Current HCV Treatment Options in

HIV Co-infected Patients

Jürgen K. RockstrohDepartment of Medicine IUniversity Hospital Bonn

Germany

2

Conflict of interest

I have received honoraria for speaking at educational events or consulting from:

Abbott, Abbvie, Bionor, BMS, Boehringer, Gilead, Janssen, Merck, Novartis, Pfizer, Roche, Tibotec, Tobira and ViiV

Anti-HCV antibody prevalence in different EuroSIDA regions

• South: 28.8%• West: 20.1%• North: 17.3%• East Central: 34.0%• East: 57.7%• Argentina: 20.6%

Peters L et al., BMC Infect Dis. 2014;14 Suppl 6:S13

HCV co-infection in EuroSIDA

EuroSIDA: prospective, European study of 18,295 HIV-1–infected patients at 105 centres across Europe, Israel and Argentina

Prevalence of HCV seropositivity in EuroSIDA is 31% (4,044 patients), 74;2% of which were serum HCV RNA-positive

4Rockstroh J et al. J Hepatol 2013;59(2):213-220

Progression to liver-related death in HIV-positive population

Multivariate analysis adjusted for gender, exposure group, race, prior AIDS, region of Europe, CD4+ T-cell nadir, HCV treatment status at baseline, age, and baseline date. Starting cART, HBsAgstatus, diagnosis of a new AIDS-defining illness and CD4+ T-cell count were included as time-updated variables.

HCVAb, anti-HCV antibodies; PYFU, person years of follow-up; IRR, incidence rate ratio;

001/IHQ/14-09//1138h

HCVAb serostatus: Events (PYFU) IRR (95% CI; p value)Negative 43 (66,653) 1Positive 175 (26,494) 8.90 (5.60–14.14; p<0.0001)

HCV genotypeGT 1 55 (8122) 1GT 2 2 (554) 0.27 (0.07–1.13; p=0.073)GT 3 28 (4503) 0.99 (0.62–1.59; p=0.98)GT 4 9 (2188) 0.91 (0.44–1.89; p=0.80)

HCV-RNA viremiaHCVAb- 43 (66,653) 0.18 (0.10–0.32; p<0.0001)Ab+/RNA- 21 (4838) 1Ab+/RNA+ 86 (11,302) 2.11 (1.30–3.42; p=0.0025)Ab+/unknown 68 (10,354) 1.42 (0.86–2.35; p=0.17)

0.01 0.1 1 10 100

Adjusted incidence rate ratio (95% CI)

Ingiliz & Rockstroh, Current Opinion HIV 2015

HIV HCV

FibrosisCirrhosis

LPS

HIV

HCV

• Direct effect on stellate cells

• Immune dysregulation• Cytokine alteration• Hepatocyte apoptosis

• Higher HCV chronicity rate• Increased viral replication• Decreased HCV-specific immune

response

HAART

HCC

6

What is the optimal treatment strategy in HIV/HCV co-infected patients?

Treat HCV first?

Treat HIV first?

Treat HIV/HCV simultaneously?

7

EACS guidelines: when to startInitiation of ART

– ART is always recommended if CD4 count <350 cells/mm3

EACS treatment guidelines, Version 7.0 2013. Accessed November 2013. . Available at: http://www.europeanaidsclinicalsociety.org C, consider; D, defer; R, recommended

ConditionCurrent CD4+ lymphocyte

count350–500 >500

HBV requiring anti-HBV treatment R RHBV not requiring anti-HBV treatment R CHCV for which anti-HCV treatment is being considered or given R C

HCV for which anti-HCV treatment not feasible R C

8

Antiretroviral therapy reduces the rate of hepatic decompensationamong HIV- and hepatitis C virus-coinfected veterans

Objective: To evaluate 10,090 HIV/HCV-co-infected

males from the Veterans Aging CohortStudy Virtual Cohort, who had notinitiated ART at entry, for incidenthepatic decompensation between1996 and 2010

Results: Initiation of ART significantly reduced the rate of hepatic decompensation by

28–41% on average

Anderson JP, et al. Clin Infect Dis 2014; 58(5): 719–27.8

9

x 1.5

HCV disease progression remains faster in coinfected patients, despite effective ART

ART, antiretroviral therapy Adapted from: Lo Re 3rd V, et al. Ann Intern Med 2014;160:369–79.

