Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Hepatitis B and Hepatitis C in Patients with HIV Infection HAIVN Harvard Medical School AIDS Initiative in Vietnam 1 Learning Objectives By the end of this session, participants will be able to: Explain how liver disease affects PLHIV Explain the mechanics of HIV/HBV and HIV/HCV interactions Describe how to prevent HBV and HCV Explain treatment options for HIV/HBV and HIV/HCV co-infection 2 Mortality (%) Mortality from End-stage Liver Disease as a Percentage of all Deaths Among HIV Patients 60 Pre-ART era 50 ART era 40 35% 50% 45% 30 20 13% 10 0 12% 5% Italy (Brescia) Spain (Madrid) USA (Boston) 3 Hepatitis B Virus (HBV) 4 HBV Basics Hepatitis B is a viral infection that attacks the liver It can cause both acute and chronic disease Symptoms of acute infection include: • yellowing of skin and eyes (jaundice) • dark urine • extreme fatigue • nausea, vomiting • abdominal pain Chronic liver infection can lead to: • liver fibrosis (cirrhosis) • liver cancer 5 HBV Transmission Infected Person IDU/Blood Unsafe Sex Occ. Exposure Infected Mother Infected Adult 30-50% symptomatic 0.5-1% mortality Infected Baby (< 10% symptomatic) 90% Resolve Infection 5-10% 90% Chronic Infection Global Epidemiology of HBV 2 billion HBV infections 6 billion people in the world 25% mortality from HCC or cirrhosis 300–400 million chronic HBV 7 Global Epidemiology of Chronic HBV HBsAg prevalence > = 8% - High 2% - 8% - Medium < 2% - Low 8 Epidemiology of HBV Infection in Vietnam Vietnam is a country with a high prevalence (>8%) of chronic HBV HBV prevalence (HBsAg+) in different populations includes: • General population: 10-20% • Healthcare workers: 8-18% • HIV +: 10-15% Nguyen TTM. Liver International 2008 Nguyen TC. CROI Abstract 2010 9 HBV Prevention HBV is preventable with a safe, effective vaccine All infants should receive HBV vaccine series Adults in high risk groups should also be vaccinated, including: • persons with high-risk sexual behavior • partners and household contacts of HBV infected persons • injecting drug users • HIV-infected patients • Health care workers Have you been vaccinated? 10 HBV Diagnosis HBsAg AntiHBs AntiHBc IgM AntiHBc Interpretation - - - Susceptible - + + Immune due to natural infection - + - Immune due to vaccination + - + + Acutely infected + - + - Chronically infected 11 HBV/HIV Interaction Compared to HIV- individuals, patients with HIV and HBV are more likely to: • Develop chronic infection (21% vs. 7%) • Be “e antigen” positive and have higher levels of HBV DNA • Experience faster progression of liver disease with increased rates of cirrhosis and liver cancer HBV does not appear to affect progression of HIV infection 12 HIV/HBV Treatment (1): When to Treat Treatment of chronic HBV in a PLHIV is indicated when: • HIV treatment is indicated AND / OR • HBV treatment is indicated 13 HIV/HBV Treatment (2): Criteria for HBV Treatment Elevated HBV DNA and elevated ALT HBeAg positive HBeAg negative • • • • HBV DNA ALT > 2X HBV DNA ALT > 2X > 20,000 IU/ml and normal > 2,000 IU/ml and normal Presence of HBsAg and repeatedly elevated liver enzymes suggests active disease and need for HBV therapy 14 Dose HBV Treatment Drug Lamivudine 100 mg/day (HBV Options mono-infection) (3TC, Epivir) 3TC, TDF, Entecavir have activity against both HIV and HBV 300 mg/day (HIV coinfection) Tenofovir (TDF, Viread) 300 mg/day Adefovir (Hepsera) 10 mg/day 0.5 mg/day Entecavir (Baraclude) 1 mg/day if 3TC resistant Telbivudine 600 mg/day Peg180 mcg SQ/wk Interferon HIV/HBV Treatment Options (1) Indication Treatment If HIV treatment is indicated Start ART and include anti-HBV drugs (TDF+3TC) If HIV treatment is not indicated and HBV treatment is indicated Consider early ART and include anti-HBV drugs (TDF+3TC) or Treat with anti-HBV drug (without ART) that has no effect against 16 HIV HIV/HBV: Treatment Options (2) These drugs also fight/treat HIV: Drugs that do not work against HIV: Lamivudine Adefovir Tenofovir Telbivudine Entecavir Interferon-alpha Do not use as monotherapy for HBV due to risk of HIV developing resistance OK to use as monotherapy for HBV: no risk of HIV resistance to ARV 17 ART Drug Selection for HIV/HBV Co-Infection TDF and 3TC for all patients with HIV/HBV co-infection • Work against both HIV and HBV • High rate of HBV drug resistance if 3TC alone is used Efavirenz preferred over Nevirapine • Due to risk of hepatotoxicity In Vietnam, preferred 1st line regimen is TDF + 3TC + EFV 18 HIV/HBV Treatment Algorithm HBsAg Positive Meets criteria for ART according to MOH guidelines? No Yes Meets criteria for HBV treatment? Start ART TDF+3TC+EFV Yes Consider early ART No Reassess need for HIV and/or HBV treatment every 3-6 