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Renata Smith Pharm.D.

Renata Smith Pharm.D. HIV and Hepatitis Co-infection June 4 th , 2008. Recognize the modes of transmission for HIV, HCV, and HBV Recognize the epidemiology of HIV, HCV, and HBV Describe the fundamentals of HIV+HCV and HIV+HBV treatment

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Renata Smith Pharm.D.

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  1. Renata SmithPharm.D. HIV and Hepatitis Co-infection June 4th, 2008

  2. Recognize the modes of transmission for HIV, HCV, and HBV Recognize the epidemiology of HIV, HCV, and HBV Describe the fundamentals of HIV+HCV and HIV+HBV treatment Identify the common systemic side effects of antiviral/antiretroviral therapies Identify drug interactions with the agents used to treat HBV and HCV Objectives:

  3. Major Hepatitis Viruses

  4. Prevalence of HCV infection in selected subgroups in the U.S. • Injection drug users: 52-90% • Hemophiliacs: 60-85% (if infected prior to 1987) • HIV infected individuals: 9-40% • incarcerated HIV+: 50% • MSM: 4-8%

  5. Hepatitis C Epidemiology • 130 million people have HCV worldwide based on the 2007 WHO data • 4 million Americans have chronic hepatitis C (HCV RNA+) • 2%-20% progress to cirrhosis in 20 years • The rate of progression to cirrhosis increases by 3 fold if co-infected with HIV • This accelerated rate is further magnified in patients with low CD4 count • Unclear if HCV adversely affects the rate of HIV progression • Unclear if ART improves morbidity/mortality of untreated HCV

  6. Hepatitis C Virus Disease: Epidemiology • Six genotypes • Genotype 1: 75% of HCV infections in United States • Genotypes 2 and 3: more prevalent in Western Europe • Transmission: percutaneous exposure (most common), mother-to-child transmission, sexual exposure • High rate of HCV coinfection in HIV-infected injection drug users and hemophiliacs

  7. HIV/HCV Treatment • Predictors of success in achieving a sustained viral response (SVR): • CD4 count greater than 200 • HIV RNA levels below 10,000 copies • HCV RNA < 1,000,000 • No alcohol consumption

  8. HCV Treatment Decisions in HIV Coinfected • Treat Hepatitis C if HIV stable and if CD4 > 200 cells/ml ) • Treat HIV first if CD4 < 200 cells/ml

  9. Hepatitis C Virus Disease:Treatment • Pegylated (PEG) interferon (IFN) in combination with ribavirin: higher rates of SVR than standard IFN plus ribavirin or PEG IFN without ribavirin • Recommended: 24-48 weeks based on genotype PEG IFN (Pegasys) alfa-2a 180 mg SQ weekly, or PEG IFN alfa-2b (PEG-Intron) 1.5 mcg/kg SQ weekly + Ribavirin (Copegus) 600 mg PO BID if weight >75 kg(400 mg Q AM, 600 mg Q PM if weight <75 kg)

  10. PEG-IFN virologic response rates across studies 49 % Response 40 41 37 27 27 Abstracted from 11th CROI

  11. APRICOT: SVR rates * 62 * SVR % * 40 36 * 29 20 20 14 12 7 *p<0.05 compared to IFN/RBV Torriani F, 11th CROI, Abstract 112

  12. Flu-like symptoms Headache Fatigue or asthenia Myalgia, arthralgia Fever, chills Neuropsychiatric disorders Depression Mood lability Anxiety Lab alterations Neutropenia Anemia Thrombocytopenia Alopecia Asthma like symptoms ( 20%-30% of patients) Nausea Diarrhea Weight loss Injection-site reaction Side Effects of Interferon

  13. Side Effects of Ribavirin • Hemolytic anemia-dose dependent • Teratogenicity • Cough, dyspnea, sinus congestion • Rash and pruritus • Insomnia • Anorexia COPEGUS® (ribavirin, USP) [package insert]. Nutley, NJ: Hoffmann-La Roche; 2002.

  14. Rare side effects of HCV treatment • Acute congestive heart failure • Renal failure • Seizures • Hearing loss • Retinopathy resulting in vision loss • Pulmonary fibrosis or pneumonitis, and sepsis • Severe depression with suicidal ideations • Deaths have been reported from acute myocardial infarction, stroke, suicide, and sepsis.

  15. Treatment of Side Effects • Neupogen® for Neutropenia • Procrit® for anemia • Appetite stimulants • Antidepressants • Ibuprofen for flu like symptoms and bone pain • Antihistamines for itching

  16. Drug interactions in HIV/HCVCoinfection • Didanosine and Stavudine plus Ribavirin appear to cause mitochondrial toxicity resulting in lactic acidosis, peripheral neuropathy • Retrovir and Ribavirin may result in increase risk of anemia • Avoid using these drugs together

  17. Ribavirin and Adverse Events Ribavirin (continued): • Teratogenic; women with potential for pregnancy and men receiving ribavirin must use contraception consistently during ribavirin therapy and for 6 months after completion of therapy

  18. Hepatitis CINTERFERON AND RIBAVIRIN • Serious, less common side effects • Bacterial infections • Thyroid disease • Severe depression, suicide • Seizures • Vision or hearing loss • Kidney or heart failure • Fetal abnormalities/fetal loss

  19. Adherence Matters Pegasys + Ribavirin Study at AASLDA • 45% genotype 1 had SVR • 67% had SVR if >80% adherent • 40% had SRV if < 80% adherent • 76% genotype 2 had SVR • 86% had SVR if > 80% adherent Pegasys/RBV 1000/1200 mg 48 week NV15942 study • 76% SVR with 80% adherence

