Clinical trial results for direct-acting antivirals against hepatitis C virus (HCV) may have limited generalizability for patients coinfected with HIV and HCV, a recent study suggested.
A research team led by Dr. Marina Klein of the division of infectious diseases at McGill University Health Centre, Montreal, determined it was important to assess the generalizability of clinical trial results for direct-acting antivirals (DAA) since the drugs have been described as revolutionary treatments for HCV. Clinical trial results have generally shown that DAAs are well tolerated, more conveniently dosed, and highly efficacious, compared with earlier, interferon-based HCV therapies.
The Canadian researchers noted, however, that DAA trials have included relatively small numbers of participants (subgroups ranging from 6 to 60) and have applied very strict eligibility criteria, likely excluding a substantial segment of the coinfected patient population.
To assess DAA trial generalizability, investigators applied the eligibility criteria from five efficacy trials evaluating simeprevir; sofosbuvir; ombitasvir, paritaprevir/ritonavir, and dasabuvir (3D); sofosbuvir/ledipasvir; and daclatasvir/sofosbuvir to the Canadian Co-Infection Cohort, representing about 23% of the total coinfected Canadian population in care.
The results confirmed the researchers’ suspicions, as only 5.9% of coinfected patients in the cohort would have been eligible for enrollment in the simeprevir trial, 9.8% in the sofosbuvir trial, 6.3% in the 3D trial, and 8.1% in the sofosbuvir/ledipasvir trial. Eligibility into the daclatasvir/sofosbuvir study was more inclusive – 43% of the cohort would have been eligible. The most exclusive eligibility criteria across all trials, with the exception of the daclatasvir/sofosbuvir study, were restriction to specific antiretroviral therapies (63%-79%) and active illicit drug use (53%-55%).
The exclusions “appeared to be related to improving treatment outcomes by not including those at higher risk of poor adherence and reinfection – individuals for whom real world data is urgently needed,” Dr. Klein and her coauthors concluded.
Read the full report in Clinical Infectious Diseases (Clin Infect Dis. 2016 Jan 6. doi: 10.1093/cid/civ1222).
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