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Simeprevir Plus PegIFN/RBV Yields 74% SVR12 in HCV/HIV Patients
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CROI 2014, March 3-6, 2014, Boston
Mark Mascolini
Simeprevir, a once-daily HCV NS3/4A protease inhibitor, yielded a sustained virologic response for 12 weeks after treatment ended (SVR12) in 74% of HCV/HIV-coinfected people when combined with pegylated interferon plus ribavirin (PR) in an international phase 3 open-label trial [1]. This SVR12, noted principal investigator Douglas Dieterich (Mount Sinai, New York), is equivalent to that achieved by people infected with HCV alone.
Active against HCV genotypes 1, 2, 4, 5, and 6, simeprevir (TMC435) is the first once-daily HCV protease inhibitor licensed as part of a regimen containing PR for genotype 1-infected adults with compensated liver disease, including cirrhosis.
Study C212 combined simeprevir with PR in HCV genotype 1 patients with HIV 1. Study participants could be treatment naive or relapsers. Everyone received simeprevir plus PR for 12 weeks. Noncirrhotic treatment-naive people and prior relapsers received response-guided PR for 24 or 48 weeks. All prior partial or null responders and people with cirrhosis got PR for 48 weeks. Study participants could take lamivudine, emtricitabine, tenofovir, abacavir, rilpivirine, enfuvirtide, raltegravir, or maraviroc. Primary endpoints were SVR12, safety, and tolerability.
The trial involved 106 people: 53 were naive to HCV therapy, 15 relapsers, 10 partial responders, and 28 null responders. Overall, 82% of participants were white and 14% black. Median age stood at 48 years and median HCV RNA at 7 log10 IU/mL. Most patients, 82%, had HCV genotype 1a, 28% had the Q80K polymorphism, 27% had an IL28B CC genotype, and 13% had cirrhosis. Median baseline CD4 count stood at 629, 88% of participants took antiretrovirals, and 89% had a viral load below 200 copies.
Overall SVR12 in the intention-to-treat population was 74%. SVR12 stood at 79% in treatment-naive people, 87% in relapsers, 70% partial responders, and 57% in null responders. Among people who met criteria for 24 weeks of treatment, SVR12 was 87% overall, 88% in treatment-naive people, and 85% in relapsers.
While 96% of participants with the IL28B CC genotype attained SVR12, 68% with the CT genotype and 61% with the TT genotype did so. Three quarters of antiretroviral-treated people achieved SVR12, compared with 62% of those not taking antiretrovirals. Baseline CD4 count above or below 500 did not affect SVR12 overall. Everyone with an undetectable viral load maintained virologic suppression through HCV therapy.
The safety profile of the regimen was similar to that seen in HCV patients without HIV, and rates of grade 3 or 4 adverse events or serious adverse events were similar in people taking or not taking antiretrovirals. Six people (5.7% of 106) had a serious adverse event in the first 12 weeks of treatment, and 10 (9.4%) had a serious adverse event during the entire treatment phase. Four people stopped simeprevir because of serious adverse event. Neutropenia developed in 37 people (35%) throughout treatment. Only 2 of 105 people had grade 3 hemoglobin or bilirubin abnormalities. No one had grade 3 or 4 rash or pruritus.
The researchers concluded that baseline characteristics--including fibrosis score, HCV genotype 1 subtype, Q80K polymorphism, IL28B genotype, and baseline CD4 count--did not affect SVR12 with this regimen.
Reference
1. Dieterich D, Rockstroh JK, Orkin C, et al. Simeprevir (TMC435) plus pegIFN/ribavirin in HCV genotype-1/HIV-1 coinfection (study C212). CROI 2014. Conference on Retroviruses and Opportunistic Infections. March 3-6, 2014. Boston. Abstract 24.
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