5/12/2016

1

Debika Bhattacharya, MD, MSc

Associate Clinical Professor of Medicine

University of California Los Angeles School of Medicine

Los Angeles, California

Management of Direct-Acting Antiviral Failures

San Francisco, California: May 5, 2016

FLOWED: 04/28/16

Slide 2 of 24

Considerations in patients failing a DAA-based regimen

• Was interferon part of the regimen– What was the specific response?– Dose reductions on treatment?

• What specific medication classes were used– What role does resistance play?

• Stage of liver disease• Indications of other problems

– Adherence?– Significant drug interactions?– Immunosuppression?

Slide 3 of 24

A prior non-responder to Boceprevir + PegIFN/RBV should be treated with:

0%

0%

0%

0%

0% 1. LDV/SOF

2. SMV/SOF

3. PrOD+RBV

4. SOF+PegIFN/RBV

5. No data to support retreatment with a DAA

5/12/2016

2

Treatment of HCV: 5-2016 USA

No Cirrhosis GT Regimen Naive Experienced

1a Elbasvir+grazoprevir(+RBV with NS5A r)

12 wks16 wks

12 wks (+ RBV*)16 wks*

LDV+SOF(If Viral Load <6 million)

12 wks8 wks

12 wks*

PrOD+RBV 12 wks 12 wks

SMV+SOF 12 wks 12 wks

DCV+SOF 12 wks 12 wks*

1b Elbasvir+grazoprevir 12 wks 12 wks (+ RBV*)

LDV+SOF 12 wks 12 wks*

PrOD 12 wks 12 wks

SMV+SOF 12 wks 12 wks

DCV+SOF 12 wks 12 wks*

Note: Alternative regimens are listed gray font, experienced refers to PR-experience, *recommended in

1st gen PI failures

Treatment of HCV: 5-2016 USACirrhosis

GT Regimen Naive Experienced

1a Elbasvir+grazoprevir(+RBV with NS5A r)

12 wks16 wks

12 wks(+RBV*)16 wks*

LDV+SOF(+RBV)

12 wks 24 wks*12 wks*

PrOD+RBV 24 wks 24 wks

SMV+SOF (+RBV) 24 wks 24 wks

DCV+SOF (+RBV) 24 wks 24 wks*

1b Elbasvir+grazoprevir 12 wks 12 wks(+RBV)*

LDV+SOF(+RBV)

12 wks 24 wks*12 wks*

PrOD 12 wks 12 wks

SMV+SOF (+RBV) 24 wks 24 wks

DCV+SOF (+RBV) 24 wks 24 wks*

Note: Alternative regimens are listed gray font, experienced refers to PR-experience, *recommended in 1st gen PI failures

Slide 6 of 24

93 96 100 9894 97 98 100

0

20

40

60

80

100

Failed PEG-IFN+RBV Failed Protease Inhibitor + PEG-IFN+RBV

SV

R12 (

%)

40/43 62/66 45/47 62/64 58/58 49/50 58/59 51/51

12 Weeks 24 Weeks

LDV/SOF + RBV LDV/SOF + RBVLDV/SOF LDV/SOF

SOF/LDV:SVR12 in PEG-IFN+RBV vs. PI+PEG-IFN+RBV Failures: ION-2

Afdhal N, et al. N Engl J Med. 2014;370:1483-1493.

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3

Slide 7 of 24

EBR+GZR+RBV in PI-Experienced HCV GT1

96.2 95.5 91.7 94.1

0

20

40

60

80

100

All Patients Prior VirologicFailure

NS3 +/= NS5ARAVs

Cirrhosis

C-SALVAGE: SVR24* by Baseline Factors

SVR

24 (

%)

*Analysis per protocol: excluding patients who dropped out due to reasons other than virologic failure RAVs=resistance-associated variants (at baseline)

