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HIV / Hepatitis C Coinfection : From guesswork to Guidelines

Chris Fraser, MD Medical Director, Cool Aid Community Health Centre Clinical Faculty, UBC Faculty of Medicine. HIV / Hepatitis C Coinfection : From guesswork to Guidelines. HIV / Hepatitis C CoInfection. HIV infection as a roadmap for HCV and Coinfection HIV/ Hep C Coinfection overview

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HIV / Hepatitis C Coinfection : From guesswork to Guidelines

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  1. Chris Fraser, MD Medical Director, Cool Aid Community Health Centre Clinical Faculty, UBC Faculty of Medicine HIV / Hepatitis C Coinfection:From guesswork to Guidelines

  2. HIV / Hepatitis C CoInfection • HIV infection as a roadmap for HCV and Coinfection • HIV/ Hep C Coinfection overview • Coinfection guidelines • Coinfection trial outcomes • Future coinfection regimens • Pharmacology of ART/ DAA

  3. “Working with drug addicts brings out some of health careproviders’ worst fears, prejudices, and feelings of powerlessness.” “It is arrogant for a doctor (nurse) to presume - yet we do it all the time - that we can suddenly put a stop to a patient’s drug addiction, which by the time we first see the patient has become a powerful, biologically reinforced behaviour that has lasted for years if not decades.” “Our role as care providers is to be there, to bear witness, to be willing to accompany patients through their illness, and to refrain from passing judgment. Neither can we save them nor do we have the right to condemn them.” Peter A. Selwyn, Surviving the Fall: The personal journey of an AIDS doctor.

  4. “The only non compliant people are physicians (nurses) . If the patient doesn’t get better, it’s your own fault. Fix it.” Dr. Paul Farmer Mountains Beyond Mountains: Healing the World: The Quest of Dr. Paul Farmer

  5. Stopping HIV: Giving Pregnant Women Hope

  6. Stopping HIV:Children free of HIV

  7. Stopping HIV:Walking long miles to help

  8. Living with HIV: Winifrida’s smile is bigger

  9. Living with HIV:Income Generating Projects

  10. The Challenges:Stop AIDS, TB, ESLD

  11. HIV impact on Hep C Infection

  12. HIV/ Hep C CoInfectionOverview: • Teamwork  THANK YOU CAHN nurses ! • Open doors: more room at the inn • Increasing clinical and cultural competence • Adherence, adherence , adherence • Beyond coinfection  treatment as engagement in life change

  13. Coinfection Overview • HCV 2013 = HIV 1999 • Guidelines: here today … gone tomorrow • IFN = child who won’t leave home • Leaky cascade: increase treatment • Health Infrastructure – merge HIV/ HCV treatment systems • Peer involvement : Navigators / Facilitators • Ways forward: look to Europe / cohorts

  14. Higher Discontinuation Rates in Real-World Settings Than in Clinical Trials 40 30 498 GT1 Patients Evaluated[1] 174 GT1 Patients StartedTVR-Based Triple Therapy[2] 21 50 20 40 33[2] 10 30 21 Patients (%) 22 0 18 17 20 D/CBeforeWk 12 11 10 91/ 498 69/ 407 89/ 407 43/ 407 58/ 174 36/ 174 n/N = 0 D/C TVR < 12 wks Due to AEs Started Therapy PatientChoice Wait forBetterTherapies MildDisease Did Not Start 1. Chen EY, et al. AASLD 2012. Abstract 133. 2. Bichoupan K, et al. AASLD 2012. Abstract 1755.

  15. Inner City Primary Care: Untold Clinical Stories: • 24 year shorter life expectancy • many patients declining contact with health care system • large numbers of patients declining treatment after engaged in care • total drug abstinence NOT required for treatment  Mental health, Hepatitis C , HIV

  16. Cool Aid CHC : Overview • 5000 clients served • Interdisciplinary: NP, MD , onsite pharmacy, counselors, psychiatry, nutrition • Multi-site outreach program • Concurrent diagnoses the norm: Mental health, chemical dependency, HIV, Hepatitis C, Chronic pain

  17. Meanwhile in the clinic... 34 yo Male • polydrug chemical dependency  IDU • HIV+ 2006; HCV+ 2003 ; HBV+ 2002 • Untreated depression • Unstable housing • Criminal charges pending

  18. EACS Guideline Recommendations for Use of PegIFN in HCV/HIV-Coinfected Pts European AIDS Clinical Society HIV Treatment Guidelines, 2011, Version 6.0.

  19. Study 110: TVR + PegIFN for Treatment of HCV in HCV/HIV-Coinfected Pts Dieterich D, et al. CROI 2012. Abstract 46.

  20. Study 110: SVR24 With TVR + PegIFN/RBV in HCV GT1/HIV-Coinfected Patients • Higher SVR24 rate with TVR-based therapy • No significant drug–drug interactions with TVR and ART • TVR plasma levels similar in patients with or without ART • EFV and ATV/RTV plasma levels similar in patients with or without TVR • No HIV breakthroughs in patients using ART during HCV treatment • Safety and tolerability similar to treatment in patients with HCV monoinfection Telaprevir + PR 100 Placebo + PR 80 80 74 71 69 60 50 50 SVR24 (%) 45 40 33 20 5/ 7 2/ 6 11/ 16 4/ 8 12/ 15 4/ 8 28/ 38 10/ 22 n/N = 0 No ART EFV-Based ART ATV-Based ART Overall Population Sulkowski MS, et al. AASLD 2012. Abstract 54. Reproduced with permission.

