CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

566 INTERFERON-FREE REGIMENS IMPROVE RENAL FUNCTION IN PATIENTS WITH CHRONIC HEPATITIS C Nicola Coppola 1 , Federica Portunato 1 , Antonio Riccardo Buonomo 2 , Laura Staiano 2 , Riccardo Scotto 2 , Biagio Pinchera 2 , Stefania De Pascalis 1 , Salvatore Martini 1 , Mariantonietta Pisaturo 1 , Daniela Caterina Amoruso 2 , Guglielmo Borgia 2 , Carmine Coppola 2 , Ivan Gentile 2 1 Second University of Naples, Caserta, Italy, 2 University of Naples Federico II, Naples, Italy Background: In literature there are few data on the impact of direct-acting antivirals regimens (DAAs) on renal function. We examined estimated glomerular filtration rate (eGFR) trend during and post treatment with DAAs. Methods: A retrospective analysis of a multicentre Italian cohort enrolling 403 patients with chronic HCV infection treated with DAAs between March 2015 and December 2017 for up to 12 weeks post treatment (12WPT) was performed. Patients with HIV, Child C cirrhosis, hepatocellular carcinoma or that refused consent were excluded. Impaired renal function (IRF) was defined as a CKD (chronic kidney disease) stage G3-G5 according to the KDIGO (Kidney Disease Improving Global Outcomes) stage. The reduction in CKD of at least 1 KDIGO stage was defined as an improvement. Results: Of the 403 patients, 40% had a KDIGO stage of G1, 43%were stage G2, 15%were G3 and 1.4%were G4-5. Sofosbuvir(SOF) plus Ledipasvir(LDV)±Ribavirin(RBV) and Ombitasvir(OMB), Paritaprevir(PAR), Dasabuvir(DAS)+Ritonavir(r)±RBV were the most used regimens [34% and 30%, respectively] with an overall SVR12 rate of 98%. The median eGFR increased from 12WPT and baseline of +3.6 (IQR: -12.1/+22.6). The rate of patients with a CKD stage of G3-G5 significantly decreased from 16.9% to 12.2% at 12WPT (p<0.05). Figure1 shows the change in eGFR between baseline and 12WPT according to different comorbidities(1A) DAAs(1B), CKD stage(1C) and presence of SVR(1D). Patients without diabetes showed an improvement in eGFR from 84.05 ml/min/1.73m2 at baseline to 95.01 ml/min/1.73m2 at 12WPT (p<0.001), as well as patients with cirrhosis (from 79.06 to 84.61 ml/ min/1.73m2 p<0.05), and patients with decompensated cirrhosis (from 71.07 to 79.46 ml/min/1.73m2 p<0.001). SOF-based regimens (from 88.49 to 91.44 ml/min/1.73m2 p<0.01) and patients not receiving RBV (from 84.46 to 89.37 ml/min/1.73m2 p<0.05) improved too. Finally, the 395 patients who achieved SVR12 showed an increased in eGFR (from 84.60 to 88.30 ml/min/1.73m2 p<0.05). At multivariate analysis, independent factors associated with renal improvement were decompensated cirrhosis at baseline [aHR 3.43 (95IC 1.44-8.18) p<0.05] and the achievement of SVR12 [aHR 12.20 (95CI 1.26-118.11) p<0.05]. Conclusion: Conclusions: Our findings suggest that DAAs correlates with an improvement in renal function, especially if SVR12 is achieved and in patients with baseline IRF or cirrhosis. However, further studies are needed to confirm these data.

567 PCSK9 LEVELS DECLINE WITH HCV DIRECT-ACTING ANTIVIRAL THERAPY IN HIV/HCV COINFECTION Malini M. Gandhi 1 , Kim-Lien Nguyen 1 , Jordan E. Lake 2 , Diana Liao 1 , Mario Guerrero 3 , Wilbert C. Jordan 4 , Eric Daar 3 , Debika Bhattacharya 1 , Kara W. Chew 1 1 University of California Los Angeles, Los Angeles, CA, USA, 2 University of Texas at Houston, Houston, TX, USA, 3 Harbor–UCLA Medical Center, Torrance, CA, USA, 4 Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA Background: Proprotein convertase subtisilin/kexin 9 (PCSK9) regulates levels of low-density lipoprotein (LDL) cholesterol, which are altered in hepatitis C virus (HCV) infection. PCSK9 levels may also be associated with inflammation and immune activation. We hypothesized that PCSK9 levels would be higher in HIV/HCV co-infected compared to HIV mono-infected individuals, and decline to levels in mono-infected persons with HCV clearance with direct-acting antivirals (DAAs). Methods: HIV-infected adults on antiretroviral therapy with HIV RNA<50 copies/mL, HCV RNA>10,000 IU/mL or HCV antibody negative and without cardiovascular disease (CVD) were enrolled. Circulating PCSK9 and CVD/ inflammatory biomarkers (sCD14, sCD163, sE-selectin, Lp-PLA2, IL-6, sTWEAK and standard lipid panel), and HOMA-IR were measured at entry and post- treatment. Baseline characteristics and biomarker levels were compared by chi-square, Fisher’s exact, or Wilcoxon rank sum tests. Within-person changes (absolute and %) in PCSK9 level with HCV therapy were examined by Wilcoxon signed-rank test, and correlations between changes in PCSK9 and changes in biomarkers by Spearman rank correlations. Results: Twenty-four HIV and 35 HIV/HCV-infected persons were included (85% male, 85% non-white or Hispanic). Median age was 52 years and CD4 count 622 cells/mm³. Co-infected persons had higher ALT, FIB-4 scores, and HOMA-IR, and lower LDL-C and CD4 counts. Twenty-nine completed DAA therapy, all of whom achieved sustained virologic response. The Figure summarizes comparisons of PCSK9 levels at baseline, post-treatment 1 (median 7.3 weeks after end of treatment (EOT)), and post-treatment 2 (median 43.5 weeks after EOT). PCSK9 dropped significantly from baseline to post-treatment 1 and post-treatment 2: median within-person change was -20.8% (p= 0.006) and -18.2% (p= 0.033), respectively. Change in PCSK9 correlated with change in sE-selectin and sCD163 from baseline to post-treatment 1 (r=0.46, p=0.016 and r=0.39, p=0.047, respectively) and to post-treatment 2 (r=0.64, p=0.002 and r=0.58, p=0.008, respectively), but not with change in LDL or other biomarkers. Conclusion: Prior to HCV treatment, PCSK9 levels trended towards being higher in HIV/HCV co-infected persons compared to HIV mono-infected persons. PCSK9 levels declined significantly with HCV treatment, to levels similar to or below those in HIV mono-infection. Elevated PCSK9 levels in the setting of HCV infection may reflect HCV-associated inflammation rather than cholesterol homeostasis.

Poster Abstracts

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