Download - Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Transcript
Page 1: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Eliot Godofsky, MD, Director

University Hepatitis Center

Sarasota, Florida

Treatment of HCV in Patients

with HIV Coinfection

Recorded on 6/17/2014

Page 2: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Slide 2 of XX

Disclosure

Dr. Godofsky has received research support from

Janssen, AbbVie, Achillion Pharmaceuticals, Inc,

Bristol-Myers Squibb, Gilead Sciences, Inc,

Boehringer Ingelheim, GSK and Vertex

Pharmaceuticals, Inc.

Dr. Godofsky has served as a scientific advisor or as a

consultant to AbbVie, Genetech and Janssen

Pharmaceuticals (Past 2 years, updated 6/14)

Page 3: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Slide 3 of XX

Lecture Outline

Evolution of HCV Treatment in Patients with HIV

Coinfection

Timing of Treatment

Patient Evaluation and Selection

Important Drug-Drug Interactions

Therapy Considerations for Patients on HIV ART

Summary of Current AASLD/IDSA/IAS-USA Treatment

Recommendations

Page 4: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Evolution of HCV Treatment in HIV

Coinfection

Page 5: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Slide 5 of XX

HCV/HIV Treatment Outcomes:

PegIFN plus RBV

0

25

50

75

100

G1 G2/3

Monoinfection

APRICOT

ACTGRIBAVICLaguno et al.

PRESCO

Genotype 1

SVR 14–38%

Genotype 2/3

SVR 44–73%

Genotype

SV

R (

%)

Fried et al, NEJM 2002, 347: 975-982, Torriani et al, NEJM 2004; 351: 438-50, Chung R, et al, NEJM 2004: 351; 451-9,

Carrat F, et al, JAMA 2004: 292: 2839-42, Laguno et al, AIDS 2004; 18: F27-F36, Nunez et al, JAIDS 2007: 45: 439-44

Page 6: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Slide 6 of XX

No ARTEFV/TDF/FTCATV/ritonavir + TDF/FTC

Total

SV

R (

%)

n/N = 5/7

11/16

12/15

28/38

Telaprevir + PegIFN/RBV

PegIFN/RBV

2/6

4/8

4/8

10/22

Sulkowski MS, et al. Ann Intern Med. 2013;159:86-96. Sulkowski M, et al. Lancet Infect Dis. 2013;13:597-605. Poordad F, et

al. N Engl J Med. 2011;364:1195-1206. Jacobson IM, et al. N Engl J Med. 2011;364:2405-2416.

100

80

60

40

20

0

71 69

8074

33

50 5045

First Generation HCV Protease Inhibitors

plus PegIFN/RBV in GT 1 Coinfection

0

20

40

60

80

100

SV

R (

%)

PegIFN/RBV

n/N =

29

63

Boceprevir + PegIFN/RBV

SVRs comparable to GT1 HCV-monoinfected patients:

Boceprevir 68% Telaprevir 75%

Page 7: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Slide 7 of XX

Recently Released DAAs

Multi-genotypic

NS3/4A PI

QD dosing

Second Wave PI

Low barrier to

resistance

+ DDI with ARVs

Rash, photosensitivity

HIV not a special pop

Simeprevir Sofosbuvir

Pan-genotypic NS5B

QD dosing

Nucleotide analogue

Exceptional barrier to

resistance

No significant DDI

No AE

Approved for HIV/HCV

as special population

Page 8: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Slide 8 of XX

Sofosbuvir + PR for 12 weeks in HCV/HIV

Coinfection:Treatment Outcomes

No change in ART regimens

SVR12 rates by ART regimen

PI: 93%

NNRTI: 91%

Raltegravir: 100%

No on-treatment breakthroughs

Relapse (n=1)

HIV breakthroughs (n=2)

Discontinuations due to adverse events:

9%

Most common adverse events

Anemia (52%), fatigue (35%), neutropenia

(17%), thrombocytopenia (17%),

myalgia (13%)

Hyperbilirubinemia (17%)

Pa

tie

nts

(%

)

SVR12 Rates

91%87%

Overall(n=23)

100%

Genotype

Rodriguez-Torres M, et al. IDWeek 2013. Abstract 714.

