 Design Open-label 18-70 years Chronic HCV infection Genotype 1 HCV RNA > 10,000 IU/mL HIV co-infection Stable ART* with HIV RNA < 50 c/mL ≥ 24 weeks.

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Forns X. J Hepatology 2015; 63: C-SALVAGE Study: grazoprevir + elbasvir + RBV in genotype 1 with failure to PI-based regimen –NS3 and NS5A RAVs.

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Asselah T. AASLD 2015, Abs. 714 Randomisation 1:1 Open-label years HCV genotype 4 HCV RNA ≥ 1,000 IU/ml Naïve or pre-treated with PEG-IFN + RBV (Part.

Sulkowski M. Lancet 2015;385: C-WORTHY  Design Randomisation* Open-label > 18 years HCV genotype 1, treatment naïve HCV RNA ≥ 10,000 IU/ml No cirrhosis.

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SAPPHIRE-I Feld JJ. NEJM 2014;370: SAPPHIRE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for genotype 1  Treatment regimens.

Open-label W24 ≥ 18 years Chronic HCV infection All genotypes HCV RNA ≥ 10,000 IU/ml Liver transplantation months earlier Child Pugh ≤ 7 and MELD.

SOF/VEL 400/100 mg qd N = 120 W12 SOF + RBV > 18 years Chronic HCV infection Genotype 2 Naïve or pre-treatment with IFN-based regimen Compensated cirrhosis.

Placebo + PR W24 DCV + PR Placebo + PR Yes Dore GJ. Gastroenterology 2015;148: COMMAND GT2/3 COMMAND GT2/3 Study: daclatasvir + PEG-IFN + RBV for.

Dore G. J Hepatol 2016; 64:19-28 MALACHITE TVR + PEG-IFN + RBV Randomisation Open-label years HCV genotype 1 HCV RNA > 10,000 IU/ml Naïve (MALACHITE-I)

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Poordad F. NEJM 2014;368: D Phase IIa  Design  Treatment regimens – Paritaprevir/rironavir (PTV/r) : PTV 250 or 150 mg qd/ritonavir 100 mg qd (2.

PHOTON-1  Design  Objective –SVR 12 with 2-sided 95% CI, descriptive analysis –Multivariate analyses of predictors of SVR 12 SOF + RBV, N= 114 SOF +

SOF/VEL 400/100 mg qd N = 106 W12 > 18 years Chronic HCV infection Genotype 1-6 Naïve or pre-treatment with IFN-based regimen Compensated cirrhosis allowed*

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Genotype 1 HCV infection Stable immunosuppressive therapy

PHOTON-2 Study: SOF + RBV in HCV-HIV co-infection

CONCERTO-2 Study: SMV + PEG-IFNa-2a + RBV for genotype 1

No cirrhosis or compensated cirrhosis** No HBV or HIV co-infection

Failure to achieve SVR on No HBV or HIV co-infection

SOF/VEL + GS-9857 in genotypes 1-6 Phase II

LEAGUE-1 study: daclatasvir + SMV + RBV for genotype 1

No HBV or HIV co-infection

ION-3 Study: LDV/SOF + RBV for naïve genotype 1

ARV-trial.com TURQUOISE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV in HIV co-infected patients Randomisation 1 : 1 Open-label.

ASPIRE Study: SMV + PEG-IFN + RBV for genotype 1 experienced patients

LDV/SOF ± RBV in genotype 3 or 6 – Phase 2

CONCERTO-4 Study: SMV + PEG-IFNa-2b + RBV for genotype 1

Presentation transcript:

 Design Open-label years Chronic HCV infection Genotype 1 HCV RNA > 10,000 IU/mL HIV co-infection Stable ART* with HIV RNA < 50 c/mL ≥ 24 weeks CD4 ≥ 300/mm 3 if on ART, > 500/mm 3 if no ART N = 53 W24W48 C-212 C-212 Study: SMV + PEG-IFN + RBV for genotype 1 in HIV co-infection Dieterich D. CID 2014;59: SMV + PEG-IFN + RBV W12 SMV 150 mg : 1 pill qd ; PEG-IFN  -2a : 180  g SC once weekly RBV : 1000 or 1200 mg/day (bid dosing) according to body weight (< or ≥ 75 kg) Response-guided therapy : Patients with HCV RNA < 25 IU/ml at W4 and < 15 IU/ml at W12 stopped treatment at W24, otherwise they continued until W48 Virological stopping rules : SMV discontinued if HCV RNA >1000 IU/mL at W4 or W12, or if HCV RNA confirmed ≥ 25 IU/mL at W24 or W36 Naïve or prior relapse Partial or null response or cirrhosis * Permitted ART : 3TC/FTC, ABC, TDF, RPV, RAL, MVC  Objective : SVR 12 (HCV RNA < 25 IU/mL) by intention to treat