Buti M, et al. Clin Infect Dis. 2016;62:32-6

Slide 8 of 24

Recommendations

GT SOF+RBV+PEG-IFN Failure SMV+SOF Failure

1Non-cirrhotic: LDV/SOF+RBV x 12 wks

Cirrhotic: LDV/SOF+RBV x 24 wks

Deferral of treatment (non-cirrhotic); Test for

resistance-associated variants that decrease susceptibility to NS3 PIs and NS5A inhibitors

(cirrhotic); Nucleotide-based dual DAA (24 wks,

+ RBV unless contraindicated). If available,

nucleotide-based triple or quad DAA regimens

may be considered (12 or 24 wks, +RBV)

2DCV+SOF+RBV x 24 wks (IFN ineligible);

SOF+PegIFN/RBV x 12 wks (IFN eligible)

3DCV+SOF+RBV x 24 wks (IFN ineligible);

SOF+PegIFN/RBV x 12 wks (IFN eligible)

AASLD/IDSA Guidance 2016

Slide 9 of 24

SV

R12 (

%)

SV

R12 (

%)

24

98 100 100 98 98 98

0

20

40

60

80

100

Retreatment of GT1, SOF Failures with LDV/SOF+RBV x 12 wks

Retreatment of GT1, LDV/SOF Failures with LDV/SOF x 24 wks

71 68

80

100

74

46

60

0

20

40

60

80

100

No Yes 8 wk 12 wk No Yes

Wyles Hepatology 2015, Lawitz E. EASL 2015.

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4

Slide 10 of 24

Case

• 54 yo HIV/HCV AA male on EFV/TDF/FTC and PPI

• GT 1a, non-cirrhotic

• Relapse after 12 weeks of SOF/LDV

• Wants re-treatment

Slide 11 of 24

What are his options?

0%

0%

0%

0% 1. Defer therapy until newer agents available

2. Change ARV regimen and discontinue PPI and re-treat with SOF/LDV x 12 wks

3. Change ARV regimen and discontinue PPI and re-treat with SOF/LDV + RBV x 24 wks

4. Re-treat with SOF/SMV+ RBV x 24 wks

Slide 12 of 24

Recommendations for NS5A Failures

GT 1:

– Deferral of treatment (non-cirrhotic)

– Test for resistance-associated variants that decrease susceptibility to NS3 PIs and NS5A inhibitors (cirrhotic)

– Nucleotide-based dual DAA (24 wks, + RBV unless contraindicated)

– If available, nucleotide-based triple or quad DAA regimens may be considered (12 or 24 wks, +RBV)

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Slide 13 of 24

Emergence and Persistence of NS5A RAVs

16%

84%

Before LDV Treatment

Pts with NS5A RAVs

Pts without NS5A RAVs

64/76

12/76

1%

99%

At Virologic Failure with LDV Tx

Pts with NS5A RAVs

Pts without NS5A RAVs

1/73

72/73

98% 100% 98% 100%95%

86%

0%

20%

40%

60%

80%

100%

Registry Study

42/43

45/45

52/55

50/58

62/63

58/58

*NS5A RAVs persisted in majority of patients for 96 weeksDvory-Sobol et al., EASL 2015; Wyles D et al., EASL 2015

Slide 14 of 24

Impact of baseline RAVs

58%

99%94%

100%

0%

20%

40%

60%

80%

100%

GT1a GT1b

Bs NS5A RAVs No Bs NS5A RAVs

N=135 N=112N=18

SVR Rate for EBR+GZR x 12 weeks C-EDGE: GT1, Tx-naïve, w/o cirrhosis

N=19

97%92%

0%

20%

40%

60%

80%

100%

No RAVs Any RAV

SVR Rate for SOF+LDV+RBV x 12 weeks ION-1/2/3

N=1629 N=318

Zeuzem et al., Ann Intern Med 2015; Dvory-Sobol et al., International Workshop on Antiviral Drug Resistance 2014

RAVs and GT3

• SOF+DCV x 12 wks (ALLY-3)

– 54% SVR12 with BL Y93H (7/13)

