Update on HCV Treatment

Transcription

1 Update on HCV Treatment Ajay Bharti, MD Associate Professor of Medicine Division of Infectious Diseases University of California San Diego 2018 April 28, 2018

2 Clinically relevant questions in HCV-HIV coinfected patients What is the goal of treatment? When and who should be treated? How should they be managed? Before, during, and after 2

3 HCV Disease Burden 3

4 HCV prevalence in all countries 4

5 Number of HCV infected people worldwide 5

6 Countries accounting for 80% of HCV infections 6

7 HCV Prevalence in India 7

8 HCV Prevalence in PWID in India Established Epidemics Large Cities Emerging Epidemics (documented) Solomon, et. al., Lancet Infect Dis 2014 Emerging Epidemics (anecdotal) 8

9 HIV/HCV Prevalence in India IDU Established Epidemics Large Cities Emerging Epidemics (documented) Solomon, et. al., Lancet Infect Dis 2014 Emerging Epidemics (anecdotal) 9

10 10

11 The Polaris Study Key Findings 2015 global HCV prevalence was 1% or 71 million infections Much lower infection rates in India and China Rates in adults extrapolated to entire population Use of anti-hcv Ab China, Pakistan, India, Egypt, Russia, and USA account for over half of all HCV infections globally In 2015, ~1 million patients received treatment for HCV Two-thirds with DAAs 700,000 achieved sustained virologic response 11

12 Clinically relevant questions in HCV-HIV coinfected patients What is the goal of treatment? When and who should be treated? How should they be managed? Before, during, and after 12

13 13 IDSA/AASLD HCV Treatment Guidance 2017

14 HCV RNA (log 10 IU/mL) The Goal of HCV Treatment HCV Therapy 8 24 weeks Relapse 2 3% Weeks After Start of Therapy EOT SVR 95-98% 14

15 15 IDSA/AASLD HCV Treatment Guidance 2017

16 16

17 Indian HCV Treatment Guidelines Update

18 Pre-treatment Assessment (2016 INASL) History and physical exam Baseline liver and kidney tests Hepatitis B and HIV HCV RNA (quantitative) HCV genotyping Liver fibrosis Psychiatric evaluations Pregnancy test for women of child-bearing age 18

19 CDC-Recommended HCV Testing Algorithm 19

20 20

21 HCV Diagnosis Anti-HCV antibodies False negative in: acute infection, immunosuppressed PCR Qualitative and quantitative HCV core Ag Cost-effective alternative to HCV RNA testing Abbott Architect can detect anti-hcv Ab and HCV core Ag 21

22 Determining the Extent of Liver Disease Clinical Only useful in decompensated cirrhosis Biopsy Old Gold Standard Morbid/Expensive Sampling errors occur Biochemical tests: APRI, FIB-4 Imaging: Ultrasound, MRI Fibroscan: New Gold Standard 22

23 Hepatic Elastrography: Fibroscan 23

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25 HCV Treatment Options 25

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27 Direct Acting Antivirals 2016: SOF/velpatasvir, elbasvir/grazoprevir 2017: Glecaprevir/pibrentasvir, SOF/velpatasvir/voxilaprevir Gutierrez, et al. Journal of Viral Hepatitis, 2015, 22:

28 INASL HCV Treatment Guideline Update

29 INASL HCV Treatment Update 2016: GT3 29

30 SVR12( %) SOF/DCV in HIV Co-Infection: ALLY-2 12-Week Naive GT 1 (N = 168) Week Experienced 8-Week Naive Failures (12 week arms): 1 withdrawal at week 1 1 detectable HCV RNA at EOT 2 relapses Safety and tolerability: 2% Serious AEs No discontinuations due to AEs 1 death 2 HIV VL >400 copies on study 100% SVR12 in 1b and non-gt1 with 12 weeks. 30

31 AASLD HCV Treatment Guidelines Update 2016: GT3 Non-Cirrhotic Comp Cirrhotic Sofosbuvir/velpatasvir x x Daclatasvir/sofosbuvir x Daclatasvir/sofosbuvir 24 + Ribavirin x 31

32 DAA Selection Considerations Efficacy against specific genotype Drug-drug interactions Cost 32

33 DAA and ARV Drug-Drug Interactions Poizot-Martin I, Naqvi A, Obry-Roguet V, Valantin MA, Cuzin L, et al. (2015) Potential for Drug-Drug Interactions between Antiretrovirals and HCV Direct Acting Antivirals in a Large Cohort of HIV/HCV Coinfected Patients. PLOS ONE 10(10): e

