CROI 2016 Abstract eBook
Abstract Listing
Poster Abstracts
N-terminal pro-peptide (PIIINP), a tubulointerstitial fibrosis marker; and albumin-creatinine ratio (ACR), a marker of glomerular injury. We used multivariable robust regression analyses and the least absolute shrinkage and selection operator (LASSO) method to determine which of multiple ARVs were associated with each biomarker. Results: 573 (65%) participants were current TDF users, and 112 (13%) were former users. In adjusted analyses that controlled for LASSO-selected ARVs simultaneously, each year of TDF exposure was associated with 3.3% higher urine IL-18 (95%CI: 0.8%, 5.8%), 3.4% higher KIM-1 (1.1%, 5.7%), and 3.1% higher PIIINP (0.8, 5.5). By contrast, the associations of TDF with ACR did not reach statistical significance (2.8% per year; -0.6%, 6.2%). Lopinavir/ritonavir exposure was associated with higher IL-18 (3.7% per year; 0.8%, 6.7%) and ACR (6.8%; 2.6%, 11.1%), and efavirenz exposure was associated with lower IL-18 (-3.0%; -4.8%, -1.3%) and KIM-1 (-3.9%; -5.7%, -2.2%). Conclusions: Cumulative TDF exposure was associated with biomarkers of proximal tubular injury and fibrosis in HIV-infected men. These biomarkers may be useful for early detection and monitoring of subclinical toxicity from TDF. 686 Nature of Immunosuppression and Chronic Kidney Disease Risk in HIV-Positive Persons Lene Ryom 1 ; Jens D. Lundgren 1 ; Peter Reiss 2 ; Michael Ross 3 ; Christoph A. Fux 4 ; Philippe Morlat 5 ; Eric Fontas 6 ; Colette Smith 7 ; Amanda Mocroft 7 ; for the D:A:D Study Group 1 Rigshospitalet, Univ of Copenhagen, Copenhagen, Denmark; 2 Amsterdam Inst for Global Hlth and Develop, Amsterdam, Netherlands; 3 Mount Sinai Sch of Med, New York, NY, USA; 4 Kantonsspital Aarau, Aarau, Switzerland; 5 Univ de Bordeaux, Bordeaux, France; 6 Nice Univ Hosp, Nice, France; 7 Univ Coll London, London, UK Background: Immunosuppression is a known independent predictor of chronic kidney disease (CKD) in HIV-positive persons, but the nature of the association between different measures of immunosuppression and CKD is unknown. Methods: D:A:D study participants without CKD and with >2 Cockcroft Gault (estimated glomerular filtration rate) eGFR measurements after 1/1/2004 (baseline) were followed until the earliest of CKD (eGFR<60, confirmed >3 months apart), last eGFR plus 6 months or 1/2/2014. Measures of immunosuppression included baseline, current and nadir CD4, 6-months’ time-lagged CD4, % of follow-up time (%FU) with CD4<200, time-averaged AUC for CD4 and CD4 recovery (baseline CD4<200 followed by current CD4>200). Poisson regression models were used to determine the relationship between CKD and each measure of immunosuppression accounting for relevant confounders, and tested for interactions with the D:A:D CKD risk score, demographics, HCV and HIV-related factors. Akaike Information Criteria (AIC) was used to indicate which measures were better CKD predictors. Results: Of the 33,144 persons included in analyses 1,588 developed CKD (incidence rate (IR) 7.2 [95%CI 6.8-7.5]/1000 PYFU) during a median 7.2 years FU (IQR 5.0-8.9). Those included were predominately white (47.6%), male (74.0%) with a baseline median age of 41 years (IQR 35-47) and median CD4 of 440 (292-626). The crude CKD IR varied for different measures of immunodeficiency (Fig). Univariately, all measures of immunosuppression were significantly associated with CKD, most strongly for nadir CD4 (>500 vs. <50, IR 0.39 [0.31–0.48]) and %FU CD4<200 (>25% vs. 0%, IR 1.86 [1.62-2.13]). Multivariately, the strongest CKD predictor was %FU CD4<200 (>25% vs. 0%, 1.29 [1.11-1.30]). There was a significant (p<0.0001) interaction between %FU CD4<200 and the D:A:D CKD risk score; those at lowest estimated CKD risk had a significantly higher CKD IR (>25% vs. 0%, 3.57 [2.23-5.70]) compared to those at highest CKD risk (>25% vs. 0%, 1.24 [1.05-1.46]). There was no significant interaction between measures of immunosuppression and ethnicity, age, HIV-RNA, ART status or use of nephrotoxic antiretrovirals including tenofovir, indinavir, atazanavir/r and lopinavir/r. Conclusions: The strongest association between CKD and immunosuppression was observed for the relative duration of severe immunosuppression, which was of greatest importance in persons at low estimated CKD risk. These new data support aggressive ART to maintain/restore immune function.
