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

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Presentation transcript:

PHOTON-2 Study: SOF + RBV in HCV-HIV co-infection ARV-trial.com PHOTON-2 Study: SOF + RBV in HCV-HIV co-infection Design Not randomised Open -label W12 W24 ≥ 18 years Chronic HCV infection Genotype 1, 2 , 3 or 4 HCV RNA ≥ 10,000 IU/ml Treatment-naïve (GT 1, 2, 3, 4) or experienced (GT 2 and 3) Chronic HIV infection On ARV with HIV RNA < 50 c/ml, or not on ARV with CD4 > 500/mm3 Compensated cirrhosis allowed Genotype 1, 3, 4 Naïve SOF + RBV, N = 200 Genotype 2 Naïve SOF + RBV, N = 19 Genotype 2, 3 Experienced SOF + RBV, N = 55 SOF : 400 mg qd RBV (bid dosing) : 1000 mg/day if < 75 kg or 1200 mg/day if ≥ 75 kg Objective SVR12 with 2-sided 95% CI, descriptive analysis Multivariate analyses of predictors of SVR12 PHOTON-2 Molina JM. Lancet 2015;385:1098-1106 1

PHOTON-2 Study: SOF + RBV in HCV-HIV co-infection ARV-trial.com PHOTON-2 Study: SOF + RBV in HCV-HIV co-infection Baseline characteristics GT1 naïve N = 112 GT2 N = 19 GT 2 experienced N = 6 GT 3 N = 57 N = 49 GT 4 N = 31 Mean age, years 45 55 47 49 Female 11% 21% 33% 22% 23% HCV RNA log10 IU/ml, mean 6.3 6.7 6.4 5.9 Cirrhosis 15% 5% 47% 26% No response/relapse to previous HCV treatment - 50% / 50% 27% / 51% CD4/mm3, mean 627 499 633 572 575 545 On ARV 97% 89% 100% 94% ARV = TDF/FTC + EFV RAL DRV/r ATV/r RPV Other 31% 17% 14% 5% 8% 35% 6% 29% 29% 33% 17% 16% 32% 12% 30% 13% 4% 20% 27% 7% 10% PHOTON-2 Molina JM. Lancet 2015;385:1098-1106 2

PHOTON-2 Study: SOF + RBV in HCV-HIV co-infection ARV-trial.com PHOTON-2 Study: SOF + RBV in HCV-HIV co-infection SVR12 (HCV RNA < 25 IU/ml), % (95% CI) SOF + RBV 24W SOF + RBV 12 W SOF + RBV 24 W % 88 (69-98) 89 (81-94) 85 (77-91) 91 91 84 (66-95) 100 89 83 83 86 75 50 25 N 112 100 11 25 19 6 106 57 49 31 All 1a 1b All Naïve Experienced All Naïve Experienced Genotype 4 Naïve Genotype 1 Naïve Genotype 2 Genotype 3 SVR12 not affected by the presence of cirrhosis, except in patients with genotype 1 PHOTON-2 Molina JM. Lancet 2015;385:1098-1106 3

PHOTON-2 Study: SOF + RBV in HCV-HIV co-infection Multivariate analysis of factors associated with SVR12 in genotype 1 OR (95% CI) p No cirrhosis 4.9 (1.42 to 16.86) 0.012 HCV RNA < 6 log10 IU/ml 34.35 (0.88 to 21.39) 0.07 PHOTON-2 Molina JM. Lancet 2015;385:1098-1106

PHOTON-2 Study: SOF + RBV in HCV-HIV co-infection Virologic failure GT1 naïve N = 112 GT2 N = 19 GT 2 experienced N = 6 GT 3 N = 57 N = 49 GT 4 N = 31 Virologic breakthrough 1 Relapse In treatment completers 12 (11%) 1 (5%) 1 (20%) 2 (4%) 5 (11%) 5 (16%) In treatment non completers 2 (33%) 2 (67%) 1 (100%) Deep sequencing of NS5B in 31 failures No emergence of S282T variant Low-levels of emergent variants, N = 2 1 virologic breakthrough, genotype 3a, L159F variant 1 with slow response, genotype 3a, L159N + S282N + V321A variants 2 patients (genotype 1, genotype 3a) with L159F at relapse PHOTON-2 Molina JM. Lancet 2015;385:1098-1106

PHOTON-2 Study: SOF + RBV in HCV-HIV co-infection Adverse events and laboratory abnormalities, N (%) GT 1, 3, 4 Naïve 24W N = 200 GT2 Naïve 12W N = 19 GT 2, 3 Experienced 24W N = 55 Discontinuation because of an AE 5 (3%) 1 (2%) Serious adverse event 10 (5%) 5 (9%) Adverse event ≥ 10% overall Fatigue 20% 60% Insomnia 18% 16% 9% Asthenia 5% Headache 13% Nausea 7% Diarrhea 12% Hemoglobin < 10 g/dl Grade 3-4 total bilirubin increased* 21% 19% * 83% on ATV/r PHOTON-2 Molina JM. Lancet 2015;385:1098-1106

PHOTON-2 Study: SOF + RBV in HCV-HIV co-infection ARV-trial.com PHOTON-2 Study: SOF + RBV in HCV-HIV co-infection Summary Patients co-infected with HIV and HCV genotypes 1-4 achieved high SVR12 with an interferon-free regimen of SOF plus RBV For treatment-naïve genotypes 1, 3, 4, SVR12 was 84-91% with 24 weeks of SOF + RBV Higher SVR12 in genotype 1b (91%) than in genotype 1a (84%) Presence of cirrhosis was a negative predictor of SVR12 only in genotype 1 patients For treatment-naïve genotype 2, SVR12 was 89% with 12 weeks of SOF + RBV For treatment-experienced genotypes 2 and 3, SVR12 was 83-86% with 24 weeks of SOF + RBV Compared to studies in HCV mono-infection, HIV co-infection does not have a negative effect on response to SOF-based therapy Unclear clinical relevance of NS5B variants emerging at failure PHOTON-2 Molina JM. Lancet 2015;385:1098-1106 7