1a(n=19)

1b(n=4)

2(n=1)

3(n=2)

4(n=1)

100% 100% 100%

Page 9: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Slide 9 of XX

PHOTON-1 Study:

Treatment Outcomes SVR12 rates in genotype 1

Similar regardless of baseline HCV RNA, IL28b

genotype, presence of cirrhosis, age, gender,

race

Lower in genotype 1b versus 1a

No resistance (deep sequencing)

detected in virologic failures

HIV breakthroughs (n=2)

Discontinuations due to AEs: 3%

Most common adverse events Fatigue, insomnia, headache, nausea

Grade >3 hyperbilirubinemia in patients

receiving atazanavir versus no atazanavir (13%

versus 1%)

SVR in treatment experienced pts

receiving 24 weeks of therapy: 92%

GT2 and 88% GT3

Sulkowski MS, et al. Hepatology. 2013;58(suppl 1):313A-314. Abstract 212.

Pa

tie

nts

(%

)

SVR12 Rates

76%

88%

Genotype 1(n=114)

Genotype 2(n=26)

Genotype 3(n=42)

67%

24 WeeksTherapy*

12 WeeksTherapy*

*Sofosbuvir 400 mg qd + RBV.

Page 10: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Slide 10 of XX

Study C212: Simeprevir + PR

in HCV/HIV Infection: GT 1

Phase III open label. Naïve/Relapse

(RGT arm) and PR null/partials (48

week tx)

SVR12 rates in HCV/HIV coinfected

were similar to HCV monoinfected

trials

SVR12 rates were high,

regardless of baseline METAVIR

fibrosis score

SVR12 67% GT1a + Q80k vs.

89% GT1b

Safety profile similar to

monoinfected patients

Pruritus and photosensitivity in

20% and 2%, respectively

Grade 3/4 hemoglobin: 1.9%

Naïve(n=53)

Relapser(n=15)

Partial(n=10)

Overall(n=106)

Pati

en

ts (

%)

87%

70%

57%

74%79%

SVR12 Rate

Dieterich D, et al. 14th EACS. Brussels, 2013. Abstract LBPS9/5.

Null(n=28)

Page 11: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Slide 11 of XX

COSMOS Study: Interim Results With Simeprevir +

Sofosbuvir + RBV in HCV Monoinfection

Jacobson IM, et al. Hepatology. 2013;58(suppl 1):73A. Abstract LB-3.

Pati

en

ts (

%)

SVR12: No Cirrhosis (F0-F2)(Prior PR Null Responders)

92.9%

24 Weeks(n=24/15)

12 Weeks(n=27/14)

Simeprevir + sofosbuvir

No RBV With RBV

96.3%93.3%

79.2%

Pa

tie

nts

(%

)

SVR4: Cirrhosis (F3-F4)*(Naives and Prior PR Null Responders)

100%

Naives(n=7/12)

Overall(n=14/14)

96.3%100%

93.3%

*Interim analysis: SVR4 rates in patients receiving the 12-week regimens.

Nulls(n=7/15)

100%

Simeprevir + sofosbuvir

No RBV With RBV

Page 12: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Timing of Treatment

Page 13: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Slide 13 of XX

HIV/HCV Coinfection:

Who to Treat

All HCV/HIV coinfected patients are candidates for HCV therapy

Consider comorbid conditions that limit life expectancy or increase the risks associated with HCV therapy

HCV cure may decrease risk of ART-associated liver injury

HIV disease should be stable with or without ART

IFN-based regimens

Defer HCV treatment if CD4 <200 cells/mm3

Interferon can exacerbate pre-existing mental illness

Evaluate patients with underlying psychiatric disease before initiating HCV treatment

Decompensated cirrhosis

Refer to medical practitioner with expertise

Substance abuse

Active substance abuse is not a contraindication

Associated with high rates of treatment nonadherence and may compromise treatment outcomes

AASLD and IDSA. Available at: http://www.hcvguidelines.org/full-report-view. Version January 29, 2014.

Sulkowski MS, et al. J Viral Hepatitis. 2007;14:371-386.

Page 14: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Slide 14 of XX

Specific Risks of Deferring Therapy in HIV/HCV-

Coinfected Patients

Accelerated rate of HCV-related hepatic fibrosis progression in coinfected patients with increasing immune deficiency Progression to cirrhosis risk 3-fold higher in coinfected vs

HCV-monoinfected patients

Relative risk of decompensated liver disease 6-fold higher in coinfected vs HCV-monoinfected patients

HCC occurs earlier and more aggressive

Coinfected patients have reduced access to liver transplantation and reduced survival

ART may delay liver disease progression

Taylor LE, et al. Clin Infect Dis. 2012;55(suppl 1:S33-42). DHHS Antiretroviral Guidelines for Adults and Adolescents. February 2013. Naggie S, et al. Gastroenterology. 2012;142:1324-1334. Macías J, et al. Clin Infect Dis. 2013;57:1401-1408.

