SAN FRANCISCO – The very high sustained virologic response (SVR) rates achieved with direct-acting antiretroviral agents in clinical trials are being replicated in the real-world setting, according to data from 1,225 patients presented in a late-breaker study at the annual meeting of the American Association for the Study of Liver Diseases.
The rates of SVR, treatment failure, and discontinuation of treatment among genotype 1 HCV patients treated with such direct-acting antivirals such as ledipasvir (LDV), sofosbuvir (SOF), and ombitasvir appear to be at least as good outside of clinical studies as those reported in the phase III trials, reported Dr. Nezam H. Afdhal of Beth Israel Deaconess Medical Center, Boston.
Dr. Nezam H. Afdhal
“Overall, SVR in real-world [genotype 1] patients was 94% across regimens and patient characteristics,” Dr. Afdhal reported.
In this study, the goal was to evaluate patients with genotype 1 HCV who failed 12-weeks of a multidrug regimen containing a direct-acting antiretroviral agent. The focus was on three regimens: ledipasvir/sofosbuvir (LDV/SOF); ombitasvir/paritaprevir/ritonavir + dasabuvir (VKP); and simeprevir/sofosbuvir (SMV/SOF). All three were evaluated with or without ribavirin. The data were collected from the Trio Health Innervation Platform, a cloud-based disease management program.
Over a nearly 18-month period from January 2014 to March 2015, 1,225 patients were treated with one of the regimens. SVR 12 weeks after completion of treatment was 94% for LDV/SOF, 97% for LDV/SOF with ribavirin, 91% for VKP with or without ribavirin, and 78% for SMV/SOF with or without ribavirin.
In total, 35 patients did not achieve SVR. Of these, six discontinued therapy before completing the regimen. The 29 who completed therapy were classified as virologic failures and were compared to those who did achieve SVR to determine factors associated with failure. Failure was not associated with being treated in a community practice relative to an academic center and there was no association between failure and age, race, viral load at baseline, presence of HIV co-infection, or prior liver transplant.
However, there were significant associations for treatment failure with male gender (P = .011), presence of cirrhosis (P less than .001), platelet count less than 100,000/mL (P less than .001) and prior treatment failure (P = .016).
Discontinuation rates for the new direct-acting antivirals are “not a major issue” in real world clinical practice, Dr. Afdhal said, adding that the findings support rates of efficacy comparable to those observed in phase III trials. The data indicated that patients with cirrhosis, thrombocytopenia, and prior treatment failure represent “the most difficult to treat” who may require intensified therapy, but the “remarkable” efficacy of these newer agents previously reported in controlled trials can be anticipated in routine patient care.