognized in the era of IFN-based regimens.…”

“…The issue we highlighted in our analysis was the significantly higher percentage of patients lost to follow-up without SVR evaluation in the population of patients with mental illness compared to those without mental disorders, 4.2% vs 2.5%, respectively. The problem with adherence, concerning not only the use of drugs which was not evaluated in our study but, as in this case, keeping the dates of follow-up visits, is also raised by other authors[ 18 ]. However, some analyses did not report the difference in adherence between mentally ill patients (including those with substance abuse disorder) and the general HCV-infected population[ 3 , 40 , 44 ].…”

“…Moreover, the population of HCV-infected patients with mental diseases, which was underserved in the era of IFN, has gained its opportunity in the time of DAA therapy. The much shorter course of treatment and the lack of contraindications to the drugs has enabled patients with psychiatric disorders to access therapy on the same principles as for other HCV-infected individuals and has provided a basis for predicting HCV microelimination in this population[ 18 ]. In the current analysis, we found no statistically significant differences in the course of treatment in mentally ill patients compared to others.…”

“…However, the observations encompassing the period when DAA were introduced are scarce, include small study groups, only particular diseases ( e.g., depression), or treat them collectively as mental disorders[ 14 - 17 ]. The results of one multicenter study evaluating a single DAA regimen among psychiatric patients by type of mental disorder have recently been published, but evidence is still needed from large populations of real-world experience that discriminate between individual psychiatric diseases treated with different DAA options and compare the results to the group without mental disorders while controlling for confounding variables[ 18 ].…”