Page 15: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Slide 15 of XX

0.2

0.4

0.6

0.8

1

Bonn Cohort: Benefits of ART on

Mortality in HCV/HIV-Coinfection

HCV/HIV-coinfected patients

(n=285)

Liver-related mortality rates (per

100 person-years)

With ART: 0.45

No ART: 1.70

Predictors for increased liver-

related mortality

No ART

Low CD4 cell count

Increasing age

ART therapy can slow fibrosis

progression and decrease

mortality in coinfection

Qurishi N, et al. Lancet. 2003:362:1708-1713.

Overall Mortality

Cu

mu

lati

ve

Su

rviv

al

Days0 1000 2000 3000 4000 5000 6000

ART*

No therapy*P<0.001

0.2

0.4

0.6

0.8

1

Liver-Related Mortality

Cu

mu

lati

ve

Su

rviv

al

Days0 1000 2000 3000 4000 5000 6000

HAART*

No therapy

*P=0.018

Page 16: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Slide 16 of XX

ALIVE Study: HIV, Age, and Severity

of HCV-Related Liver Diseases

Prospective cohort of HCV-infected IDUs

(2006-2011) (n=1176)

HIV co-infected (n=394)

Baseline and semi-annual elastography

Fibrosis was significantly greater in

HCV/HIV co-infected versus HCV

monoinfection (P<0.001)

No cirrhosis (12.9% versus 9.5%)

With cirrhosis (19.5% versus 11.0%)

Independently associated with increasing

age and HIV infection

HCV/HIV patients have liver fibrosis

similar to HCV mono-infected patients

who are nearly 10 years older

Kirk GD, et al. Ann Intern Med. 2013;158:658-666.

Pre

dic

ted

Fib

roS

ca

n S

co

re (

kP

a)

30 35 40 45 50 55 60

Liver Fibrosis and Age:HCV/HIV Versus HCV Infection

Age (years)

HCV/HIV

HCV

9.2 years

ALIVE: AIDS Linked to the IntraVenous Experience.

Page 17: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Slide 17 of XX

HCV Coinfection vs Monoinfection:

Cumulative Incidence of Decompensation

10-year hepatic decompensation risk 83% higher in coinfected patients

Adjusted HR 1.83 (95% CI: 1.54-2.18)

P < .001

HIV/HCV coinfectedHCV monoinfected

0.074

0.048

. Lo Re V, et al. IAC 2012. Abstract WEAB0102.

0

0.1

0.2

0 1 2 3 4 5 6 7 8 9 10

Yrs to Hepatic Decompensation

Page 18: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Slide 18 of XX

HCV Treatment and Incidence

of ESLD, HCC, and Death

Prospective US cohort (1993-2011)

(n=638)

Liver biopsy at baseline

35% underwent HCV treatment with PR

Baseline >F2 versus <F2 fibrosis

Higher treatment rates: 54% versus

28% (P<0.001)

Similar SVR rates: 17% versus 16%

No clinical events (ESLD, HCC, and

death) among patients achieving SVR

Cu

mu

lati

ve

Su

rviv

al

0 2 4 6 8 10

Survival Free ofESLD, HCC, or Death

Time Since Biopsy (years)

Log-rank P=0.005

No HCV treatment

SVR

Relapse

Nonresponse

Limketkai BN, et al. JAMA. 2012;308:370-378.

Page 19: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Slide 19 of XX

Assessing HIV+ Patients for Immediate or

Deferred HCV Therapy

Antiretroviral therapy for HIV treatment-naive

HIV/HCV-coinfected patients

CD4+ cell count < 500 cells/mm3: initiate antiretroviral therapy

for HCV treatment optimization

CD4+ cell count > 500 cells/mm3: may defer antiretroviral

therapy until HCV therapy completed

EACS Guidelines, Version 7.0. October 2013. . DHHS Antiretroviral Guidelines for Adults and Adolescents. February 2013.

Macías J, et al. Clin Infect Dis. 2013;2013;57:1401-1408.

