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Sofosbuvir/Velpatasvir Yields 95% SVR12 in Patients With HCV/HIV
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21st International AIDS Conference (AIDS 2016), July 18-22, 2016, Durban, South Africa
Mark Mascolini
Among HCV/HIV-coinfected people taking coformulated sofosbuvir/velpatasvir (SOF/VEL) for 12 weeks, 95% attained a sustained virologic response 12 weeks after treatment stopped (SVR12) in the ASTRAL-5 trial [1]. Everyone with compensated cirrhosis reached SVR12 with SOL/VEL.
A once-daily fixed-dose formulation containing 400 mg of SOF, an HCV nucleotide polymerase inhibitor, and 100 mg of VEL, an HCV NS5A inhibitor, is in late stages of development. ASTRAL-5, a US single-arm multicenter phase 3 trial in HCV patients coinfected with HIV, aimed to assess safety and efficacy of SOF/VEL in people with HCV genotypes 1 through 6. Participants could have tried previous anti-HCV regimens or could be naive to anti-HCV therapy. All had to be taking a stable antiretroviral regimen for at least 8 weeks, have a CD4 count of 100 or higher, and have an HIV load below 50 copies. They could be taking a nonnucleoside, a protease inhibitor, or an integrase inhibitor with tenofovir/emtricitabine or abacavir/lamivudine.
The 106 study participants averaged 52 years in age (range 25 to 72), 86% were men, and 45% black. Nineteen participants (18%) had compensated cirrhosis, 29% had anti-HCV treatment experience, and HCV load averaged 6.3 log10 IU/mL. Almost three quarters of enrollees had HCV genotype 1a or 1b. About half (47%) were taking an HIV protease inhibitor, 34% an integrase inhibitor, and 12% the nonnucleoside rilpivirine. Half (53%) were taking a regimen including tenofovir and ritonavir or cobicistat as a boosting agent.
Of the 106 study participants, 101 (95%) attained SVR12, and SVR12 rates did not vary much by HCV genotype. All 19 people with compensated cirrhosis reached SVR12, as did 30 of 31 (97%) with anti-HCV treatment experience. Twelve of 103 participants (12%) had pretreatment HCV NS5A resistance-associated mutations, and all 12 attained SVR12.
Nine people (9%) had grade 3 or 4 adverse events, and 2 (2%) had serious adverse events. Neither serious adverse event was attributed to study drugs. Two people (2%) stopped treatment because of adverse events. Nineteen participants (18%) had grade 3 or 4 lab abnormalities, including 8 cases of high bilirubin in people taking atazanavir. Creatinine clearance remained stable in people taking tenofovir regimens with or without a ritonavir or cobicistat booster.
The ASTRAL-5 investigators proposed that "SOL/VEL for 12 weeks provides a simple, safe, and highly effective treatment for patients coinfected with HIV-1 and HCV."
References
1. Brau N, Wyles D, Kottilil S, et al. Sofosbuvir/velpatasvir fixed dose combination for 12 weeks in patients co-infected with HCV and HIV-1: the phase 3 ASTRAL-5 study. 21st International AIDS Conference (AIDS 2016). July 18-22, 2016. Durban, South Africa. Abstract WEAB0301.
2. ClinicalTrials.gov. Efficacy and safety of sofosbuvir/velpatasvir fixed dose combination for 12 weeks in adults with chronic hepatitis C virus (HCV) and human immunodeficiency virus (HIV)-1 coinfection. ClinicalTrials.gov identifier NCT02480712. https://clinicaltrials.gov/ct2/show/NCT02480712
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