HCV-monoinfected patients (n=6079)Antiretroviral-treated patients coinfected with HIV/HCV (n=4208)

0.074

0

0.1

0.2

0

Time to hepatic decompensation (years)

1 2 3 4 5 6 7 8 9 10

Cum

ulat

ive

inci

denc

e

0.048

p<0.001

9

10

HCV disease progression remains faster in coinfected patients, despite effective ART

If HIV RNA < 1000 copies/mL: +65% excess risk

If HIV RNA > 1000copies/mL: +82% excess risk

If CD4 < 200/mm2: +203% excess risk

If CD4 > 200/mm2: 56–63% excess risk

ART, antiretroviral therapy; HCV, hepatitis C virus; HIV, human immunodeficiency virus.Lo Re V 3rd. Ann Intern Med 2014.

11

EASL 2015 HCV recommendations and AASLD/IDSA/IAS-USA HCV recommendations

• Indications for HCV treatment in HIV/HCV co-infected patients are identical to those in HCV mono-infection (Recommendation A1)

• Same treatment regimens can be used in HIV/HCV patients as in patients without HIV infection, as the virological results of therapy are identical (Recommendation A1)

• Treatment should be prioritized regardless of the fibrosis stage in patients with HIV or HBV coinfection, (…) (Recommendation A1)

High Priority for Treatment Owing to High Risk for Complications HIV-1 coinfection (AASLD/IDSA) Rating: Class I, Level B

Journal of Hepatology DOI: (10.1016/j.jhep.2015.03.025) Copyright © 2015 European Association for the Study of the Liver

12

Treatment Options 2015

Ombitasvir/Paritaprevir/Ritonavir + Dasabuvir (± RBV)

Sofosbuvir + Simeprevir (± RBV)

Sofosbuvir + Daclatasvir (± RBV)

Ombitasvir/Paritaprevir/Ritonavir (± RBV)

PegIFNα + RBV + sofosbuvir

PegIFNα + RBV + simeprevir

Sofosbuvir + RBV

Sofosbuvir/Ledipasvir (± RBV)

IFN-free regimens

IFN-containing regimens

GT

1

1, 4

All

4

1, 4

2, 3

1, 4, 5, 6

All

(J-M Pawlotsky, ILC2015, Vienna, Austria, April 24, 2015. EASL Recommendations on Treatment of Hepatitis C 2015)

ARV Interaction Score CardSimeprevir Sofosbuvir Ledipasvir Daclatasvir AbbVie 3D

ATV/r No data ATV ↔ SOF ↔ No data DCV ↑* ATV ↔; ABT450 ↑

DRV/r SIM ↑; DRV ↔ SOF ↑; DRV ↔ No data DCV (↑) DRV ↓; 3D ↓

LPV/r No data No data No data DCV↔ LPV ↔; ABT450 ↑

TPV/r No data No data No data No data No data

EFV SIM ↓; EFV ↔ SOF ↔; EFV ↔ LDV ↓; EFV ↓ DCV ↓* No PK data**

RPV SIM ↔; RPV ↔ SOF ↔; RPV ↔ LDV ↔; RPV ↔ No data ABT450 ↑; RPV ↑

ETV No data No data No data No data No data

RAL SIM ↔; RAL ↔ SOF ↔; RAL ↔ LDV ↔; RAL ↔ No data 3D ↔; ↑ RAL

ELV/cobi No data No data No data No data No data

DLG No data No data No data No data No data

MVC No data No data No data No data No data

TDF SIM ↔; TDF ↔ SOF ↔; TDF ↔ LDV ↔; ↑TDF***

DCV ↔; TDF ↔ 3D ↔; TDF ↔

• Decrease DCV dose to 30mg QD, Increase DCV dose to 90mg QD, ** 3D + EFV led to premature study discontinuation due to toxicities***when TDF is administered with a boosted HIV-PI and LDV significantly higher TDF levels can be expected warranting closer renal monitoring