  21. Phase II Study of BOC + PegIFN in HCV/HIV-Coinfected Individuals Sulkowski M, et al. IDSA 2011. Abstract LB-37.

  22. Higher SVR12 Rates With BOC + P/R vs P/R Alone in HIV/HCV Coinfection • Interim efficacy analysis • 3 BOC pts had not yet reached SVR12 time point • HIV-1 RNA breakthrough observed in 7 pts • BOC + P/R: n = 3/64 • Placebo + P/R: n = 4/34 • Tolerability similar to that seen in HCV monoinfection • Similar rates of total and serious adverse events in BOC and placebo groups • Higher rates of discontinuation due to toxicity with BOC (20%) vs placebo (9%) • Caution needed with drug-drug interactions 100 80 60.7* 60 SVR12 (%) 40 26.5 20 n/N = 37/61 9/34 0 BOC + P/R P/R *Reflects presented data; speaker noted verbally that remaining 3 pts have now reached and achieved SVR12 Mallolas J, et al. EASL 2012. Abstract 50.

  23. Treatment Paradigm With HCV PIs in the HCV/HIV-Coinfection Setting Telaprevir PI. Boceprevir PI.

  24. Management of Newly Diagnosed Gt 1 HCV/HIV–Coinfected Pts Ingiliz P, Rockstroh J. Liver Int. 2012;[E-pub ahead of print].

  25. Management of Gt 1 HCV/HIV–Coinfected Pts by Fibrosis Stage, Prior Tx Outcome Ingiliz P, Rockstroh J. Liver Int. 2012;[E-pub ahead of print].

  26. Toward a Future of Personalized Medicine for HCV Therapy Direct-Acting Antivirals Nuc + RBV NNI + PI± RBV Nuc + NS5A Inh ± RBV PegIFN +RBV+ DAA Others?

  27. Likelihood of SVR With Current Therapies Related to IFN Responsiveness HCV RNA Reduction After 4-Wk Lead-in ≥ 1 log decline < 1 log decline 100 100 82 76 80 80 60 60 SVR (%) SVR (%) 40 40 33 33 20 20 158 0 0 RESPOND-2* (BOC)[1] REALIZE (TVR)[2] *Pooled data from RGT and arm 3. 1. Vierling JM, et al. EASL 2011. Abstract 481. 2. Foster G, et al. EASL 2011. Abstract 6.

  28. Daclatasvir and Asunaprevir in GT1 HCV Previous Null Responders • AI447-011: randomized, open-label phase IIa study with daclatasvir (NS5A inhibitor) and asunaprevir (NS3 protease inhibitor) Wk 24 Daclatasvir 60 mg QD + Asunaprevir 200 mg BID* (n = 18) Daclatasvir 60 mg QD + Asunaprevir 200 mg QD* (n = 20) Noncirrhotic pts with GT1 HCV and previous null response to pegIFN/RBV(N = 101) Daclatasvir 60 mg QD + Asunaprevir 200 mg BID + PegIFN/RBV (n = 20) Daclatasvir 60 mg QD + Asunaprevir 200 mg QD + PegIFN/RBV (n = 21) Daclatasvir 60 mg QD + Asunaprevir 200 mg BID + RBV (n = 22) *Only pts with GT1b HCV included in dual-therapy arms. Lok AS, et al. AASLD 2012. Abstract 79.

  29. Outcomes With Daclatasvir + Asunaprevir± PegIFN or RBV in Null Responders • High response rates with 4-drug regimen of DCV + ASV + pegIFN/RBV • Lower response rates with 2-drug regimen (all GT1b pts) • Better response with ASV 200 mg BID vs ASV 200 mg QD • SVR data from 3-drug arm not reported due to high rate of virologic breakthrough in GT1a but not in GT1b • 10 GT1a pts with virologic breakthrough • All triple-therapy pts offered pegIFN • No virologic breakthrough with addition of pegIFN • Virologic breakthrough in 8 pts in 2-drug arms but none in 4-drug arm • 3 relapses • 1 with DCV + ASV QD • 2 with DCV + ASV + PR • All regimens generally well tolerated, with no discontinuations due to toxicity DCV + ASV (BID) + PR DCV + ASV (QD) + PR DCV + ASV (BID) DCV + ASV (QD) 100 100 95 100 90 89 78 80 70 65 60 HCV RNA < LLOQ (%) 40 20 20/ 20 21/ 21 18/ 20 20/ 21 16/ 18 14/ 20 14/ 18 13/ 20 n/N = 0 EOT SVR24 EOT SVR12 Lok AS, et al. AASLD 2012. Abstract 79.

  30. Drug–Drug Interaction Resource

  31. Summary of Boceprevir Drug–Drug Interactions With Antiretrovirals

  32. DHHS Recommendations on Use of BOC or TVR in Gt 1 HCV/HIV–Coinfected DHHS Guidelines March 2012. .

  33. HIV / Hepatitis C CoInfection • HIV infection as a roadmap for HCV and Coinfection • HIV/ Hep C Coinfection overview • Coinfection guidelines • Coinfection trial outcomes • Future coinfection regimens • Pharmacology of ART/ DAA

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