CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

557 The Impact of Cannabinoid Receptor2-63 Variants in Liver Biopsy of HIV/HCV Patients Caterina Sagnelli 1 ; Marco Merli 2 ; Caterina Uberti Foppa 3 ; Hamid Hasson 4 ; Giulia Bellini 1 ; Carmine Minichini 1 ; Stefania Salpietro 4 ; Emanuela Messina 4 ; Nicola Coppola 1 ; Adriano Lazzarin 4 ; Evangelista Sagnelli 1 ; Francesca Rossi 1 1 Second Univ of Naples, Naples, Italy; 2 Vita-Salute San Raffaele Univ, Milan, Italy; 3 San Raffaele Scientific Inst, Milan, Italy; 4 Vita-Salute Univ, San Raffaele Scientific Inst, Milan, Italy Background: This is the first study analyzing the impact of the rs35761398 variant of the CNR2 gene leading to the substitution of Gln (Q) of codon 63 of the cannabinoid receptor 2 (CB2) with Arg (R) on the clinical history of chronic hepatitis in HIV/HCV coinfected patients. Methods: One hundred and sixty-six consecutive HIV/HCV coinfected patients, naïve for HCV-treatment were enrolled. A pathologist unaware of the patients’ condition graded liver fibrosis and necroinflammation (Ishak). All patients were screened for CBR2 rs35761398 polymorphism by a TaqMan assay. Results: Of the 166 HIV/HCV coinfected patients, 72.9%were males, 42.5%were infected with HCV-genotype 3, 74.1% had a history of previous intravenous drug use. The median age was 40.58 years and the immunological condition was quite good (median CD4+ cells/mm3 =507, IQR: 398.0-669.5). Thirty-five (20.8%) patients were naive for HAART and 131(78.9%) were on HAART. The CBR2-RR variant was detected in the 45.8% of patients, QR in 38.55% and QQ in 15.66%. The mean degree of necroinflammation (HAI) was 5.4±3.0 (SD), of fibrosis 2.3±1.6 and steatosis 1.7±1.3. The 64 subjects with CBR2-QR variant and 76 CBR2-RR variant more frequently than the 26 patients with CBR2-QQ variant had a history of previous IVDU (76.79% and 73.3%, respectively vs. 22.41%, p < 0.01). Patients with CBR2-RR showed a high degree of HAI (>9) more frequently than those with CBR2-QQ or CBR2-QR than in those (38.9% vs. 11.5% and 14.1%%, respectively, p<0.001). No other significant difference was observed in demographics and in laboratory and histological data. The 37 patients with moderate or severe HAI (>9), compared with the 129 patients with a lower HAI score showed higher serum level of AST (p=0.0000016), ALT (p=0.00039), and ALP (p=0.008) and higher degree of fibrosis and steatosis (3.59±1.48 vs 1.94±1.42 p<0.0001 and 2.03±1.26 vs 1.59±1.31, p=0.03, respectively). The association between the CBR2-RR variants and a HAI > 9 was also analyzed in a multivariate analysis considering also the CD4+> 500 cell/mL, fibrosis, HAART regimen and HAART naive, age as covariants. Both the severe fibrosis (p=0.0001) and the CBR2-RR variant (p=0.03) were found to be independently associated with severe necroinflamation. Conclusions: The CBR2-RR variant was identified as an independent predictor of severe necroinflamation in HIV/HCV coinfected patients with chronic hepatitis. 558 Poorly Controlled HIV Infection Is a Risk Factor for Liver Fibrosis in CNICS Cohort Nina Kim 1 ; Robin Nance 1 ; StephenVan Rompaey 1 ; Joseph A. Delaney 2 ; Heidi M. Crane 1 ; Katerina A. Christopoulos 3 ;Wm. Christopher Mathews 4 ; Richard Moore 5 ; Mari M. Kitahata 1 ; for the Center for AIDS Research Network of Integrated Clinical Systems 1 Univ of Washington, Seattle, WA, USA; 2 Univ of Washington Sch of PH and Community Med, Seattle, WA, USA; 3 Univ of California San Francisco, San Francisco, CA, USA; 4 Univ of California San Diego, San Diego, CA, USA; 5 Johns Hopkins Univ, Baltimore, MD, USA Background: Liver disease is a major cause of morbidity among HIV-infected persons. There is limited information about the extent to which HIV disease severity influences liver disease progression, particularly early in the disease course when interventions may have the greatest impact. Methods: We determined the incidence and predictors of advanced hepatic fibrosis measured by the FIB-4 index in a large and diverse population of HIV-infected patients without significant liver disease at baseline (FIB-4 <1.45). We used Cox proportional hazards analysis to examine factors associated with progression to FIB-4 ≥3.25, stratified by hepatitis C (HCV) status. Results: A total of 14,198 HIV-infected patients in care between January 2000 and March 2014 were included in the analysis, the majority of whomwere male (82%) and had sex with men (58%) as a transmission risk factor. The prevalence of HCV coinfection was 15% and alcohol use disorder 9%. Progression to advanced fibrosis occurred in 1,386 patients (10%) in a median of 3 years during a total of 61,904 person-years of follow-up (PYFU) for an incidence of 2.2 per 100 PYFU overall and 4.7 per 100 PYFU among HIV-HCV coinfected patients. In multivariable analysis, HCV coinfection (adjusted hazard ratio [aHR] 1.85, 95% CI 1.63-2.11), HBV coinfection (aHR 1.45, 95% CI 1.17-1.81), alcohol use disorder (aHR 1.36, 95% CI 1.17-1.58) and diabetes (aHR 1.87, 95% CI 1.56-2.25) were associated with progression to advanced fibrosis. In addition, patients with lower time-varying CD4 count were more likely to progress, with the greatest risk in those with CD4 <100 cells/mm 3 (aHR 6.93, 95% CI 5.80-8.27) compared with CD4 ≥500 cells/mm 3 . An increasing gradient of risk was also observed among patients with higher time-varying HIV viral load (VL), with the greatest risk in those with VL ≥100,000 copies/ml (aHR 2.60, 95% CI 2.19-3.08) compared with those who were suppressed. We observed similar findings for both HIV monoinfected and HIV-HCV coinfected patients in stratified analyses. Conclusions: We found that both lower CD4 count and higher HIV VL were significantly associated with progression to advanced hepatic fibrosis, independent of the risk associated with traditional factors including HCV and HBV coinfection, alcohol, and diabetes. Our findings suggest that early treatment of HIV infection could mitigate liver disease.

Poster Abstracts

220

CROI 2016