  20. Case study HIV/HCV • 42F diagnosed with HIV/HCV 15 years ago on HAART. HIV RNA < 50, CD4 count 765 cells/ml. • HCV RNA 2 million IU • HCV genotype 1A • LFTs elevated, AFP elevated, moderate fibrosis, liver biopsy shows no cirrhosis • No other preexisting conditions • No other medications • No psychiatric illness • NKDA

  21. Would you treat this patient for HCV?

  22. YES!!!!!

  23. What would you use??? Peg-IFN 180 mcg SQ weekly + Ribavirin 600 mg bid if > 75Kg or Ribavirin 400 mg am, 600 mg pm if < 75 Kg

  24. Duration of Therapy???

  25. 48 weeks

  26. Counseling parameters • Flu like symptoms • Bone pain/muscle pain/hair loss/lethargy • Bone marrow suppression • Teratogenesity of Ribavirin • Psychiatric adverse effects • ART drug interactions with Ribavirin

  27. Monitoring parameters • HCV viral load • Early viral response (EVR)> 2 log2 decrease at 12 weeks • Rapid viral response (RVR)= undetectable at 4 weeks • Sustained viral response (SVR)= undetectable 24 weeks after end of therapy • Slow responders= 2 log reduction in HCV RNA but did not suppress viral load very quickly • CBC (anemia/neutropenia/thrombocytopenia) • Pregnancy test

  28. HIV and HBV coinfection

  29. 40 million worldwide 1 million in the US Target: CD4 cells Reverse Transcriptase Nucleos(t)ide Analogues and other ARV Mutations=Resistance 400 million worldwide 1.25 million in the US Target: hepatocytes Reverse Transcriptase Nucleos(t)ide Analogues and immunomodulators Mutations=Resistance HBV HIV

  30. CURRENT TREATMENT OPTIONS FOR HBV/HIV Coinfected • Peg-Inf &2a (Pegasys®) x 6 months • Lamivudine (LM/Epivir®) 300 mg daily • Adefovir (ADV/Hepsera®) 10 mg daily • Entecavir (ETV/Baraclude®) 0.5-1 mg daily • Telbivudine (L-dt/Tyzeka®) • Tenofivir (TDF/Viread®) 300 mg daily • Emtricitabine (FTC/Emtriva®) 200 mg daily • Truvada® (300/200 mg) 1 tab daily

  31. DHHS Recommendations ForTreatment of HBV/HIV Coinfection1 For HBV/HIV co-infected patients, ETV should not be used for treatment of HBV infection w/o concomitant treatment for HIV2 1. DHHS. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents - October 10, 2006. http://AIDSinfor.nih.gov; 2. Supplement to Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, April 30, 2007

  32. AASLD GUIDELINES for Treatment of HBV/HIV Coinfection1 • Treat patients meeting criteria for chronic hepatitis B (CHB) • Patients not on HAART and not anticipated to require HAART in the near future should be treated with therapy that does not target HIV such as Peg-IFN-α • Telbivudine should not be used in this circumstance because of the risk of selection of the major LAM resistance mutation M204I in the YMDD motif • Patients should receive therapies effective against both viruses: LAM + TDF or FTC + TDF are preferred • Patients on effective HAART that does not include a drug active against HBV may be treated with Peg-IFN-α, ADV, or ETV • Add ADV or TDF in patients with LAM resistance

  33. To Construct an Antiretroviral Regimen, Select 1 Component from Column A + 1 from Column B

  34. Case 1 HIV/HBV • 22 yo MSM infected with HIV/HBV x 12 years • HIV RNA 180, 000, CD4 275 cells/ml, • HBV DNA 1,000,000 copies/ml • HBeAg(+) • LFTs elevated • AFP normal • Liver biopsy-no cirrhosis • Does this patient therapy for HIV and HBV?

  35. December 1st, 2007 Updated HIV Treatment Guidelines Table 5. Indications for Initiating Antiretroviral Therapy for the Chronically HIV-1 Infected Patient Clinical Condition and/or CD4 Count Recommendations • History of AIDS-defining illness • CD4 count <200 cells/mm3 (AIDS diagnosis) • CD4 count 200-350 cells/mm3 • Pregnant women* • Persons with HIV-associated nephropathy • Persons coinfected with hepatitis B virus (HBV), when HBV treatment is indicated (Treatment with fully suppressive antiviral drugs active against both HIV and HBV is recommended.) Antiretroviral therapy should be initiated. • Patients with CD4 count >350 cells/mm3 who do not meet any of the specific conditions listed above. The optimal time to initiate therapy in asymptomatic patients with CD4 count >350 cells/mm3 is not well defined. Patient scenarios and comorbidities should be taken into consideration.

  36. What would you start therapy with? • ABAC/3TC/EFV • AZT/3TC/LPV/rtv • TDF/FTC/EFV • TDF/FTC/NVP • Peg-INF

  37. To Construct an Antiretroviral Regimen, Select 1 Component from Column A + 1 from Column B

  38. What would you start therapy with? • ABAC/3TC/EFV • AZT/3TC/LPV/rtv • TDF/FTC/EFV • TDF/FTC/NVP • Peg-INF

  39. Case 2 HIV/HBV • 36F HIV/HBV infected on HAART with AZT/3TC/fosAPV/rtv x 2 years • HBVeAg(-) seroconverted • HBV DNA undetectable (< 60 copies/ml) • LFTs normal • Would you change anything in this patient’s regimen???

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