Naïve N = 53 Prior relapse N = 15 Prior Partial response N = 10 Prior null response N = 28 Median age, years Female9%33%10%18% White / Black76% / 19%80% / 13%90% / 10%93% / 7% Genotype 1a / 1b79% / 19%80% / 20%90% / 10%86% / 14% Baseline HCV RNA, log 10 IU/ML, median Metavir score F3-F421%18%60%59% IL28B genotype CC29%47%10%18% HIV treatment at baseline81%100%90%93% RAL / RPV / MVC, %79 / 23 / 587 / 20 / 089 / 11 / 0100 / 0 / 4 Discontinued study, n (%) Adverse event Lost to follow-up Non-compliance Other Baseline characteristics and patient disposition C-212 C-212 Study: SMV + PEG-IFN + RBV for genotype 1 in HIV co-infection Dieterich D. CID 2014;59:

SVR 12 (HCV RNA < 25 IU/mL) % N AllNaïve RelapseNull Partial 88  Response guided therapy (RGT) : –Patients with HCV RNA < 25 IU/ml at W4 (undetectable or detectable) and <15 IU/ml at W12 (undetectable) stopped treatment after W24 –Of the 54 (58%) patients who met RGT, 87% had SVR 12 Treatment-experienced GT 1b GT 1a All GT 1a Q80K+ GT 1a Q80K- C-212 C-212 Study: SMV + PEG-IFN + RBV for genotype 1 in HIV co-infection Dieterich D. CID 2014;59:

SVR 12 (HCV RNA < 25 IU/mL) C-212 C-212 Study: SMV + PEG-IFN + RBV for genotype 1 in HIV co-infection Dieterich D. CID 2014;59: Metavir F0-F2Metavir F3-F % N OverallNaïveRelapseNullPartial Treatment-experienced 0

SVR 12 (HCV RNA < 25 IU/mL) IL28B CCIL28B non-CC C-212 C-212 Study: SMV + PEG-IFN + RBV for genotype 1 in HIV co-infection Dieterich D. CID 2014;59: % Overall NaïveRelapseNullPartial Treatment-experienced N

 Emergence of resistance – Paired baseline and failure NS3 sequencing in 26/29 failure – Emergence of NS3 mutations in 25/26 (96%)  HIV endpoints –Confirmed failure : 2/93 (2.2%) of patients on antiretroviral therapy ; both had SVR 12  Virologic failure NaïvePrior partial respondersPrior null responders On-treatment failure5 (9.4%)2 (20%)11 (39%) Viral breakthrough3 (5.8%)1 (10%)8 (27%) Relapse5 (10.4%)-2 (12%) C-212 C-212 Study: SMV + PEG-IFN + RBV for genotype 1 in HIV co-infection Dieterich D. CID 2014;59:

All patients N = 106 Discontinuation due to adverse event5 (4.7%) Grade 3 AE27.4% Grade 4 AE6% Fatigue41% Headache28% Nausea26% Neutropenia28% Anemia21% Pruritus20% Rash16% Sunburn3% Photosensitivity2% Total bilirubin increase5% Adverse events C-212 C-212 Study: SMV + PEG-IFN + RBV for genotype 1 in HIV co-infection Dieterich D. CID 2014;59:

C-212 Study: SMV + PEG-IFN + RBV for genotype 1 in HIV co-infection  Summary –Oral, once-daily treatment with SMV 150 mg for 12 weeks plus PEG-IFN + RBV for either 24 or 48 weeks led to high rates of SVR 12 in patients with HCV genotype 1 and HIV-1 coinfection, regardless of prior HCV treatment response –Most eligible patients met response-guided therapy criteria enabling a shorter, 24-week overall duration of PEG-IFN + RBV therapy –SMV was generally well tolerated, with safety similar to that reported in larger studies in patients without HIV coinfection –Limitations No control arm C-212 Dieterich D. CID 2014;59: