Safe and effective sofosbuvir-based therapy in patients with mental health disease on hepatitis C virus treatment

Abstract

AIMTo study impact of baseline mental health disease on hepatitis C virus (HCV) treatment; and Beck’s Depression Inventory (BDI) changes with sofosbuvir- and interferon-based therapy.METHODSThis is a retrospective cohort study of participants from 5 studies enrolled from single center trials conducted at the Clinical Research Center of the National Institutes of Health, Bethesda, MD, United States. All participants were adults with chronic HCV genotype 1 infection and naïve to HCV therapy. Two of the studies included HCV mono-infected participants only (SPARE, SYNERGY-A), and 3 included human immunodeficiency virus (HIV)/HCV co-infected participants only (ERADICATE, PFINPK, and ALBIN). Patients were treated for HCV with 3 different regimens: Sofosbuvir and ribavirin in the SPARE trial, ledipasvir and sofosbuvir in SYNERGY-A and ERADICATE trials, and pegylated interferon (IFN) and ribavirin for 48 wk in the PIFNPK and ALBIN trials. Participants with baseline mental health disease (MHD) were identified (defined as either a DSM IV diagnosis of major depression, bipolar disorder, schizophrenia, generalized anxiety, and post-traumatic stress disorder or requiring anti-depressants, antipsychotics, mood stabilizers or psychotropics prescribed by a psychiatrist). For our first aim, we compared sustained virologic response (SVR) and adherence (pill counts, study visits, and in 25 patients, blood levels of the sofosbuvir metabolite, GS-331007) within each study. For our second aim, only patients with HIV coinfection were evaluated. BDI scores were obtained pre-treatment, during treatment, and post-treatment among participants treated with sofosbuvir-based therapy, and compared to scores from participants treated with interferon-based therapy. Statistical differences for both aims were analyzed by Fisher’s Exact, and t-test with significance defined as a P value less than 0.05.RESULTSBaseline characteristics did not differ significantly between all participants with and without MHD groups treated with sofosbuvir-based therapy. Among patients treated with sofosbuvir-based therapy, the percentage of patients with MHD who achieved SVR was the same as those without (SPARE: 60.9% of those MHD compared to 67.6% in those without, P = 0.78; SYNERGY-A: 100% of both groups; ERADICATE: 100% compared to 97.1%). There was no statistically significant difference in pill counts, adherence to study visits between groups, nor mean serum concentrations of GS-331007 for each group at week 2 of treatment (P = 0.72). Among patients with HIV co-infection, pre-treatment BDI scores were similar among patients treated with sofosbuvir, and those treated with interferon (sofosbuvir-based 5.24, IFN-based 6.96; P = 0.14); however, a dichotomous effect on was observed during treatment. Among participants treated with directly acting antiviral (DAA)-based therapy, mean BDI scores decreased from 5.24 (pre-treatment) to 3.28 during treatment (1.96 decrease, P = 0.0034) and 2.82 post-treatment. The decrease in mean score from pre- to post-treatment was stat...

Antidepressant effects of direct‐acting antivirals against hepatitis C virus—Results from a pilot study

“…Previous studies included more therapy‐naive patients with presumably shorter infection times. Concerning depressive symptoms under DAA treatment, the depression scores reduced by 50% in this study, whereas in another study a reduction of only 20% was described …”

“…Concerning depressive symptoms under DAA treatment, the depression scores reduced by 50% in this study, whereas in another study a reduction of only 20% was described. 39 Our findings could have important implications for HCV-infected patients, since many suffer from impaired quality of life. 6,7 A current survey reported that HCVinfected patients are four times more likely to develop depression in comparison with the general population.…”

“…The effect of these comorbidities in HCV‐infected patients on healthcare costs due to time off‐work and the use of psychological support facilities is largely unknown; however, the annual depression‐related healthcare costs for HCV‐infected patients in the United States have recently been estimated at $430 million . On the other hand, effective treatment does not only avoid progressive liver disease, but also impacts the frequency of depressive symptoms …”

“…40 On the other hand, effective treatment does not only avoid progressive liver disease, 41 but also impacts the frequency of depressive symptoms. 39…”

Applications of mechanistic modelling to clinical and experimental immunology: an emerging technology to accelerate immunotherapeutic discovery and development

“…The model was parameterised using Phase I and II trials that included telaprevir, and subsequently used to accurately predict sustained virological response rates in Phase II and III trials [13]. This has since been confirmed in the clinic [8,15,16]. This has since been confirmed in the clinic [8,15,16].…”