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Daclatasvir/Sofosbuvir Combo Shows Promise in Hepatitis C Patients Co-Infected With HIV
Positive results have been announced from a phase III clinical trial evaluating the investigational once-daily combination of daclatasvir, a nonstructural protein 5A (NS5A) complex inhibitor, and sofosbuvir, a nucleotide analog NS5B polymerase inhibitor, for the treatment of patients with chronic hepatitis C virus (HCV) co-infected with human immunodeficiency virus (HIV) –– a patient population that has been challenging to treat largely because of potential drug–drug interactions between the therapeutic regimens used to treat each infection.
The combination therapy is being developed by Bristol-Myers Squibb. Sofosbuvir is marketed by Gilead Sciences as Sovaldi.
The open-label ALLY-2 trial randomly assigned 151 treatment-naïve and 52 treatment-experienced HCV (genotypes 1 through 4) patients co-infected with HIV-1 receiving antiretroviral regimens into three cohorts. Among the treatment-naïve patients, one cohort received daclatasvir 30, 60, or 90 mg plus sofosbuvir 400 mg once daily for 12 weeks, and another received the same dosage and combination for 8 weeks. The treatment-experienced cohort also received daclatasvir 30, 60, or 90 mg plus sofosbuvir 400 mg once daily for 12 weeks.
Daclatasvir was dose-adjusted to accommodate concomitant antiretrovirals: 30 mg with ritonavir-boosted protease inhibitors, and 90 mg with non-nucleoside reverse transcriptase inhibitors, except rilpivirine.
All cohorts were followed through post-treatment week 24. The study’s primary endpoint was the rate of sustained virologic response 12 weeks after completing therapy (SVR12) among genotype-1 treatment-naïve patients.
High SVR rates occurred among all patients treated for 12 weeks, regardless of prior treatment experience, HCV genotype, cirrhosis status, concurrent combination antiretroviral therapy regimen, or race. Among both treatment-naïve and treatment-experienced patients treated for 12 weeks, 97% (149/153) achieved a cure (i.e., SVR12). The study met its primary endpoint, with 96% (80/83) of treatment-naïve genotype-1 patients achieving SVR12. African-American patients comprised 34% of study participants; in this cohort, the SVR12 rate was 98% (49/50).
The ALLY-2 trial also included an 8-week arm; 38 of 50 (76%) treatment-naïve patients with HCV achieved SVR12. However, the investigators concluded that further studies are needed to assess the potential of shorter-duration, all-oral treatment regimens.
Approximately 170 million people worldwide are infected with HCV, with an estimated 2.7 million to 3.9 million chronically infected in the U.S. Up to 90% of those infected with HCV will not spontaneously clear the virus and will become chronically infected. According to the World Health Organization, up to 20% of people with chronic HCV infection will develop cirrhosis; of those, up to 20% percent may progress to liver cancer.
The Centers for Disease Control and Prevention estimates that approximately 25% of HIV-infected persons in the U.S.–– about 300,000 people –– are also infected with HCV. HCV infection progresses more rapidly to liver damage in people with HIV.
Source: Bristol-Myers Squibb; February 26, 2015.