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HCV in the HIV infected Patient

HCV in the HIV infected Patient. David L. Thomas, MD. Advisory Board – Merck & Co. HCV Treatment Future is Bright. HCV Treatment Present is Challenging for HIV/HCV Coinfected Patients. 2008 Management of HIV/HCV Coinfected Patients. Whom to treat How to treat When to stop.

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HCV in the HIV infected Patient

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  1. HCV in the HIV infected Patient David L. Thomas, MD Advisory Board – Merck & Co.

  2. HCV Treatment Future is Bright

  3. HCV Treatment Present is Challenging for HIV/HCV Coinfected Patients

  4. 2008 Management of HIV/HCV Coinfected Patients • Whom to treat • How to treat • When to stop

  5. 56 year old Caucasian male with HIV and HCV infection • HIV and HCV diagnoses early 1990s; exposures late 1970s • No ART: CD4+ lymphocyte 782/mm3, HIV RNA <400c/ml • HCV genotype 1a; HCV RNA 6.4 log IU/ml • ALT 77; INR 1, TB 1.9; creat 1; plts 219K • Liver biopsy 2001: mild fat; no fibrosis

  6. Which would you do next? • Repeat liver biopsy • Check FibroSure • Peg IFN and RBV, check HCV RNA 4 and 12 wks • Compliment him on his DNA and follow • Check CD4+ lymphocyte percent

  7. Which would you do next? Repeat liver biopsy • Could be progression • Could be an error

  8. Three Year Predictive Value of Liver Biopsy Represents Error and Natural History • 175 HIV/HCV coinfected persons biopsied twice, median 2.9 yrs • 41 (24%) had ≥ 2pt increase • Must repeat test Sulkowski et al AIDS 2007

  9. Sampling error of liver biopsy Fibrosis area: 65% Fibrosis area: 15% Courtesy of M. Pinzani, Florence

  10. Liver Biopsy Readings Have Limited Validity Sampling error (metavir 2-4 fibrosis) • 161 > 3cm biopsies ‘reduced’ 1.5cm and 1cm and re-scored1 • % “mild”: 3cm 59%; 1.5 cm 68%; 1cm 80% • Specimen diameter reduced: • 63% mild increased to 87% • sampling error underestimates fibrosis 1 Colloredo J Hepatol 2003

  11. Which would you do next? Check FibroSure Reasonable validity in HIV/HCV coinfected persons, especially considering lack of sensitivity and specificity of biopsy

  12. Which would you do next? Peg IFN and RBV, check HCV RNA 4 and 12 wks • Liver disease staging is inaccurate • Therapeutic trial provides information on adverse events and response for this patient

  13. FibroSure=0.9; repeat liver biopsy (>2 cm) shows metavir 3 (of 4) fibrosis; mild macro-vesicular fat, moderate activity. Now what? • Peg IFN and RBV • Wait for new HCV drugs • AZT-based ART • ABC-based ART • TDF-based ART Peg IFN and RBV after

  14. HAART and Treatment of HCV • ART should be given if indicated by HIV stage • Insufficient evidence that PegIFN/RBV response is improved • By ART • By higher CD4 • Many recommend it anyway, especially with high HIV RNA or CD4 350-500/mm3

  15. NRTI Choice and RBV • Don’t use ddI and RBV • Avoid AZT and RBV • ? ABC and RBV • 1493 HIV/HCV coinfected getting PegRBV • 62% No SVR: associated with GT 1/4; viral load; low RBV trough; ABC (OR 2.22, 0.91-5.40) • 2No difference in SVR in 238 TDF versus 52 ABC2 Effect: Bani Sadr J AIDS 2007; 1Vispo Antivir Ther 2008; Mira et al CROI 2008 ABST 1074; No effect: 2Gonzales-Garcia CROI 2008 ABST 1076

  16. Peg and RBV 1.2 g/d was started without ART. Treatment is well tolerated. HCV RNA drops 6.4 to 4.99 log IU at 30 days. Which is best? • Stop, no chance of SVR • Increase Peg dose • Continue current therapy • Start pioglitazone • Start ART

  17. Baseline HCV RNA was retested with assay with high upper range=7.5 log IU/ml (vs 6.2). Treatment continued. HCV RNA drops to 3.7 log IU at 12 weeks. Which is best? • Stop • Reduce Peg IFN dose, stop RBV • Continue current therapy

  18. Treatment continued. HCV RNA drops to 3.42 log IU at 24 weeks. ALT 58. Which is best? • Stop • Reduce Peg IFN dose, stop RBV • Continue current therapy for 18 months • Stop, start pioglitazone and ART and restart ART in 6 months

  19. Forms of Virologic Response ~44% PEG/RBV Log IU HCV RNA Weeks of HCV Treatment

  20. No cure No control HCV Therapy Generally Should be Stopped Unless >2 logs at 12 wks and undetectable at 24 wks

  21. Rare SVR Without Early Virologic Response in HIV/HCV Coinfected Patients Chung NEJM 2004; Torriani NEJM 2004; Carrat JAMA 2004

  22. No Control of HCV Infection in ACTG 5178 (SLAM C) PegIFN 2a EVR _ RANDOMIZE PegIFN 2a RBV 1-1.2g/d OBSERVE + CONTINUE 72 Weeks Bx1 Bx2 Bx3 Sherman and 5178 team CROI 2008

  23. 329 295 ACTG 5178 SLAM C EVR Was Common 112 44.4% PegIFN 2a EVR _ RANDOMIZE PegIFN 2a RBV 1-1.2g/d OBSERVE + CONTINUE 183 55.6% 72 Weeks Bx1 Bx2 Bx3 Sherman and 5178 team CROI 2008

  24. 329 295 ACTG 5178 SLAM C Maintenance Versus Observation 44 112 44.4% PegIFN 2a EVR _ RANDOMIZE PegIFN 2a RBV 1-1.2g/d OBSERVE + CONTINUE 42 183 55.6% 72 Weeks Bx1 Bx2 Bx3 Sherman and 5178 team CROI 2008

  25. No benefit of 18 months of maintenance DSMB stopped study Cirrhosis 18% and 21% of maintenance and observation arms PEG-IFN N=24 Observe N=21 ACTG 5178 No Benefit of Maintenance Sherman and 5178 team CROI 2008

  26. Treatment stopped. Creat 1.0; ALT 74 IU; INR 1.0; which is best? • Refer to Dr. Sulkowski for investigational HCV drug • Refer to Dr. Fierer for counseling to prevent secondary transmission • Refer to Dr. Afdhal for management of cirrhosis and transplant evaluation • All of the above

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