– ALLY3+ SVR12 93% (38/41) vs 88% (7/8) (No RAVS vs RAVs)

• SOF+VEL x 12 wks (ASTRAL-3)

– SVR12: 97% (225/231) vs 88% (38/43) (No RAVs vs RAVs)

• GZR/MK-3682/MK-8408 (C-CREST 1&2)

– 97% (72/74) vs 45% (5/11) vs (No RAVs vs RAVs)

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Slide 16 of 24

DAA Re-Treatment Studies with Available Agents

Failed Regimen Population Retreatment Regimen SVR 12

SOF/LDV+RBV, GS-9669 8-12 wks

GT 1, incl cirrhotics SOF/LDV x 24 wks 71%

DCV-containing GT1 and 4, incl cirrhotics

SIM/SOF x 12 wks 87% (13/15)All GT

EBR/GZR+SOF 4-8 wks

GT1C-SWIFT Retx

EBR/GZR+SOF+RBVx12 wks 100%

Multiple (>50% PrOD failures)

GT1, incl cirrhoticsQuartz

PrOD+SOF+RBVx12-24 wks 93%

Lawitz EASL 2015, Hezode European Resistance Workshop 2015, Lawitz AASLD 2015, Poordad AASLD 2015

Slide 17 of 24

Investigational Agents for DAA Failures(EASL 2016 Update)

Failed Regimen Population Retreatment Regimen SVR 12

Multiple 50% NS5A Failures

GT 1, noncirrhotic(Magellan)

ABT-493/ABT-530+RBV x 12 wksABT-493/ABT-530 x 12 wks

95% (mITT)95% (mITT)

Multiple41% NS5A Failures

GT1, cirrhotics inclTrilogy-3

SOF/VEL/GS-9857 x 12 wksSOF/VEL/GS-9857+RBV x 12 wks

100%96%

Multiple27% NS5A Failures

GT 1-6 SOF/VEL/GS-9857 x 12 wks 100% (GT1)

Poordad EASL 2016, Lawitz EASL 2016, Lawitz EASL 2016 (b)

Slide 18 of 24

Cross-resistance among HCV PIs

Telaprevir Boceprevir Simeprevir Asunaprevir ABT-450/r

V36A/M

T54A/S

V55A

Q80K

R155K

A156S

A156T,V

D168A/V/E

V170A/T

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Slide 19 of 24

Similar pattern with decay of SMV resistant variants

Lenz O. EASL 2014.

91% of nonSVR with resistance1a: R155K +/- Q80K

1b: D168V

Slide 20 of 24

NS5A Inhibitor Resistance

• Similar resistance pattern for 1st gen NS5A with respect to GT 1a and 1b

Kitrinos KM. #1949 AASLD 2014. Wang C. AAC 2013

Slide 21 of 24

Not all NS5A inhibitors are created equal

EC50 (pM) 1a 2a 3 4 6

LDV 34 21000 35000 110 120

DCV 50 71 150 12 --

GS-5816 12 9 12 9 6

Elbasvir 4 3 20 3 --

ACH-3102 26 <10x FC in EC50

ABT-530 2 2 2 2 3

Wang C. AAC 2012. Zhao Y. #A845 EASL 2012. Ng T. #639 CROI 2014.

Later generation compounds retain activity against variants at polymorphic site (Q30, L31) and those associated with resistance (28, 30, 31, 58, and 93).

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Slide 22 of 24

Resistance Profiles of Select NS5A InhibitorsReplicon (in vitro)

– GT-1a and GT-1b activity profiles are generally comparable

– Activity profiles differ against GT-2 and GT-3 reference strains

– In clinical trials, the activity of a DAA against RAVs depends on the other drugs in the regimen

• Note: EC50 values are from different assays and do not represent a direct comparison.• DAA=direct-acting antiviral; DCV=daclatasvir; EC50=50% effective concentration; GT=genotype; LDV=ledipasvir; OMB=ombitasvir; RAV=resistance-

associated variant.• aDCV is an investigational compound.• 1. Gao M et al. Curr Opin Virol. 2013;3:514-520. 2. DeGoey DA et al. J Med Chem. 2014;57:2047-2057.

