1 / 38

When to Treat HCV in our HIV coinfected patients 2013 Perspective

When to Treat HCV in our HIV coinfected patients 2013 Perspective. Brad Hare, MD Annie Luetkemeyer, MD Associate Professor of Medicine, UCSF Assistant Professor of Medicine, UCSF. Disclosures.

gavan
Download Presentation

When to Treat HCV in our HIV coinfected patients 2013 Perspective

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. When to Treat HCV in our HIV coinfected patients2013 Perspective Brad Hare, MD Annie Luetkemeyer, MD Associate Professor of Medicine, UCSF Assistant Professor of Medicine, UCSF

  2. Disclosures • Brad has received grant support to UCSF from Vertex Pharmaceuticals, Genentech, and serves in an advisory capacity to Bristol-Myers Squibb • Annie has received research grant support to UCSF from Bristol-Myers Squibb, Gilead, & Vertex

  3. Goals of this activity • Changing paradigms in HCV treatment with availability of new HCV drugs: FDA approved and in clinical trials • What to do NOW for HCV-coinfected patients? • Who should be treated, who can wait?

  4. Glossary • DAA: Direct Acting Agent. Anti-HCV medications that target specific aspects of HCV viral replication • PEG: Pegylated interferon • RBV: Ribavirin • PR: PEG + ribavirin • Genotype: Strains of HCV that affect treatment response (1-6) • Genotypes 1&4 harder to cure than 2&3 • IL28b – human gene that contributes to response to IFN-based treatment • Response from best to worst: CC>CT>TT

  5. Glossary (2) • SVR: Sustained virologic response (HCV viral load undetectable off of treatment) SVR12 and SVR24 considered cures • Null response: Failure to attain at least 2 log10 drop in HCV after 12 weeks of treatment • Response Guided Therapy: Shortening therapy based on good early virologic response (1st 12 weeks)

  6. Case #1 • 35 year old African American man, CD4+ 450, HIV RNA <40 copies/ml, on Atripla • HCV treatment naïve, HCV RNA 500,000 IU/ml • Genotype 1a, IL28b genotype T/T (least favorable) • Biopsy: Fibrosis Stage 2 (scale 0-4), Inflammation Grade 1 (scale 0-4) • No other comorbidities, including psychiatric • In terms of HCV treatment readiness: “I’ll do whatever you say, Doc”

  7. Case #1 Audience vote, pre-debate 1) Treat now? 2) Wait to treat? Case: 35 y.o. man, HCV Treatment Naïve, Genotype 1a, IL28B genotype T/T (least favorable), Fibrosis Stage 2. HIV well controlled on Atripla

  8. Argument to Treat Now Telaprevir Boceprevir in coinfection in coinfection 74% 60.5% 45% 26.5% Dieterich D, et al. CROI 2012, Abstract 46. Sulkowski M, et al CROI 2012. Abstract 47

  9. Telaprevir works with Atripla(Remember to dose adjust) Dieterich D, et al. CROI 2012, Abstract 46.

  10. Telaprevir and IL28b In ADVANCE Study (HIV-negative), TPV improved response across all IL28b genotypes, including T/T SVR Rates in Patients Genotyped for IL28B SVR Rates in Patients With RVR T12PR T8PR PR 100 100 94 100 93 90 88 84 88 77 80 72 73 71 64 59 57 60 SVR (%) 40 25 23 20 0 n/N = 45/50 38/45 35/55 48/68 43/76 20/80 16/22 19/32 6/26 n/N = 39/42 30/32 9/9 36/41 34/47 2/2 10/13 14/16 0/0 CC CT TT CC CT TT Jacobson I, et al. EASL 2011. Abstract 1369.

  11. Even Fibrosis F2 is Bad Risk of End-Stage Liver Disease, Hepatocellular Carcinoma and Liver Related Death by Fibrosis Score in Co-Infected Patients N = 638 adults Fraction not meeting an endpoint F0 F1 F2 F3 F4 Sulkowski MS et al. CROI 2010. Abstract 166.