Personal communication Jennifer Kiser, University of Colorado, Denver, USA

14

Improved SVR12/24 rates over time in HCV GT 1 patients co-infected with HIV

Dieterich D et al. CROI 2014; P#24; Rodriguez-Torres M et al. IDWeek 2013; P#714; Sulkowski M et al. Lancet Infect Dis 2013;13:597–605; Sulkowski M et al. Ann Intern Med 2013;159:86–96; Sulkowski M et al Lancet 2014;314:653–61; Sulkowski M et al. AIDS 2014; P#104 LB; Torriani FJ, et al. N Engl J Med 2004;351:438–50

3D, ABT-450/ritonavir/ombitasvir; BOC, boceprevir; DAA, direct-acting antiviral agent; P/R, pegylated interferon/ribavirin;

SMV, simeprevir; SOF, sofosbuvir; TVR, telaprevir

714

29

63

74 74

89

76

96 96

0

20

40

60

80

100

SVR

(%)

IN THE DAA ERA HIV+ PATIENTS WILL ACHIEVE SIMILAR SVR RATES

15

General: 18 studiesn=29,269Avg. FU=4.6 years

No SVRSVR

Cirrhotic: 9 studiesn=2,734Avg. FU=6.6 years

HIV/HCV: 5 studiesn=2,560Avg. FU=5.1 years

Simmons et al CID 2015

5 year all cause mortality after treatment

1616

SVR12 from VALENCE includes pooled analysis from all patients (treatment-naïve and –experienced) by genotype and duration of therapy*GT1 SVR24 of 75%; GT3 TE SVR24 of 88%

100

28/42

SVR1

2 (%

)

90 89

0

20

40

60

80

100

NEUTRINO1

HCV19102

HCV/HIV

GT 1 SOF + RBV + PegIFN

12 weeks

GT 1 SOF + RBV 24 weeks

6876*

0

20

40

60

80

100

SPARE3

HCVPHOTON-14

HCV/HIV

87/11417/25 95/112

85

PHOTON-26

HCV/HIV

GT 3SOF + RBV 24 weeks

8594*

0

20

40

60

80

100

VALENCE5

HCVPHOTON-14

HCV/HIV

16/17212/250

PHOTON-26

HCV/HIV

89

94/106

GT 2SOF + RBV 12 weeks

9388

0

20

40

60

80

VALENCE5

HCVPHOTON-14

HCV/HIV

68/73 23/26

88

22/25

PHOTON-26

HCV/HIV

262/292 17/19

Photon 1 & 2: SOF + RBV Comparison HCV monoinfection and HIV/HCV coinfection trials

1. Lawitz E, et al. APASL 2013. Singapore. Oral #LB-02. 2. Rodriguez-Torres M, et al. IDWeek 2013; San Francisco, CA. Poster 714. 3. Osinusi A, et al. JAMA. 2013;310(8):804-811. 4. Naggie S, et al. CROI 2014. Boston, MA. Oral #26. 5. Zeuzem S, et al. AASLD 2013. Washington, DC. #1085. 6. Molina JM, et al. IAS Melbourne Abstract MOAB0105LB

Study DesignHIV-HCV (ION-4)

Phase 3, multicenter, open-label study (NCT02073656) HCV GT 1 or 4 patients in US, Canada, and New Zealand Broad inclusion criteria HCV treatment-naïve or treatment-experienced 20% with compensated cirrhosis Platelets ≥50,000/mm3; hemoglobin ≥10 mg/dL, CrCl ≥60 mL/min HIV-1 positive, HIV RNA <50 copies/mL; CD4 cell count >100 cells/mm3

ART regimens included emtricitabine and tenofovir disoproxilfumarate plus efavirenz, raltegravir, or rilpivirine

Wk 0 Wk 12 Wk 24

SVR12LDV/SOFN=335

Naggie S et al. CROI 2015 abstract #152LBCooper C, et al. 50th EASL; Vienna, Austria; April 22-26, 2015. Abst. P1353.