Re

pli

co

n E

C5

0 (n

M)

GT-1b (con1) GT-2a (JFH-1)GT-1a (H77c)

1,a 1 2

22

0.001

0.01

0.1

1

10

100

1000

DCV LDV OMB

Slide 23 of 24

Slide 24 of 24

PEG/RBV Failures, GT1a

EBR+GZR x 12 wks (non-cirrhotic)

LDV+SOF x 12 wks (non-cirrhotic)

PrOD+RBV x 12 wks (non-cirrhotic)

SMV+SOF x 12 wks (non-cirrhotic)

DCV+SOF x 12 wks (non-cirrhotic)

EBR+GZR x 12 wks (cirrhotic, no baseline NS5A RAVs

for EBR)

LDV+SOF x 24 wks (cirrhotic)

LDV+SOF+RBV x 12 wks (cirrhotic)

PEG/RBV and PI Failures, GT1a

LDV+SOF x 12 wks (non-cirrhotic)

DCV+SOF x 12 wks (non-cirrhotic)

EBR+GZR+RBV x 12 wks (non-cirrhotic)

EBR+GZR+RBV x 16 wks (non-cirrhotic, baseline high

fold-change NS5A RAVs for EBR)

LDV+SOF+RBV x 12 wks (cirrhotic)

LDV+SOF x 24 wks (cirrhotic)

DCV+SOF+RBV x 24 wks (cirrhotic)

EBR+GZR+RBV x 12 wks (cirrhotic)

EBR+GZR+RBV x 16 wks (cirrhotic, baseline high fold-

change NS5A RAVs for EBR)

PEG/RBV Failures, GT1b

EBR+GZR x 12 wks (non-cirrhotic)

LDV+SOF x 12 wks (non-cirrhotic)

PrOD x 12 wks (non-cirrhotic)

SMV+SOF x 12 wks (non-cirrhotic)

DCV+SOF x 12 wks (non-cirrhotic)

EBR+GZR x 12 wks (cirrhotic)

PrOD x 12 wks (cirrhotic)

LDV+SOF x 24 wks (cirrhotic)

LDV+SOF+RBV x 12 wks (cirrhotic)

PEG/RBV and PI Failures, GT1b

LDV+SOF x 12 wks (non-cirrhotic)

DCV+SOF x 12 wks (non-cirrhotic)

EBR+GZR+RBV x 12 wks (non-cirrhotic)

LDV+SOF+RBV x 12 wks (cirrhotic)

LDV+SOF x 24 wks (cirrhotic)

DCV+SOF+RBV x 24 wks (cirrhotic)

EBR+GZR+RBV x 12 wks (cirrhotic)

PR and PI/PR GT 1 Recommendations table

5/12/2016

1

Alexander Monto, MDProfessor of Clinical Medicine

University of California San FranciscoSan Francisco, California

Treatment of Hepatitis C: Specific

Patient Populations, Cases

FORMATTED: 03/15/2016

San Francisco, California: May 5, 2016

Slide 2 of 22

Learning Objectives

After attending this presentation, participants will

be able to:

List staging options for extent of liver damage in hepatitis

C virus (HCV)-infected patients

Monitor for hepatocellular carcinoma in appropriate

patients at necessary intervals

Slide 3 of 22

It is easy to tell when someone has liver disease.

