Research

Impact of HCV Therapy on CNS Outcomes

Agency: NIH
Agency Award Number: R01 DA039775

This is a partially blinded study that will observe the effects of newly developed direct-acting antiviral (DAA) treatments on the central nervous system (CNS) of individuals with chronic Hepatitis C (HCV). The goals of this study are to determine the CNS impact of curing chronic HCV disease with newly established direct-acting antiviral (DAA) therapies and how HIV alters this relationship. Even though neurocognitive (NC) and mood disorders commonly occur in the course of chronic HCV infection, their response to HCV treatment has been obscured by the neurotoxicity of older, interferon-based (IFN) therapies. New, highly effective DAAs do not have the neurotoxicity of IFN-based therapies. Considering the prominent NC and neuropsychiatric effects of IFN, newer DAAs should more clearly treat the CNS injury caused by HCV disease.¹² Despite this, no clinical trials have been performed to determine the CNS benefits of DAAs in mono- or HIV co-infected substance users. This presents a critical barrier to progress in the field that this clinical trial will directly address. Our findings will also improve scientific knowledge by determining the biological and imaging correlates of the CNS and systemic effects of DAAs as well as the distribution of these drugs into the CNS. Our findings will also inform clinical guidelines and practice regarding the safety and benefits of treating HCV in substance using populations. This could lead to earlier initiation of HCV therapy to prevent or treat CNS disease, not only liver disease, which would be a fundamental shift in the current approach to identifying candidates for therapy based on severity of liver fibrosis. In people who have HIV-associated NC disorder (HAND) and HCV infection, treatment with DAAs may prove to be a critical adjunct to ART for improving NC function and returning patients to more productive lives.