WASHINGTON – Early studies show that a new, combined antiviral regimen seems to suppress hepatitis C viremia while keeping HIV viremia stable in coinfected patients.
Dr. Joseph Eron presented phase II data from 63 patients who were enrolled in TURQUOISE-I. A total of 94% (59/63) of patients achieved a sustained virologic response (SVR) 12 weeks after completing 12 weeks of therapy, and 61 of 63 patients achieved an SVR 4 weeks after completing 12 or 24 weeks of therapy, Dr. Eron reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
Alicia Ault/Frontline Medical News
Dr. Joseph Eron
The regimen included ABT-450 (an NS3-4A protease inhibitor that was identified by AbbVie and Enanta), which was combined with ritonavir and ombitasvir (another AbbVie drug, also known as ABT-267) into a single tablet, plus dasabuvir (ABT-333) and ribavirin. Ombitasvir is an NS5A inhibitor and dasabuvir is a non-nucleoside NS5B polymerase inhibitor.
To be included in TURQUOISE-I, patients have to be aged 18-70 years; be treatment naive or have previous pegylated interferon/ribavirin treatment experience; have hepatitis C virus (HCV) genotype 1 infection; have plasma HIV-1 RNA less than 40 copies/mL; and be taking a stable, qualifying HIV-1 antiretroviral therapy regimen, said Dr. Eron, a professor of medicine at the University of North Carolina, Chapel Hill.
Patients with cirrhosis are not excluded, but will not be enrolled if they have had prior therapy with direct-acting antivirals for HCV, or any current or past clinical evidence of liver decompensation.
All patients will be followed for 48 weeks after therapy is stopped. Thirty-one patients were given therapy for 12 weeks and then assessed for SVR at 12 weeks. Thirty-two patients were given therapy for 24 weeks and assessed 4 weeks later. Patients also were evaluated for end-of-treatment response, on-treatment virologic failure, and post-treatment HCV viral relapse.
At baseline, 59 patients in each arm were male, and 16 were African American. The mean age was 51 years. Six patients in each arm (19%) had cirrhosis. A high proportion in each arm (53/63 in the 12-week and 49/63 in the 24-week arm) had the interleukin-28B genotype, which is known to indicate a much harder-to-treat disease, Dr. Eron said.
At the end of treatment, only one patient in each arm was not responsive. Four weeks post therapy, 29 of 31 patients in the 12-week arm and 31 of 32 patients in the 24-week arm had an SVR.
Two patients had virologic failure. Both had been unresponsive to previous therapies, and both had the IL-28B genotype and resistance-associated variants at the time of failure.
No patient withdrew because of adverse events, but about 90% (57/63) experienced some side effect, with the most common being fatigue and insomnia. Six patients had to reduce their ribavirin dose because of a decline in hemoglobin levels, but they were still responsive to therapy. Five patients had a confirmed increase in HIV RNA higher than 40 copies/mL, but not above 200 copies/mL, said Dr. Eron. And all the patients remained suppressed on the same HIV regimen and without interrupting their HCV therapy, he said.
Soon, a cohort of patients on stable darunavir antiretroviral therapy will be enrolled and given the three-drug HCV regimen for 12 weeks. The full global TURQUOISE study will begin later in 2014, Dr. Eron said.
The study was sponsored by AbbVie. Dr. Eron received grant and research support from, and/or served as a consultant to, AbbVie, Bristol-Myers Squibb, and other companies. Other authors had numerous additional disclosures.
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