HCV Therapy in HIV/HCV-Coinfected, HCV Treatment-Naive Patients

Liver FibrosisConsider

HCV Therapy

Eligible to

Defer HCV Therapy

No/minimal fibrosis (F0-F2) ●

Advanced fibrosis (F3-F4); cirrhosis[ ●

Page 20: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Slide 20 of XX

Staging of Liver Disease

Staging is disease assessment with meaningful

information for patients and providers

Liver stage is the CD4 count of HCV

Who and When to treat (i.e. now or later?)

Screening for HCC and varices

Modalities:

Liver biopsy

Blood markers,

Elastography,

Combination

Page 21: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Slide 21 of XX

Noninvasive Serum-Based Tests for Detection

of Fibrosis

FibroTest

Combines 5 markers: α2-macroglobulin, haptoglobin, GGT, total bilirubin, and

apolipoprotein A1

FibroSpect II

Combines 3 markers: α2-macroglobulin, hyaluronic acid, and tissue inhibitor of

metalloproteinase-1

APRI

AST-to-platelets ratio index

Forns fibrosis index

Age, platelet count, GGT, cholesterol

FIB-4

Combines 4 markers: platelets, ALT, AST, and age

Page 22: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Slide 22 of XX

Validity of Noninvasive Methods of

Detecting Cirrhosis

Test % Sens % Spec AUROC Pos LR Neg LR

Fibrotest1 >.56 85 74 .86 3.3 0.2

Fibrotest > .73 56 81 - 2.9 0.54

FIB42, >1.45 90 58 .87 2.1 0.17

APRI3, >1.0 77 75 0.73 3.1 0.31

Forns4, >4.2 98 27 87 1.3 0.07

Chou Ann Intern Med 2013

Page 23: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Slide 23 of XX

FibroScan (Elastography)

• The probe induces an elastic wave through the liver

• The velocity of the wave is evaluated in a region located from 2.5 to 6.5 cm below the skin surface

• Diagnostic accuracy:• Significant fibrosis: 0.79• Advanced fibrosis: 0.91• Cirrhosis: 0.97

8.8 9.6 14.6

FibroScan (kPa)

Liver Fibrosis(METAVIR)

F0-F1 F2 F3 F4

Ziol M, et al. Hepatology. 2005;41:48-54.

Page 24: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Slide 24 of XX

Which staging test should be done?

297 HIV/HCV coinfected patients with Liver Stiffness Model and biopsy within 12 months Dec 2005-Dec 2011.

LSM-based models performed 8.4% better than liver biopsy prediction survival and liver-decompensation

Macias AIDS 2013

Page 25: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Slide 25 of XX

Which staging test should be done?

Elastography provides the most, currently useful

information when valid

Elastography and noninvasive can confidently rule

out cirrhosis when concordant

Serum alone may confidently rule out cirrhosis

Biopsy done by specialists and when discordance or

other questions

Do something

Page 26: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Drug-Drug Interactions

Page 27: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Slide 27 of XX

DAA Drug Interactions

Phase III Study: Rilpivirine (15%), Raltegravir (87%), Maraviroc, Enfuvirtide, NRTIs

ARV BOC TPV SMV SOF* DCV FDV

ATV/r CAUTION STAND CONTRA STAND DCV FDV

DRV/r CONTRA CONTRA CONTRA STAND N/A FDV

EFV CONTRA TPV CONTRA STAND DCV FDV

RPV STAND CAUTION STAND STAND STAND N/A

ETV CAUTION CAUTION CONTRA STAND N/A N/A

RGV STAND STAND STAND STAND STAND STAND

DGV N/A N/A CAUTION STAND N/A N/A

MVC MVC MVC STAND STAND STAND STAND

*Tipranavir CONTRA with SOFOuwerkerk-Mahadevan et al. IDSA 2012 Abstract #49; Hulskotte et al. Clin Infect Dis 2013; de Kanter et al. CROI 2012; Bifano et al. CROI 2012; Kirby et al. AASLD 2012

Page 28: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Slide 28 of XX

AASLD and IDSA Guidelines:

Preferred HCV Regimens in HCV/HIV Coinfection

HCV treatment-naïve and prior PR relapsers

IFN eligible

IFN ineligible

Sofosbuvir + PR 12 weeks

Sofosbuvir + RBV 24 weeks

Sofosbuvir + simeprevir† + RBV 12 weeks

HCV treatment experienced* Sofosbuvir + simeprevir† + RBV 12 weeks

*Prior PR non-responders regardless of IFN eligibility. †For genotype .

Allowable ART: Sofosbuvir: all except the NRTIs didanosine and zidovudine.

