1. Elimination of Hepatitis C in Individuals With HIV Infection
David L. Thomas, MD, MPH
Professor of Medicine
The Johns Hopkins Medical Institutions
Baltimore, Maryland

2. Financial Relationships With Commercial Entities
Dr Thomas has no relevant financial affiliations to disclose. (Updated 11/12/18)

3. Learning Objectives
After attending this presentation, learners will be able to:
List two 2030 elimination goals for HCV infection
Compare treatment of HCV infection in a person with HIV infection and someone without

4. ARS Question 1: Which is most true about the expected future (2040) mortality from chronic HCV and HBV?
Should decrease in parallel with HIV
Will exceed HIV
Will exceed TB
Will exceed malaria
Will exceed HIV+TB+malaria

5. ARS Question 1: Which is most true about the expected future (2040) mortality from chronic HCV and HBV?
Should decrease in parallel with HIV
Will exceed HIV
Will exceed TB
Will exceed malaria
Will exceed HIV+TB+malaria

6. Global health importance of hepatitis
Foreman Lancet 2018; IHME,

7. WHO Hepatitis Elimination Goals
90% reduction in incidence
2015
2020 (30%)
2030
~1.75 million
~1.23 million
175,000
HCV
So question is how will we know if incidence is reduced by 90% by
WHO Global Hepatitis Report 2017

8. WHO Hepatitis Elimination Goals
65% reduction in mortality
2015
2020 (10%)
2030
~400,000
~360,000
140,000
HCV
How will we know if liver related mortality has reduced by 65%
These slides also raise the highly correlated question of when should we know…or when should we check to see if we are on track.
WHO Global Hepatitis Report 2017

9. Targets to eliminate hepatitis C
Intervention
2015
2020
2030
HCV diagnosed
20%
30%
90%
HCV treatment 1%
3 million
80%
Donations screened
97%
97.5%
100%
Harm reduction (syr/person/yr) 27
200
300
Safe injection
95%
WHAT IT IS, HOW VIA PUBLIC HEALTH, TAYLORED
WHO Global Hepatitis Report 2017

10. Global cascade of HCV care and 2030 WHO elimination goals: 90/80 target
WHO Global Hep Report 2017

11. Elimination prefix cascade
Eradication
Elimination
Micro-elimination
HIV positive
Nano-elimination
National
Pico-elimination
Clinic
Patient
Elimination prefix cascade

12. ARS Question 2: A 53 year old man with 1a HCV and HIV on r/DRV, FTC, and TDF with F1-2 disease presents for HCV treatment. Which is true?
Needs 24 weeks of treatment due to HIV
Doesn’t need treatment due to low F score
Change ART first
Add ribavirin to regimen
Must screen for HCC before starting

13. ARS Question 2: A 53 year old man with 1a HCV and HIV on r/DRV, FTC, and TDF with F1-2 disease presents for HCV treatment. Which is true?
Needs 24 weeks of treatment due to HIV
Doesn’t need treatment due to low F score
Change ART first
Add ribavirin to regimen
Must screen for HCC before starting

14. Efficacy of SOF/LDV in HIV Co-infected patients
335 patients SOF/LDV x 12 wk
82% male, 34% AA, 98% geno 1
55% experienced
20% cirrhosis
All 10 relapses were in AA
8/10 on EFV
20% with baseline NS5A RAVs; 94% SVR
Naggie S. NEJM 2015.

15. Efficacy of SOF/VEL in HIV/HCV Coinfection
106 patients SOF/VEL x 12 wks
86% male
45% AA
18% cirrhosis
62% GT1a, 11% GT3
SVR
cirrhosis: 19/19 (100%)
SVR treatment-experienced: 29/31 (94%)
Patients With SVR12, %
2 Relapse
1 LTFU
1 Withdrew Consent
1 LTFU
101
106 63 66 11 12 11 11 12 5
Wyles CID 2017

16. Efficacy of GLE/PIB in HIV/HCV Coinfection
150 patients G/P x 8 or 12 wks
18% Black
19% TE
16% GT3
88% F0-F1
SVR:
93% SVR in cirrhosis (14/15)
1 breakthrough GT3 cirrhosis
Patients With SVR12, %
150
153
150
151
ITT
mITT
Noninferiority Threshold
Rockstroh CID 2018

17. GLE/PIB for 8 weeks works well in cirrhosis
280 patients G/P x 8 wks
10% Black
Treatment naive
Compensated cirrhosis
NO HIV
60 Genotype 3 + cirrhosis not yet known
150
153
150
151
Brown AASLD 2018

18. Efficacy of elbasvir/grazoprevir in HIV Co-infection
218 patients ELB/GRA x 12 wks
175 male
38 African American
35 cirrhosis
164 on TDF containing
Rockstroh Lancet HIV 2015

19. Treatment of HCV in HIV/HCV Coinfection
Patients With SVR12, % 1 2 3 4
Composite slide adapted from Naggie S, Duke University. 1. Wyles D, et al. Clin Infect Dis. 2017;65(1):6-12; 2. Rockstroh JK, et al. Lancet HIV. 2015;2(8):e ; 3. Naggie S, et al. N Engl J Med. 2015;373(8): ; 4. Rockstroh JK, et al. European Association for the Study of the Liver (EASL) − The International Liver Congress™ April 19−23, 2017; Amsterdam, the Netherlands. Abstract LB-522.

