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

Susanna Naggie1, Curtis Cooper, Michael Saag

  • 1From Duke Clinical Research Institute, Durham, NC (S.N.); University of Ottawa, the Ottawa Hospital, Ottawa (C.C.), and Department of Hepatology, Immunodeficiency Clinic, Toronto General Hospital, University of Toronto, Toronto (D.K.W.) - both in Canada; University of Alabama at Birmingham, Birmingham (M. Saag); Emory University, Emory Healthcare, Atlanta (K.W.); Ruane Medical and Liver Health Institute (P.R.) and Kaiser Permanente Los Angeles Medical Center (W.J.T.), Los Angeles, University of California, San Francisco, San Francisco General Hospital, San Francisco (A.L.), and Gilead Sciences, Foster City (L.M.S., J.C.Y., P.G., H.D.-S., L.N., P.S.P., J.G.M.) - all in California; Weill Cornell Medical College (K.M.), Icahn School of Medicine at Mount Sinai (N.B., D.D.), New York, and James J. Peters Veterans Affairs Medical Center, Bronx (N.B.) - all in New York; Beth Israel Deaconess Medical Center (R.P.B.), Brigham and Women's Hospital and Harvard Medical School (P.E.S.), and Community Research Initiative of New England (A.E.C.) - all in Boston; University of Auckland, Auckland City Hospital, Auckland (E.G.), and Christchurch Hospital and University of Otago, Christchurch (C.A.M.S.) - both in New Zealand; University of Puerto Rico School of Medicine (J.S.-B.) and Clinical Research Puerto Rico (J.O.M.-R.) - both in San Juan; University of Miami, Miami (D.J.); University of Pennsylvania, Philadelphia (P.T.); and Johns Hopkins University School of Medicine, Baltimore (M. Sulkowski).

The New England Journal of Medicine
|July 22, 2015
PubMed

Insights

Ledipasvir and sofosbuvir effectively treated hepatitis C virus (HCV) in patients with HIV-1 coinfection. This 12-week regimen achieved high sustained virologic response rates without impacting HIV-1 viral load.

Area of Science:

  • Infectious Diseases
  • Hepatology
  • Virology

Background:

  • Hepatitis C virus (HCV) coinfection with human immunodeficiency virus type 1 (HIV-1) presents significant treatment challenges.
  • Developing effective therapeutic strategies for this population is a critical unmet medical need.

Purpose of the Study:

  • To evaluate the efficacy and safety of a 12-week treatment regimen of ledipasvir and sofosbuvir in patients coinfected with HIV-1 and HCV genotypes 1 or 4.
  • To assess the sustained virologic response rate at 12 weeks post-treatment.

Main Methods:

  • A multicenter, single-group, open-label study was conducted.
  • Patients received a 12-week fixed-dose combination of ledipasvir (NS5A inhibitor) and sofosbuvir (nucleotide polymerase inhibitor).
  • Patients were on a stable antiretroviral regimen including tenofovir and emtricitabine with efavirenz, rilpivirine, or raltegravir.

Main Results:

  • An overall sustained virologic response rate of 96% was observed at 12 weeks post-therapy.
  • High response rates were consistent across HCV genotypes 1a, 1b, and 4, irrespective of prior treatment or cirrhosis.
  • No confirmed HIV-1 virologic rebound occurred, and treatment was well-tolerated with no discontinuations due to adverse events.

Conclusions:

  • Ledipasvir and sofosbuvir combination therapy for 12 weeks is highly effective for treating HCV genotypes 1 and 4 in patients coinfected with HIV-1.
  • The regimen demonstrates excellent safety and tolerability, maintaining HIV-1 viral suppression.
  • This treatment offers a promising option for managing HCV in the HIV-1 coinfected population.
Abstract

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