Skip to main content
Top
Published in: Journal of NeuroVirology 2/2017

01-04-2017

Greater decline in memory and global neurocognitive function in HIV/hepatitis C co-infected than in hepatitis C mono-infected patients treated with pegylated interferon and ribavirin

Authors: Theodore R. Miller, Jeffrey J. Weiss, Norbert Bräu, Douglas T. Dieterich, Alicia Stivala, Monica Rivera-Mindt

Published in: Journal of NeuroVirology | Issue 2/2017

Login to get access

Abstract

The human immunodeficiency virus (HIV), hepatitis C virus (HCV), and the treatment of HCV with pegylated interferon and ribavirin (IFN/RBV) have been associated with neurocognitive and psychiatric abnormalities. The goal of this research was to prospectively evaluate neurocognitive functioning among a group of HCV mono-infected and HIV/HCV co-infected patients during the first 24 weeks of IFN/RBV treatment while accounting for practice effects, normal variations in change over time, and variations in IFN/RBV treatment exposure. Forty-four HCV mono-infected and 30 HIV/HCV co-infected patients were enrolled in a prospective study of patients beginning on IFN/RBV for chronic HCV infection. Patients were administered a depression inventory, a measure of fatigue, a structured psychiatric interview, and a neurocognitive battery at baseline and 24 weeks after initiation of treatment. Analyses were conducted to explore possible associations between neurocognitive functioning and the following: HIV/HCV co-infection vs. HCV mono-infection, IFN and RBV treatment exposure, psychiatric status, liver disease stage, and other medical characteristics. At baseline, there were no significant differences between the two groups’ neuropsychiatric or neurocognitive function other than the mono-infected group had significantly higher reports of fatigue (p = 0.033). Over the course of 24 weeks of treatment after controlling for practice effects, the HIV/HCV co-infected patients experienced significantly greater declines in memory (t(56) = 2.14, p = 0.037) and global neurocognitive functioning (t(53) = 2.28, p = 0.027). In a well-characterized sample of mono-infected and co-infected patients, it appears that persons with HIV/HCV co-infection are potentially more vulnerable to neurocognitive sequalae during HCV treatment.
Literature
go back to reference Aaron BT (2000) BDI-fast screen for medical patients: manual. The Psychological Corporation, San Antonio, TX Aaron BT (2000) BDI-fast screen for medical patients: manual. The Psychological Corporation, San Antonio, TX
go back to reference Asnis GM, 2nd dela Garza R, Miller AH (2004) Ribavirin may be an important factor in IFN-induced neuropsychiatric effects. Asnis GM, 2nd dela Garza R, Miller AH (2004) Ribavirin may be an important factor in IFN-induced neuropsychiatric effects.
go back to reference Averhoff, G (2012) Global burden of hepatitis C: considerations for healthcare providers in the United States. doi:10.1093/cid/cis361 Averhoff, G (2012) Global burden of hepatitis C: considerations for healthcare providers in the United States. doi:10.1093/cid/cis361
go back to reference Banerjee D, Reddy KR (2016) Review article: safety and tolerability of direct-acting anti-viral agents in the new era of hepatitis C therapy. Aliment Pharmacol Ther 43(6):674–696CrossRefPubMed Banerjee D, Reddy KR (2016) Review article: safety and tolerability of direct-acting anti-viral agents in the new era of hepatitis C therapy. Aliment Pharmacol Ther 43(6):674–696CrossRefPubMed
go back to reference Beck AT, Steer B (1996) Beck depression inventory-II. Beck AT, Steer B (1996) Beck depression inventory-II.
go back to reference Calabresi PA, Kieseier BC, Arnold DL, Balcer LJ (2014) Pegylated interferon beta-1a for relapsing-remitting multiple sclerosis (ADVANCE): a randomised, phase 3, double-blind study. Calabresi PA, Kieseier BC, Arnold DL, Balcer LJ (2014) Pegylated interferon beta-1a for relapsing-remitting multiple sclerosis (ADVANCE): a randomised, phase 3, double-blind study.