0%

0% 1. Agree

2. Disagree

10

5/12/2016

2

Slide 4 of 22

Case Presentation

• 47 yo man with HCV/HIV

– AST 48 (Lab normal 10-45)

– ALT 39 (Lab normal 10-40)

– Alk Phos 143 (Lab normal 25-140)

– Total Bili 1.1 (Lab normal .2-1.2)

– Platelets 129K (Lab normal >140)

– No symptoms; PE normal

– CD4+ cell count: 325 cells/mm3

– HIV-1 RNA: <50 copies/ml on raltegravir/emtricitabine/tenofovir disoproxil fumarate

Slide 5 of 22

The patient is found to have HCV genotype 1 (no subtype available),

HVL. He wants to know if “the stuff on the HCV commercial would

work”. You now…

0%

0%

0%

0% 1. Ultrasound

2. Liver Biopsy

3. Other Non-invasive Marker Assay

4. Obtain Subtype

10

Slide 6 of 22

An ultrasound is performed.

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Slide 7 of 22

You will now…

0%

0%

0%

0%

0% 1. Refer to general surgeon for resection

2. Refer to interventional radiology for biopsy

3. Refer to transplant center

4. Start DAA for HCV

5. Order biphasic CT

10

Slide 8 of 22

Question

The biphasic CT shows the lesion has characteristics of a hemangioma.Enhancement in all phases matches the blood pool. HCCs exhibit

“washout” early after peak arterial filling.

Slide 9 of 22

Question

• The transient elastography is performed and the results

are as follows…

– 17.5 kPascals

– IQR/M= 31%

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Slide 10 of 22

You would now

0%0%0% 1. Treat patient with DAAs

2. Obtain liver biopsy

3. Obtain FibroTest

10

Slide 11 of 22

Question

• The liver biopsy is obtained and is shown below.

Slide 12 of 22

Your next management step is:

0%

0%

0%

0% 1. Obtain EGD for variceal screening

2. Immediately start treatment for HCV

3. Order EGD and start treatment

4. Refer to hepatologist for treatment/evaluation

10

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Slide 13 of 22

While you are waiting for insurance approval and the EGD, the patient calls to say

that his ankles are swollen and he has gained 15 lbs. You would:

0%

0%

0%

0% 1. Start furosemide

2. Repeat Ultrasound

3. Tell him to raise his legs when sitting and wait for

approval of HCV meds

4. Call for help—Transplant Center

10

Slide 14 of 22

QUESTION

• An ultrasound is obtained

Slide 15 of 22

You would now…

0%0%0%0%0%0% 1. Start spironolactone 50 mg and furosemide 20 mg

2. Do diagnostic tap

3. Contact transplant center

4. 1 and 2

5. 1, 2, and 3

6. Send for TIPSS

10

5/12/2016

6

Slide 16 of 22

Which regimen would you use for HCC screening in

this patient?

0%

0%

0%

0%

0%

0% 1. AFP every six months and US yearly

2. AFP every 6 months only

3. US every 6 months

4. US and AFP every 6 months

5. CT yearly

6. Would not surveil HCC

10

Slide 17 of 22

How would you stage liver disease?

0%

0%

0% 1. Child-Pugh

2. MELD

3. No need to stage. When patient looks ill enough, will

refer to transplant center

10

Slide 18 of 22

LDV/SOF + RBV in GT-1 or -4, Decompensated Cirrhosis and Post-Transplant Patients ± Cirrhosis (SOLAR-2)

LDV/SOF + RBV for 12 or 24 weeks in GT-1 or -4 patients with decompensated cirrhosis (CP-B or -C) and post-transplant patients

± cirrhosis (F0-F3, CP-A) in the Phase 2 study SOLAR-2

Efficacy

Charlton M et al, Gastroenterology 2015;149:649

Safety

Discontinuation due to AEs: 0%–5%

Treatment-related SAEs: 0%–5%

Deaths: 10 patients (none considered treatment-related)

Patient population

Post-transplant F0-F3 + CP-A

(CP score 5–6)

– GT-1 (n=147); GT-4 (n=21)

– 79%–84% TE

– MELD >15: 0

Patient population

Pre/Post-transplant CP-B + CP-C

(CP score 7–12)

– GT-1 (n=144); GT-4 (n=16)

