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Sofosbuvir With Ribavirin in Gt1/2/3 HCV/HIV Coinfected Patients
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CROI 2014, March 3-6, 2014, Boston
CROI: All-Oral Therapy With Sofosbuvir Plus Ribavirin For the Treatment of HCV Genotype 1, 2, and 3 Infection in Patients Co-infected With HIV (PHOTON-1) - (03/04/14)
CROI Webcast link:
http://www.croiwebcasts.org/console/player/22047?mediaType=slideVideo&
Mark Mascolini
Sofosbuvir, a direct-acting antiviral active against HCV genotypes 1 through 6, produced high 12- or 24-week sustained virologic responses (SVRs) in HCV-treatment-naive and experienced people with HIV coinfection [1].
A nucleotide HCV polymerase inhibitor, sofosbuvir has been licensed for treatment of chronic HCV infection in people with or without HIV. In people without HIV infection, sofosbuvir plus ribavirin has yielded high SVRs in people infected with HCV genotypes 1, 2, and 3. To test the efficacy and safety of this regimen in people with HIV, researchers conducted the PHOTON-1 study.
The trial had three arms. Arm GT1-N enrolled 114 HCV treatment-naive people with genotype 1 who took sofosbuvir plus ribavirin for 24 weeks. Arm GT2/3-N had 68 treatment-naive people with genotype 2 or 3 who took the same regimen for 12 weeks. In Arm GT2/3-E 41 treatment-experienced genotype 2 or 3 patients took sofosbuvir plus ribavirin for 24 weeks. Participants could have cirrhosis, with no platelet cutoff. They could be taking antiretrovirals (with a viral load below 50 copies and a CD4 count above 200) or not taking antiretrovirals (with a CD4 count above 500). The primary endpoint was SVR12, an undetectable load 12 weeks after treatment ends as measured by an assay with a lower limit of 25 IU/mL.
Across the three treatment groups, GT1-N, GT2/3-N, AND GT2/3-E, age averaged 48, 49, and 54; 82%, 81%, and 90% were men; and 32%, 12%, and 17% were black. Ninety people (79%) in the GT1-N arm had genotype 1a. Proportions with the favorable IL28B CC genotype was 27% in GT1-N, 37% in GT2/3-N, and 49% in GT2/3-E. Respective proportions with cirrhosis were 4%, 10%, and 24%, and proportions on antiretroviral therapy 98%, 90%, and 95%. Mean CD4 counts were 636, 585, and 658.
Discontinuations numbered 11 (10%) in arm GT1-N, 6 (9%) in GT2/3-N, and 1 (2%) in GT2/3-E. Respective withdrawals for adverse events were 3 (3%), 3 (4%), and 1 (2%). One person in GT1-N stopped treatment for lack of efficacy.
End-of-treatment (EOT), SVR12, and SVR24 among treatment-naive people were all 67% or higher:
-- Genotype 1 naive: EOT 100%, SVR12 76%, SVR24 75%
-- Genotype 2 naive: EOT 96%, SVR12 88%, SVR24 88%
-- Genotype 3 naive: EOT 98%, SVR12 67%, SVR24 67%
Among treatment-naive people, HCV virologic failure rates were 23% with genotype 1, 4% with genotype 2, and 29% with genotype 3. Respective relapse rates were 22%, 0%, and 29%.
Among treatment-experienced people, 92% with genotype 2 and 94% with genotype 3 attained SVR12. HCV virologic failure rates were 4% with genotype 2 and 6% with genotype 3 for treatment-experienced people. Respective relapse rates were 4% and 6%. Deep sequencing revealed no resistance mutations in people with virologic failure.
Grade 3 or 4 adverse events arose in 10% of patients treated for 12 weeks and in 12% treated for 24 weeks. Respective serious adverse event rates were 7% and 6% and discontinuations for adverse events 4% and 3%. There was one death, a suicide, in a person with a history of depression who was being treated for attention deficit hyperactivity disorder and insomnia.
Grade 3 or 4 lab abnormalities arose in 12% of people treated for 12 weeks and 21% treated for 24 weeks. Hemoglobin levels below 10 mg/dL were recorded in 10% treated for 12 weeks and 17% treated for 24 weeks. But one only 1 person in each treatment duration group had a hemoglobin below 8.5 mg/dL.
Two people had transient HIV RNA breakthroughs, both with documented nonadherence to their antiretrovirals. CD4 percent did not drop with treatment. Absolute CD4 counts did fall, probably reflecting the well-appreciated lymphocyte decline with ribavirin.
Reference
1. Naggie S, Sulkowski M, Lalezari J, et al. Sofosbuvir plus ribavirin for HCV genotype 1-3 infection in HIV coinfected patients (PHOTON-1). CROI 2014. Conference on Retroviruses and Opportunistic Infections. March 3-6, 2014. Boston. Abstract 26.
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