CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

Methods: We analysed stored urine for albumin:creatinine (ACR) and retinol-binding protein:creatinine (RBPCR) ratio, and fractional excretion of phosphate (FE-PO4) and urate (FE-urate). BMD at the lumbar spine (LS) and femoral neck (FN) was measured by dual X-ray absorptiometry (expressed in g/cm2). ART exposure was stratified into four groups (no-TDF/no-PI, no-TDF/ PI, TDF/no-PI, TDF/PI). We used linear regression models to assess associations between tubular markers and BMD, adjusting for clinical characteristics and ART exposure. Results: 228 individuals (median [IQR] age 57 [53, 64] years, 47% female, time on ART 10 [6, 16] years, CD4 643 [473, 811] and 98%with VL <200 c/mL) contributed to the analyses. The prevalence of osteoporosis (T score <-2.5) at LS and FN ranged from 21-30% and 14-28% in the four ART exposure groups, respectively (p=0.24 and p=0.08). In univariate analysis, lower LS-BMD was associated with female sex and lower BMI but not with RBPCR (p=0.673), and lower FN-BMD with older age, female sex, lower BMI and higher RBPCR (β -0.014 [95%CI -0.025, -0.002], p<0.0001); neither BMD at LS or FN was associated with eGFR, ACR, FE-PO4, FE-urate or ART exposure group. In multivariable models adjusting for age, gender and BMI, RBPCR was no longer associated with BMD-FN (Table, Model 1). Further adjustment for TDF exposure fully attenuated the relationship between RBPCR and FN BMD (Model 2). Using no TDF/no-PI as the ART reference group, exposure to no-TDF/PI and TDF/no-PI was associated with lower LS BMD, and exposure to TDF/no-PI and TDF/PI with lower FN BMD. Conclusion: In this cohort of older PWH with a high prevalence of osteoporosis, RBPCR was the only marker of RTD associated with BMD, but the association lessened with demographic adjustment and was fully abrogated after adjustment for TDF exposure. Continuous TDF exposure was associated with significantly lower BMD at the femoral neck. 690 GENETIC AND CLINICAL RISK FACTORS FOR CHRONIC KIDNEY DISEASE IN HIV Léna G. Dietrich 1 , Catalina Barcelo 2 , Christian Thorball 3 , Lene Ryom 4 , Stephen R. Cole 5 , Felix Burkhalter 1 , Chantal Csajka 2 , Jacques Fellay 3 , Bruno Ledergerber 6 , Philip E. Tarr 1 1 Kantonsspital Baselland, Bruderholz, Switzerland, 2 Lausanne University Hospital, Lausanne, Switzerland, 3 École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, 4 Copenhagen HIV Program, Copenhagen, Denmark, 5 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 6 University Hospital Zurich, Zurich, Switzerland Background: In the general population, 53 common single nucleotide polymorphisms (SNPs) have been found to associate with chronic kidney disease (CKD) through genome-wide association studies (GWAS). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CKD has not been evaluated in the setting of HIV infection. Methods: We performed genome-wide genotyping in HIV-positive, white Swiss HIV Cohort Study participants with normal baseline estimated glomerular filtration rate (eGFR >90 mL/min/1.73 m2). We applied a 1:1 case-control design with incidence density matching. Since we had more cases than controls, we repeated the matching process 2000 times with random resampling from cases and controls. The averaged odds ratio (OR) of CKD from conditional logistic regression analyses was calculated as the antilog of the mean of the 2000 log-transformed ORs and the 95% confidence interval (CI) was based on the 2.5 and 97.5 percentiles. We present uni- and multivariable analyses of CKD and the effects of genetic background, clinical D:A:D CKD risk score, and potentially nephrotoxic antiretrovirals. Results: We included 754 cases with CKD defined as confirmed eGFR drop to <60 mL/min/1.73 m2 (n=144) or eGFR drop of >25% (n=610), and 323 controls with eGFR drop of <15%. A genome-wide genetic risk score built from

consecutive years (2016 and 2017) for diagnosis of hypoPT were included in the study. HypoPT was defined as confirmed PTH <65 pg/mL and albumin- corrected calcium<2.12 mmol/L. Results: In total, 496 PLWH were included; median age was 47 (IQR, interquartile range: 40-54 years), 393 (79.2%) were male. TDF was used by 51.8% and 39.9% of PLWH in 2016 and 2017, respectively. Laboratory criteria for hypoPT was met in 15.3 % of PLWH (76/496) in 2016 and in 8.3 % (41/496) in 2017. 14/496 PLWH (2.8 % [95% CI: 1.6-4.7]) presented with confirmed hypoPT. Characteristics of PLWH with and without confirmed hypoPT are shown in Table 1. Univariate associations between potential covariables and confirmed hypoPT were as follows in crude analysis: male sex (OR 1.0 [95% CI: 0.3-3.5]; P = 0.95), age ≥55 years (OR 0.3 [95% CI: 0.0-1.9]; P = 0.19), average cystatin c ≥1.0 mg/dl (OR 0.4 [95% CI: 0.1-1.8]; P = 0.22), being vitamin D deficient in both years (OR 0.2 [95% CI: 0.0-1.8]; P = 0.16), and use of tenofovir disoproxil fumarate (TDF) in both years (OR 4.3 [95% CI: 1.3-14.1]; P = 0.01). TDF remained significantly associated with hypoPT after adjusting for sex, age (≥55 years), and vitamin D deficiency (OR 4.2 [95% CI: 1.3-13.9]; P = 0.02). Conclusion: Prevalence of hypoPT was unexpectedly high in our cohort of PLWH with 2.8% compared to 0.01-0.04 % as reported in general populations. TDF containing therapy was the only factor significantly associated with hypoPT. This is consistent with a much higher prevalence of hypoPT in 2016, before the more wide-spread use of tenofovir alafenamide starting end of 2016 (proportion of PLWH on TAF were 18.6% and 30.0% (P<0.001) in 2016 and 2017, respectively). Although our results on hypoPT seem to be in contrast to previous findings of high PTH levels in PLWH on TDF, a possible link might be hypocalcemia resulting in secondary hyperparathyroidism in some, and hypoPT in other PLWH, that have HIV-associated impaired PTH-secretion.

Poster Abstracts

689 IMPACT OF RENAL TUBULE FUNCTION ON BONE MINERAL DENSITY IN OLDER PEOPLE WITH HIV Elena Alvarez-Barco 1 , Lucy Campbell 2 , Keith Burling 3 , Sebastian Noe 4 , Mingjin Yan 5 , Hiba Graham 5 , Martin Rhee 5 , Patrick W. Mallon 1 , Frank Post 6 1 University College Dublin, Dublin, Ireland, 2 Kings College London, London, UK, 3 Cambridge University, Cambridge, UK, 4 MVZ Karlsplatz HIV Research and Clinical Care Center, Munich, Germany, 5 Gilead Sciences, Inc, Foster City, CA, USA, 6 King’s College Hospital NHS Foundation Trust, London, UK Background: Whether renal tubule dysfunction (RTD), common in people with HIV (PWH), contributes to low bone mineral density (BMD) remains controversial. We studied the relationship between RTD and BMD in a cross- sectional study (GS-US-104-0423) in a group of older (men >50 years and post-menopausal women) PWH on stable antiretroviral therapy (ART) that had always or never contained tenofovir (TDF), with or without exposure to protease inhibitors (PI) for the past three years.

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