ALLY-2: Daklinza/Sovaldi effective in HCV patients with HIV, cirrhosis

WASHINGTON — Combination therapy with Daklinza and Sovaldi yielded an overall 97% 12-week sustained viral response rate in a broad cross-section of patients with HCV.

Kenneth E. Sherman, MD, PhD, of the University of Cincinnati College of Medicine, and colleagues investigated Sovaldi (sofosbuvir, Gilead Sciences) 400 mg and Daklinza (daclatasvir, Bristol Myers Squibb) 60 mg (which was dose adjusted for concomitant combination antiretroviral therapy [cART]: 30 mg with ritonavir-boosted protease inhibitors, 90 mg with non-nucleoside reverse transcriptase inhibitors except rilpivirine [Edurant, Janssen Therapeutics]) in patients coinfected with HIV/HCV coinfection.

“HCV is accelerated in coinfected populations,” Sherman said. “Effective treatment has to be compatible with cART.”

The study included 203 patients with genotypes 1 through 4 HCV. There were 101 treatment-naïve patients treated for 12 weeks, 50 treatment-naïve patients treated for 8 weeks and 52 treatment-experienced patients treated for 12 weeks.

“Prior NS5A inhibitor exposure was prohibited,” Sherman said.

Eligible participants had HIV RNA less than 50 copies/mL and CD4 cell counts greater than 100 cells/mm³ or if not on antiretroviral therapy, their CD4 cell count was greater than 350 cells/mm³.

The researchers evaluated patients for 12-week sustained virologic response (SVR12).

Results indicated that 97% of treatment-naive patients and 98% of treatment-experienced patients treated for 12 weeks reached SVR12, while 76% of naive patients treated for 8 weeks reached this endpoint.

Among patients with genotype 1 disease, SVR12 rates were nearly identical, with 96% of naïve patients treated for 12 weeks, 98% of experienced patients treated for 12 weeks and 76% of patients treated for 8 weeks reaching this endpoint.

Two patients in the combined 12 week groups (treatment-naive and -experienced) and 10 patients in the 8-week arm relapsed, according to Sherman.

“We saw a slight decrease in response in patients with cirrhosis,” Sherman said. The sample size of this group was relatively small. “Virtually nothing else showed up as a factor in response.”

He added, however, that a slightly lower response was reported among patients receiving darunavir for HIV in the 8 week arm. Sherman noted that pharmacokinetic studies suggest that higher doses of daclatasvir may be utilized in darunavir-treated patients in the future, which might improve response rates in the 8-week regimens.

Baseline NS5A resistance-associated variants (RAVs) did not appear to impact treatment outcomes, according to Sherman. SVR12 was reached by 96% of patients with NS5A RAVs who were treated for 12 weeks. Among patients with NS5A RAVs treated for 8 weeks, the SVR12 rate was 70%.

The regimen was generally well tolerated. “Increases in bilirubin occurred in a small proportion of patients, but these patients were treated with atazanavir,” Sherman said.

“There was no compromise of HIV control and no modification of cART due to daclatasvir and sofosbuvir,” Sherman concluded.

For more information:

Sherman K, et al. Abstract 901d. Presented at: Digestive Disease Week; May 16-19, 2015; Washington, D.C.

Disclosure: Sherman reports financial disclosures with Abbvie, Bristol Myers Squibb, Gilead, Merck, Janssen, Medpace, Sanofi and SynteractHCR. Please see the DDW faculty disclosure index for all other researchers’ relevant financial disclosures.

Editor's note: This article was updated on May 27, 2015, with clarifications from the presenter.