Results: Demographics and Baseline CharacteristicsHIV-HCV (ION-4)

LDV/SOF 12 weeksN=335

Mean age, y (range) 52 (26-72)

Male, n (%) 276 (82)

Black, n (%) 115 (34)

Hispanic or Latino, n (%) 56 (17)

Mean BMI, kg/m2 (range) 27 (18-66)

IL28B CC, n (%) 81 (24)

GT 1 327 (98)

HCV treatment experienced, n (%) 185 (55)

Cirrhosis, n (%) 67 (20)

Mean HCV RNA, log10 IU/mL ± SD 6.7 ± 0.6

Median CD4 cell count, cells/µL (range) 628 (106-2069)

HIV ARV Regimen

Efavirenz + FTC + TDF 160 (48)

Raltegravir + FTC + TDF 146 (44)

Rilpivirine + FTC + TDF 29 (9)

Naïve vs Experienced Cirrhosis StatusOverall

96 95 97 96 94

0

20

40

60

80

100

LDV/SOF 12 Weeks

ExperiencedNaïve No Cirrhosis Cirrhosis

321/335 142/150 179/185 63/67258/268

SVR

12 (%

)Results: SVR12 by Prior Treatment Experience and Cirrhosis StatusHIV-HCV (ION-4)

Error bars represent 95% confidence intervals.

Results: SVR12 in SubgroupsHIV-HCV (ION-4)

LDV/SOF 12 Weeks, N=335Overall

Sex MaleFemale

Race BlackNon-Black

HCV Genotype1a1b4

Baseline HCV RNA (IU/mL) <800,000≥800,000

Baseline BMI (kg/m2) <30≥30

IL28BCCCTTT

Cirrhosis NoYes

Prior HCV Treatment NoYes

ARV RegimenEFV + FTC + TDFRAL + FTC + TDFRPV + FTC + TDF

Baseline CD4 (cells/μL) <350≥350

60 70 80 90 100SVR12, % (95% CI)

Statistically significantin multivariate analysis

Results: Safety SummaryHIV-HCV (ION-4)

*Serious AEs in >1 patient were hepatocellular carcinoma (n=2) and portal vein thrombosis (n=2) in patients with cirrhosis.†Confirmed IV drug user developed Staphylococcus aureus sepsis, endocarditis with associated embolic brain abscesses, and multi-organ system failure.

Patients, n (%)LDV/SOF 12 Weeks

N=335

Overall safety

AEs 257 (77)

Grade 3‒4 AE 14 (4)

Serious AE 8 (2)*

Treatment D/C due to AE 0

Death 1 (<1)†

Grade 3‒4 laboratory abnormality 36 (11)

♦ Stable CD4 counts through treatment and follow-up phase

♦ No patient had confirmed HIV virologic rebound

21

Results: Renal FunctionHIV-HCV (ION-4)

EFV+FTC+TDF (n=160)

RAL+FTC+TDF (n=146)

RPV+FTC+TDF (n=29)

LDV/SOF +

60708090

100110120130140150

Cre

atin

ine

Cle

aran

ce(m

L/m

in),

mea

n ±

SD

WeekBL 1 2 4 6 8 10 12 FU-4

♦ 4 patients (1%) had change in creatinine ≥ 0.4 mg/dL– 2 completed treatment with no ART change– 1 had dose reduction of TDF, 1 discontinued TDF

22

Data presented to 3 significant figures; N=23 (LDV/SOF + DRV/r + TVD; simultaneous administration)

Drug-Drug Interactions Between Anti-HCV Regimen Ledipasvir/Sofosbuvir and Antiretrovirals

German P, et al. 22nd CROI; Seattle, WA; February 23-26, 2015. Abst. 82.

Moderate (~ 30-60%)increases in TFV exposure with LDV/SOF added to Pl/r + TVD regimen versus Pl/r + TVD regimen alone

May be attributed to persistent inhibition of efflux drug transporters

TFV PK Parameter N=24

Mean (%CV)LDV/SOF + ATV/r + TVD LDV/SOF + DRV/r + TVD

Simultaneous Staggered Simultaneous StaggeredAUCtau (ng-h/mL) 5460 (27.7) 5740 (25.0) 5490 (31.2) 4260 (24.2)

Cmax (ng/mL) 530 (26.2) 559 (22.0) 523 (28.0) 410 (27.6)

Ctsu (ng/mL) 120 (30.5) 116 (27.1) 117 (30.6) 87.3 (25.0)

Effect of LDV/SOF on TFV PK

CtauCmaxAUCtau

SimultaneousAdministration

Staggered (12 hours)Administration

GM

R%

(90%

Cl)