Simeprevir: INSTI (raltegravir); NNRTI (rilpivirine); Entry/Fusion Inhibitor (maraviroc, enfuvirtide);

NRTIs (tenofovir, emtricitabine, lamivudine, abacavir).

AASLD and IDSA. Available at: http://www.hcvguidelines.org/full-report-view. Version January 29, 2014.

Genotype 1

Regardless of HCV treatment history Sofosbuvir + RBV 12 weeks

Genotype 2

Genotype 3

Regardless of HCV treatment history Sofosbuvir + RBV 24 weeks

Regardless of HCV treatment history

IFN eligible

IFN ineligible

Sofosbuvir + PR 12 weeks

Sofosbuvir + RBV 24 weeks

Genotype 4

Genotypes 5 or 6Regardless of HCV treatment history Sofosbuvir + PR 12 weeks

Page 29: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Slide 29 of XX

AASLD and IDSA Guidelines:

Alternative HCV Regimens in HCV/HIV Coinfection

HCV treatment-naïve and prior PR relapsers

IFN eligible

IFN ineligible

Simeprevir† 12 weeks + PR 24 weeks

None

HCV treatment experienced*

IFN eligible

IFN ineligible

Sofosbuvir + PR 12 weeks

Sofosbuvir + RBV 24 weeks

*Prior PR non-responders.†For genotype 1a, baseline resistance testing for Q80K should be performed and alternative treatments considered if present.

Allowable ART: Sofosbuvir: all except the NRTIs didanosine and zidovudine.

Simeprevir: INSTI (raltegravir); NNRTI (rilpivirine); Entry/Fusion Inhibitor (maraviroc, enfuvirtide);

NRTIs (tenofovir, emtricitabine, lamivudine, abacavir).

Genotype 1

None

HCV treatment-naïve and prior PR relapsers None

HCV treatment experienced*

IFN eligible

IFN ineligible

Sofosbuvir + PR 12 weeks

None

Genotypes 2 or 3

AASLD and IDSA. Available at: http://www.hcvguidelines.org/full-report-view. Version January 29, 2014.

Genotypes 4, 5, or 6

Page 30: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Slide 30 of XX

AASLD and IDSA Guidelines: HCV Regimens

Not Recommended in HCV/HIV Coinfection

Telaprevir + PR 24 or 48 weeks (RGT)

Boceprevir + PR 28 or 48 weeks (RGT)

PR 48 weeks

Simeprevir 12 weeks + PR 48 weeks

Genotype 1

Any regimen with telaprevir, boceprevir, or simeprevir

PR 24 to 48 weeks

Genotypes 2 or 3

Any regimen with telaprevir, boceprevir, or simeprevir

PR 48 weeks

Genotypes 4, 5, or 6

AASLD and IDSA. Available at: http://www.hcvguidelines.org/full-report-view. Version January 29, 2014.

Page 31: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Slide 31 of XX

NIAID ERADICATE Study: Sofosbuvir/Ledipasvir in HCV

Genotype 1 With HIV Coinfection (Interim Analysis)

No change within groups

CD4 counts or CD4 T-cell percentages

Serum creatinine or estimated GFR

HIV RNA status during HCV treatment

ART-naïve: no clinically significant change

On ART: transient HIV RNA breakthrough

(missed ART for 4 days), re-suppressed

No change within groups

Sofosbuvir/ledipasvir was well tolerated

No deaths, grade 4 adverse events or

discontinuations due to adverse events

Laboratory abnormalities

Grade 3: neutropenia (n=1), AST (n=1)

Grade 4: creatinine phosphatase (n=1)

Osinusi A, et al. J Hepatol. 2014;60(suppl 1):S7. Abstract O14.

SV

R (

%)

100% 100% 100%

Not Yet

Available

SVR Rates(Interim, Observed)

ART-Naïve(n=12/10)

SVR4

SVR12

On ART(n=22/0)

Page 32: Treatment of HCV in Patients with HIV Coinfectiondepts.washington.edu/hepstudy/presentations/... · HCV/HIV co-infected versus HCV monoinfection (P

Slide 32 of XX

HCV/HIV Coinfection:

Summary

Liver disease is a leading cause of morbidity and mortality

Controlling HIV with ART may slow progression of HCV-

related liver disease

All HIV patients should be screened for HCV

First-generation PIs + PR regimens present significant

challenges and limitations

Newer, once-daily DAAs

Simplify and shorten duration of regimens

Improve SVR rates with fewer adverse events

Minimize drug-drug interactions