– 74%–80% TE

– MELD >15: 23%–28%

9687 85

95

50

98 96

72

100

75

0

20

40

60

80

100

F0-F3 + CP-A CP-B CP-C CP-B CP-C

SV

R1

2 (

%)

SVR12 in GT-1 Patients (N=266)

91

57

10086

0

20

40

60

80

100

F0-F3 + CP-A CP-B + C

12 weeks

24 weeks

SVR12 in GT-4 Patients (N=32)

SV

R1

2 (

%)

1 relapse

2 deaths

1 death

3 relapses

1 relapse

1 death3 relapses

1 death

72/

75

F0-F3 +CP-A

Post-transplant

CP-B CP-C

Pre-transplant

F0-F3 +CP-A

Post-transplantCP B-C

Pre/post-transplant

57/

5822/

23

20/

23 10/

11

7/

74/

7

6/

7

Virologic response was associated with improvements in MELD and

CP scores (attributed to decreases in bilirubin and increased albumin)

CP-B CP-C

Post-transplant

13/

18

17/

20 16/

16

19/

203/

41/

2

1 relapse

2 deaths

1 relapse

3 deaths

1 death 1 death

1 death

Key Takeaways

SOLAR-2: European; design and results are similar to SOLAR-1 (primarily US study) (GT-1, -4)

Longer-term follow-up is needed to demonstrate clinical benefit for CP-B/C patients

8596 87

95

75

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Slide 19 of 22

Do you think liver transplantation is an option for your

HIV-infected patients with liver disease?

0%

0%

0% 1. Yes

2. No

3. Don’t Know

10

Slide 20 of 22

Patient Survival: HCV

P=0.01P=0.01

HCV mono-infected N=135 N=67 N=22

HCV-HIV co-infected N=46 N=28 N=14

% P

AT

IEN

T S

UR

VIV

AL

0

20

40

60

80

100

YEAR

0.0 0.5 1.0 1.5 2.0 2.5 3.0

HCV-HIV CoinfectedHCV Monoinfected

P=0.01

Terrault et al. HEPATOLOGY 2009 Abs AASLD

Slide 21 of 22

Time to First Acute

Rejection

% R

EJE

CT

ION

0

20

40

60

80

100

YEAR

0.0 0.5 1.0 1.5 2.0 2.5 3.0

HCV-HIV CoinfectedHCV Monoinfected

HCV mono-infected: N=106 N=52 N=17

HCV-HIV co-infected: N=31 N=14 N=7

50% of AR episodes

occurred ≤21 days of LT

Stock , HIV and Liver Disease 2010

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Slide 22 of 22

Summary: Management of Liver Disease

• Early recognition of liver disease is critical

• Staging helps determine not only viral disease

management, but liver disease management

• Failure to recognize decompensated liver disease

decreases patient survival

• Liver transplant is a viable option for both decompensated

liver disease and HCC in many patients with HIV

5/12/2016

1

Lucas Hill, PharmDClinical Instructor

University of California San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences

San Diego, California

Treatment of Hepatitis C Virus in Renal Impairment

FORMATTED: 05/02/2016

San Francisco, California: May 5, 2016

Slide 2 of 19

Case • 27 year-old man with HIV and HCV acquired via mother-to-child

transmission • Medical history is complicated • End-stage renal disease requiring hemodialysis with difficult

vascular access– Collapsing focal segmental glomerulosclerosis (FSGS) due to HIVAN

• Cardiac disease including MV endocarditis resulting in MR s/p MVR complicated by cardiogenic shock, Tricuspid regurgitation, and history of atrial fibrillation– Long-term warfarin

Slide 3 of 19

Case continued

HIV infection is currently well controlled

• HIV RNA < 20 copies/mL

• CD4 count 616; CD4 count nadir 108 (2010)

• Antiretrovirals: Lamivudine, Darunavir/ritonavir, Tenofovir– Mutations: DLV, EFV, NVP resistance (NNRTIs)

– History of sporadic non-adherence, largely resolved

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Slide 4 of 19

Case continuedHCV infection – no prior treatment • HCV genotype 1a • HCV RNA 278,000 IU/mL• HAV antibody total reactive; HBsAb reactive s/p

vaccination • Hb 8.2 g/dL; platelet count 190,000/mm3

• ALT 105 U/L; AST 143 U/L; Total bilirubin 0.5 mg/dL; Albumin 3.9 g/dL; INR 3.1

Slide 5 of 19

Multiple staging modalities were used but which is correct?