AR

V+LD

V/SO

F vs

. AR

V

ATV/r+TVD DRV/r+TVD ATV/r+TVD DRV/r+TVD

300

200

143

100

70

24Wyles, AASLD 2014 #1939

HIV-HCV Coinfection study: TURQUOISE-I: 3 DAAs + RBV

ALLY-2: Study Design

DCV 30/60/90 mg +SOF 400 mg QD

24

DCV 30/60/90 mg +SOF 400 mg QD

12

NaiveRandomize 2:1

Experienced

DCV 30/60/90 mg + SOF 400 mg QD

Week 0 8

SVR12*

Primary endpoint: SVR12 in treatment-naive patients with GT 1 treated for 12 weeks

Standard DCV dose is 60 mg Dose-adjusted for concomitant ARV therapy: 30 mg with ritonavir-boosted

PIs, 90 mg with NNRTIs except RPV

Wyles D et al, CROI 2015 abstract # 151LB

* HCV RNA <LLOQ (TD or TND) at posttreatment Week 12, assessed using the Roche HCV COBAS TaqMan Test v2.0 (LLOQ 25 IU/mL).

52

50

101

N

Wyles D, et al. 50th EASL; Vienna, Austria; April 22-26, 2015. Abst. LP01.

ParameterNaive

12 WeekN = 101

Experienced12 WeekN = 52

Naive8 WeekN = 50

Age, median years (range) 52 (24–71) 57 (43–66) 50 (28–75)

Male, n (%) 92 (91) 43 (83) 42 (84)

Race, n (%)

White 66 (65) 31 (60) 28 (56)

Black 30 (30) 20 (38) 19 (38)

Other 5 (5) 1 (2) 3 (6)

HCV GT, n (%)

1a 71 (70) 33 (63) 35 (70)

1b 12 (12) 11 (21) 6 (12)

2 11 (11) 2 (4) 6 (12)

3 6 (6) 4 (8) 3 (6)

4 1 (1) 2 (4) 0

HCV RNA, mean log10 IU/mL (SD) 6.50 (0.76) 6.52 (0.79) 6.40 (0.71)

Cirrhosis, n (%)* 9 (9) 15 (29) 5 (10)

*Cirrhosis status determined by liver biopsy (METAVIR >F3), Fibroscan (>14.6 kPa), or Fibrotest >0.74 with APRI >2.

Demographic and HCV Disease Characteristics

26

HIV Disease Characteristics and Regimens

ParameterNaive

12 WeekN = 101

Experienced12 WeekN = 52

Naive8 WeekN = 50

HIV RNA < 50 copies/mL, n/N (%) 94/100 (94) 47/49 (96) 45/48 (94)

CD4 cells/mm3, median (range) 520 (122–1147) 636 (262–1470) 575 (157–1430)

Receiving HIV treatment, n (%) 100 (99) 51 (98) 48 (96)

PI regimens*

Darunavir/r 19 (19) 11 (21) 21 (42)

Atazanavir/r 19 (19) 12 (23) 5 (10)

Lopinavir/r 9 (9) 0 3 (6)

NNRTI regimens

Efavirenz 18 (18) 8 (16) 8 (16)

Nevirapine 5 (5) 3 (6) 1 (2)

Rilpivirine 5 (5) 1 (2) 1 (2)

Other regimens

Raltegravir 22 (22) 10 (20) 8 (16)

Dolutegravir 3 (3) 4 (8) 1 (2)

Nucleosides only 0 2 (4) 0

*DCV dose reduced to 30 mg/day with PI regimens; based on recent data, DCV 60mg/day is recommended when used with DRV/r or LPV/r regimens [Eley et al. HIVDART 2014; Poster 63]

ALLY-2: SVR12

0

20

40

60

80

100

Ast

itel

SVR

12, %

𝟖𝟖𝟖𝟖𝟖𝟖𝟖𝟖

𝟒𝟒𝟖𝟖𝟒𝟒𝟒𝟒

𝟖𝟖𝟑𝟑𝟒𝟒𝟑𝟑

12-WeekNaive

12-WeekExperienced

8-WeekNaive

0

20

40

60

80

100

𝟗𝟗𝟖𝟖𝟑𝟑𝟖𝟖𝟑𝟑

𝟓𝟓𝟑𝟑𝟓𝟓𝟓𝟓

𝟖𝟖𝟖𝟖𝟓𝟓𝟖𝟖

12-WeekNaive

12-WeekExperienced

8-WeekNaive

Relapse(n = 1)

