CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

729 CHRONIC KIDNEY DISEASE RISK FACTORS AND URINE KIDNEY INJURY MARKERS IN HIV+ PERSONS Anthony Muiru 1 , Michael Shlipak 2 , Rebecca Scherzer 2 , William Zhang 1 , Simon Ascher 3 , Chirag Parikh 4 , Carl Grunfeld 2 , Frank J. Palella 5 , Ruibin Wang 6 , Phyllis Tien 2 , Qibin Qi 7 , Michelle Estrella 2 1 University of California San Francisco, San Francisco, CA, USA, 2 San Francisco VA Medical Center, San Francisco, CA, USA, 3 University of California Los Angeles, Los Angeles, CA, USA, 4 Yale University, New Haven, CT, USA, 5 Northwestern University, Chicago, IL, USA, 6 Johns Hopkins University, Baltimore, MD, USA, 7 Albert Einstein College of Medicine, Bronx, NY, USA Background: HIV+ persons bear an excess burden of chronic kidney disease (CKD), yet conventional methods to assess kidney health are insensitive and non-specific. We hypothesized that CKD risk factors would be differentially associated with unique patterns of urine kidney injury markers. Methods: Cross-sectional study of HIV+ persons studied prior to TDF- based ART initiation in the Multicenter AIDS Cohort Study and the Women’s Interagency HIV Study between 2009 and 2015. By multiplex assays, we measured levels of 14 biomarkers, capturing multiple dimensions of kidney injury (Figure 1, Panel A). We evaluated associations of known CKD risk factors with urine biomarkers using separate multivariable adjusted models for each biomarker. Results: We included 198 HIV+ persons. Median age was 48 years, 64%were black, and 56%were women. Median CD4 count was 483 cells/mm 3 , 33%were on ART, 48%were hypertensive, 17% had diabetes, and 17%were HCV-infected. Median eGFRSCR by CKD-EPI equation was 103 mL/min|1.73 m2 (IQR 88-116). Each CKD risk factor was associated with a distinct pattern of urine biomarkers; the magnitudes of association between each CKD risk factor and biomarker varied (Figure 1, Panel B). For example, older age was associated with nearly all measures of kidney injury. Advancing age per decade was strongly associated with: 1) increases in biomarker levels of proximal tubular dysfunction/injury (52% KIM1, p<0.0001; 31% α1m, p<0.0001; 30% β2m, p=0.009; 27% clusterin, p=0.0002; 27% NGAL, p=0.002; 12% higher IL-18, p=0.021); 2) changes in biomarker levels of inflammation (38% higher MCP1, p<0.0001; 12% lower protective marker, EGF, p<0.0001; 3) 26% lower UMOD levels (p<0.0001) indicative of Loop of Henle injury; and 4) to a lesser degree, glomerular injury (18% higher ACR, p=0.03). In contrast, HIV viral load (per 10-fold increase) was most associated with 2 dimensions of injury: Glomerular (20% higher ACR, p=0.01; 9% higher CysC level, p=0.001) and proximal tubular (12% higher KIM1, p=0.008; 21% higher IL-18, p<0.0001). The latter marker though, may also reflect inflammation. Conclusion: Among HIV+ persons, known CKD risk factors are associated with unique patterns of changes in urine biomarkers. To establish the clinical value of biomarker level measurement, future work is needed to confirm our findings in larger, diverse populations and to develop algorithms that discern the site of kidney injury and identify the related associated risk factors for individual patients.

