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...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 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).CONCLUSIONSofosbuvir-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.展开更多
文摘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 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).CONCLUSIONSofosbuvir-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.