Follow-up Wk 12 data missing (n = 1)Detectable at EOT (n = 1)

Relapse (n = 1)Relapse (n = 10)

Follow-up Wk 12 data missing (n = 2)

GT 1 (N = 168) All Patients (N = 203)

7696 98

7696 98

ALLY-2: On-Treatment Safety and Tolerability

Event, n (%) 12-Week GroupsN = 153

8-Week GroupN = 50 Total

Deathsa 0 1 (2) 1 (0.5)

Serious AEsb 4 (3) 0 4 (2)

AEs leading to discontinuation 0 0 0

Opportunistic infections 0 0 0

Treatment-emergent grade 3 or 4 lab abnormalities

INR > 2.0 x ULN 2 (1) 0 2 (1)

ALT > 5.0 x ULN 0 0 0

AST > 5.0 x ULN 0 1 (2) 1 (0.5)

Total bilirubin > 2.5 x ULNc 7 (5) 1 (2) 8 (4)

Lipase > 3.0 x ULNd 6 (4) 1 (2) 7 (3)

a One death of 52 year-old male with cardiac arrest at posttreatment Week 4 (not related to study therapy).b Serious AEs all non-related: priapism, chest pain/presyncope, drug abuse/pulmonary embolism, hypertensive crisis/syncope.c All patients were receiving concomitant ATV/r.d Transient hyperlipasemia without reported AEs of pancreatitis. ULN, upper limit of normal

29

Elbasvir(50 mg)

Grazoprevir(100 mg)

STUDY DESIGN: C-EDGE COINFECTION

An open-label, single-arm, multicenter study across Europe, USA, and Australia

Primary endpoint: SVR12 (HCV RNA <15 IU/mL*) Treatment-naive patients with HCV GT1, 4 or 6 infection with or

without cirrhosis Co-infected with HIV-1:

Naive to ART with CD4+ >500 cells/mm3 and HIV RNA <50,000 copies/mL On stable on ART† for ≥8 weeks and CD4+ >200 cells/mm3 and

undetectable HIV RNA

GZR 100 mg / EBR 50 mg

D1 TW4 TW8 TW12 FW4 FW8 FW12

n=218

*COBAS TaqMan v2.0 [LLoQ <15 IU/mL]† Stable antiretroviral therapy (ART) included tenofovir or abacavir, and either emtricitabine or lamivudine plus raltegravir, dolutegravir, or rilpivirine

Follow-up

Rockstroh J, et al. 50th EASL; Vienna, Austria; April 22-26, 2015. Abst. P0887.

Elbasvir(50 mg)

Grazoprevir(100 mg)STUDY DESIGN: C-EDGE COINFECTION

• An open-label, single-arm, multicenter study across Europe, USA, and Australia

• Primary endpoint: SVR12 (HCV RNA <15 IU/mL*)

• Treatment-naive patients with HCV GT1, 4 or 6 infection with or without cirrhosis

• Co-infected with HIV-1:– Naive to ART with CD4+ >500 cells/mm3 and HIV RNA <50,000 copies/mL – On stable on ART† for ≥8 weeks and CD4+ >200 cells/mm3 and undetectable HIV

RNA

GZR 100 mg / EBR 50 mg

D1 TW4 TW8 TW12 FW4 FW8 FW12

n=218

*COBAS TaqMan v2.0 [LLoQ <15 IU/mL]† Stable antiretroviral therapy (ART) included tenofovir or abacavir, and either emtricitabine or lamivudine plus raltegravir, dolutegravir, or rilpivirine

Follow-up

Elbasvir(50 mg)

Grazoprevir(100 mg)DEMOGRAPHICS: C-EDGE COINFECTION

All PatientsN = 218

Age, years mean (SD) 48.7 (8.9)Sex, n (%)

Male, 183 (83.9)Female 35 (16.1)

Race, n (%)White 167 (76.6)Black or African-American 38 (17.4)Asian 6 (2.8)Other 7 (3.2)

Ethnicity, n (%)Hispanic / Latino 14 (6.4)Not Hispanic / Latino 194 (89.0)Not reported 10 (4.6)

HCV genotype, n (%)1a 144 (66.1)1b/other 45 (20.7)4 28 (12.8)6 1 (0.5)

Baseline HCV RNA >800,000 IU/mL, n (%) 130 (59.6)Cirrhotic*, n (%) 35 (16.1)IL28B CC (%) , n (%) 77 (35.3)

*Of the 35 patients (16.1%) with cirrhosis, 27 were diagnosed by Fibroscan, 6 by biopsy, and 2 by Fibrotest and APRI.

