The UC San Diego AntiViral Research Center sponsors weekly presentations by infectious disease clinicians, physicians and researchers. The goal of these presentations is to provide the most current research, clinical practices and trends in HIV, HBV, HCV, TB and other infectious diseases of global significance. The slides from the AIDS Clinical Rounds presentation that you are about to view are intended for the educational purposes of our audience. They may not be used for other purposes without the presenter’s express permission. AIDS CLINICAL ROUNDS
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HIV/HCV Co-Infection: The Journey of a Special Population
Susanna Naggie, M.D., M.H.S., of Duke Clinical Research Center, presents "HIV/HCV Co-Infection: The Journey of a Special Population" at AIDS Clinical Rounds
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The UC San Diego AntiViral Research Center sponsors weekly presentations by infectious disease clinicians, physicians and researchers. The goal of these presentations is to provide the most current research, clinical practices and trends in HIV, HBV, HCV, TB and other infectious diseases of global significance. The slides from the AIDS Clinical Rounds presentation that you are about to view are intended for the educational purposes of our audience. They may not be used for other purposes without the presenter’s express permission.
AIDS CLINICAL ROUNDS
HIV/HCV Co-infection: The Journey of a Special Population
Susanna Naggie, MD, MHS Assistant Professor of Medicine
Director, Infectious Diseases Research Duke Clinical Research Institute
Disclosure
Commercial Research support: AbbVie Pharmaceuticals, Bristol-Myers Squibb, Gilead Sciences, Janssen Therapeutics, and Vertex Pharmaceuticals
Scientific advisor/consultant: AbbVie Pharmaceuticals, Bristol Myers Squibb. (Updated 12/11/14) **Off label use of FDA approved medications
Mr. KB 34 y/o man with HIV/HCV co-infection Diagnosed with HIV in his 20s, quite ill at the time with disseminated MAC and PCP, CD4 count was 9 He was simultaneously diagnosed with HCV Since diagnosis, he has had excellent control of his HIV
PMHx ►HIV dx 1990s
– Nadir CD4 9 – + history of OI: PCP, MAC
►HCV dx 1990s – GT1b, VL 1.2 million IU/mL – Cirrhosis dx by liver biopsy 2009 – No history of decompensation – Portal HTN with thrombocytopenia, splenomegaly and
portal gastropathy (last EGD 3/2014) – HAV and HBV immune
►Complex regimens ►Still require pegylated interferon and ribavirin ►~50% still require 48 weeks of treatment ►Worsened safety profile ►SVR = cure only 70% ►Significant drug interactions ►Phase II in HIV/HCV delayed by 3 years
– Still not FDA approved in HIV – Limited access in many states
New Kids on the Block in 2013
►Multi-genotypic NS3/4A PI
►QD dosing ►Second Wave PI ►Low barrier to
resistance ►+ DDI with ARVs ►Rash, photosensitivity ►HIV not a special pop
resistance ►No significant DDI ►No AE ►Approved for HIV/HCV as
special population
SMV: HCV versus HIV/HCV, genotype 1 in Clinical Trials Not head to head comparison
80 77
65
53
79 87
70
57
0102030405060708090
100
Tx Naïve Prior Partial
HCV HIV/HCV
Prior Relapse Prior Null 7/10 13/15 16/28 419/521
Antiviral Drugs Advisory Committee Meeting, FDA review, 10/24/13 C208, C216, C206, C212, HPC3007, Dieterich, 14th European AIDS Conference, 2013; Lawitz et al. NEJM 2013