34 Effect of DAAs on HCV Management x Pangenotypic Regimens 34 HCV Genotype

35 Current Challenges 35

36 Impact of HIV co-infection on DAA response? Data from 2 prospective Spanish cohorts (HEPAVIR-DAA and GEHEP-MONO) HCV (N=404) HCV/HIV (N=423) Male 67% 82% Two similar sized cohorts (USC, VA) showed no impact of HIV co-infection on HCV SVR12. IDU 29% 84% Montes ML. #SAT-206. EASL McGinnis J. #LBP-514. EASL a 29% 42% Cirrhosis 52% 64% Partial/ Null 27% 31% HIV (aor 0.592; p=0.02) and cirrhosis (aor 0.601, p=0.02) associated with non-svr 36

37 CROI 2018 Abstract #610 DAA treatment response among HIV/HCV co-infected patients (Kitahata et al) SVR12 was 98.2% (95% CI 96.1,99.3) LDV-SOF (84.2%) Simeprevir/sofosbuvir Sofosbuvir/daclatasvir (3.2%) Paritaprevir-ritonavir-ombitasvir/dasabuvir (2.1%) Elbasvir-grazoprevir (1.1%) Sofosbuvir-velpatasvir (0.8%) 37

38 HCV Re-infections 38

39 High rate of HCV re-infection in HIV/HCV MSM in Western Europe 2 nd (n=29), 3 rd (n=4), and even 4 th (n=1) re-infections were seen (2 nd : 19.9/100py) 39

40 HCV Treatment Cascade in the US HCV Genotype VL Re, PLoS ONE,

41 CROI

42 CROI 2018: Improving Access to Care Community based approach to testing and treatment (#594 Saag) State-wide, community-based test and treat program Disease awareness, testing, patient navigation, and Hepatitis C treatment co-location in Primary Care Treatment as prevention (#81LB Fehr) HIV+ MSM in the Swiss HIV Cohort Study 50% reduction in new infections (reduced from 31 to 16) Grazoprevir/elbasvir ± ribavirin for GT1 or 4 42

43 CROI 2018: HCV Treatment Outcomes HCV treatment outcome in HIV+ PWID (#605 Sulkowski) 91% cure rate 33% had heavy alcohol use Predictors of lack of hepatitis C clearance among PLWH (#609 Mathews et al) Psychiatric illness (p<.0001) and illicit drug use (p=0.006) in bivariate analysis Only psychiatric illness in logistic regression analysis SVR12 92% overall; 91% in cirrhotics; 87% with prior liver decompensation 43

44 CROI 2018: Treating Acute HCV Infections Treating acute HCV infections The Dutch Acute HCV in HIV study no. 2 (DAHHS2) 52/53 HIV+ MSM with acute HCV infection (26 weeks or less) on 8-week course achieved SVR12 44

45 CROI 2018: Resource Limited Settings Estimating HIV and HCV incidence among PWID in India (#587 Mehta) Cumulative incidence based approach Evaluation of DBS HCV RNA quantification and genotyping (#580 Saravanan) Good correlation between Abbott plasma and DBS HCV RNA assay (r = 0.97, r = 0.94, p<0.001) Feasibility, efficacy, and safety of DAAs in resource-limited settings (#602 Attia) TAC ANRS Trial in Senegal, Ivory Coast, and Cameroon GT 2 (SOF+RBV), GT1 and 4 (SOF+LDV) 90% achieved SRV12 (36/120 were HIV+) 45

46 Direct Acting Antivirals 2017: Glecaprevir/pibrentasvir, SOF/velpatasvir/voxilaprevir 2016: SOF/velpatasvir, elbasvir/grazoprevir Gutierrez, et al. Journal of Viral Hepatitis, 2015, 22:

47 Eliminating Hepatitis C: A Real Possibility Remarkable advances in HCV cure with short-course and welltolerated therapy Possibility of eliminating the disease worldwide WHO global targets for HCV by 2030: 90% reduction in new infections 65% reduction in hepatitis C mortality 80% treated Strategy includes Prevent: PWID, needle safety; vaccine Test: improved diagnostics, active case finding Treat 47

48 Summary DAAs have simplified HCV treatment Briefer regimen Minimal monitoring New drug availability and guidelines are constantly evolving Present and future challenges include- Identifying cases Reinfections Resistance associated substitutions Drug-drug interactions It may be possible to eradicate Hepatitis C 48

49 Acknowledegement YRG CARE N. Kumarasamy Beulah Kavitha Pearl Pradeep Saravanan Syed Iqbal Balakrishnan Sunil Solomon Univ of California, San Diego Scott Letendre Davey Smith Chip Schooley David Wyles Constance Benson 49

50 Thank you! 50