months Clinical Consideration: HBV Flares on ART HBV flare: rapid increase in liver enzyme levels, with signs and symptoms of hepatitis Caused by: • Immune reconstitution inflammatory syndrome (IRIS) • Discontinuation of anti-HBV drugs (3TC, TDF) when ART is stopped • Development of resistance to anti-HBV drugs 20 Clinical Consideration: HBV Flares and IRIS HBV flares secondary to IRIS - first few months of treatment Can be difficult to distinguish from ARTinduced hepatic toxicity Drugs active against HBV should be continued during a suspected flare If no way to distinguish serious HBV flare from grade 4 ART toxicity, then withhold all ARV drugs until condition improves 21 HBV Flares When ART is Stopped Stopping anti-HBV drugs in a patient with HIV/HBV can lead to severe HBV flares • Fatal cases of acute HBV have occurred in this setting HIV/HBV patients who need to stop the HBV-active drugs in the HIV treatment regimen (3TC, FTC or TDF) should be monitored closely 22 Hepatitis C Virus (HCV) 23 HCV Basics Hepatitis C is a viral infection that attacks the liver Like HBV, it can cause both acute and chronic disease. • Most patients have mild or no symptoms at the time of infection but go on to have chronic life-long infection There are 6 genotypes of HCV • Genotype affects treatment response 24 HCV Transmission 25 Source: WHO 1999 HCV: A Global Health Problem 170 Million Carriers Worldwide, 3-4 MM new cases/year FAR EAST ASIA 60 M WEST EUROPE 9 M EAST MEDITERRANEAN 20M SOUTH EAST ASIA 30 M AFRICA 32 M U.S.A. 4M SOUTH AMERICA 10 M AUSTRALIA 0.2 M HCV Prevalence in Vietnam General population: 1-5% Hemodialysis patients: 54% IV drug users: 60-90% Nakata S: J Gastroenterol Hepatol. 1994 Jul-Aug;9(4):416-9. Nguyen VTT. Hepatol Int (2007) 1:387–393 27 HCV Prevention No currently available medications or vaccines are protective against HCV infection 28 HCV Progression (1) Rarely fulminant and fatal Acute infection causes symptoms in <20% After acute infection: • 15% clear virus from blood and have full recovery • Other ~ 85% have viremia that persists for life Seroconversion may take 3 months 29 HCV Progression (2) Chronic HCV Infection 20 years Annual rate Factors that Speed HCV Progression: • HIV • HBV • Alcohol • Male sex • Age > 40 Cirrhosis 20 % Decompensation 6% HCC 4% Death 4% Hoofnagle, Hepatology, 1997; Di Bisceglie, Hepatology, 2000 Clinical Course of HCV Disease progression cannot be predicted by laboratory tests • Pattern of ALT elevation does not correlate well with disease outcome • Neither does HCV RNA (viral load) Liver biopsy the best predictor of disease course 31 HIV/HCV Interaction Effects of HIV on HCV Faster progression to fibrosis, liver failure and liver cancer than patients with HCV alone Higher HCV viral loads Higher rate of MTCT of HCV Effects of HCV on HIV No effect on natural progression of HIV, but Increased risk of hepatotoxicity from ARV 32 HCV Treatment: Indications Positive HCV RNA Persistent ALT Liver biopsy with fibrosis and at least moderate inflammation Stable HIV infection No contraindications for use of PEGinterferon or ribavirin Treatment available 33 HCV Treatment: Regimen Drug Dosing Pegylated Interferon alpha α2a: 180 mcg SQ once per week Ribavirin Common Side Effects • Myelosuppression • Depression • Myalgias α2b:1.5 mcg/kg SQ • Fevers once per week PLUS 800-1200 mg daily • Hemolytic anemia • Teratogenicity • Duration: 48 weeks • Response rates vary by genotype HIV/HCV Treatment: Considerations Combination Risk Ribavirin and ddI Increased risk of combination mitochondrial toxicity contraindicated (pancreatitis, lactic acidosis) Avoid Ribavirin and AZT if Increased risk of anemia possible EFV and Interferon can Increased risk of be used together but: neuropsychiatric side effects Interferon therapy is associated with a decline in CD4 count (CD4% not affected) 35 HCV Treatment Algorithm for HIV/HCV Co-infection Decision made to treat patient based on clinical and laboratory data Initiate pegylated interferon + ribavarin Obtain quantitative HCV RNA after 12 weeks of therapy HCV RNA undetectable or detectable with ≥ 2 log10 reduction HCV RNA detectable with < 2 log10 reduction Reassess HCV RNA at 24 weeks Stop Therapy HCV RNA undetectable No Stop Therapy Yes Complete 48 weeks of therapy HIV/HCV: Important Recommendations Abstain from all alcohol intake Vaccinate against HAV and HBV, if not immune already 37 Case Study 38 Key Points HBV and HCV are both prevalent in Vietnam HIV accelerates HBV and HCV induced liver disease HBV/HIV can both be treated with ARV using tenofovir and lamivudine In Vietnam, most patients do not have access to HCV treatment • important to minimize liver damage by avoiding alcohol 39 Thank You Questions? 40