CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

653 SVR Durability: HCV Patients TreatedWith IFN-Free DAA Regimens Aurielle M. Thomas 1 ; Sarah Kattakuzhy 1 ; Sarah Jones 2 ; Anita Kohli 1 ;Wilson Eleanor 2 ; Angie Price 2 ; Rachel Silk 2 ; Zayani Sims 1 ; Anu Osinusi 3 ; Shyam Kottilil 3 1 The National Institutes of Health, Bethesda, MD, US; 2 Leidos Biomedical Research, Inc., Bethesda, MD, US; 3 Institute of Human Virology, University of Maryland, Baltimore, MD, US

Background: IFN-based treatment of chronic hepatitis C has demonstrated a late relapse rate of <5%, usually occurring within 2 years of treatment. While high rates of SVR12 weeks after completion of directly-acting antiviral combinations has been established, data on long-term durability of SVR achieved through IFN-free regimens are lacking. The objective of this analysis was to analyze data frommultiple studies utilizing IFN-free DAA-based regimens to define the durability of SVR and evaluate for associated changes in biomarkers related to liver and metabolic fitness. Methods: Data on patients who achieved SVR12 from the following clinical trials were included: SPARE (HCV monoinfected, SOF+ RBV x 24 wks, n=38); SYNERGY (HCV monoinfected, SOF/LDV x 12 wks, n=20, SOF/LDV + GS-9669 X 6 weeks, n=19, SOF/LDV + GS-9451 X 6 weeks n=19) and ERADICATE (HIV/HCV coinfected, SOF/LDV X 12 weeks, n=49). HCV viral loads and serum biomarkers were collected up to SVR108. HCV viral loads were measured with Abbott M2000 RealTime HCV assay, with a limit of quantification of <12 IU/mL. Results: Of 138 patients followed for a period ranging from 1 to 96 weeks (averaging 35 weeks) post SVR12, 138 patients (100%) maintained HCV viral loads at <12 IU/mL (Table 1) with no current evidence of late relapse. At SVR12 timepoint, 86% of patients had ALT within normal range. At the current furthest timepoint, averaging 35 weeks after SVR12, 91% of patients had ALT within normal range.

Durability of Sustained Virologic Response Conclusions: This study shows the long-term durability of SVR associated with DAA-based therapy during ongoing assessment of up to 2 years. While the rise in percentage of ALT within normal range over the average follow up period was minimal, it may suggest an association with SVR durability. It is plausible that this change reflects the long-term histologic regression of necroinflammation and fibrosis described in patients who achieve SVR. Ongoing data collection including liver biopsy and radiologic studies are underway to continue analysis of this novel population. 654 Five–Year Risk of Late Relapse or ReinfectionWith Hepatitis C After Sustained Virological Response: Meta-analysis of 49 Studies in 8534 Patients AndrewM. Hill 1 ; Bryony Simmons 2 ; Jawaad Saleem 2 ; Graham Cooke 2 1 Chelsea and Westminster Hospital, London, United Kingdom; 2 St Mary’s Hospital–Imperial College Healthcare NHS Trust, London, United Kingdom Background: Combination treatment with direct acting antivirals can lead to sustained virological response (SVR) in over 90% of people with Hepatitis C (HCV) infection. However, subsequent recurrence of HCV (either from late relapse or re-infection) reverses the beneficial effects of SVR. This analysis aimed to estimate the 5-year risk of HCV late relapse or re-infection post-SVR, by risk group. Methods: The MEDLINE and EMBASE databases were searched for studies analysing late relapse or re-infection post-SVR (typically 24 weeks post-treatment, using pegylated interferon/ribavirin). All studies with >6 months of follow up post-SVR were included. Three groups of patients were analysed: 1. Mono-HCV infected “low risk” patients; 2. Mono-HCV infected “high risk” patients (IV drug users or prisoners); 3. HIV/HCV co-infected patients. Studies of liver transplant patients were excluded. Recurrence was defined as confirmed HCV RNA detectability after SVR (at least 6 months after end of treatment). Results: Results were available from 49 studies in 8534 patients. In each risk group, there were progressive rises in the risk of HCV recurrence with longer follow up time. In the 24 studies of HCV mono-infected “low risk” patients (n=6046) there were 45 HCV recurrences during a mean 4.1 years of follow up (estimated 5 year rate=0.9%). For the 15 studies of HCV mono-infected “high risk” patients (n=1203) there were 102 HCV recurrences during a mean 5.0 years of follow up (estimated 5-year rate=8.1%). For the 10 studies of HIV/HCV co-infected patients (n=1285) there were 178 HCV recurrences during a mean 3.3 year follow up (estimated 5-year rate=21.8%). For the studies of HIV/HCV co-infected patients, 5-year rates of HCV recurrence were significantly lower for patients followed up after randomised clinical trials (1.25%), compared to unselected patient cohorts (24.0%) (p<0.001). 5-year HCV re-infection rates by risk group Conclusions: In this analysis of 49 studies, the 5-year risk of late relapse or re-infection post-SVR was 0.9% in HCV mono-infected “low risk” patients, 8.1% in HCV mono-infected IV drug users or prisoners, and 21.8% in HIV/HCV co-infected patients. The large differences in event rates by risk group suggest that re-infection is more significantly more common than late relapse. Studies which follow up HIV/HCV co-infected patients originally enrolled in clinical trials may underestimate the risk of HCV re-infection in the general population 655 Incidence of Extrahepatic Complications in HIV/HCV Patients Who Achieved SVR Sebastiano Leone 1 ; Mattia Prosperi 2 ; Silvia Costarelli 1 ; Francesco Castelli 3 ; Franco Maggiolo 4 ; Simona Di Giambenedetto 5 ; Annalisa Saracino 6 ; Massimo Di Pietro 7 ; Fabio Zacchi 8 ; Andrea Gori 1 1 “San Gerardo Hospital”, University of Milano-Bicocca, Monza, Italy; 2 University of Manchester, Manchester, United Kingdom; 3 University of Brescia, Brescia, Italy; 4 Ospedali Riuniti, Bergamo, Italy; 5 Policlinico Gemelli, Rome, Italy; 6 Policlinico of Bari, Bari, Italy; 7 S.M Annunziata Hospital, Firenze, Italy; 8 Istituti Ospeitalieri di Cremona, Cremona, Italy Background: There is increasing evidence that the achievement of sustained virologic response (SVR) after interferon plus ribavirin treatment reduces the incidence of liver- related events. Data on the effects of SVR on the outcome of extrahepatic complications are scarce. Therefore, we conducted this study to assess the impact of SVR on the incidence of chronic kidney disease (CKD), diabetes mellitus (DM), and cardiovascular disease (CVD) in a cohort of HIV/HCV patients.

Poster Abstracts

409

CROI 2015