go back to reference Cattie J, Letendre S, Woods S, Barakat F, Perry W, Cherner M et al (2014) Persistent neurocognitive decline in a clinic sample of hepatitis C virus-infected persons receiving interferon and ribavirin treatment. Journal of NeuroVirology 20:561570. doi:10.1007/s13365-014-0265-3 CrossRef Cattie J, Letendre S, Woods S, Barakat F, Perry W, Cherner M et al (2014) Persistent neurocognitive decline in a clinic sample of hepatitis C virus-infected persons receiving interferon and ribavirin treatment. Journal of NeuroVirology 20:561570. doi:10.​1007/​s13365-014-0265-3 CrossRef
go back to reference Cha L, Berry CM, Nolan D, Castley A, Fernandez S, French MA (2014) Interferon-alpha, immune activation and immune dysfunction in treated HIV infection. Clinical & Translational Immunology 3(2):e10CrossRef Cha L, Berry CM, Nolan D, Castley A, Fernandez S, French MA (2014) Interferon-alpha, immune activation and immune dysfunction in treated HIV infection. Clinical & Translational Immunology 3(2):e10CrossRef
go back to reference Chiu W-C, Tsan Y-T, Tsai S-L et al (2014) Hepatitis C viral infection and the risk of dementia. European journal of neurology : the official journal of the European Federation of Neurological Societies 21:1068–1e59. doi:10.1111/ene.12317 CrossRef Chiu W-C, Tsan Y-T, Tsai S-L et al (2014) Hepatitis C viral infection and the risk of dementia. European journal of neurology : the official journal of the European Federation of Neurological Societies 21:1068–1e59. doi:10.​1111/​ene.​12317 CrossRef
go back to reference Cysique LA, Franklin D Jr, Abramson I (2011) Normative data and validation of a regression based summary score for assessing meaningful neuropsychological change. J Clin Exp Neuropsychol. doi:10.1080/13803395.2010.535504 Cysique LA, Franklin D Jr, Abramson I (2011) Normative data and validation of a regression based summary score for assessing meaningful neuropsychological change. J Clin Exp Neuropsychol. doi:10.​1080/​13803395.​2010.​535504
go back to reference Dieperink, W (2000) Neuropsychiatric symptoms associated with hepatitis C and interferon alpha: a review. Dieperink, W (2000) Neuropsychiatric symptoms associated with hepatitis C and interferon alpha: a review.
go back to reference Fontana RJ, Bieliauskas LA, Back-Madruga C (2010) Cognitive function does not worsen during long-term low-dose peginterferon therapy in patients with chronic hepatitis C. Fontana RJ, Bieliauskas LA, Back-Madruga C (2010) Cognitive function does not worsen during long-term low-dose peginterferon therapy in patients with chronic hepatitis C.
go back to reference Fontana RJ, Bieliauskas LA, Lindsay KL (2007) Cognitive function does not worsen during pegylated interferon and ribavirin retreatment of chronic hepatitis C. Hepathology. doi:10.1002/hep.21633 Fontana RJ, Bieliauskas LA, Lindsay KL (2007) Cognitive function does not worsen during pegylated interferon and ribavirin retreatment of chronic hepatitis C. Hepathology. doi:10.​1002/​hep.​21633
go back to reference Forton, T-R (2006) Central nervous system changes in hepatitis C virus infection. Forton, T-R (2006) Central nervous system changes in hepatitis C virus infection.
go back to reference Heaton RK, Kirson D, Velin RA, Grant I (1994) The utility of clinical ratings for detecting cognitive change in HIV infection. Heaton RK, Kirson D, Velin RA, Grant I (1994) The utility of clinical ratings for detecting cognitive change in HIV infection.
go back to reference Heaton RK, Clifford DB, Franklin DR Jr, Woods SP (2010a) HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy CHARTER study. Neurology. doi:10.1212/WNL.0b013e318200d727 Heaton RK, Clifford DB, Franklin DR Jr, Woods SP (2010a) HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy CHARTER study. Neurology. doi:10.​1212/​WNL.​0b013e318200d727​
go back to reference Heaton RK, Franklin DR, Deutsch R, et al (2015) Neurocognitive change in the era of HIV combination antiretroviral therapy: the longitudinal CHARTER study. doi: 10.1093/cid/ciu862 Heaton RK, Franklin DR, Deutsch R, et al (2015) Neurocognitive change in the era of HIV combination antiretroviral therapy: the longitudinal CHARTER study. doi: 10.1093/cid/ciu862
