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Ting Tan created on 2008-11 Epsom & St Helier’s Healthcare Trust HIV and HCV Co-Infection Treatment Guidelines 2008 (Ting Tan, Clinical Nurse Specialist, Dr S. Moodie & Dr A. G. Lim Consultants Gastroenterology) Contents 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. Background Patient Selection - Inclusion Criteria, Exclusion Criteria Assessment & initial work-up Drug interactions When to start treatment Treatment options Length of treatment Dosage Treatment side-effects Treatment response and discontinuation Patient Monitoring Post treatment monitoring Dosage Modification Guidelines Counselling patients (see mono infection protocol 2004) General monitoring for patient who NOT on treatment Algorithm-BHIVA References Appendices 1. Patient Information Sheet - Combination treatment 2. Liver histology scores 3. Patient Monitoring Sheets 1 Ting Tan created on 2008-11 1.Background Primary Goal of therapy(2) Viral eradication (sustained viral response (SVR) defined as negative HCV PCR RNA 6 months after end of treatment). Secondary Goal of therapy(4) Improvement of fibrosis and necroinflammation and decreasing the risk of hepatotoxicity 2.Patient Selection: (i).Inclusion Criteria Similar to those in mono HCV infected patient 2004 Note: Ideally include information on histology obtained from liver biopsy, for accurate assessment of the stage and severity of disease However, due to high degree of success rate, Genotype 2 and 3 does not required biopsy (1) CD4 count > 200cells/mm³ 2 Ting Tan created on 2008-11 (ii)Exclusion Criteria HIV RNA > 100,000 copies/mL – Patient to initiate High Active Antiviral Therapy (HAART first, for minimum of 4-6 weeks before initiating HCV treatment (2) See mono HCV infected patient protocol 2004 HIV/HCV coinfection patient with decompensated liver disease. Referred patient to transplant centre 3.(i)Assessment: Clinical History Family History of liver disease Personal History - Any Intravenous Drug use - Previous and current alcohol intake - Psychiatric illness - Previous test for HCV - Any indication of possible time of first infection e.g. jaundice, tattoing, piercings, major operations, blood transfusions, date of first injected drug use Sex with a HCV-positive partner Examine the patient for clinical stigmata of chronic liver disease i.e. jaundice, spider angiomata, palmar erythema, splenomegaly and caput medusa 3 Ting Tan created on 2008-11 3.(ii)Initial work-up (1, 2) 1. HBsAg, anti-HBs 2. anti-HAV IgG 3. FBC 4. Clotiing Studies 5. Liver function tests (including albumin and GGT) 6. TFT 7. random glucose 8. prothrombin time 9. lipid profile 10. Serum Ferritin, serum iron and TIBC 11. Liver autoantibodies 12. Liver ultrasound 13. HCV Genotype and Viral load (note- if repeated exposure to HCV is suspected, genotype may change over time, hence need to be measure again later) 14. CD4 absolute counts and percentage 15. HIV RNA 16. Counselling including discussion of routes of transmission, complications of disease, treatment options and advise regarding alcohol intake 17. Opthalmologic evaluation (1,2) 18. Mental assessment 4.Drug Interactions (1,2) AZT/d4T Didanosine (ddl) (10) Stavudine/Zidovudine (10) 4 Ting Tan created on 2008-11 Concurrent administration of drugs as listed increases the risk of anaemia (16,17), increased mitochondrial toxicity such as pancreatitis and lactic acidosis (6,12,13), spontaneous hepatic decompensation (14,15) 5..When to start treatment HCV should be treated first if the HIV infection is stable and not requiring treatment (11) HIV should be treated prior to HCV if the CD4 count is low (CD4 count <200 cells/microL) (2) or patient deemed to be at risk of HIV progression Patient stabilized on HAART and has been on the medications for minimum of 46 weeks (2) 6.Treatment Options This treatment options and regime was drawn up in line with BHIVA(1) and UptoDate(2) recommendations. Note, that these are based upon higher SVR rate (5,7) Standard interferon is not recommended Pegylated Interferon (PegIFN) alpha and Ribavirin 7.Length of Treatment Pegylated Interferon and Ribavirin for 48 weeks for ALL Genotypes (1,2,5,6,7) For Genotype 1 with slow declining HCV RNA levels, and advanced liver disease, treat for additional 9 months after a non detectable viral load is achieved if patient is tolerating treatment.(21) 5 Ting Tan created on 2008-11 8.Dosage As per mono HCV infected patient protocol 2004 (pg 9) NOTE: Weight based Ribavirin (10.6mg/kg) for Genotype 1 and 4 (2,18,19,20) 9.Treatment side-effects Approximately 0.5 log fall in HIV viral load (5) Drop in absolute CD4 count CD4 percentage not affected (7) Opportunistic infections (5) See per mono HCV infected patient protocol 2004 10.Treatment response and discontinuation As per mono HCV infected patient protocol 2004 Note: In individual failing to achieve HCV RNA less than 50iu, or less than a 2 log drop in HCV RNA at 12 weeks, treatment is to continue if the aim is to achieve histological improvement rather than HCV eradiction (1) 11. Patients monitoring during treatment FBC every 1-2 weeks for 2 months TFT quarterly HIV RNA and CD4 counts and percentage every quarterly Lipid every 6mths HCV RNA at 12 weeks (4) Others as per mono HCV infected patient protocol 2004 6 Ting Tan created on 2008-11 12. Post treatment monitoring Late relapse or re-infection may occur and individuals who undergo SVR should have PCR performed yearly post successful therapy. 