ASTRAL-5 study: SOF/VEL in HIV coinfection

 Design
Open-label W12

> 18 years
Chronic HCV infection
Genotype 1-6
Naïve or pre-treatment
with IFN-based regimen
Compensated cirrhosis allowed* N = 106 SOF/VEL
Chronic HIV infection 400/100 mg QD SVR12
Stable ART ≥ 8 weeks,
CD4 ≥ 100/mm3,
HIV RNA ≤ 50 c/ml
eDFG (Cockcroft-Gault) > 60 ml/min
No HBV co-infection

* Metavir F4 or Ishak 5-6 or Fibroscan > 12.5 kPa

or Fibrotest > 0.75 and APRI > 2

 Objective
– SVR12 (HCV RNA < 15 IU/ml), by ITT with two-sided 95% CI (≤ 5.9% in both
directions from an expected SVR12 of 90%)
ASTRAL-5 Wyles D, Clin Infect Dis 2017 ; 65 :6-12
 ASTRAL-5 study: SOF/VEL in HIV coinfection

Baseline characteristics
SOF/VEL
N = 106
Mean age, years 54
Female, % 14
Race: Black, % 45
Mean BMI, kg/m² 27.2
Genotype: 1a / 1b / 2 / 3 / 4 (%) 62 / 11 / 10 / 11 / 5
Mean HCV RNA, log10 IU/ml 6.3
IL28B CC, % 23
Cirrhosis, % 18
HCV treatment naïve, (%) 71
Mean CD4 count, cells/µl 598
Antiretroviral therapy, %
NRTI backbone: TDF-based / ABC-based 86 / 14
PI (DRV, LPV or ATV) / NNRTI (RPV) / II (RAL or EVG) 47 / 12 / 34
Other ARVs (> 1 of the above classes) 7

ASTRAL-5 Wyles D, Clin Infect Dis 2017 ; 65 :6-12

 ASTRAL-5 study: SOF/VEL in HIV coinfection

SVR12 overall, by genotype and by cirrhosis or prior treatment, % (95% CI), ITT
% 100 10
95.3 95 92 (72-100) 92 (48-100) 100
100 (89-99) (87-99 93 96 94
(62-100) (62-100)

80
2 relapses
2 lost to follow-up
60 1 withdrew consent

2 relapse 1 relapse
40 1 lost to follow-up 1 lost to follow-up
1 withdrew 1 withdrew consent
1 lost to consent
1 relapse
20 follow-up 1 lost to follow-up

N= 106 66 12 11 12 5 87 19 75 31
0
Total 1a 1b 2 3 4 No Yes Yes No
Genotype Cirrhosis Treatment-naïve
 No impact of baseline NS5A RAVs: all 13 patients with baseline NS5A RASs
(cutoff 15%) achieved SVR12

ASTRAL-5 Wyles D, Clin Infect Dis 2017 ; 65 :6-12

 ASTRAL-5 study: SOF/VEL in HIV coinfection

Adverse events, %
N = 106
Any adverse event 71
Grade 3-4 AE 8
2 (acute radial nerve palsy,
Serious AE
toe infection/sepsis)
Discontinuation due to adverse event 2
Death 0
Grade 3 or 4 laboratory abnormality 18
Most common adverse events, %
Fatigue 25
Headache 13
Arthralgia 8
Upper respiratory tract infection 8
Diarrhea 8
Insomnia 7
Nausea 7

No HIV rebound
ASTRAL-5 Wyles D, Clin Infect Dis 2017 ; 65 :6-12
 ASTRAL-5 study: SOF/VEL in HIV coinfection

Laboratory abnormalities, %
N = 106
Neutrophils, 500-750/mm3 2
INR > 2 x ULN 1
ASAT > 10 x ULN 1
Creatinine kinase < 10 x ULN 2
Creatinine > 3 mg/dl 1
Lipase > 3 x ULN 1
Hypophosphatemia < 1 mg/dl 1
Hyperglycemia > 250 mg/dl 2
Hyperbilirubinemia > 2.5 x ULN 8
Hyperuricemia < 1 mg/dl 1
Hematuria > 75 red blood cells/high powered field 8
Urine blood, 3+ 1
Glycosuria, 4+ 2
3 patients, all receiving TDF-containing regimens, had a change from baseline of ≥ 0.4 mg/dl in serum
creatinine while on treatment
CD4+ counts remained stable and no patient experienced HIV virologic rebound

ASTRAL-5 Wyles D, Clin Infect Dis 2017 ; 65 :6-12

 ASTRAL-5 study: SOF/VEL in HIV coinfection

 Summary

– SOF/VEL for 12 weeks resulted in overall 95% SVR12 in HIV

coinfected patients
• 100% SVR12 in patients with cirrhosis

• 96% SVR12 in patients with prior failure to HCV therapy

– Presence of baseline RAVs did not impact efficacy

– Treatment was safe and well tolerated, including with TDF-based
boosted regimens
– In conclusion, SOF/VEL for 12 weeks provides a simple, safe,
and highly effective treatment for patients coinfected with HCV
and HIV-1

ASTRAL-5 Wyles D, Clin Infect Dis 2017 ; 65 :6-12