20. Cure of HCV in HIV-infected reduces ESLD and HCC
: This was a multicentre prospective cohort study recruiting HIV/HCV-coinfected patients with a new diagnosis of compensated cirrhosis. Patients were followed up until HCC, death or the censoring date (March 2017). The primary endpoint was the emergence of HCC. The incidence rate (IR) (95% CI) of HCC in different groups was computed. Time-to-event analyses were performed to identify predictors of HCC emergence. Results: The study included 495 HIV/HCV-coinfected patients with cirrhosis. After a median (IQR) follow-up of 59 (27–84) months, 22 (4.4%; 95% CI 2.6–6.3) patients developed an HCC. The IR (95% CI) of HCC was 0.93 (0.06–1.42) per 100 person-years (PY). Three hundred and three (61%) patients achieved sustained virological response (SVR) during follow-up, 79 after interferon (IFN)-based regimens and 224 after an all-oral DAA regimen. The IR (95% CI) of HCC after all-oral DAA was 0.35 (0.14–0.85) per 100 PY whereas it was 1.79 (1.11–2.88) per 100 PY in the remaining cohort (P " ). When only patients with SVR were considered, the IR (95% CI) of HCC after all-oral DAA was 0.32 (0.12–0.86) whereas it was 0 per 100 PY among those with SVR after IFN-based therapies (P" 0.27). Achieving SVR with an all-oral DAA regimen during follow-up was independently associated with a lower risk of HCC emergence (subhazard ratio 0.264; 95% CI 0.070–0.991; P " 0.049).
Limketkai JAMA 2012; Berenguer Hepatol 2009; Merchante J Antimicrobiol Ther 2018

21. Kiser, HCVguidelines.org

24. Elimination of HCV in HIV infected in Netherlands
Athena cohort >98% of HIV pos in recognized in Netherlands
69% MSM, 15% PWID
DAAs made available in 2015
15 months of data through Feb 2017
The incidence of HCV among Dutch human immunodeficiency virus (HIV)–positive men who have sex with men (MSM) has been
high for >10 years. In 2015 DAAs became available to all Dutch HCV patients and resulted in a rapid treatment uptake in HIVpositive
MSM. We assessed whether this uptake was followed by a decrease in the incidence of HCV infections.
Methods. Two prospective studies of treatment for acute HCV infection enrolled patients in 17 Dutch HIV centers, having 76%
of the total HIV-positive MSM population in care in the Netherlands. Patients were recruited in 2014 and 2016, the years before and
after unrestricted DAA availability. We compared the HCV incidence in both years.
Results. The incidence of acute HCV infection decreased from 93 infections during 8290 person-years of follow-up (PYFU)
in 2014 (11.2/1000 PYFU; 95% confidence interval [CI], 9.1–13.7) to 49 during 8961 PYFU in 2016 (5.5/1000 PYFU; 4.1–7.2). The
incidence rate ratio of 2016 compared with 2014 was 0.49 (95% CI, .35–.69). Simultaneously, a significant increase in the percentage
positive syphilis (+2.2%) and gonorrhea (+2.8%) tests in HIV-positive MSM was observed at sexual health clinics across the
Netherlands and contradicts a decrease in risk behavior as an alternative explanation.
Boerekamps CID 2018

25. Elimination of HCV in HIV infected in Netherlands
The incidence of HCV among Dutch human immunodeficiency virus (HIV)–positive men who have sex with men (MSM) has been
high for >10 years. In 2015 DAAs became available to all Dutch HCV patients and resulted in a rapid treatment uptake in HIVpositive
MSM. We assessed whether this uptake was followed by a decrease in the incidence of HCV infections.
Methods. Two prospective studies of treatment for acute HCV infection enrolled patients in 17 Dutch HIV centers, having 76%
of the total HIV-positive MSM population in care in the Netherlands. Patients were recruited in 2014 and 2016, the years before and
after unrestricted DAA availability. We compared the HCV incidence in both years.
Results. The incidence of acute HCV infection decreased from 93 infections during 8290 person-years of follow-up (PYFU)
in 2014 (11.2/1000 PYFU; 95% confidence interval [CI], 9.1–13.7) to 49 during 8961 PYFU in 2016 (5.5/1000 PYFU; 4.1–7.2). The
incidence rate ratio of 2016 compared with 2014 was 0.49 (95% CI, .35–.69). Simultaneously, a significant increase in the percentage
positive syphilis (+2.2%) and gonorrhea (+2.8%) tests in HIV-positive MSM was observed at sexual health clinics across the
Netherlands and contradicts a decrease in risk behavior as an alternative explanation.
Boerekamps CID 2018