Elbasvir(50 mg)

Grazoprevir(100 mg)DEMOGRAPHICS: C-EDGE CO-INFECTION

All PatientsN = 218

Antiretroviral therapy, n (%)Receiving ART with undetectable HIV RNA 211 (96.8)NaIve to ART 7 (3.2)

Baseline CD4 count (cells/µL)Mean (SD)Median (1st quartile – 3rd quartile)

613 (0.57)568 (424-766)

Antiretroviral therapy, backbone n (%)Abacavir-containing regimen 47 (21.6)Tenofovir-containing regimen 164 (75.2)

Antiretroviral therapy, third agent n (%)Raltegravir 113 (51.8)Dolutegravir 59 (27.1)Rilpivirine 38 (17.4)

Elbasvir(50 mg)

Grazoprevir(100 mg)

SVR12 – C-EDGE CO-INFECTIONFULL ANALYSIS SET

LTFU or discontinued unrelated to VF 4 3 1 0

Breakthrough 0 0 0 0Relapse 6 4 1 1Reinfection 1 1 0 0

Patie

nts,

%

All Patients

136/144

42/44

207/218*

94.4 95.595.0

GT1a GT1b GT4

96.4

27/28

0

25

50

75

100

*1 patient with GT6 infection and 1 patient with GT1 not-otherwise subtyped were also included; both patients achieved SVR12.GT = genotype; LTFU = long-term follow-up

Elbasvir(50 mg)

Grazoprevir(100 mg)

RESISTANCE ASSOCIATED VARIANTS: NS5AC-EDGE TN + C-EDGE CO-INFECTION

†The resistance analysis population includes all patients from the full analysis set who have sequencing data available and who either achieved SVR12 or met criteria for virologic failure

N = number of patients who achieved SVR12. m = number of patients with evaluable baseline sequencen = number of patients with or without a baseline RAV

RAV Status in Patients with

Baseline Sequence % (n/m)

SVR12 All Patients

% (N/n)

SVR12 NS5A RAVs

≤5-fold potency loss

SVR12 NS5A RAVs

>5-fold potency loss

Genotype 1a RAVS

Baseline NS5A RAVS 9.9 (29/294) 65.5 (19/29) 87.5 (14/16) 38.5 (5/13)

No baseline NS5A RAVs 90.1 (265/294) 98.1 (260/265) — — — —

Genotype 1b RAVS

Baseline NS5A RAVS 13.3 (23/173) 95.7 (22/23) 100 (1/1) 95.5 (21/22)

No baseline NS5A RAVs 86.7 (150/173) 99.3 (149/150) — — — —

Resistance analysis population†

Rockstroh J, et al. 50th EASL; Vienna, Austria; April 22-26, 2015. Abst. P0887.Zeuzem S, et al. 50th EASL; Vienna, Austria; April 22-26, 2015. Abst. G07.

36

Coinfected patients: treat-all or prioritize?

Zahnd C, CROI 2015, #150

Cost of HCV therapy influence the debate „right“ indication of treatment

mathematical model from the Swiss Cohort: 100% treatment-uptake, SVR 90%

Influence of timepoint of treatment on liver-related endpoints and infectious duration: 1 month or 1 year after diagnosis or at F2, F3, F4

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Summary

In the DAA era, HIV/HCV-coinfected patients show the same high cure rates (over 90%) under IFN-free DAA combinations –therefore, guidelines no longer separate between mono- and co-infected patients

Indication for HCV therapy as well as DAA drug selection has become the same for all patients

The only special consideration in HIV/HCV-coinfected patients is the need to check for DDIs between HIV and HCV drugs

Considering the faster fibrosis progression and higher risk for hepatic decompensation in coinfected patients (even in the era of ART), the uptake of modern HCV therapy needs to be encouraged and HCV therapy should be discussed with all coinfected patients

ART, antiretroviral therapy; DAA, direct-acting antiviral; DDI, drug–drug interaction; HCV, hepatitis C virus; HIV, human immunodeficiency virus; IFN, interferon.