CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

1). There was no significant mean (95%CI) difference between groups in percent change in TBS at 24 months (-0.05 [-2.9 to 2.8]). Conclusion: In this osteopenic population with relatively preserved bone microarchitecture, both TDF cessation and zoledronic acid were associated with small increases in TBS that were not significantly different by randomised arm, unlike the significant increase in BMD. The results are consistent with an increase in BMD due primarily to mineral accretion by both interventions rather than an improvement in bone micro-architecture.

1 Cleveland Clinic, Cleveland, OH, USA, 2 University of California San Diego, San Diego, CA, USA, 3 Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA Background: Chronic kidney disease (CKD) remains a serious complication in people with HIV (PWH), despite effective antiretroviral therapy (ART), and early markers of renal injury are needed. Iron homeostasis, involving the iron- storage and delivery proteins ferritin and transferrin, has an emerging role in renoprotection and is dysregulated by HIV and inflammation. Since PWH have persistent inflammation on suppressive ART, we hypothesized that these iron- regulatory proteins are markers of renal injury and/or renal function in PWH. Methods: Ferritin, transferrin, beta-2-microglobulin, and neopterin were quantified by ELISA in serum or plasma in 94 PWH with available markers of renal function [blood urea nitrogen (BUN), creatinine] and renal outcome (serum albumin) from a large, observational HIV study. Glomerular filtration rate was estimated using the CKD-EPI equation (eGFR). Ferritin and transferrin associations with renal function, injury, and outcome markers were evaluated using Pearson’s correlations and multivariable regression models, adjusting for potential confounders. Results: Study participants included in this analysis were 19%women, 30% black, 9.6% diabetic, and all virologically suppressed [mean age 48±9 years, median nadir CD4 158 cells/µL (interquartile range, IQR 30-263, mean hgb 14.4±2 g/dL]; 63%were on tenofovir. Median ferritin levels were 135 ng/mL (IQR 73-250) and transferrin 314 mg/dL (IQR 268-364). Ferritin was correlated to serum creatinine (r=0.73, p<0.0001), BUN (r=0.58, p<0.0001), the eGFR (r=- 0.20, p<0.05), immune activation, renal injury and outcome markers (r=0.74 for neopterin, p<0.0001; beta-2-microglobulin, r=0.75, p<0.0001; serum albumin, r=-0.23, p=0.02), but not to transferrin. Transferrin was weakly correlated to creatinine, eGFR, and serum albumin (r=-0.23, 0.30, and 0.21, respectively, all p<0.05). Higher serum ferritin and transferrin were each associated with higher (better) eGFR, adjusting for age, black race, hemoglobin, tenofovir use, hypertension, beta-2-microglobulin, and each other (p=0.037 for ferritin; p=0.001 for transferrin). Adjustment for diabetes had minimal effect on results. Conclusion: Higher levels of transferrin and ferritin are associated with better renal function in virologically suppressed PWH, independent of inflammation, immune activation, and other factors; these proteins may actively contribute to renal iron homeostasis during ART, dysregulation of which can promote renal injury and CKD. 692 CHANGE IN TRABECULAR BONE SCORE (TBS) AFTER ZOLEDRONIC ACID INFUSION OR TDF SWITCH Jennifer Hoy 1 , Stephen J. Kerr 2 , Didier Hans 3 , Nicholas Pocock 4 , Andrew Carr 4 , for the ZeST Study Group 1 Alfred Hospital, Melbourne, VIC, Australia, 2 HIV–NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand, 3 University of Lausanne, Lausanne, Switzerland, 4 St. Vincent's Hospital, Sydney, NSW, Australia Background: Significantly greater increase in bone mineral density (BMD) occurred in osteopenic adults on suppressive Tenofovir Disoproxil Fumarate (TDF)-based ART randomized to receive 2 annual infusions of zoledronic acid versus switching off TDF. The aim of this study was to determine the impact of TDF switch versus zoledronic acid on TBS (an indirect measurement of bone microarchitecture and independent predictor of fracture risk in the general population). Methods: TBS scores were derived from annual lumbar spine dual-energy x-ray absorptiometry (DXA) images following extraction of the raw data using TBS insight software (Medimaps SA, France). TBS was calculated as the mean value of the L1-L4 vertebral images, corrected for weight. Change between the zoledronic acid arm and TDF switch arm over 24 months of follow-up was compared using regression models in a post-hoc, per-protocol analysis. microarchitecture). The mean (SD) baseline TBS was 1.3 (0.11) for the zoledronic acid group and 1.31 (0.13) for the TDF switch group. The mean (SD) percent increase in BMD in 37 individuals on zoledronate was 6.3 (2.9)% at month (M)12 and 7.4 (3.5)% at M24 while in 38 individuals who switched off TDF it was 3.1 (3.9)% at M12, and 2.9 (4.2)% at M24. The absolute and percent changes in BMD from baseline were significantly different between zoledronate and TDF switch groups (p<0.001). In contrast, the mean (SD) increase in TBS was 1.08 (6.11)% at M12 and 0.99 (6.79)% at M24 for the zoledronic acid group compared with 0.68 (5.01)% at M12 and 1.04 (5.47)% at M24 for the TDF-switch group (Figure Results: At baseline, 41.3% of participants had a TBS >1.35 (normal bone microarchitecture) and 17.5% had a TBS <1.2 (degraded bone