  12. Argument to Wait 48 weeks of PEG/RBV + Telaprevir 12 weeks of 3-4 oral drugs 74% 45% N=76 N=44 Dieterich D, et al. CROI 2012, Abstract 46. Kowdley AASLD 2012

  13. Argument to Wait • IL28b T/T: up to 25% worse SVR compared to C/C1 (HIV negative) • African American response with HCV PI’s < White patients (SVR AA 50-62% vs. non-AA 68-75%2) • No data yet to support response guided therapy in HIV+ • Therefore 48 weeks of therapy • Relatively young patient with intermediate fibrosis - can afford to wait and will spare himself a year of toxicity by doing so 1 Kwo Liver Int 2011; 32(S1):39 2 Burton SMJ 2012;105(8):431

  14. Rebuttal: Treat Now

  15. Rebuttal: Wait to treat

  16. Case #1 Audience vote, post-debate 1) Treat now? 2) Wait to treat? Case: 35 y.o. man, HCV Treatment Naïve, Genotype 1a, IL28B genotype T/T (least favorable), Fibrosis Stage 2. HIV well controlled on Atripla

  17. Case #2 • 60 year old Caucasian man, CD4+ 815, HIV RNA < 40 copies/ml on Raltegravir/Epzicom • Treatment naïve, HCV Genotype 3a, HCV RNA 1.2 million IU/ml, HCV infection “since the 70’s” • Normal platelets and coagulation • Ultrasound: no evidence of cirrhosis • Mild depression, well controlled on SSRI, no other comorbidities. • “I’ll do whatever you recommend, except stick a needle in my liver!”

  18. Case #2, Audience vote, pre-debate 1) Treat now? 2) Wait to treat? Case: 60 y.o. man, HCV treatment naïve, Genotype 3a, no cirrhosis by imaging, HIV well controlled on raltegravir+ Epzicom

  19. Argument to Treat now 4 Nunez M AIDS Research and Human Retroviruses 2007 5 Rodriguez-Torres AASLD 2009 #1561 1Carrat F JAMA 2004 2 Chung R NEJM 2004 3 Torriani FJ NEJM 2004

  20. Argument to Treat now Treating at a younger age associated with better cure rates Our patient is 60 years old Mauss CROI 2012 #763

  21. More Fibrosis in HIV+ Liver fibrosis and age among persons coinfected with HIV and HCV and those with only HCV. For each age, predicted liver fibrosis scores were calculated using a regression equation that included the race, sex, alcohol use, body mass index, hepatitis B virus surface antigen level status, and HCV RNA level values for a representative participant (black overweight male who has no regular alcohol use, is hepatitis B virus surface antigen–negative, and has high HCV viral load) for persons coinfected with HIV and HCV (dashed line) and for persons with only HCV (solid line). For example, a 40-year-old HIV and HCV coinfected person with these characteristics was calculated to have a predicted FibroScan score of 9.04 kPa. For this same degree of fibrosis, the predicted age in a similar person but with only HCV was 49.2 years. Over the entire age range, the average difference in estimated age between persons coinfected with HIV and HCV and those with only HCV was 9.2 years (90% coverage limit, 5.2 to 14.3 years). HCV = hepatitis C virus. Kirk GD HIV, Age, and the Severity of Hepatitis C Virus–Related Liver Disease: A Cohort StudyAnn Intern Med. 2013

  22. Argument to Wait Treatment related side effects in Apricot study of HIV/HCV coinfection IFN PEG PEG + RBV + placebo + RBV (n = 285) (n = 286) (n = 288) Fatigue 36% 36% 40% Pyrexia 32% 35% 41% Headache 34% 29% 35% Myalgia 27% 29% 32% Nausea 19% 19% 22% Insomnia 23% 16% 19% Asthenia 23% 20% 26% Depression 20% 16% 20% Torriani et al. 11th CROI, 2004; Abstract 112

  23. What’s coming for Geno 2/3 100[1] 100[1] 100 96[2] 80 60 SVR12 or 24 (%) 40 20 0 Geno 2/3 Naive Sofosbuvir (nuc) + RBV x 12 wks + pegIFN x 4-12 wks Sofosbuvir (nuc) + RBV x 12 wks Sofosbuvir (nuc) + daclatasvir (NS5A) ± RBV x 24 wks 1. Gane EJ, et al. AASLD 2012. Abstract 229. 2. Sulkowski M, et al. AASLD 2012. Abstract LB-2.

