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HIV & Viral Hepatitis How to Educate Clients & Physicians Care, Treatment & Policy Issues

HIV & Viral Hepatitis How to Educate Clients & Physicians Care, Treatment & Policy Issues. Tracy Swan Treatment Action Group ADAP TA Meeting July 2008. HIV/ Hepatitis Coinfection Hepatitis B (HBV) Hepatitis C (HCV). Epidemiology & Implications Transmission & Prevention Diagnostics

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HIV & Viral Hepatitis How to Educate Clients & Physicians Care, Treatment & Policy Issues

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  1. HIV & Viral HepatitisHow to Educate Clients & PhysiciansCare, Treatment & Policy Issues Tracy Swan Treatment Action Group ADAP TA Meeting July 2008

  2. HIV/ Hepatitis CoinfectionHepatitis B (HBV) Hepatitis C (HCV) Epidemiology & Implications Transmission & Prevention Diagnostics Natural History Treatment & Treatment Issues New Treatments: Planning for the Future Role of ADAPs

  3. HBV Epidemiology HBV (chronic) US: 2 million people Worldwide: ~350 million people HIV & HBV US: ~10% of HIV-positive people also have HBV Worldwide: 2-4 million are HIV/HBV coinfected

  4. HCV Epidemiology HCV (chronic) US: 4–5 million people Worldwide: 120–170 million people HIV & HCV US:~30% of HIV-positive people also have HCV Worldwide: 4-5 million are HIV/HCV coinfected

  5. Who Are We Talking About? HBV & HCV testing recommended for all HIV+ people (DHHS Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-1 Infected Adults and Adolescents; June 2008) HBV coinfection prevalent among MSM & current and former IDUs HCV coinfection prevalent among current & former IDUs: up to 90% are coinfected Coinfected people more likely to be poor, African American, have multiple co-morbidities, & a history of incarceration

  6. HBV Transmission HBV is 100x more infectious than HIV • Mainly transmitted through blood, also semen & vaginal fluid; same as HIV: unprotected sex with an infected person, IDU with shared equipment, birth from an infected mother, needlesticks • Lives outside the body for up to 7 days • Bleach is effective

  7. What Can Be Done: HBV Prevention HBV is vaccine-preventable: All susceptible HIV+ people should be vaccinated against HBV (but not with twinrx) • HBV vaccine more effective with CD4 count >500 & HIV RNA is undetectable; recommended when CD4 cell count is >350; less effective with nadir CD4 count of < 200 (DHHS Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-1 Infected Adults and Adolescents; June 2008; Laurence Am J Med 2005; Overton et al; CID 2005; Tedaldi et al; CID 2004) • Doubled dosing and adjuvants may increase response rate (Brook; J Hepatol 2005; Cooper et al; CID 2008; Rey et al; Vaccine 2000) HIV+ people need anti-HBs titer 1 month after completing the HBV vaccination series; re-vaccination should be considered for non-responders & annual boosters for people at ongoing risk (CDC 2008; DHHS Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-1 Infected Adults and Adolescents; June 2008)

  8. HBV Prevention There is PEP for HBV HBV vaccination & HBIG (considered after assessment of source) MTCT can be prevented with HBIG and vaccination (for infant)

  9. HCV Transmission HCV is 10x more infectious than HIV • Bloodborne, mainly transmitted through IDU, blood transfusion/products before 1992, needlestick accidents, dialysis & other invasive medical procedures w/o adequate infection control; also sexually (less common but increasing reports among HIV+ MSM), & MTIT (increased risk if mother is HIV+) • Lives outside the body for up to 4 days • Bleach is not effective

  10. HCV Prevention • No preventive vaccine available • No recommended PEP (but HCV TX is more effective during acute infection) • ART and elective C-section reduce risk of MTIT

  11. HCV Prevention Outbreaks of new, sexually transmitted HCV infections recently reported among HIV+ MSM in US, UK, Europe & Australia • HCV may be even more aggressive in people who are already HIV+ • Important to discuss risk factors, and risk reduction • Ongoing testing for people at risk Prevention for IDUs is important -- so they can avoid HCV & HCV reinfection, & exposure to other bloodborne pathogens • Refer to NEP, provide information on safer injection, offer buprenorphine & refer to drug treatment upon request

