Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1

N Engl J Med. 2015 Aug 20;373(8):705-13. doi: 10.1056/NEJMoa1501315. Epub 2015 Jul 21.

Abstract

Background: Effective treatment for hepatitis C virus (HCV) in patients coinfected with human immunodeficiency virus type 1 (HIV-1) remains an unmet medical need.

Methods: We conducted a multicenter, single-group, open-label study involving patients coinfected with HIV-1 and genotype 1 or 4 HCV receiving an antiretroviral regimen of tenofovir and emtricitabine with efavirenz, rilpivirine, or raltegravir. All patients received ledipasvir, an NS5A inhibitor, and sofosbuvir, a nucleotide polymerase inhibitor, as a single fixed-dose combination for 12 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy.

Results: Of the 335 patients enrolled, 34% were black, 55% had been previously treated for HCV, and 20% had cirrhosis. Overall, 322 patients (96%) had a sustained virologic response at 12 weeks after the end of therapy (95% confidence interval [CI], 93 to 98), including rates of 96% (95% CI, 93 to 98) in patients with HCV genotype 1a, 96% (95% CI, 89 to 99) in those with HCV genotype 1b, and 100% (95% CI, 63 to 100) in those with HCV genotype 4. Rates of sustained virologic response were similar regardless of previous treatment or the presence of cirrhosis. Of the 13 patients who did not have a sustained virologic response, 10 had a relapse after the end of treatment. No patient had confirmed HIV-1 virologic rebound. The most common adverse events were headache (25%), fatigue (21%), and diarrhea (11%). No patient discontinued treatment because of adverse events.

Conclusions: Ledipasvir and sofosbuvir for 12 weeks provided high rates of sustained virologic response in patients coinfected with HIV-1 and HCV genotype 1 or 4. (Funded by Gilead Sciences; ION-4 ClinicalTrials.gov number, NCT02073656.).

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Retroviral Agents / therapeutic use
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Benzimidazoles / adverse effects
  • Benzimidazoles / pharmacokinetics
  • Benzimidazoles / therapeutic use*
  • Drug Resistance, Viral
  • Drug Therapy, Combination
  • Female
  • Fluorenes / adverse effects
  • Fluorenes / pharmacokinetics
  • Fluorenes / therapeutic use*
  • Genotype
  • HIV Infections / complications*
  • HIV Infections / drug therapy
  • HIV-1*
  • Hepacivirus* / drug effects
  • Hepacivirus* / genetics
  • Hepacivirus* / isolation & purification
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • RNA, Viral / blood
  • Sofosbuvir
  • Uridine Monophosphate / adverse effects
  • Uridine Monophosphate / analogs & derivatives*
  • Uridine Monophosphate / pharmacokinetics
  • Uridine Monophosphate / therapeutic use
  • Viral Load

Substances

  • Anti-Retroviral Agents
  • Antiviral Agents
  • Benzimidazoles
  • Fluorenes
  • RNA, Viral
  • ledipasvir
  • Uridine Monophosphate
  • Sofosbuvir

Associated data

  • ClinicalTrials.gov/NCT02073656