title: Safe and effective sofosbuvir-based therapy in patients with mental health disease on hepatitis C virus treatment.
abstract: OBJECTIVE
  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, andt-test with significance defined as aPvalue 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Lydia Shuk Yee Tang, Jack Masur, Amy Nelson, Sarah Kattakuzhy, Shyam Kottilil, Institute of Human Virology, Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, United States.
authors.forename: Lydia Shuk Yee
authors.initials: LS
authors.lastname: Tang
authors.affiliation: Lydia Shuk Yee Tang, Jack Masur, Amy Nelson, Sarah Kattakuzhy, Shyam Kottilil, Institute of Human Virology, Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, United States.
authors.forename: Jack
authors.initials: J
authors.lastname: Masur
authors.affiliation: Lydia Shuk Yee Tang, Jack Masur, Amy Nelson, Sarah Kattakuzhy, Shyam Kottilil, Institute of Human Virology, Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, United States.
authors.forename: Zayani
authors.initials: Z
authors.lastname: Sims
authors.affiliation: Lydia Shuk Yee Tang, Jack Masur, Amy Nelson, Sarah Kattakuzhy, Shyam Kottilil, Institute of Human Virology, Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, United States.
authors.forename: Amy
authors.initials: A
authors.lastname: Nelson
authors.affiliation: Lydia Shuk Yee Tang, Jack Masur, Amy Nelson, Sarah Kattakuzhy, Shyam Kottilil, Institute of Human Virology, Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, United States.
authors.forename: Anu
authors.initials: A
authors.lastname: Osinusi
authors.affiliation: Lydia Shuk Yee Tang, Jack Masur, Amy Nelson, Sarah Kattakuzhy, Shyam Kottilil, Institute of Human Virology, Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, United States.
authors.forename: Anita
authors.initials: A
authors.lastname: Kohli
authors.affiliation: Lydia Shuk Yee Tang, Jack Masur, Amy Nelson, Sarah Kattakuzhy, Shyam Kottilil, Institute of Human Virology, Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, United States.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kattakuzhy
authors.affiliation: Lydia Shuk Yee Tang, Jack Masur, Amy Nelson, Sarah Kattakuzhy, Shyam Kottilil, Institute of Human Virology, Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Polis
authors.affiliation: Lydia Shuk Yee Tang, Jack Masur, Amy Nelson, Sarah Kattakuzhy, Shyam Kottilil, Institute of Human Virology, Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, United States.
authors.forename: Shyam
authors.initials: S
authors.lastname: Kottilil
keywords: Beck’s Depression Inventory; Depression; Direct acting antivirals; Directly acting antiviral; Hepatitis C; Interferon; Mental health disease; Sofosbuvir