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Original Investigation |

Sofosbuvir and Ribavirin for Hepatitis C in Patients With HIV Coinfection

Mark S. Sulkowski, MD1; Susanna Naggie, MD2; Jacob Lalezari, MD3; Walford Jeffrey Fessel, MD4; Karam Mounzer, MD5; Margaret Shuhart, MD6; Anne F. Luetkemeyer, MD7; David Asmuth, MD8; Anuj Gaggar, MD, PhD9; Liyun Ni, MS9; Evguenia Svarovskaia, PhD9; Diana M. Brainard, MD9; William T. Symonds, PharmD9; G. Mani Subramanian, MD, PhD9; John G. McHutchison, MD9; Maribel Rodriguez-Torres, MD10; Douglas Dieterich, MD11 ; for the PHOTON-1 Investigators
[+] Author Affiliations
1Viral Hepatitis Center, Johns Hopkins University, Baltimore, Maryland
2Duke Infectious Diseases, Duke University, Durham, North Carolina
3Clinical Research, Quest Clinical Research, San Francisco, California
4Internal Medicine, Kaiser Permanente, San Francisco, California
5Philadelphia FIGHT, Philadelphia, Pennsylvania
6Harborview Medical Center, University of Washington, Seattle
7Division of HIV/AIDS, San Francisco General Hospital, University of California, San Francisco
8Internal Medicine, University of California Davis Medical Center in Sacramento
9Liver Disease Therapeutic Area, Gilead Sciences, Foster City, California
10Fundacion De Investigacion San Juan, Puerto Rico
11Department of Medicine–Liver Diseases, Mount Sinai School of Medicine, New York, New York
JAMA. 2014;312(4):353-361. doi:10.1001/jama.2014.7734.
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Importance  Treatment of hepatitis C virus (HCV) infection in patients also infected with human immunodeficiency virus (HIV) has been limited due to drug interactions with antiretroviral therapies (ARTs) and the need to use interferon.

Objective  To determine the rates of HCV eradication (sustained virologic response [SVR]) and adverse events in patients with HCV-HIV coinfection receiving sofosbuvir and ribavirin treatment.

Design, Setting, and Participants  Open-label, nonrandomized, uncontrolled phase 3 trial conducted at 34 treatment centers in the United States and Puerto Rico (August 2012-November 2013) evaluating treatment with sofosbuvir and ribavirin among patients with HCV genotypes 1, 2, or 3 and concurrent HIV. Patients were required to be receiving ART with HIV RNA values of 50 copies/mL or less and a CD4 T-cell count of more than 200 cells/μL or to have untreated HIV infection with a CD4 T-cell count of more than 500 cells/μL. Of the treatment-naive patients, 114 had HCV genotype 1 and 68 had HCV genotype 2 or 3, and 41 treatment experienced participants who had been treated with peginterferon-ribavirin had HCV genotype 2 or 3, for a total of 223 participants.

Interventions  Treatment-naive patients with HCV genotype 2 or 3 received 400 mg of sofosbuvir and weight-based ribavirin for 12 weeks and treatment-naive patients with HCV genotype 1 and treatment-experienced patients with HCV genotype 2 or 3 received the same treatment for 24 weeks.

Main Outcomes and Measures  The primary study outcome was the proportion of patients with SVR (serum HCV <25 copies/mL) 12 weeks (SVR12) after cessation of HCV therapy.

Results  Among treatment-naive participants, 87 patients (76%) of 114 (95% CI, 67%-84%) with genotype 1, 23 patients (88%) of 26 with genotype 2 (95% CI, 70%-98%), and 28 patients (67%) of 42 with genotype 3 (95% CI, 51%-80%) achieved SVR12. Among treatment-experienced participants, 22 patients (92%) of 24 with genotype 2 (95% CI, 73%-99%) and 16 patients (94%) of 17 (95% CI, 71%-100%) achieved SVR12. The most common adverse events were fatigue, insomnia, headache, and nausea. Seven patients (3%) discontinued HCV treatment due to adverse events. No adverse effect on HIV disease or its treatment was observed.

Conclusions and Relevance  In this open-label, nonrandomized, uncontrolled study, patients with HIV who were coinfected with HCV genotype 1, 2, or 3 who received the oral, interferon-free combination of sofosbuvir and ribavirin for 12 or 24 weeks had high rates of SVR12. Further studies of this oral regimen in diverse populations of coinfected patients are warranted.

Trial Registration  clinicaltrials.gov Identifier: NCT01667731.

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Figure 1.
Flow Diagram of PHOTON-1 Patients

ART indicates antiretroviral therapy; HCV, hepatitis C virus; HIV, human immunodeficiency virus. aPatients could be excluded for more than 1 criterion. See eTable 12 in the Supplement. bPatient who did not receive the study treatment was not included in the efficacy analysis per protocol.

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Figure 2.
Rates of 12-Week Sustained Virologic Response by Subgroup in Treatment-Naive Patients With Hepatitis C Virus Genotype 1 Receiving 24 Weeks of Sofosbuvir and Ribavirin

The position of the solid squares indicates the rate of virologic response 12 weeks after the end of treatment for each subgroup; the horizontal lines indicate 95% confidence intervals. The vertical line represents the overall rate of sustained virologic response (SVR) for all patients with genotype 1. Body mass index is calculated as weight in kilograms divided by height in meters squared. ARV indicates antiretroviral therapy; NNRTI, nonnucleoside reverse transcriptase inhibitor; PI, protease inhibitor; SVR12, sustained virological response for 12 weeks; and ULN, upper limit of normal.

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