Interferon-free directly-acting antiviral (DAA) regimens for HCV provide a major advance in clinical management, including in HIV/HCV co-infection. Drug-drug interactions (DDI) with combination antiretroviral therapy (cART) will require consideration. The aim of this analysis was to characterise the cART regimens in HIV/HCV co-infected individuals and their suitability for co-administration with the following DAA HCV regimens: sofosbuvir/ledipasvir, paritaprevir/ritonavir/ombitasvir and dasabuvir, grazoprevir/elbasvir and sofosbuvir plus daclatasvir.
CEASE-D is a prospective cohort of HIV/HCV co-infected individuals in Sydney, Australia. This analysis included all individuals enrolled between July 2014 and August 2015 (n=191). The primary endpoint was the proportion of individuals receiving suitable cART for co-administration with approved or investigational (Phase III) interferon-free DAA regimens.
In individuals receiving cART with HCV genotype (GT) 1 and 4 (n=92), no clinically significant DDI were expected in 41% with sofosbuvir/ledipasvir, 25% with paritaprevir/ritonavir/ombitasvir plus dasabuvir, 37% with grazoprevir/elbasvir and 61% with sofosbuvir plus daclatasvir. DDIs requiring DAA or antiretroviral dose adjustment or additional monitoring for toxicity were noted in 34% with sofosbuvir plus daclatasvir, 7% with paritaprevir/ritonavir/ombitasvir plus dasabuvir and 26% with sofosbuvir/ledipasvir. Contra-indicated antiretroviral agents were noted in 47% with paritaprevir/ritonavir/ombitasvir plus dasabuvir and 45% with grazoprevir/elbasvir, but only 5% with sofosbuvir/ledipasvir and 0% with sofosbuvir plus daclatasvir. In individuals receiving cART with HCV GT 2 or 3 (n=45), no clinically significant DDI were expected in 67% and DDI requiring DAA dose adjustment were noted in 33% with sofosbuvir plus daclatasvir, allowing co-administration in 100%.
Potential DDIs will impact on DAA prescribing in HIV/HCV co-infection. HCV infection can be safely and successfully treated provided DDI are recognised and managed appropriately.