Twice-weekly pegylated interferon-α-2a and ribavirin results in superior viral kinetics in HIV/hepatitis C virus co-infected patients compared to standard therapy

Murphy, Alison; Herrmann, Eva; Osinusi, Anu; Wu, Lynn Xue; Sachau, William; Lempicki, Richard A.; Yang, Jun; Chung, T.L.; Wood, Bradford J.; Haagmans, Bart L.; Kottilil, Shyam; Polis, Michael A.

doi:10.1097/qad.0b013e3283471d53

Cited by 17 publications

(13 citation statements)

References 29 publications

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“…Likewise, faster HCV-RNA clearance and higher rates of EVR were observed with high doses of pegIFN-a induction, supporting our results. However, these results did not translate into higher SVR rates, most likely due to reversal of the initial effect after a reduction to the standard dose after the first 4-12 weeks of therapy [15, [44][45][46][47][48][49].…”

Section: Discussionmentioning

confidence: 99%

Impact of the peginterferon‐α 2a and ribavirin plasma levels on viral kinetics and sustained virological response in genotype 1 HCV/HIV‐co‐infected patients with the unfavourable non‐CC IL28B genotypes

Torres-Cornejo

Ruiz-Valderas

Jiménez-Jiménez

et al. 2013

Journal of Viral Hepatitis

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Studies on the association between the peginterferon-α and ribavirin levels and sustained virological response (SVR) have shown yielded conflicting results, but most of them were performed before the influence of IL28B polymorphisms was known. Our aim was to assess the effects of peginterferon-α 2a and ribavirin plasma levels on viral kinetics and SVR in hepatitis C virus genotype 1 HCV-1/HIV-co-infected patients according to IL28B genotype. This was a cohort study of HCV-1/HIV-co-infected patients who were HCV-treatment naïve and for whom the efficacy of peginterferon-α 2a plus ribavirin was evaluated by per-protocol analysis. The peginterferon-α 2a and ribavirin levels were measured by ELISA and HPLC-UV, respectively. The relationships among host and viral factors, the trough drugs levels and virological responses were analysed by multivariate regression analyses. A total of 131 Caucasian patients were included (cirrhosis:38.9%). Overall, SVR rate was 39.6%. In patients with CC IL28B genotype, SVR was related neither to peginterferon-α 2a nor to ribavirin plasma levels, while higher levels of both drugs were the only variables independently associated with SVR in individuals with CT/TT IL28B genotypes (OR, 5.02; CI95 , 1.45-17.1; P = 0.001 and 4.0; CI95 , 1.08-14.7; P = 0.038, respectively). Moreover, faster viral declines were observed in CT/TT patients when pegIFN-α 2a and ribavirin plasma levels were greater than 3400 pg/mL and 1.6 μg/mL, respectively. In contrast to the results for CC patients, the results in patients carrying the unfavourable CT/TT IL28B genotypes showed that plasma levels of both drugs have significant effects on viral kinetics and SVR.

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Section: Discussionmentioning

confidence: 99%

Impact of the peginterferon‐α 2a and ribavirin plasma levels on viral kinetics and sustained virological response in genotype 1 HCV/HIV‐co‐infected patients with the unfavourable non‐CC IL28B genotypes

Torres-Cornejo

Ruiz-Valderas

Jiménez-Jiménez

et al. 2013

Journal of Viral Hepatitis

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“…In the ALBIN study, Alb-interferon (albumin/interferon alfa 2b fusion protein 900 μg subcutaneous injection every two weeks, Peg-Intron; Schering-Plough) was evaluated. Eligibility criteria as previously published[26-28]. …”

Section: Methodsmentioning

confidence: 99%

“…In this study, we present data from five National Institute of Allergy and Infectious Diseases (NIAID) trials - SPARE[19] (using sofosbuvir and ribavirin), SYNERGY-A[18], and ERADICATE[25] (both using ledipasvir and sofosbuvir), and PIFNPK[26] and ALBIN[27] [studies of interferon (IFN)-ribavirin-based therapy among patients with human immunodeficiency virus (HIV)/HCV co-infection]. This study has two aims.…”

Section: Introductionmentioning

confidence: 99%

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

Tang¹,

Masur²,

Sims³

et al. 2016

WJH

Self Cite

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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...

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“…Mathematical modelling of HCV viral kinetics from week −6 to week 12 was performed as previously described . A maximum‐likelihood approach was applied to account for data below the detection limit.…”

Section: Methodsmentioning

confidence: 99%

Impact of ribavirin priming on viral kinetics and treatment response in chronic hepatitis C genotype 1 infection

Mihm

Welker

Teuber

et al. 2013

Journal of Viral Hepatitis

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Ribavirin amplifies the interferon-alpha (IFN) signalling cascade. As ribavirin needs 4 weeks to reach steady state, ribavirin priming may optimize hepatic IFN sensitivity before starting a pegylated (PEG)-IFN/ribavirin combination therapy. This study investigated potential benefits of ribavirin priming prior to PEG-IFN2a/ribavirin combination therapy on viral kinetics, on-treatment and sustained virological response (SVR) in chronic hepatitis C virus (HCV) genotype 1 infection. Sixty-eight treatment naive patients were randomized 2:2:1 to ribavirin (ribavirin arm) or placebo (placebo arm) or PEG-IFN2a (PEG-IFN2a arm) for 6 weeks prior to 12 weeks of PEG-IFN2a/ribavirin combination therapy within a double-blind, placebo-controlled trial. Then, standard PEG-IFN2a/ribavirin combination therapy according to the German guidelines was continued under the responsibility of the investigators. Ribavirin was given according to body weight and PEG-IFN2a at a dose of 180 μg subcutaneously once/week. During ribavirin priming, HCV RNA showed a decline of -0.58 log10 IU/mL (P < 0.001) that was unrelated to the IL28B rs12979860 genotype (CC vs CT/TT, P = 0.244). Ribavirin priming did neither increase the PEG-IFN2a-induced first- or second-phase viral decline (P values >0.100) nor on-treatment response or SVR (HCV RNA undetectable at week 12 of combination therapy: ribavirin arm 56%, placebo arm 38%, PEG-IFN2a arm 50%; SVR: ribavirin arm 41%, placebo arm 54%, PEG-IFN2a arm 50%; P values >0.300). In conclusion, ribavirin monotherapy showed a significant antiviral activity that was not influenced by the IL28B genotype. Ribavirin priming prior to PEG-IFN2a/ribavirin combination therapy did neither increase the first- or second-phase viral decline nor on-treatment response or SVR.

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Twice-weekly pegylated interferon-α-2a and ribavirin results in superior viral kinetics in HIV/hepatitis C virus co-infected patients compared to standard therapy

Cited by 17 publications

References 29 publications

Impact of the peginterferon‐α 2a and ribavirin plasma levels on viral kinetics and sustained virological response in genotype 1 HCV/HIV‐co‐infected patients with the unfavourable non‐CC IL28B genotypes

Impact of the peginterferon‐α 2a and ribavirin plasma levels on viral kinetics and sustained virological response in genotype 1 HCV/HIV‐co‐infected patients with the unfavourable non‐CC IL28B genotypes

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

Impact of ribavirin priming on viral kinetics and treatment response in chronic hepatitis C genotype 1 infection

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