  12. Hepatitis A Virus (HAV) Can cause sudden liver failure in people with hepatitis C Vaccination against HAV recommended for: people w/ chronic liver disease, MSM, IDUs & susceptible HIV+ people who are at risk • Vaccination more effective when CD4 cell count is >200 • Response should be checked, & revaccination is recommended for non-responders (DHHS Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-1 Infected Adults and Adolescents; June 2008)

  13. Survival After AIDS Diagnosis in 2002 CDC 2008

  14. Why is Viral Hepatitis Coinfection a Problem? HIV worsens liver disease from HBV & HCV • Liver damage from viral hepatitis more likely and more rapid in HIV+ people HCV-associated cirrhosis can develop in <10 years (vs.15 to 50 years in HIV-negative people) • People with <200 CD4 cells at greatest risk • Viral hepatitis coinfection can complicate HIV treatment

  15. In places where HIV treatment is widely available (US & Western Europe), end-stage liver disease from viral hepatitis coinfection isthe leading cause of non AIDS- related deathamong PLWHA (Weber et al; Arch Intern Med 2006)

  16. HBV Natural History Acute,chronic or cleared? • Not always chronic; >95% of HIV-negative adults will clear hepatitis B without treatment within months: spontaneous viral clearance • More likely to become chronic in HIV+ people • Can only be infected once

  17. HBV: Range of Outcomes Causes mild to serious liver damage • ~25% of people infected as adults will develop serious liver damage • Cirrhosis • Hepatocellular carcinoma (HCC; often initially asymptomatic) develops in <1% year--cirrhosis not always a precursor • Liver failure HIV coinfection accelerates HBV progression • HCC is more aggressive & more difficult to treat • HIV coinfection increases liver related mortality (Braü et al; J Hepatol 2007; Puoti et al; AIDS 2004; Puoti et al; J Hepatol 2006; Thio et al; Lancet 2002)

  18. HBV Progression: Cofactors • HIV coinfection • HCV coinfection • HDV coinfection (limits treatment options, & increases risk for HCC) • High HBV viral load • HBV genotype • Alcohol consumption • Being male

  19. HCV Natural History Acute,chronic or cleared? • Some people spontaneously clear hepatitis C without treatment (15% to 45%) within a year • Young people, especially females, and Caucasians more likely to clear HCV • HIV+ people are less likely to clear hepatitis C, although some do (~25%) • A person can be reinfected with HCV

  20. HCV:Range of Outcomes • No symptoms, no liver damage • Symptoms (fatigue & depression) & some liver damage • Fat in the liver (steatosis) • Liver scarring (fibrosis) • Cirrhosis (serious liver scarring, making it difficult for the liver to function): 20-30%, occurs 15 to 50 years after infection for HIV negative people; can develop in <10 years in HIV+ people • Liver cancer (1% to 5% per year) • Liver failure (3% to 4% per year)

  21. HCV Progression: Cofactors • HIV coinfection • Age >40 at infection • Insulin resistance, obesity, steatosis • Aging/duration of HCV infection • Chronic HBV coinfection • Being male • Alcohol (accelerates HCV progression, especially >50 grams/day) Many physicians won’t treat people who drink, despite their increased risk for cirrhosis (imagine this happening with HIV)

  22. Viral Hepatitis Diagnostics • Diagnostic, monitoring and screening tests provide some information about liver disease progression, & likelihood of response to treatment • These tests also create additional barriers to care and treatment, because some are expensive and/or invasive

  23. Liver Biopsy Described as the “CD4 count of HCV” • Only test that grades (assesses inflammation) & stages (identifies extent of scarring) liver disease • Can identify other causes of liver disease • Can detect additional liver damage, such as steatosis (fatty liver) and drug-induced liver injury

  24. BUT….. • Biopsy is expensive • Invasive/painful • Carries risk of complications • Very small (<1 in 10,000) mortality risk • Not always accurate--or interpreted accurately • Not always necessary for HCV or HBV treatment decisions, although some providers may require one before initiating treatment

