BOSTON — A simeprevir-containing regimen with pegylated interferon and ribavirin was associated with similar safety outcomes in patients with hepatitis C virus/HIV coinfection as those previously reported in patients with hepatitis C virus monoinfection, according to findings presented here.
Douglas Dieterich, MD, professor of medicine and liver diseases at Icahn School of Medicine at Mount Sinai Hospital, presented data from an ongoing phase 3, open-label trial investigating simeprevir (Olysio, Janssen) plus pegylated interferon and ribavirin in both treatment-naive and treatment-experienced patients with HCV genotype 1 and HIV.
Eligible participants received 150 mg simeprevir once daily for 12 weeks plus pegylated interferon for 24 weeks and ribavirin for 48 weeks. Clinicians treated non-cirrhotic, treatment-naive individuals, along with those who had a previous relapse, in a response-guided regimen of pegylated interferon and ribavirin for 24 or 48 weeks. Cirrhotic individuals and those who had a previous partial or null response received this therapy for 48 weeks.
Twelve-week sustained virologic response (SVR) served at the primary outcome measure. The researchers evaluated this endpoint in subgroups, including those with genotype 1a or 1b disease, by Metavir score and by concomitant antiretroviral therapy. HIV virologic response and safety served as secondary outcome measures. The researchers also compared 12-week responses in treatment-naive patients and previous null responders with historic controls using a predefined single-sided z-test.
The cohort was 84.9% male, 82.1% white and 14.2% black. The median patient age was 48 years, and patients had median baseline absolute CD4+ counts of 628.5/mm3, median baseline log HIV RNA of 4.18 copies/mL (including patients not receiving ART).
HCV genotype 1a was reported in 82.1% of the cohort, while 12.3% were cirrhotic and 87.7% were receiving ART (98.9% were receiving nucleoside reverse transcriptase inhibitors, 87.1% were receiving integrase inhibitors and 15.1% were receiving non-nucleoside reverse transcriptase inhibitors), according to the findings.
The overall 12-week SVR rate was 73.6%. Treatment-naive patients experienced a 79.3% 12-week response rate, whereas patients with a previous relapse responded at 86.7%; prior partial responders at 70%; and prior null responders at 57.1%.
Despite low patient numbers, the investigators said the response rates were high in subgroups.
Among nine patients with Metavir score of F4, seven (77.8%) achieved a 12-week SVR.
The investigators defined HIV virologic failure as confirmed HIV RNA of at least 200 copies/mL. This rate was 2.2% (two of 93 patients) among patients receiving ART. This endpoint occurred in one patient at 36 weeks and in another patient at 48 weeks after completion of simeprevir regimen.
Simeprevir plus pegylated interferon and ribavirin was associated with a 33% rate of grade 3 or 4 adverse events. This treatment yielded serious adverse events in 5.7% of patients and a discontinuation rate of simeprevir in 3.8%. Most of the discontinuations occurred together with interferon and ribavirin, according to the results.
ART was associated with a 35.5% rate of grade 3 or 4 adverse events, a 6.5% rate of serious events and a 4.3% discontinuation rate.
“[Simeprevir] with [pegylated interferon and ribavirin] was well tolerated when co-administered with ART and did not impact HIV treatment outcome,” the researchers concluded.
“The Q80k polymorphism made no difference in SVR rates,” Dieterich said. “Side effect profiles were similar for the coinfected and monoinfected groups.”
For more information:
Dieterich D. Abstract #24. Presented at: CROI 2014; March 3-6, 2014; Boston.
Disclosure: Dieterich reports associations with companies that include AbbVie, Achillion Pharmaceuticals, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, Gilead Sciences, Idenix Pharmaceuticals and Merck.