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.

Keywords: HIV–hepatitis C coinfection; clinical trials; direct-acting antivirals; generalizability; people who inject drugs.

Figure 1.

Green figures represent the number of Canadian Coinfection Cohort participants who would be eligible to be screened in NCT01479868 (trial evaluating simeprevir); PHOTON-1: NCT01667731 (trial evaluating sofosbuvir); TURQUOISE-I: NCT01939197 (trial evaluating ombitasvir, paritaprevir/ritonavir/dasabuvir [3D]); ION-4: NCT02073656 (trial evaluating ledipasvir/sofosbuvir); and ALLY-2: NCT02032888 (trial evaluating daclatasvir/sofosbuvir). Gray figures represent participants whose only exclusion was specific antiretroviral (ARV) therapies. Red figures represent participants not eligible regardless of ARV restriction.