  25. HBV Diagnostics: 1 Chronic HBV diagnosed with a combination of blood tests: + HBsAg & anti-HBc (both tests needed; if anti-HBc alone, result may be false positive, or indicate latent infection; HBV DNA testing should be done before vaccination or ART) $53 + $45 OR + HBsAg & HBV DNA $53 + $499 OR + HBeAg (twice in six months) $149 (DHHS Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-1 Infected Adults and Adolescents; June 2008)

  26. HBV Diagnostics: 2 • There are 8 viral strains, or genotypes of HBV • Hepatitis B genotype linked with susceptibility to some treatments & HBV disease progression • Distributed geographically; genotypes A & G are most common in US

  27. HBV Diagnostics: 3 For HIV+ people with chronic HBV: • Test for HBeAg & HBV DNA, HBV genotype and HDV; make treatment plan accordingly • Hepatic imaging or ultrasound with AFP to screen for HCC every 6 months, since cirrhosis is not always a precursor • Consider liver biopsy • If no HBV or HIV treatment (unusual), monitor every six months with liver panel, CBC • If current or prior ART: Do HBV resistance testing (some drugs active against both viruses)

  28. HCV Diagnostics: 1 Antibody testing:screening, not diagnostic Viral load testing (HCV RNA):Confirms or rules out chronic HCV, helps predict likelihood of response to TX, but does not indicate/predict disease progression or liver damage ($665 for Super Quant; $765 for qualitative PCR) check super quant Liver Panel: Blood tests; part of a routine physical exam, includes liver enzyme levels (ALT, AST) • Liver enzymes can be elevated by medication, toxic fumes, heavy drinking, viral hepatitis or other infections, during detox, and from other causes-so they don’t indicate or predict liver disease severity • Many ARVs can cause liver enzyme elevations- coinfected people on ART should have regular monitoring

  29. HCV Diagnostics: 2 More than 6 different viral strains of HCV, called genotypes & numbered in order of discovery HCV genotype can be determined by a blood test • Genotype is not linked to HCV progression or severity of liver damage • Key factor in determining length & predicting outcome of HCV treatment • Genotype 1 is most common in the US & harder to treat than genotype 2 or 3

  30. Viral Load Testing In HBV, viral load testing is necessary for: • Predicting disease progression • Predicting response to treatment • Deciding to initiate treatment • Monitoring response to treatment / possible development of resistance In HCV, viral load testing is necessary for: • Diagnosis • Predicting response to treatment • Monitoring response to treatment Lack of access to viral load testing is a major barrier for both mono-and coinfected people

  31. Non-Invasive Testing Serum markers “not ready for prime time” yet • Good for detecting cirrhosis, but not as good for identifying mild to moderate liver damage • Less reliable in HIV+ people, because of inflammation and certain ARVs • Expensive >$450 Elastometry (“Fibroscan”) may be more precise • More research on accuracy in HIV+ people needed • Not reliable in overweight people • Machine is very expensive, thus access is limited

  32. Who Needs HBV Treatment? HBV treatment should be considered earlier for HIV/HBV coinfected people; treatment initiation based on: • HBV DNA (>2000 IU/mL) • ALT (if elevated) • Extent of liver fibrosis (No treatment needed when HBV DNA <2000 IU/mL, or HBV DNA >2000 IU/mL with normal ALT & mild liver damage) (Soriano et al; AIDS 2008)

  33. HBV Treatment HBV treatment is also HIV treatment • Upcoming HIV treatment guidelines will recommend ART for all coinfected people (regardless of CD4 count) • ARV regimen should contain tenofovir + 3TC or FTC, since both are also active against HBV In cases where ART is not indicated, or refused, the only HBV treatment options are PEG-IFN for 12 months, or LdT/adefovir (because of dual activity)

  34. HBV & Drug Resistance Cross-resistance is a big problem • If lamivudine (3TC) resistance develops, FTC & LdT may not be effective, since one HBV mutation can confer resistance • Resistance to other anti-HBV drugs may also develop • Lamivudine should be discontinued & treatment with new drug (s) initiated (entecavir, adefovir, tenofovir) • Monitoring HBV DNA is crucial to detect resistance

