HCV Drug Uptake and Efficacy Jump After Arrival of Newer DAAs

According to a new Swiss study, uptake of anti-hepatitis C (HCV) therapy by people coinfected with HIV rose dramatically with the advent of direct-acting antivirals (DAAs), especially second-generation DAAs. Sustained virologic response 12 weeks after therapy stopped (SVR12) nearly doubled over the 2009-2015 study period.

HCV infection ranks as a leading comorbidity in some HIV populations, and HCV heightens death risk in people with HIV. The arrival of DAAs in recent years has transformed HCV care, encouraged wider use of anti-HCV therapy in HCV/HIV-coinfected people and led to comparable SVRs in HCV/HIV-coinfected and HCV-monoinfected patients.

To track trends in DAA impact on uptake, SVR and liver fibrosis, Swiss HIV Cohort Study (SHCS) investigators conducted a three-period study. The SHCS prospectively enrolls and regularly monitors HIV-positive people in Switzerland and now includes 73% of all diagnosed HIV cases in the country. Researchers divided follow-up time into three periods:

  • Period 1: Jan. 2009 to Aug. 2011, the interferon/ribavirin era before DAAs.
  • Period 2: Sept. 2011 to Mar. 2014, the first-generation DAA era limited to boceprevir and telaprevir.
  • Period 3: Apr. 2014 to Dec. 2015, the second-generation DAA era.

Primary outcomes were (1) anti-HCV treatment uptake, (2) treatment efficacy (SVR12) and (3) liver fibrosis stage by Metavir score.

When period 3 began, 876 SHCS members had chronic HCV infection, of whom 180 (20.5%) started treatment with a second-generation DAA. Among these 180 people, median age stood at 52 years, 92% were Caucasian, 70% were men and 99% had a suppressed HIV load. While 62% of these 180 participants injected drugs, 18% reported current use of illicit drugs and only 9% were men who have sex with men. Three-quarters of these 180 people (76%) had advanced fibrosis (Metavir F3-F4), and 62% had cirrhosis.

Among those with genotype 1 HCV, the median age of the 99 participants treated in period 3 was older than that of the 57 participants treated in period 2 (52 versus 48 years). The period 3 group also had a higher prevalence of advanced fibrosis (77% versus 58%, P < .01) and cirrhosis (64% versus 35%, P < .01).

Treatment uptake rose dramatically over the three treatment eras, from 4.5 per 100 person-years in period 1, to 5.7 per 100 in period 2 and to 22.4 per 100 in period 3 (a four-fold increase from period 2). SVR12 rates also spiked across the three eras, from 55% in period 1, to 70% in period 2 and to 96% in period 3. In period 3, SVR12 exceeded 90% for all HCV genotypes in the SHCS.

At the end of period 2, 204 of 623 cohort members (33%) had advanced fibrosis (Metavir F3-F4). By the end of period 3, 67 of 438 people (15%) had advanced fibrosis. Among patients with advanced fibrosis, the proportion of people with cirrhosis fell from 77% at the end of period 2 to 12% at the end of period 3. Only three patients died during period 3, two of them with decompensated cirrhosis and only one had to stop DAA therapy.

Together, these findings confirm that second-generation DAAs dramatically improved HCV response rates in people with HIV in Switzerland, even though the group taking these newer drugs was older and had more advanced liver disease than people taking first-generation DAAs. Efficacy of second-generation DAAs proved comparable in this real-world HCV/HIV setting and in registrational trials. At the same time, treatment uptake quintupled from the interferon/ribavirin era to the second-generation DAA period.

The researchers note that many HCV patients with mild fibrosis remain untreated because of reimbursement limitations. "[W]e will only be able to further reduce the burden of replicating HCV infection," they stress, "if reimbursement is not restricted to those with advanced fibrosis."