How Generalizable Are the Results From Trials of Direct Antiviral Agents to People Coinfected With HIV/HCV in the Real World?

Abstract

BACKGROUND:

Direct-acting antivirals (DAAs) against hepatitis C virus (HCV) have been described as revolutionary. However, it remains uncertain how effective these drugs will be for individuals coinfected with human immunodeficiency virus (HIV)-HCV. Bridging this gap between efficacy and effectiveness requires a focus on the generalizability of clinical trials.

METHODS:

Generalizability of DAA trials was assessed by applying the eligibility criteria from 5 efficacy trials: NCT01479868, PHOTON-1 (NCT01667731), TURQUOISE-I (NCT01939197), ION-4 (NCT02073656), and ALLY-2 (NCT02032888) that evaluated simeprevir; sofosbuvir; ombitasvir, paritaprevir/ritonavir/dasabuvir; sofosbuvir/ledipasvir; and daclatasvir/sofosbuvir, respectively, to the Canadian Coinfection Cohort, representing approximately 23% of the total coinfected population in care in Canada.

RESULTS:

Of 874 active participants, 70% had chronic HCV, of whom 410, 26, 94, and 11 had genotypes 1, 2, 3, and 4, respectively. After applying trial eligibility criteria, only 5.9% (24/410) would have been eligible for enrollment in the simeprevir trial, 9.8% (52/530) in PHOTON-1, 6.3% (26/410) in TURQUOISE-I, and 8.1% (34/421) in ION-4. The ALLY-2 study was more inclusive; 43% (233/541) of the cohort would have been eligible. The most exclusive eligibility criteria across all trials with the exception of ALLY-2 were restriction to specific antiretroviral therapies (63%-79%) and active illicit drug use (53%-55%).

CONCLUSIONS:

DAA trial results may have limited generalizability, since the majority of coinfected individuals were not eligible to participate. 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 are urgently needed.

• Authors: Sahar Saeed, Erin C Strumpf, Sharon L Walmsley, Kathleen Rollet-Kurhajec, Neora Pick, Valerie Martel-Laferrière, Mark Hull, M John Gill, Joseph Cox, Curtis Cooper, Marina B Klein, Canadian Co-Infection Cohort Study, Jeff Cohen, Brian Conway, Curtis Cooper, Pierre Côté, Joseph Cox, John Gill, Shariq Haider, Marianne Harris, David Haase, Mark Hull, Julio Montaner, Erica Moodie, Neora Pick, Anita Rachlis, Danielle Rouleau, Roger Sandre, Joseph Mark Tyndall, Marie-Louise Vachon, Sharon Walmsley, David Wong
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 62 Issue 7 Pg. 919-926 (Apr 01 2016) ISSN: 1537-6591 [Electronic] United States
• PMID: 26743093 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Chemical References

• Antiviral Agents

Topics

• Adult
• Aged
• Antiviral Agents (therapeutic use)
• Clinical Trials as Topic (standards)
• Cohort Studies
• Coinfection (drug therapy)
• Female
• HIV Infections (complications, drug therapy)
• Hepatitis C (complications, drug therapy)
• Humans
• Male
• Middle Aged
• Young Adult