CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

602 HIGH KYNURENINE:TRYPTOPHAN RATIO IS ASSOCIATED WITH LIVER FIBROSIS IN HIV INFECTION Ani Kardashian 1 , Yifei Ma 2 , Michael T. Yin 3 , Rebecca Scherzer 2 , Olivia Nolan 4 , Francesca Aweeka 2 , Phyllis Tien 2 , Jennifer Price 2 1 University of California Los Angeles, Los Angeles, CA, USA, 2 University of California San Francisco, San Francisco, CA, USA, 3 Columbia University Medical Center, New York, NY, USA, 4 Columbia University, New York, NY, USA Background: The kynurenine:tryptophan ratio (KTR), a marker of tryptophan catabolism, is associated with impaired T-cell function. Higher KTR has been associated with increased mortality, cardiovascular disease, and neurologic conditions in HIV+ persons. Its role in liver fibrosis is unknown. We examined the association of KTR with liver fibrosis in women with and without HIV infection. Methods: Serum KTR was measured in 58 HIV-monoinfected, 42 HIV/HCV- coinfected, and 37 uninfected women from the WIHS. Fibrosis was estimated in all 137 women using FIB-4. We used multivariable linear regression to evaluate the associations of HIV monoinfection, HIV/HCV coinfection, KTR, and FIB-4 adjusting for demographic, lifestyle, metabolic, and HIV-related factors. We performed a subgroup analysis using liver stiffness measurements (LSM) to assess fibrosis among a subgroup of 83 women who had undergone LSM. Results: Median KTR[IQR] was 3.8[3.2-4.5] in HIV-monoinfected, 5.5[4.4- 6.5] in coinfected, and 3.1[2.5-3.4] in uninfected groups (p<0.001 across groups). Women with HIV/HCV and HIV monoinfection had higher FIB-4 than uninfected women (2.17[1.24-3.38] and 0.98[0.79-1.53] respectively vs. 0.63[0.57-0.92];p<0.001). FIB-4 increased as KTR increased in HIV+ women (Spearman’s rho=0.54;p<0.001) but not HIV- women (rho=-0.13,p=0.44). In the total cohort, factors associated with higher FIB-4 were older age (30% per 10 years;95%CI:16%-45%), HIV monoinfection (37%;95%CI:9%- 73%), and HIV/HCV coinfection (164%;95%CI:100%-250%)(Table1a). When further adjusting for KTR, higher KTR was associated with higher FIB-4 (27% per doubling,95%CI:5%-53%), and the associations of HIV monoinfection (29%;95%CI:2%-63%) and HIV/HCV coinfection (123%;95%CI:63%-203%) were slightly attenuated. In the HIV+ group, higher CD4 count was associated with lower FIB-4 (-5.6%;95%CI:-9.8%,-1.1%), but the effect was attenuated after adjusting for KTR. In the 83 women with LSM, higher KTR was associated with higher LSM (43% per doubling,95%CI:15%-79%)(Table1b). HIV/HCV coinfection was associated with higher LSM after adjusting for KTR (47%;95%CI:3%-110%), while HIV monoinfection was not (-0.9%;95%CI:-23%-27%). Conclusion: KTR is elevated in the setting of HIV infection and is associated with higher liver fibrosis. The associations of HIV monoinfection and HIV/ HCV coinfection with elevated fibrosis were attenuated after adjusting for KTR, suggesting that the relationship between HIV and liver fibrosis may be mediated in part by the tryptophan pathway.

Methods: We included HCV-infected adults who initiated dialysis in the administrative-linked population-based British Columbia Hepatitis Testers Cohort between 1 Jan 1990 and 31 Mar 2015. Participants were followed from dialysis initiation until death, kidney transplant, or administratively censored on 31 Mar 2016. Coinfection with HBV or HIV (identified through public health reporting linkages and/or serologic testing), demographic characteristics, alcohol and injection drug use, comorbidities (diabetes, hypertension, cirrhosis, ischemic heart disease, mental health, chronic obstructive pulmonary disease), HCV treatment, social and material deprivation indices, all assessed prior to dialysis, and calendar time were included in multivariable Cox models to estimate adjusted hazard ratios (aHR) for death. Results: A total of 2,801 individuals who initiated dialysis contributed 12,250 person-years and 1,617 deaths. The median time to death was 32 months (IQR 5, 115). Overall 69%were infected with HCV only, 9% had HBV coinfection, 15% had HIV coinfection and 7%were triply infected. Additional patient characteristics are shown in the Table. Compared with HCV monoinfection, coinfection with HIV (aHR 1.66, 95% CI: 1.42, 1.94) and triple infection (aHR 1.95, 95% CI: 1.60, 2.38) were associated with higher all-cause mortality. Existing liver disease (aHR 2.12, 95% CI: 1.88, 2.39) and diabetes (aHR 1.16, 95% CI: 1.02, 1.33) were also independently associated with mortality. After restriction to HCV treated patients, achieving sustained virologic response (SVR) prior to dialysis was associated with reduced mortality (HR 0.43, 95% CI: 0.26, 0.71) and attenuation of observed coinfection associations with mortality (HIV coinfection aHR 0.99, 95% CI: 0.42, 2.44; triple infection aHR 1.18, 95% CI: 0.40, 3.49). Conclusion: HIV coinfection was associated with elevated mortality among HCV-infected dialysis patients, however, successful HCV treatment mitigated the excess mortality. Scaling up treatment with direct-acting antiviral therapy may improve clinical outcomes in this population.

Poster Abstracts

603 WITHDRAWN MORTALITY AFTER DIALYSIS INITIATION AMONG PATIENTS WITH CHRONIC HEPATITIS C INFECTION Carmine Rossi , Zahid A. Butt, Maryam Darvishian, Geoff W. McKee, Jane Buxton, Hasina Samji, Mawuena Binka, Stanley Wong, Amanda Yu, Maria Alvarez, Mel Krajden, Naveed Z. Janjua BC Centre for Disease Control, Vancouver, BC, Canada Background: End-stage renal disease (ESRD) is an important extrahepatic manifestation among chronic hepatitis C virus (HCV)-infected individuals. However, there is little information on survival in these patients after initiating dialysis. Our objective was to investigate all-cause mortality among HCV- infected dialysis patients and whether survival differs with HIV and/or hepatitis B virus (HBV) coinfection or HCV treatment.

604 WITHDRAWN SYNDEMIC HIV AND HEPATITIS VIRAL COINFECTIONS AND INCIDENT END-STAGE RENAL DISEASE Carmine Rossi 1 , Zahid A. Butt 1 , Maryam Darvishian 1 , Jason Wong 1 , Jane Buxton 2 , Stanley Wong 1 , Amanda Yu 1 , Maria Alvarez 1 , Mel Krajden 1 , Naveed Z. Janjua 1 1 BC Centre for Disease Control, Vancouver, BC, Canada, 2 University of British Columbia, Vancouver, BC, Canada Background: Syndemic viral coinfections, including hepatitis B virus (HBV), hepatitis C virus (HCV) and/or HIV have been associated with premature mortality, however there is little data on their impact on chronic comorbidities,

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