  35. Who Needs HCV Treatment? “Patients with an increased risk of developing cirrhosis…” NIH Consensus Statement 2002 “Consider HCV treatment in all HIV/HCV- coinfected patients…” Veterans Administration 2005

  36. HCV Treatment:1 Reports of rapid (>2 stage, in <3 years) liver disease progression, & benefits of ART prompting more aggressive treatment strategies for HIV/HCV coinfected people • HCV can be treated regardless of HIV status • SVR (sustained virological response to HCV TX, meaning no detectable HCV in the bloodstream 6 months after treatment) associated with decreased morbidity and mortality • Treat to cure HCV--benefit of maintenance therapy is uncertain • ART may slow liver disease progression by maintaining immune health

  37. HCV Treatment:2 • Hepatitis C is treated with a combination of two agents: interferon and ribavirin • These were not designed to treat HCV (but may new drugs that specifically target HCV are in development) • Duration of treatment depends on: genotype, HCV viral load, early response to treatment, & HIV status--anywhere from 12 to 72 weeks

  38. Interferon A synthetic version of a chemical messenger made by the human body; it stimulates the immune system & fights viruses Pegylated Interferon (PEG-IFN) is standard of care Pegylation means thata small molecule has been attached to interferon to keep it in the body longer & increase efficacy Pegylatedinterferon is injected 1 X per week

  39. IFN: Side Effects Flu-like: fever, aches, nausea, appetite loss, weakness, & fatigue Lab Abnormalities: anemia, neutropenia, thrombocytopenia Neuropsychiatric: suicidal ideation/suicide(rare), depression, insomnia, anxiety, irritability, mood swings, mania, psychosis Other: hair loss, optic nerve damage, etc

  40. Ribavirin (RBV) • Pill or capsule, taken 2 X a day • Same family (NRTI) as some HIV drugs but it does not work against HIV • Prevents relapse, enhances SVR • RBV dosing is usually based on weight and genotype

  41. RBV Side Effects Anemia is a major, sometimes treatment-limiting side effect Cardiac events Shortness of breath, coughing Itchy skin/rash May also cause depression

  42. Managing Side Effects Flu-like symptoms: evening/Friday night shot, tylenol, anti-nausea medication Appetite/weight loss:many small, light meals, marinol Anemia: growth factor, dose reduction Neutropenia:growth factor, dose reduction Thrombocytopenia: if severe, dose reduction or d/c treatment

  43. Neuropsychiatric Side Effects A pre-treatment psychiatric assessment & ongoing mental health care and screening for depression should be standard of care • Depression, anxiety: manage with mental health care, support system from peers, family and friends & anti-depressants • Irritability/insomnia/mood swings/mania: manage with mental health care, mood stabilizers, sleeping aids

  44. HCV Treatment: Less Effective For Coinfected People

  45. Predicting Response • HCV genotype (2,3,4,1) • Race (White>African American) • Hepatitis C viral load <400,000 IU/mL • HIV status (not CD4 count or viral load) • Amount of liver damage/steatosis • Weight, insulin resistance, diabetes • Adequate dose/duration of TX & adherence (80/80/80) • Maintaining full ribavirin dose Education and support Effective side effects management

  46. HIV & HCV: What’s Happening? 845 coinfected patients at a Baltimore HIV clinic 277 referred for HCV care & TX 125 completed pre-TX evaluation 69 eligible for TX 29 treated 6 had SVR (Mehta et al; AIDS 2006)

  47. Withholding an effective treatment from the highest prevalence population is unacceptable for any other medical condition

  48. Multidisciplinary Care • Provide mental health care & peer support/education • Offer drug/alcohol treatment on request: OST, pharmacotherapy, counseling, in/out patient treatment • Explain HCV natural history, assessment process for treatment, risks/benefits of treatment

  49. Flexible Eligibility Criteria Noabstinence requirements • Willingness/interest in HCV TX • Reasonable adherence to clinic visits • Engagement in psychiatric care, when indicated

  50. HCV TX GUIDELINES “…it is recommended that treatment of active injection drug users be considered on a case-by-case basis…” NIH, 2002

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