Poster Abstracts
687 Traditional and Viral Factors AssociatedWith Iohexol-Based GFR Slope Over 3 Years Gregory M. Lucas 1 ; Mohamed G. Atta 1 ; Katie Zook 1 ; Allison M. McFall 1 ; Shruti H. Mehta 1 ; Derek M. Fine 1 ; James H. Stein 2 ; George J. Schwartz 3 1 Johns Hopkins Univ, Baltimore, MD, USA; 2 Univ of Wisconsin-Madison, Madison, WI, USA; 3 Univ of Rochester, Rochester, NY, USA Background: Monitoring kidney function is important in HIV-positive persons, but creatinine-based estimates of glomerular filtration rate (GFR) have limitations. There are little to no data assessing longitudinal GFR trends in HIV-positive persons using a gold-standard measure of GFR. Methods: We measured GFR based on iohexol plasma disappearance (iGFR) annually for 3 years in non-diabetic, HIV-positive and HIV-negative volunteers with normal estimated kidney function. Additionally, we measured carotid intima-media thickness and pulse wave velocity at baseline. We used mixed linear models to evaluate factors associated with baseline iGFR and iGFR slope. Results: 191 HIV-positive and 100 HIV-negative, predominantly black individuals (median age 49 years) participated in the study and completed a median (IQR) of 4 (3, 4) annual iGFR assessments. The average baseline iGFR values were lower in HIV-positive compared with HIV-negative participants (103.2 vs. 110.8, mL/min/1.73m 2 , P=0.004), despite similar estimated GFR by the CKD-EPI equation (average eGFR, 101 mL/min/1.73m 2 in both groups). Subsequent iGFR decline was not significantly different in HIV-positive and HIV-negative subjects (iGFR slope, -1.94 vs. -3.28 mL/min/1.73m 2 per year, respectively, P=0.092). In the HIV-positive group, lower baseline iGFR values were significantly associated with the presence of carotid plaque (98.3 vs. 109.4 mL/min/1.73m 2 , P<0.001) and hepatitis C virus coinfection (100.0 vs. 107.1 mL/min/1.73m 2 , P=0.024). A non- suppressed HIV RNA level at baseline was associated with a significantly more rapid iGFR decline compared with individuals with HIV RNA < 400 copies/mL (-4.69 vs. -1.31 mL/ min/1.73m 2 per year, P=0.005). Other factors significantly associated with iGFR slope in HIV-positive participants included albuminuria and glycosylated hemoglobin. Increased pulse wave velocity, a measure of vascular stiffness, had a near statistically significant association with more rapid iGFR decline. Conclusions: Despite similar estimated GFR in the two groups, HIV-positive participants had significantly lower baseline iGFR than HIV-negative participants. Subsequent 3-year iGFR slope was similar in the two groups. Among HIV-positive subjects, hepatitis C coinfection was associated with a lower baseline iGFR and a non-suppressed HIV RNA at baseline was strongly associated with a more rapid iGFR decline.
284
CROI 2016
Made with FlippingBook - Online catalogs