go back to reference Hilsabeck, C (2005a) Neuropsychological aspects of coinfection with HIV and hepatitis C virus. doi: 10.1086/429494 Hilsabeck, C (2005a) Neuropsychological aspects of coinfection with HIV and hepatitis C virus. doi: 10.1086/429494
go back to reference Hilsabeck, H (2005b) Effect of Interferon-[alpha] on cognitive functioning in patients with chronic hepatitis C. Hilsabeck, H (2005b) Effect of Interferon-[alpha] on cognitive functioning in patients with chronic hepatitis C.
go back to reference Hinkin CH, Aronow HA, Hilsabeck RC (2004) Psychiatric and cognitive concomitants of HIV and HCV co-infection. In: National Institute on Drug Abuse (NIDA) symposium on issues in the medical management of HIV/HCV co-infection in IDUs (Washington, DC). Hinkin CH, Aronow HA, Hilsabeck RC (2004) Psychiatric and cognitive concomitants of HIV and HCV co-infection. In: National Institute on Drug Abuse (NIDA) symposium on issues in the medical management of HIV/HCV co-infection in IDUs (Washington, DC).
go back to reference Hinton-Bayre AD (2010a) Deriving reliable change statistics from test–retest normative data: comparison of models and mathematical expressions. Hinton-Bayre AD (2010a) Deriving reliable change statistics from test–retest normative data: comparison of models and mathematical expressions.
go back to reference Hinton-Bayre AD (2010b) Specificity of reliable change models and review of the within-subjects standard deviation as an error term. doi: 10.1093/arclin/acq087 Hinton-Bayre AD (2010b) Specificity of reliable change models and review of the within-subjects standard deviation as an error term. doi: 10.1093/arclin/acq087
go back to reference Huckans M, Fuller B, Wheaton V et al (2015) A longitudinal study evaluating the effects of interferon-alpha therapy on cognitive and psychiatric function in adults with chronic hepatitis C. J Psychosom Res 78:184–192CrossRefPubMed Huckans M, Fuller B, Wheaton V et al (2015) A longitudinal study evaluating the effects of interferon-alpha therapy on cognitive and psychiatric function in adults with chronic hepatitis C. J Psychosom Res 78:184–192CrossRefPubMed
go back to reference Koziel, P (2007) Viral hepatitis in HIV infection. Koziel, P (2007) Viral hepatitis in HIV infection.
go back to reference Krefetz DG, Steer RA, Jermyn RT (2004) Screening HIV-infected patients with chronic pain for anxiety and mood disorders with the Beck anxiety and depression inventory-fast screens for medical settings. J Clin Psychol Med Settings. doi:10.1023/B:JOCS.0000045348.28440.82 Krefetz DG, Steer RA, Jermyn RT (2004) Screening HIV-infected patients with chronic pain for anxiety and mood disorders with the Beck anxiety and depression inventory-fast screens for medical settings. J Clin Psychol Med Settings. doi:10.​1023/​B:​JOCS.​0000045348.​28440.​82
go back to reference Lieb K, Engelbrecht MA, Gut O, et al (2006) Cognitive impairment in patients with chronic hepatitis treated with interferon alpha (IFNα): results from a prospective study. Lieb K, Engelbrecht MA, Gut O, et al (2006) Cognitive impairment in patients with chronic hepatitis treated with interferon alpha (IFNα): results from a prospective study.
go back to reference Maassen GH (2010) The two errors of using the within-subject standard deviation (WSD) as the standard error of a reliable change index. doi: 10.1093/arclin/acq036 Maassen GH (2010) The two errors of using the within-subject standard deviation (WSD) as the standard error of a reliable change index. doi: 10.1093/arclin/acq036
go back to reference Majer, WL, Capuron, P (2008) IFN-alpha-induced motor slowing is associated with increased depression and fatigue in patients with chronic hepatitis C. Majer, WL, Capuron, P (2008) IFN-alpha-induced motor slowing is associated with increased depression and fatigue in patients with chronic hepatitis C.