  24. Rebuttal: Treat Now

  25. Rebuttal: Wait to treat

  26. Case #2, Audience vote, post-debate 1) Treat now? 2) Wait to treat? Case: 60 y.o. man, HCV treatment naïve, Genotype 3a, no cirrhosis by imaging, HIV well controlled on raltegravir+ Epzicom

  27. Case #3 • 48 y.o. Latina woman, CD4+ 388, HIV RNA < 40 copies/ml on Atazanavir/ritonavir + Truvada • Genotype 1b, HCV RNA 750,000 IU/ml, IL28b genotype C/T (intermediate) • PEG/RBV 4 years ago, stopped after 12 weeks due to < 2 log10 HCV RNA drop (null response), tolerated reasonably well • Imaging now suggestive of early cirrhosis, biopsy Fibrosis stage 3-4, no history of decompensation • No other signficant comorbidities

  28. Case #3, Audience vote, pre-debate 1) Treat now? 2) Wait to treat? Case: 48 y.o. woman, prior null responder, HCV Genotype 1b, Fibrosis stage 3-4, IL28b C/T (intermediate). HIV well controlled on Atazanavir/ritonavir + Truvada

  29. Argument to Treat Now She has early cirrhosis – don’t wait Survival among HIV/HCV Coinfected patients with cirrhosis Lopez-Dieguez, M; AIDS. 25(7):899-904, April 24, 2011.

  30. Telaprevir is the best option REALIZE study of retreatment in individuals with prior treatment failures HIV negative Butt A, and Kanwal F Clin Infect Dis. 2012;54:96-104

  31. Argument to Wait

  32. Bourliere Liver International 2012 Feb;32 Suppl 1:113-9

  33. Cross-resistance of NS3 Protease Inhibitors D168A/V/T/H R155K/T/Q/P A156/V/T V170A/T/L T54S/A Q80R/K V36A/M A156S V55A * * Telaprevir Linear * Boceprevir Narlaprevir Danoprevir * * MK-7009 Macrocyclic TMC 435 BI 201335 *Mutations associated with in vitro resistance but not described in patients. Susser S et al. Hepatology. 2009;50:1709-18; Sarrazin C, Zeuzem S. Gastroenterology. 2010;138:447-62.

  34. DAA regimens in Nulls & Cirrhosis 12 weeks of HCV PI + NS5A in Null Responders, Genotype 1b (BMS) SOUND-C (HCV Protease inhibitor + polymerase+ RBV) cirrhosis subanalysis GT1a GT1b 86 80 80 68 60 57 60 50 43 43 42 33 40 11 2/ 18 20 3/ 7 8/ 14 2/ 4 4/ 5 0/ 0 1/ 3 40/93 84/124 11/26 37/43 15/25 n/ N = 0 Cirrhosis No Cirrhosis TID16, 28, 40+ BID28+ TID28- TID16, 28, 40+ BID28+ TID28- 80% SVR rate 90% SVR rate Chayama Hepatology 2012 Mar;55(3):742-8 Zeuzem S, et al. AASLD 2012. Abstract 232.

  35. Rebuttal: Treat Now

  36. Rebuttal: Wait to treat

  37. Case #3, Audience vote, post-debate 1) Treat now? 2) Wait to treat? Case: 48 y.o. woman, prior null responder, HCV Geno 1b, Fibrosis stage 3-4, IL28b C/T (intermediate). HIV well controlled on Atazanavir/ritonavir + Truvada

  38. Summary • HCV treatment is in a very dynamic period with the promise of improved SVR rates, shorter treatment and improved tolerability • Certain patients are likely to remain more challenging to treat: HIV coinfection, cirrhotics, prior non-responders • Less data are available for HIV co-infected patients and there may be more wrinkles • Drug-drug interactions • Possibly lower SVR rates than mono-infection • Patients and clinicians are left to apply limited data and weigh available options against hopeful, but uncertain, future options

More Related