13.Dosage modifications guidelines As per mono HCV infected patient protocol 2004 Use growth factors (eg Neupogen or erythropoietin) to avoid dose decrements 14.Counselling patients see per mono HCV infected patient protocol 2004 CD4 counts may improve after stopping alcohol(9) 15.General monitoring for patients NOT ON treatment Cirrhotic patients (2) - Diagnostic imaging every 6 -12 months - Serum alphfetoprotein every 6-12 months - Endoscopy for presence of cirrhosis Note:Liver Biopsy (2) - Every 3 years if treatment deferred in fibrotic patients 7 Ting Tan created on 2008-11 8 Ting Tan created on 2008-11 17.References 1.BHIVA Guidelines-HIV and Chronic Hepatitis (2004): Co infection with HIV and Hepatitis C virus infection 2.McGovern, B.H. et al (2008) Management and treatment of hepatitis C in the HIVinfected patient, UptoDate (www.uptodate.com) 3.Kelleher, T.B. et al (2008) Management of treatment induced side effects for chronic hepatitis C, UptoDate (www.uptodate.com) 4.McGovern, B.H. (2007) Hepatitis in the HIV-infected patient, Journal Acquired Immune Deficiency Syndrome; 45 suppl 2:S47 5.Torrriani, F.J., M. Rodriguez-Torres, J.K. Rockstroh, et al (2004) The Apricot Trial: Peg interferon Alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients, New England Journal of Medicine; 351:438 6.Carrat, F. F. Bani-Sadr, et al, (2004) The Ribavic trial: Pegylated interferon alfa-2b vs standard interferon alfa-2b, plus ribavirin, for chronic hepatitis C in HIV infected patients: a randomized controlled trail; JAMA, 292:2839 7.Chung, R.T., J. Andersen et al (2004) The AIDS Clinical Trial Group (ACTG) 5071: Peginterferon alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons, New England Journal of Medicine; 351:451 8.Nunez, M., A. Marino et al, (2007) The Presco trial; Baseline serum hepatitis C virus (HCV) RNA level and response at week 4 are the best predictors of relapse after 9 Ting Tan created on 2008-11 treatment with pegylated interferon plus ribavirin in HIV/HCV coinfected patients, J Acquir Immnune Defic Syndr; 45:439 9.Pol. S., P. Artu, et al (1996) Improvement of CD4 cell count after alcohol withdrawal in HIV-positive alcoholic patients, AIDS; 10: 1293 10.Brinkman, K., J.A. Smeitink et al (1999) Mitochondrial toxicity induced by nucleoside-analogue reverse-transcriptase inhibitors is a key factor in the pathogenesis of antiretroviral-therapy-related lipodystrophy, Lancet; 354:1112 11.Soriano, V (2006) Treatment of chronic hepatitis C individuals:selection of candidates, J Hepatology; 44:S44 in HIV-positive 12.Sulkowaski, M.S., D.L.Thomas et al (2002) Hepatotoxicity associated with nevirapine or efavirenz-containing antiretroviral therapy: role of hepatitis C and B infections, Hepatology; 35:182 13.Vento, S., T. Garofano et al (1998) Enhancement of hepatitis C virus replication and liver damage in HIV-coinfected patients on antiretroviral combination therapy, AIDS; 12:116 14.Mauss, S., W.Valenti et al (2004) Risks factors for hepatic decompensation in patients with HIV/HCV coinfection and liver cirrhosis during interferon-based therapy, AIDS; 18:f21 15.Bani-Sadr, F., F. Carrat et al (2005) Spontaneous hepatic decompensation in patients coinfected with HIV and hepatitis C virus during interferon-ribavirin combination treatment, Clinical Infection Disease; 41:1806 16.Fuster, D., J.A. Gomez et al (2005) Short communication. Baseline factors associated with haematological toxicity that leads to a dosage reduction of pegylated 10 Ting Tan created on 2008-11 interferon-alpha2a and ribavirin in HIV-and HCV-coinfected patients on HCV antiviral therapy,Antiviral Therapy;10:841 17.Brau, N, M. Rodriquez-Torres et al (2004) Treatment of chronic alpha-2b+ full course vs 16-week delayed ribavirin, Hepatology; 39: 989 18.Manns, M., J. McHutchinson et al (2001) Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomized trial, Lancet; 358:958 19.Fried, M.W., M.L. Shiffman et al (2002) Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection, New England Journal Medicine; 347:975 20.Hadziyannis, S.J., H.Jr, Sette et al (2004) Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose, Annal Internal Medicine; 140:346 21.Drusano, G.L. & S.L.Preston (2004) A 48 week duration of therapy with pegylated interferon alpha 2b plus ribavirin may be too short to maximize long term response among patients infected with genotype-1 hepatitis C virus, J Infect Dis; 189:964 11