The Case for Treatment Now
Todd Wills, MD
ETAC Infectious Disease Specialist
HEPATITIS C TREATMENT EXPANSION INITIATIVE
MULTISITE CONFERENCE CALL
JULY 17, 2013
Increases Rates of HCC in HIV/HCV
Coinfection
• Results
• Among HIV/HCV coinfected participants, HCC incidence rose
from 0.2 to 2.8 cases per 1000 person-years between 2000
and 2009, with the largest jump in 2008-2009.
• Most patients with HCC (79%) died during follow-up, all but 2
due to complications related to liver cancer.
• The median survival time after HCC diagnosis was 91 days
(interquartile range, 31 to 227 days).
• Compared with cases of HCC diagnosed before 2005, people
diagnosed during later years did not have a higher survival
rate.
N Merchante, E Merino, J López-Aldeguer, et al. Increasing Incidence of Hepatocellular Carcinoma in HIVInfected Patients in Spain. Clinical Infectious Diseases 56 (1):143-150. January 1, 2013.
High Risk for Decompensation
• F3 fibrosis (biopsy), probability of decompensation
:1% at 1 year, 2% at 3 years, 5% at 5 years.
• Among patients with cirrhosis (biopsy),
corresponding probabilities were 4%, 13%, and 23%.
• Among patients with 9.5-14.5 kPa (FibroScan),
probability of decompensation : 1% at 1 year, 3% at 3
years, 4% at 5 years.
• Among patients with >14.6 kPa (FibroScan), the
probabilities were 7%, 17%, and 27%, respectively.
J Macias, A Camacho, MA von Wichmann, et al. Advanced fibrosis and the risk of liver decompensation
among HIV/HCV-coinfected individuals: consequences for the timing of therapy against HCV. 48th Annual
Meeting of the European Association for the Study of the Liver (EASL 2013). Amsterdam. April 24-28,
2013. Abstract 474.
HCV Treatment Lowers Risk of
Cirrhosis Complications
• baseline fibrosis, 10-year survival:
– Patients with SVR: HIV/HCV coinfected 66% vs HCV
monoinfected 62% (p=0.04);
– Untreated: 7% vs 93%, respectively (p=0.009).
• Among untreated participants, coinfected
were 9 times more likely than HCV
monoinfected to progress to cirrhosis over 10
years (1.41 vs 0.18, respectively; p < 0.001).
T Poynard, MA Valantin, M Munteanu, et al (FibroFrance-GHPS Group). Long Term Survival of Liver
Fibrosis after Virological Cure (SVR) in HIV-HCV Coinfected Patients: A Worrisome Latent Disease? 48th
Annual Meeting of the European Association for the Study of the Liver (EASL 2013). Amsterdam. April 2428, 2013. Abstract 487..
Acute HCV in MSM on the Rise
• Acute HCV in MSM on rise
– 17 incident cases (among 2250 subjects) in 5 phase II/III studies of
EVG/COBI/FTC/TDF[1]
• Observational study assessed HCV reinfections in high-risk
HIV/HCV-coinfected MSM (N = 64)[2]
– GT1a HCV: 62.5% (n = 40)
– GT3a HCV: 3.1% (n = 2)
─
─
GT1b HCV: 6.3% (n = 4)
GT4d HCV: 28.1% (n = 18)
• 33 cleared virus spontaneously or following treatment[2]
• 5-yr cumulative incidence of new infection by genotype[2]
– Same HCV genotype as original infection: 6.1% (95% CI: 0% to 14.5%)
– Different HCV genotype than original infection: 25.5% (95% CI: 10.4%
to 38.0%)
• Results demonstrate continued risk of HCV reinfection after
clearance[2]
1. Quirk E, et al. CROI 2013. Abstract 705. 2. Thomas X, et al. CROI 2013. Abstract 708.
Impaired HCV Specific Immune
Response in HIV+ Patients
• HIV infection had a detrimental effect on HCV-specific
cytokine production in people with acute hepatitis C.
• The effect was particularly notable for HCV-specific interferon
gamma production.
• Interferon gamma responses were both significantly lower in
magnitude and smaller in breadth in HIV/HCV coinfected
people.
• Reduced interferon production was associated with lower
peripheral CD4 T-cell counts, but not with detectable HIV viral
load.
JK Flynn, GJ Dore, G Matthews, R Ffrench, et al (ATAHC Study Group). Impaired Hepatitis
C Virus (HCV)-Specific Interferon-Responses in Individuals with HIV Who Acquire HCV
Infection: Correlation With CD4+ T-Cell Counts. Journal of Infectious Diseases
206(10):1568-1576. November 15, 2012.