Background: The risk of chronic kidney disease (CKD) increases with both HIV infection and aging, substantially complicating clinical decision-making. Our objective was to assess the validity, in an exclusively U.S. based cohort, of an easy-to-calculate CKD risk score, developed using data from the Data collection on Adverse events of Anti-HIV Drugs (D:A:D), a prospective, international, multi-site study. Methods: HIV+ patients with no previous exposure to potentially nephrotoxic antiretroviral agents and ≥3 estimated glomerular filtration rate (eGFR) test results were identified in the OPERA® Observational Database, an aggregation of prospectively collected electronic medical records from HIV caregivers in 79 clinics across 15 states. Patients were followed from the first observed eGFR >60 ml/min/1.73 m2 (2002-2015) until last eGFR test result, the occurrence of the study outcome, lost to follow-up, or study end (31JUL2017). The study outcome was defined as a confirmed (≥2 consecutive results, >90 days apart) decrease in eGFR to < 60 ml/min/1.73m2. Three cohorts were drawn independently using Cockcroft-Gault (CG), MDRD and CKD-EPI eGFR estimation methods. Both full and short D:A:D risk scores were applied. Poisson models estimated incidence as a function of D:A:D risk score. Kaplan Meier survival curves estimated progression at five years. Incidence rate ratio’s (IRR), adjusted IRR (aIRR), and Harrell’s discrimination statistic were used to assess validity. Results: After applying study eligibility criteria, there were 19444, 22727 and 22748 patients in the CG, CKD-EPI and MDRD samples, respectively. Median short and full risk scores were -3 in all three OPERA cohorts with very similar IQR. CKD incidence (95% CI) ranged from a low of 7.3 per 1000 person years (6.8, 7.9) in OPERA CG to a high of 11.0 (10.4, 11.6) in OPERA MDRD. While overall incidence was higher than observed in the D:A:D derivation cohort at 6.2 (5.7 - 6.7), IRR’s by risk group were similar. Using the full risk score, the aIRR was 1.3 in all three OPERA cohorts, regardless of eGFR method, equivalent to the D:A:D derivation cohort. Harrell’s c-statistic ranged from 0.87 to 0.92 in the three OPERA cohorts, comparable to that reported by D:A:D (0.92). Similar findings were observed after applying the D:A:D short risk score [Table]. Conclusion: This study supports the validity of the D:A:D short and full risk scoring method for assessing the probability of CKD in an exclusively U.S. based cohort regardless of eGFR method. 731 CHRONIC KIDNEY DISEASE IN HIV POPULATIONS OF AFRICAN DESCENT IN THE UK Sophie Jose 1 , Lisa Hamzah 2 , Rachael Jones 3 , Deborah Williams 4 , Alan Winston 5 , Fiona Burns 6 , Caroline Sabin 1 , Frank Post 2 1 University College London, London, UK, 2 King’s College Hospital NHS Foundation Trust, London, UK, 3 Chelsea and Westminster NHS Foundation Trust, London, UK, 4 Brighton & Sussex University Hospitals NHS Trust, Brighton, UK, 5 Imperial College Healthcare NHS Trust, London, UK, 6 University College London Hospitals NHS Trust, London, UK Background: Black ethnicity is a major risk factor for HIV-associated nephropathy (HIVAN) and hypertensive kidney disease through carriage of apolipoprotein L1 ( APOL1 ) risk alleles. The prevalence of these alleles is highest in West Africans, intermediate in those from Southern Africa, and lowest in East Africans, while little is known about APOL1 in Caribbeans (predominantly of West African ancestry). As HIVAN is an important cause of chronic kidney disease (CKD) in these populations, we hypothesized that rates of CKD vary in people from East, Southern and West Africa and the Caribbean. Methods: Black participants in the UK CHIC cohort with at least 2 serum creatinine measurements were stratified by region of origin and followed from first creatinine measure to December 2014, their last visit or death. eGFR was estimated using the CKD-EPI formula adjusted for ethnicity and expressed in mL/min/1.73m 2 . Poisson regression assessed the association between region of birth and CKD ≥3, ≥4 and 5 (eGFR <60,<30, and <15 for >3 months respectively), with adjustment for baseline (age, sex) and significant time-

Poster Abstracts

730 VALIDATION OF A CHRONIC KIDNEY DISEASE RISK SCORE IN HIV+ PATIENTS IN THE US Anthony Mills 1 , Kathy L. Schulman 2 , Jennifer Fusco 2 , Ricky Hsu 3 , Andrew Beyer 4 , Girish Prajapati 4 , KaramMounzer 5 , Gregory Fusco 2

1 Southern California Men’s Medical Group, Los Angeles, CA, USA, 2 Epividian, Durham, NC, USA, 3 AIDS Healthcare Foundation, Los Angeles, CA, USA, 4 Merck & Co, Inc, Kenilworth, NJ, USA, 5 Philadelphia FIGHT, Philadephia, PA, USA

CROI 2018 272