Poster Abstracts

693 LOW BONE MINERAL DENSITY IN OLDER PEOPLE WITH HIV: THE RENAL- BONE AXIS AND ART Elena Alvarez-Barco 1 , Lucy Campbell 2 , Alejandro A. Garcia 1 , Ian Walsh 3 , Willard Tinago 1 , Jennifer J. Brady 3 , Keith Burling 4 , Sebastian Noe 5 , Marie Neuville 6 , Francois Jouret 6 , Mingjin Yan 7 , Hiba Graham 7 , Martin Rhee 7 , Frank Post 8 , Patrick W. Mallon 1 1 University College Dublin, Dublin, Ireland, 2 Kings College London, London, UK, 3 Mater Misericordiae University Hospital, Dublin, Ireland, 4 Cambridge University, Cambridge, UK, 5 MVZ Karlsplatz HIV Research and Clinical Care Center, Munich, Germany, 6 University of Liege, Liege, Belgium, 7 Gilead Sciences, Inc, Foster City, CA, USA, 8 King's College Hospital NHS Foundation Trust, London, UK Background: Data on low bone mineral density (BMD) in people with HIV (PWH) are mainly derived from younger adults. We explored the relative contribution of antiretroviral therapy (ART) and alterations in the renal-bone axis to lower BMD in older PWH Methods: Sub-analysis of the GS-US-104-0423 study, a cross-sectional study of ART-treated HIV-positive men >50 years and post-menopausal women. ART was stratified into 4 groups based on always or never treated with tenofovir disoproxil fumarate (TDF) and/or protease inhibitors (PI): noTDF/noPI, noTDF/ PI, TDF/noPI, TDF/PI. In stored blood we analyzed bone turnover markers: osteocalcin (OC), procollagen type 1 amino-terminal propeptide (P1NP) and C-terminal cross-linking telopeptide of type 1 collagen (CTX-1); markers of bone regulation: osteoprotegerin (OPG), surface-bound receptor activator of nuclear factor kappa-B ligand (sRANKL) and phosphatonin (FGF-23), 25(OH) vitamin D and parathyroid hormone (PTH). We analyzed renal tubular markers retinol binding protein (RBP/Cr), carbonic anhydrase III (CA3) and fractional excretion of phosphate (FEPO4) in stored urine. BMD (g/cm 2 ) at the lumbar spine (LS) and femoral neck (FN) was measured by dual X-ray absorptiometry. The relevant impact of ART exposure and bone/renal markers on BMD was explored using logistic regression adjusted for demographic factors (age, gender, ethnicity, BMI and smoking status) Results: 247 individuals (median age 57 [IQR 53, 65] years, 47% female, 87% white, time on ART 10 [6, 16] years, CD4 643 [473, 811] cells/mm 3 and 98%with HIV RNA<200c/mL) contributed to the analysis. Prevalence of low BMD (T-score <-1) at LS and FN was 55% and 60%, respectively. RBP/Cr, FEPO4, OC, P1NP, CTX-1 and PTH differed significantly by ART group, with higher values in the TDF

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