Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1
Susanna Naggie, Curtis Cooper, Michael Saag, Kimberly Workowski, Peter Ruane, William J Towner, Kristen Marks, Anne Luetkemeyer, Rachel P Baden, Paul E Sax, Edward Gane, Jorge Santana-Bagur, Luisa M Stamm, Jenny C Yang, Polina German, Hadas Dvory-Sobol, Liyun Ni, Phillip S Pang, John G McHutchison, Catherine A M Stedman, Javier O Morales-Ramirez, Norbert Bräu, Dushyantha Jayaweera, Amy E Colson, Pablo Tebas, David K Wong, Douglas Dieterich, Mark Sulkowski, ION-4 Investigators, Curtis Cooper, Mark Hull, Marina Klein, David Wong, Emmanuelle Huchet, Edward Gane, Catherine Stedman, David Asmuth, Norbert Brau, Raymond Chung, Eric Daar, Craig Dietz, Robin Henry Dretler, Richard Elion, W J Fessel, Joseph C Gathe, Eliot Godofsky, Federico Hinestrosa, Gregory Huhn, Mamta Jain, Dushyantha Jayaweera, Jay Lalezari, Charles Landis, Cynthia Mayer, Javier O Morales-Ramirez, Karam Mounzer, Bruce S Rashbaum, Peter J Ruane, Jorge L Santana-Bagur, Paul Edward Sax, Richard Sterling, Mark Sulkowski, Melanie A Thompson, Chia Wang, Kimberly Workowski, Benjamin Young, Maurizio Bonacini, Donald Kotler, Anthony Mills, William J Towner, David A Wohl, David Wyles, Kristen Marks, Rachel Baden, Philip M Grant, Michael Saag, Laura Salazar, Meena Bansal, Amy Colson, Joel E Gallant, Marc Siegel, Susanna Naggie, Annie Luetkemeyer, Karen T Tashima, Kenneth Sherman, Jason Flamm, Fritz Bredeek, Pablo Tebas, David A Wheeler, Timothy Friel, Susanna Naggie, Curtis Cooper, Michael Saag, Kimberly Workowski, Peter Ruane, William J Towner, Kristen Marks, Anne Luetkemeyer, Rachel P Baden, Paul E Sax, Edward Gane, Jorge Santana-Bagur, Luisa M Stamm, Jenny C Yang, Polina German, Hadas Dvory-Sobol, Liyun Ni, Phillip S Pang, John G McHutchison, Catherine A M Stedman, Javier O Morales-Ramirez, Norbert Bräu, Dushyantha Jayaweera, Amy E Colson, Pablo Tebas, David K Wong, Douglas Dieterich, Mark Sulkowski, ION-4 Investigators, Curtis Cooper, Mark Hull, Marina Klein, David Wong, Emmanuelle Huchet, Edward Gane, Catherine Stedman, David Asmuth, Norbert Brau, Raymond Chung, Eric Daar, Craig Dietz, Robin Henry Dretler, Richard Elion, W J Fessel, Joseph C Gathe, Eliot Godofsky, Federico Hinestrosa, Gregory Huhn, Mamta Jain, Dushyantha Jayaweera, Jay Lalezari, Charles Landis, Cynthia Mayer, Javier O Morales-Ramirez, Karam Mounzer, Bruce S Rashbaum, Peter J Ruane, Jorge L Santana-Bagur, Paul Edward Sax, Richard Sterling, Mark Sulkowski, Melanie A Thompson, Chia Wang, Kimberly Workowski, Benjamin Young, Maurizio Bonacini, Donald Kotler, Anthony Mills, William J Towner, David A Wohl, David Wyles, Kristen Marks, Rachel Baden, Philip M Grant, Michael Saag, Laura Salazar, Meena Bansal, Amy Colson, Joel E Gallant, Marc Siegel, Susanna Naggie, Annie Luetkemeyer, Karen T Tashima, Kenneth Sherman, Jason Flamm, Fritz Bredeek, Pablo Tebas, David A Wheeler, Timothy Friel
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.).
Source: PubMed