ION-4

ION-4 Study: LDV/SOF in HIV co-infection
Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1
Naggie S. N Engl J Med. 2015 Aug 20;373(8):705-13

Anti-HCV
Ledipasvir
Sofosbuvir
Genotype
1
1a
1b
Special population
HIV co-infection

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Design

  • Co-formulated ledipasvir-sofosbuvir (LDV 90mg/SOF 400 mg) : 1 pill QD
  • ARV regimens : FTC and TDF + EFV or RAL or RPV

Objective

  • Primary endpoint : SVR12 (HCV RNA < 25 IU/ml), with 2-sided 95% CI

Baseline characteristics and patient disposition

SVR12 (HCV RNA < 25 IU/ml), % (95% CI)


* 2 on-treatment failures (noncompliance) ; 1 lost to follow-up ; 10 relapses ; 1 death (IVDU-related endocarditis/sepsis)

SVR12 (HCV RNA < 25 IU/ml), % (95% CI)

  • Significantly lower response in black patients (p < 0.001)
  • Response similar in patients who had undergone previous treatment and those who had not, in patients receiving various concomitant HIV antiretroviral regimens

Virologic failure

  • 2 virologic breakthrough + 10 relapses
  • 10 relapses
    • All black
    • 7 had IL28B TT
    • 8 were on EFV

Multivariate analysis of factors associated with virologic relapse

Virologic resistance testing

  • Patients with genotype 1 : deep sequencing of NS5A at baseline : 59/325 (18% ) patients with NS5A variants (RAVs)
    • 55/59 (93%) achieved SVR12
    • 258/266 (97%) with no baseline NS5A RAVs achieved SVR12
  • 2 patients with virologic breakthrough : no baseline NS5A RAVs but emergence of NS5A RAVs at failure
  • 10 relapses: NS5A RAVs at baseline in 4, and in 8 at the time of relapse
  • No NS5B S282T in any patient at baseline or virologic failure

Adverse events, N (%)

  • Stable CD4 through treatment and follow-up; No patient had confirmed HIV rebound

Summary

  • In this Phase III study of 335 HIV/HCV- coinfected patients, 96% achieved SVR12 after 12 weeks of a once-daily, single-tablet regimen of LDV/SOF
    • Prior HCV treatment status or the presence or absence of cirrhosis did not impact outcome
    • In contrast to larger studies among monoinfected patients, a lower response rate was observed among coinfected black patients treated with LDV/SOF ( SVR12 : 90 %)
  • LDV/SOF was well tolerated, with no treatment discontinuations due to adverse events and no adverse impact on HIV disease or its treatment