go back to reference Martin EM, Novak RM, Fendrich M (2004) Stroop performance in drug users classified by HIV and hepatitis C virus serostatus. Martin EM, Novak RM, Fendrich M (2004) Stroop performance in drug users classified by HIV and hepatitis C virus serostatus.
go back to reference McAndrews M, Farcnik K, Carlen P et al (2005) Prevalence and significance of neurocognitive dysfunction in hepatitis C in the absence of correlated risk factors. Hepatology (Baltimore, Md) 41:801–808. doi:10.1002/hep.20635 CrossRef McAndrews M, Farcnik K, Carlen P et al (2005) Prevalence and significance of neurocognitive dysfunction in hepatitis C in the absence of correlated risk factors. Hepatology (Baltimore, Md) 41:801–808. doi:10.​1002/​hep.​20635 CrossRef
go back to reference McHutchison JG, Gordon SC, Schiff ER (1998) Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. McHutchison JG, Gordon SC, Schiff ER (1998) Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C.
go back to reference McSweeny JA, Naugle RI, Chelune GJ (1993) “T scores for change”: an illustration of a regression approach to depicting change in clinical neuropsychology. Clinical Neuropsychologist. doi:10.1080/13854049308401901 McSweeny JA, Naugle RI, Chelune GJ (1993) “T scores for change”: an illustration of a regression approach to depicting change in clinical neuropsychology. Clinical Neuropsychologist. doi:10.​1080/​1385404930840190​1
go back to reference Mohr P, Hauschild A, Trefzer U et al (2015) Intermittent high-dose intravenous interferon Alfa-2b for adjuvant treatment of stage III melanoma: final analysis of a randomized phase III dermatologic cooperative oncology group trial. J Clin Oncol 33:4077–4084. doi:10.1200/JCO.2014.59.6932 CrossRefPubMed Mohr P, Hauschild A, Trefzer U et al (2015) Intermittent high-dose intravenous interferon Alfa-2b for adjuvant treatment of stage III melanoma: final analysis of a randomized phase III dermatologic cooperative oncology group trial. J Clin Oncol 33:4077–4084. doi:10.​1200/​JCO.​2014.​59.​6932 CrossRefPubMed
go back to reference Pavan MH, Velho PE, Vigani AG et al (2007) Treatment of human papillomavirus with peg-interferon alfa-2b and ribavirin. Braz J Infect Dis 11:383–384CrossRefPubMed Pavan MH, Velho PE, Vigani AG et al (2007) Treatment of human papillomavirus with peg-interferon alfa-2b and ribavirin. Braz J Infect Dis 11:383–384CrossRefPubMed
go back to reference Pawelczyk T, Pawelczyk A, Strzelecki D, Rabe-Jablonska J (2008) Pegylated interferon and ribavirin therapy may induce working memory disturbances in chronic hepatitis C patients. Gen Hosp Psychiatry 30:501–508CrossRefPubMed Pawelczyk T, Pawelczyk A, Strzelecki D, Rabe-Jablonska J (2008) Pegylated interferon and ribavirin therapy may induce working memory disturbances in chronic hepatitis C patients. Gen Hosp Psychiatry 30:501–508CrossRefPubMed
go back to reference Poynard T, Marcellin P, Lee S et al (1998) Randomised trial of interferon 2b plus ribavirin for 48 weeks or for 24 weeks versus interferon 2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. Lancet 352:1426–1432CrossRefPubMed Poynard T, Marcellin P, Lee S et al (1998) Randomised trial of interferon 2b plus ribavirin for 48 weeks or for 24 weeks versus interferon 2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. Lancet 352:1426–1432CrossRefPubMed
go back to reference Reichenberg A, Gorman J, Dieterich D (2005) Interferon-induced depression and cognitive impairment in hepatitis C virus patients: a 72 week prospective study. AIDS (London, England) 19(Suppl 3):S174–S178CrossRef Reichenberg A, Gorman J, Dieterich D (2005) Interferon-induced depression and cognitive impairment in hepatitis C virus patients: a 72 week prospective study. AIDS (London, England) 19(Suppl 3):S174–S178CrossRef
go back to reference Schaefer M, Hinzpeter A, Mohmand A, Janssen G (2007) Hepatitis C treatment in “difficult-to-treat” psychiatric patients with pegylated interferon-alpha and ribavirin: response and psychiatric side effects. Hpatology. doi:10.1002/hep.21791 Schaefer M, Hinzpeter A, Mohmand A, Janssen G (2007) Hepatitis C treatment in “difficult-to-treat” psychiatric patients with pegylated interferon-alpha and ribavirin: response and psychiatric side effects. Hpatology. doi:10.​1002/​hep.​21791
