CROI 2016 Abstract eBook

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Poster Abstracts

599 Hepatic & Peripheral Responses to 2 Different DAA Regimens in HIV/HCV Coinfection Louisa C. Howard 1 ; Anita Kohli 2 ; Julia Purdy 1 ; Elana S. Rosenthal 1 ; Shikha Shrivastava 3 ; Bhawna Poonia 3 ; Henry Masur 1 ; Shyam Kottilil 4 ; Eleanor M.Wilson 5 1 NIH, Bethesda, MD, USA; 2 Dignity Hlth, St. Joseph’s Hosp, Phoenix, AZ, USA; 3 The Inst of Human Virology, Univ of Maryland, Baltimore, MD, USA; 4 Univ of Maryland Med Cntr, Baltimore, MD, USA; 5 Inst of Human Virology, Baltimore, MD, USA Background: While new combination directly acting antiviral (DAA) regimens for treatment of HCV are equally effective in HIV/HCV co-infected and HCV mono-infected patients, HIV/HCV co-infected subjects are known to have higher levels of immune activation and accelerated fibrogenesis. We compare hepatic and peripheral cellular response in HIV/HCV co-infected subjects successfully treated for HCV with one of two DAA-only regimens. Methods: Two prospective, single center, phase II studies were conducted at the NIH Clinical Center using DAA only, 12-week treatment regimens (either sofosbuvir/ledipasvir in ERADICATE (NCT01878799) or daclatasvir/asunaprevir/BMS-791325 in CONQUER (NCT02124044)) in HIV/HCV genotype 1 co-infected subjects. Paired pre/post-treatment liver biopsies were obtained on a subset of patients and evaluated by a single pathologist using Knodell-HAI and Ishak scoring systems. We also assessed changes in peripheral immune activation markers on T cell subsets (CD38, HLA DR, CD25) before, during, and after therapy. Median values are reported and comparisons were made using Wilcoxon Rank tests. Results: Subjects in ERADICATE (n=36) and CONQUER (n=12) were predominately male (83%, 58%) and black (86%, 50%), with median age of 58 and 52 years, respectively. Both cohorts demonstrated early liver disease with an HAI fibrosis score <2 in 75% and 67%, respectively. While all ERADICATE subjects were treatment naïve, 58% of CONQUER subjects were treatment experienced. In both studies, there was a significant decline in both the percentage of peripheral T cells with activated profile (CD4+ CD38+ HLADR+, 17% in ERADICATE, P<0.001, and 42% in CONQUER, P=0.002) and HAI inflammation score in the liver (median decline in CONQUER patients was 3.5 ± 2.7 (P=0.04), compared to 1.5 ± 2.8 in ERADICATE (P=0.01)) by the end of therapy. Interestingly, we also observed a statistically significant decline in Ishak fibrosis score in CONQUER (P=0.03), not observed in ERADICATE (P>0.99). Conclusions: Effective therapy with either DAA regimen is associated with a substantial decline in peripheral immune activation markers and intrahepatic cellular response in HIV/HCV co-infected subjects. In this analysis, sustained virologic response after treatment with daclatasvir/asunaprevir/BMS-791325, a three DAA regimen, was also associated with regression of liver fibrosis within 3 months, which is encouraging for better long-term outcomes in this patient population.

Poster Abstracts

241

CROI 2016