Sofosbuvir-Velpatasvir in HIV-HCV Coinfected Patients ASTRAL-5

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Presentation transcript:

Sofosbuvir-Velpatasvir in HIV-HCV Coinfected Patients ASTRAL-5 Phase 3 Treatment Naïve & Experienced HIV Coinfection Sofosbuvir-Velpatasvir in HIV-HCV Coinfected Patients ASTRAL-5 Wyles D, et al. Clin Infect Dis. 2017 March 29. [Epub ahead of print]

Sofosbuvir-Velpatasvir in HIV-HCV Coinfected Patients ASTRAL-5: Study Features ASTRAL-5 Trial Design: Single-arm, open-label, multicenter, phase 3 trial of sofosbuvir- velpatasvir in HIV-HCV coinfected treatment-naïve and treatment- experienced patients with genotypes 1-6 HCV Setting: Multiple sites in US Entry Criteria - Chronic HCV GT 1-6 - Age ≥18 years - HIV coinfection and on stable ART for ≥ 8 weeks - CD4 count ≥100 cells/mm3 and HIV RNA ≤50 copies/mL - On stable ART for ≥ 8 weeks - Prior treatment failure allowed (but no prior NS5A or NS5B) - Patients with compensated cirrhosis allowed Primary End-Point: SVR12 Source: Wyles D, et al. Clin Infect Dis. 2017 March 29. [Epub ahead of print]

Sofosbuvir-Velpatasvir Sofosbuvir-Velpatasvir in HIV-HCV Coinfected Patients ASTRAL-5: Study Design Week 12 24 HIV-HCV Coinfected Treatment-naïve & experienced GT 1, 2, 3, 4, or 6 Sofosbuvir-Velpatasvir n =106 SVR12 Drug Dosing: Sofosbuvir-velpatasvir (400/100 mg): fixed-dose combination; one pill once daily Source: Wyles D, et al. Clin Infect Dis. 2017 March 29. [Epub ahead of print]

Sofosbuvir-Velpatasvir (N=106) Sofosbuvir-Velpatasvir in HIV-HCV Coinfected Patients ASTRAL-5: Participants Baseline Characteristic Sofosbuvir-Velpatasvir (N=106) Age, mean, years (range) 54 (25-72) Male, n (%) 91 (86) Black race, n (%) 48 (45) HCV genotype, n (%) 1a 1b 2 3 4 66 (62) 12 (11) 11 (10) 5 (5) IL28B non-CC, n (%) 82 (77) Mean HCV RNA, log10 IU/ml (range) 6.3 (5.0-7.4) Cirrhosis, n (%) 19 (18) Treatment experienced, n (%) 31 (29) Source: Wyles D, et al. Clin Infect Dis. 2017 March 29. [Epub ahead of print]

Sofosbuvir-Velpatasvir (N=106) Sofosbuvir-Velpatasvir in HIV-HCV Coinfected Patients ASTRAL-5: Participants HIV Baseline Characteristics Sofosbuvir-Velpatasvir (N=106) Mean CD4 cell count, (range) 598 (183-1513) Nucleos(t)ide pair TDF with boosted agent (RTV or Cobi) TDF without boosted agent Abacavir-lamivudine 56 (53) 35 (33) 15 (14) Other antiretroviral agent(s) PI (DRV, LPV or ATV) NNRTI (RPV) Integrase inhibitor (RAL or EVG) Other (>1 of above classes) 50 (47) 13 (12) 36 (34) 7 (7) Abbreviations: TDF = Tenofovir disoproxil fumarate; RTV = ritonavir; Cobi = cobicistat; PI = HIV protease inhibitor; DRV = darunavir; LPV = lopinavir; ATV = atazanavir; PRV = rilpivirine; RAL = raltegravir; EVG = elvitegravir Source: Wyles D, et al. Clin Infect Dis. 2017 March 29. [Epub ahead of print]

Sofosbuvir-Velpatasvir in HIV-HCV Coinfected Patients ASTRAL-5: Results ASTRAL-5: SVR12 Results by Genotype 101/106 63/66 11/12 11/11 11/12 5/5 Source: Wyles D, et al. Clin Infect Dis. 2017 March 29. [Epub ahead of print]

Sofosbuvir-Velpatasvir in HIV-HCV Coinfected Patients ASTRAL-5: Results ASTRAL-5: SVR12 Results by Genotype 2 Relapses 1 LTFU 1 LTFU 1 Withdrew Consent 101/106 63/66 11/12 11/11 11/12 5/5 Source: Wyles D, et al. Clin Infect Dis. 2017 March 29. [Epub ahead of print]

Sofosbuvir-Velpatasvir in HIV-HCV Coinfected Patients ASTRAL-5: Results ASTRAL-5: SVR12 Results by Cirrhosis & Treatment Experience 101/106 71/75 30/31 82/87 19/19 210/218 139/144 42/44 27/28 Treatment Experience Cirrhosis Status Source: Wyles D, et al. Clin Infect Dis. 2017 March 29. [Epub ahead of print]

Sofosbuvir-Velpatasvir in HIV-HCV Coinfected Patients ASTRAL-5: Resistance Baseline NS5A Resistance-Associated Variants and SVR12 Total, n = 103 100 98% SVR12 100% SVR12 90 80 70 88% No NS5A RAVs 90/103 13% NS5A RAVs 13/103 SVR12 (%) 60 50 40 30 20 10 88/90 13/13 83/86 58/65 24/25 104/104 Source: Wyles D, et al. Clin Infect Dis. 2017 March 29. [Epub ahead of print] 9

Sofosbuvir-Velpatasvir (N=106) Sofosbuvir-Velpatasvir in HIV-HCV Coinfected Patients ASTRAL-5: Adverse Events Adverse Event (AE), n (%) Sofosbuvir-Velpatasvir (N=106) Discontinuation due to AE 2 (2) Serious AEs Deaths Any AE in >5% of patients Fatigue Headache Arthralgia Upper respiratory tract infection Diarrhea Insomnia Nausea 26 (25) 14 (13) 9 (8) 7 (7) The majority of AEs were mild in severity (grade 1 or 2). No patient with confirmed on-treatment HIV virologic breakthrough. Source: Wyles D, et al. Clin Infect Dis. 2017 March 29. [Epub ahead of print]

Sofosbuvir-Velpatasvir in HIV-HCV Coinfected Patients ASTRAL-5: Conclusions Conclusions: “Sofosbuvir-velpatasvir for 12 weeks was safe and provided high rates of SVR12 in patients coinfected with HCV and HIV-1.” Source: Wyles D, et al. Clin Infect Dis. 2017 March 29. [Epub ahead of print]