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

AIM: To 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.

METHODS: This 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.

RESULTS: Baseline 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 statistically significant (-2.42, P = 0.0012). Among participants treated with IFN-based therapy, mean BDI score increased from 6.96 at pre-treatment to 9.19 during treatment (an increase of 2.46 points, P = 0.1), and then decreased back to baseline post-treatment (mean BDI score 6.3, P = 0.54). Overall change in mean BDI scores from pre-treatment to during treatment among participants treated with DAA-based and IFN-therapy was statistically significant (-1.96 and +2.23, respectively; P = 0.0032). This change remained statistically significant when analysis was restricted to participants who achieved SVR (-2.0 and +4.36, respectively; P = 0.0004).

CONCLUSION: Sofosbuvir-based therapy is safe and well tolerated in patients with MHD. A decline in BDI associated with sofosbuvir-based HCV treatment suggests additional MHD benefits, although the duration of these effects is unknown.