Liver biopsies have been performed in the past with the most recent in January 2015 (1.5 cm in length)- MILD PORTAL AND LOBULAR INFLAMMATION - FOCAL PORTAL AND SINUSOIDAL FIBROSIS- MODERATE IRON ACCUMULATION IN RETICULOENDOTHELIAL CELLS - NO STEATOSIS

Slide 6 of 19

What would you do next?

4%

0%

14%

0%

43%

39% 1. Prescribe HCV treatment

2. Change antiretroviral therapy

3. Liver transplant evaluation

4. Kidney transplant evaluation

5. Nothing

6. Something else

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Slide 7 of 19

Kidney transplantation may be facilitated by the use of organs from HCV + deceased donors

Reese PP, et al. N Engl J Med. 2015;373:303-305.

Slide 8 of 19

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Slide 11 of 19

The patient opts not to pursue kidney transplant at this time, what next step would you recommend?

7%

3%

69%

21% 1. Prescribe HCV treatment

2. Change antiretroviral therapy, then prescribe HCV treatment

3. Defer treatment decisions until the patient consents to transplant

4. Defer treatment until liver disease progresses (biopsy stage 1)

Slide 12 of 19

In addition to individual benefit, treatment may prevent transmission in HD clinics

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Slide 13 of 19

NS5A resistance testing is performed and shows a M28V polymorphism. Which of the following HCV drug regimens would you recommend for this patient [genotype 1a and no cirrhosis on biopsy]?

0%

5%

38%

19%

14%

24% 1. Ledipasvir/Sofosbuvir for 12 weeks

2. Paritaprevir/ritonavir/Ombitasvir + Dasabuvir for 12 weeks

3. Paritaprevir/ritonavir/Ombitasvir + Dasabuvir + Ribavirin for 12 weeks

4. Grazoprevir/Elbasvir for 12 weeks

5. Grazoprevir/Elbasvir + Ribavirin for 12 weeks

6. Daclatasvir + Sofosbuvir for 12 weeks

Slide 14 of 19

SOF in renal impairment

Cornpropst M, Denning J, Clemons D, et al. The Effect of Renal Impairment and End Stage Renal Disease on the Single-Dose Pharmacokinetics of GS-7977. EASL 47th Annual Meeting. April 18th-22nd 2012.

Slide 15 of 19

Regimens that do not include a nucleotide analogue are recommended in patients with ESRD

RUBY-I, PrOD – 12 weeks

Pockros PJ. Gastroenterology 2016 in press

• 8/13 geno 1a patients had interruption of ribavirin

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Slide 16 of 19

C-SURFER (EBR/GZR)

Roth D, et al. The Lancet. 2015

Slide 17 of 19

C-SURFER Results

• SVR12 in 16/17 patients with baseline RAVs (only failure was geno 1b)

Slide 18 of 19

Ribavirin• Renally cleared

• 120-170 hour T1/2

ribavirin

Ribavirin Dose

peginterferon should be reduced for creatinine clearance less than

Peginterferon Dose

Peginterferon Package Insert].

5/12/2016

7

Slide 19 of 19

Which of the following HIV drug regimens would you recommend for this patient during HCV treatment with

Nuc NS5B sparing HCV treatment?

13%

13%

33%

40%

0% 1. Continue DRV/r + TDF + 3TC

2. Dolutegravir/Abacavir/3TC

3. Dolutegravir + Abacavir + 3TC

4. Dolutegravir + TDF + 3TC

5. DRV/r + Dolutegravir