SVR
Rate
42/53 206/260 15/23 9/17
SOF: HCV versus HIV/HCV in GT 1, 2, 3
89
68
95 94 93
79
89 81
89 90 91 88
0
10
20
30
40
50
60
70
80
90
100
SOF/P/R SOF/R GT 2 naïve GT 2experienced
GT 3 naïve** GT 3experienced
HCV HIV/HCV
Sust
aine
d Vi
rolo
gic R
espo
nse
Torres-Rodriguez et al., IDSA 2013 Osinusi et al., JAMA 2013;310(8):804-11; Sulkowski et al. JAMA 2014 (PHOTON-1), Lawitz et al. NEJM April 2013; Zeuzem et al NEJM May 2014, Rockstroh et al, AASLD 2014 (pooled PHOTON 1 and 2)
COSMOS: SOF/SMV no longer off label
90 94 89
81
97 94 95 94 96 95 95 92 88 94
0102030405060708090
100
Overall GT1b GT1a GT1a+Q80K GT1a-Q80KCohort 1 Cohort 2 Pooled
ATV/r No data No data DRV/r SIM ↑; DRV ↔ SOF ↑; DRV ↔ LPV/r No data No data TPV/r No data No data EFV SIM ↓; EFV ↔ SOF ↔; EFV ↔ RPV SIM ↔; RPV ↔ SOF ↔; RPV ↔ ETV No data No data RAL SIM ↔; RAL ↔ SOF ↔; RAL ↔ ELV/cobi No data No data DLG No data No data MVC No data No data TDF SIM ↔; TFV ↔ SOF ↔; TFV ↔ Sl
ION-1 Afdhal et al. NEJM 2014, ION-2 Afdhal et al. NEJM 2014; 370(16):1483, ION-3 Kowdley et al. NEJM; Osinusi et al. AASLD 2014, Abstract 84
Cirrhosis* -RBV +RBV 12W 24W
Cirrhosis 12W 24W 12W
HIV Naive Non-cirrhotic
Efficacy and Safety of Ledipasvir/Sofosbuvir Fixed-Dose Combination for 12 Weeks in Subjects With Chronic Genotype 1 or 4 HCV and HIV-1 Co-infection (ION-4)
ClinicalTrials.gov Identifier: NCT02073656
100 95 95 100 100
0
10
20
30
40
50
60
70
80
90
100
Tx Naïve Triple Failures
Sofosbuvir plus Daclatasvir: GT1
24W 12W +RBV -RBV
24W +RBV -RBV
Sulkowski et al. NEJM 2014; 370:211-221
N= 44 41 41 20 21
A Phase 3 Evaluation of Daclatasvir Plus Sofosbuvir in Treatment-naïve and Treatment-experienced Chronic Hepatitis C (Genotype 1, 2, 3, 4, 5, or 6) Subjects Coinfected With
Human Immunodeficiency Virus (HIV) (ALLY 2) ClinicalTrials.gov Identifier: NCT02032888
ARV Interaction Score Card Ledipasvir Daclatasvir AbbVie 3D
ATV/r ↑ LDV, ↑ATV** DCV ↑* ATV ↔; ABT450 ↑
DRV/r ↑ LDV, ↔DRV** No data DRV ↓/↑; 3D ↓
LPV/r No data No data LPV ↔; ABT450 ↑
TPV/r No data No data No data
EFV LDV ↓; EFV ↓ DCV ↓* No PK data**
RPV LDV ↔; RPV ↔ No data ABT450 ↑; RPV ↑
ETV No data No data No data
RAL LDV ↔; RAL ↔ No data 3D ↔; ↑ RAL
ELV/cobi No data No data No data
DLG No data No data No data
MVC No data No data No data
TDF LDV ↔; ↑TFV DCV ↔; TFV ↔ 3D ↔; TFV ↔ * Decrease DCV dose to 30mg QD, Increase DCV dose to 90mg QD, ** 3D + EFV led to premature study discontinuation due to toxicities
Slid
e co
urte
sy o
f Jen
nife
r Kis
er
Back to our patient 2012 – enrolled into PHOTON-1 received 6 months of sofosbuvir + WBR -SVR4, relapsed by week-12 off treatment December 2013 – labs remain reassuring with normal synthetic function, renal function, thrombocytyopenia has worsened over time now in 90s, imaging stable -Enrolled into the ION-4 with SOF/LDV X 12W -Achieved SVR12
– ESRD – Transplant – ESLD: CP B/C and decompensated – Children – Pregnant women
Acknowledgements Mentors Andrew Muir Ken Schmader Chuck Hicks John McHutchison John Guyton Mariano Garcia-Blanco Keyur Patel Hans Tillmann Leadership Chris Woods Rodger Liddle John Perfect Mary Klotman
Collaborators CHGV: David Goldstein Kevin Shianna NIAID: Shyam Kottilil Anu Osinusi Eric Meissner Diehl Laboratory: Anna Mae Diehl Steve Choi Marzena Swiderska-Syn
Funding: NIAID K23 AI096913 Duke CFAR Duke Department of Medicine AIDS Clinical Trials Group