go back to reference Schaefer M, Engelbrechta M, Gut O et al (2002) Interferon alpha (IFN) and psychiatric syndromes: a review. Prog Neuro-Psychopharmacol Biol Psychiatry 26:731–746CrossRef Schaefer M, Engelbrechta M, Gut O et al (2002) Interferon alpha (IFN) and psychiatric syndromes: a review. Prog Neuro-Psychopharmacol Biol Psychiatry 26:731–746CrossRef
go back to reference Shrestha NK, Hamrock DJ (2010) Successful treatment of disseminated human papillomavirus infection with pegylated interferon and ribavirin. Clin Infect Dis 51:e4–e6. doi:10.1086/653428 CrossRefPubMed Shrestha NK, Hamrock DJ (2010) Successful treatment of disseminated human papillomavirus infection with pegylated interferon and ribavirin. Clin Infect Dis 51:e4–e6. doi:10.​1086/​653428 CrossRefPubMed
go back to reference Statistical Package for Social Sciences for Windows, Version 22.0. Chicago, Illinois. 2015. Statistical Package for Social Sciences for Windows, Version 22.0. Chicago, Illinois. 2015.
go back to reference Tanaka, M, Shigekawa, U (2006) Neuropsychological impairment and decreased regional cerebral blood flow by interferon treatment in patients with chronic hepatitis: a preliminary study. doi: 10.1007/s10238–006–0107-6 Tanaka, M, Shigekawa, U (2006) Neuropsychological impairment and decreased regional cerebral blood flow by interferon treatment in patients with chronic hepatitis: a preliminary study. doi: 10.1007/s10238–006–0107-6
go back to reference Thein HH, Yi Q, Dore GJ, Krahn MD (2008) Natural history of hepatitis C virus infection in HIV-infected individuals and the impact of HIV in the era of highly active antiretroviral therapy: a meta-analysis. AIDS. doi:10.1097/QAD.0b013e32830e6d51 PubMed Thein HH, Yi Q, Dore GJ, Krahn MD (2008) Natural history of hepatitis C virus infection in HIV-infected individuals and the impact of HIV in the era of highly active antiretroviral therapy: a meta-analysis. AIDS. doi:10.​1097/​QAD.​0b013e32830e6d51​ PubMed
go back to reference Thein H, Maruff P, Krahn M, Kaldor J (2007) Cognitive function, mood and health-related quality of life in hepatitis C virus (HCV)-monoinfected and HIV/HCV-coinfected individuals commencing HCV. HIV Med. doi:10.1111/j.1468-1293.2007.00452.x Thein H, Maruff P, Krahn M, Kaldor J (2007) Cognitive function, mood and health-related quality of life in hepatitis C virus (HCV)-monoinfected and HIV/HCV-coinfected individuals commencing HCV. HIV Med. doi:10.​1111/​j.​1468-1293.​2007.​00452.​x
go back to reference Wobrock T, Mihm U, Löhr C et al (2008) Cognition in hepatitis C patients treated with pegylated interferon. The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry 10:819–826. doi:10.1080/15622970701714362 CrossRef Wobrock T, Mihm U, Löhr C et al (2008) Cognition in hepatitis C patients treated with pegylated interferon. The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry 10:819–826. doi:10.​1080/​1562297070171436​2 CrossRef
go back to reference Woods, R, Frol, L (2004) Interrater reliability of clinical ratings and neurocognitive diagnoses in HIV. doi: 10.1080/13803390490509565 Woods, R, Frol, L (2004) Interrater reliability of clinical ratings and neurocognitive diagnoses in HIV. doi: 10.1080/13803390490509565
Metadata
Title
Greater decline in memory and global neurocognitive function in HIV/hepatitis C co-infected than in hepatitis C mono-infected patients treated with pegylated interferon and ribavirin
Authors
Theodore R. Miller
Jeffrey J. Weiss
Norbert Bräu
Douglas T. Dieterich
Alicia Stivala
Monica Rivera-Mindt
Publication date
01-04-2017
Publisher
Springer International Publishing
Published in
Journal of NeuroVirology / Issue 2/2017
Print ISSN: 1355-0284
Electronic ISSN: 1538-2443
DOI
https://doi.org/10.1007/s13365-016-0494-8

Other articles of this Issue 2/2017

Journal of NeuroVirology 2/2017 Go to the issue