26. Elimination of HCV in HIV infected in Netherlands
The incidence of HCV among Dutch human immunodeficiency virus (HIV)–positive men who have sex with men (MSM) has been
high for >10 years. In 2015 DAAs became available to all Dutch HCV patients and resulted in a rapid treatment uptake in HIVpositive
MSM. We assessed whether this uptake was followed by a decrease in the incidence of HCV infections.
Methods. Two prospective studies of treatment for acute HCV infection enrolled patients in 17 Dutch HIV centers, having 76%
of the total HIV-positive MSM population in care in the Netherlands. Patients were recruited in 2014 and 2016, the years before and
after unrestricted DAA availability. We compared the HCV incidence in both years.
Results. The incidence of acute HCV infection decreased from 93 infections during 8290 person-years of follow-up (PYFU)
in 2014 (11.2/1000 PYFU; 95% confidence interval [CI], 9.1–13.7) to 49 during 8961 PYFU in 2016 (5.5/1000 PYFU; 4.1–7.2). The
incidence rate ratio of 2016 compared with 2014 was 0.49 (95% CI, .35–.69). Simultaneously, a significant increase in the percentage
positive syphilis (+2.2%) and gonorrhea (+2.8%) tests in HIV-positive MSM was observed at sexual health clinics across the
Netherlands and contradicts a decrease in risk behavior as an alternative explanation.
Boerekamps CID 2018

27. Elimination of HCV in HIV infected persons in France
Cotte CROI 2018

28. ARS Question 3: How many HCV infected people need to be cured to eradicate HCV from HIV-infected population?
20,000
200,000
2,000,000
20,000,000

29. ARS Question 3: How many HCV infected people need to be cured to eradicate HCV from HIV-infected population?
20,000
200,000
2,000,000
20,000,000

30. 2.27 million persons are HIV/HCV coinfected
Platt Lancet ID 2016

31. Elimination prognosis?
Eradication
Elimination
Micro-elimination
HIV positive
Nano-elimination
National
Pico-elimination
Your patients
Elimination prognosis?

32. Elimination prognosis?
Eradication
Elimination
Micro-elimination
HIV positive
Nano-elimination
National
Pico-elimination
Your patients
Elimination prognosis?

33. Public health response to eliminate HCV
Requires shifting to public health response
HIV example
ART given to >20 million persons (>240 million person months)/year
Cost of HIV ~20 billion USD/year
Can build on HIV infrastructure for HIV/HCV elimination
2 million/2-3 months each <6 million person months TOTAL
Must avoid 2040 forecast for status quo
When HIV meds first improved and got people talking about elimination, there was a huge amount of skepticism like you hear now for hep. But some very resourceful persons marshalled the resources to tackle the problem.

34. Thanks! JHU HIV WHO HCV/HIV Mark Sulkowski Seun Falade-Nwulia
Kathleen Ward
Richard Moore
Shruti Mehta
Yvan Hutin
Godfrey
John Ward
HCV/HIV
David Wyles
Susanna Naggie

35. Question-and-Answer

36. WHO elimination indicators and targets
Point 1 is So how we will know is by the targets and we will evaluate them in 5 years to see if we are on track.
Ask how do we measure the targets?
WHO Global Hepatitis Report 2017

37. WHO goals for elimination of hepatitis C
“A world where viral hepatitis transmission is stopped and everyone has access to safe, affordable and effective treatment and care” WHO
Elimination: Reduction to zero of the incidence of infection caused by a specific agent in a defined geographical area as a result of deliberate efforts; continued measures to prevent re-establishment of transmission are required. Example: measles, poliomyelitis.
Cost is just low and middle income
WHO Global Hepatitis Report 2017; Hill J Virus Elimin 2016

38. Why elimination and not eradication?

39. HCV could be eradicated
Every HCV-infected person can be detected
Eradicate infection by treatment
Humans are only source
Transmission can be prevented
Public health importance
If these are true, then surely the logical conclusion is global eradication campaign. rEason is

40. HCV could be eradicated
Every HCV-infected person can be detected
Eradicate infection by treatment
Humans are only source
Transmission can be prevented
Public health importance
International commitment
If these are true, then surely the logical conclusion is global eradication campaign. rEason is