CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

684 Short-Term Renal Impact of Tenofovir Among HIV-Infected Patients in North America

RuibinWang 1 ; Gregory M. Lucas 2 ; Michelle Estrella 3 ; Michael Shlipak 4 ; Marianne Harris 5 ; Michael A. Horberg 6 ; Mari M. Kitahata 7 ; Angel M. Mayor 8 ; Sonia Napravnik 9 ; Alison Abraham 1 1 Johns Hopkins Bloomberg Sch of PH, Baltimore, MD, USA; 2 Johns Hopkins Univ, Baltimore, MD, USA; 3 Johns Hopkins Univ Sch of Med, Baltimore, MD, USA; 4 Univ of California San Francisco, San Francisco, CA, USA; 5 British Columbia Cntr for Excellence in HIV/AIDS, Vancouver, BC, Canada; 6 Mid-Atlantic Permanente Med Group, Rockville, MD, USA; 7 Univ of Washington, Seattle, WA, USA; 8 Univ Central del Caribe, Bayamon, PR, USA; 9 Univ of North Carolina at Chapel Hill, Chapel Hill, NC, USA Background: The short-term renal effect of tenofovir disoproxil fumarate (TDF) remains uncertain. Our objective was to assess estimated glomerular filtration rate (eGFR) changes within 1 year of TDF initiation among HIV-infected patients in care in North America. Methods: NA-ACCORD participants who initiated TDF or other nucleoside reverse transcriptase inhibitor (NRTI)-based antiretroviral therapy (ART) in 2000-2009 were included. Baseline was defined as date of TDF/NRTI initiation. To assess eGFR (CKD-EPI) changes during the first year of ART, nonlinear mixed effects joint models were used with a knot at month 6. Persons who discontinued TDF or other NRTI within 1 year of initiation were censored at the time of ART cessation. We stratified analyses on baseline eGFR and accounted for informative dropout due to end-stage renal disease (ESRD) or death. Models adjusted for age, race, sex, baseline CD4 cell count and viral load, prior ART exposure, diabetes mellitus, hypertension, hepatitis C infection and pre-TDF/NRTI eGFR loss. Results: 18,596 HIV+ adults were included with median (interquartile range) baseline age 43 years (37-49), eGFR 102 mL/min (88-114) and CD4 295/mm 3 (157-462). 71%were TDF-treated. 35%were blacks; 78%were men. Among persons with baseline eGFR≥90mL/min, eGFR changes in the first year following ART initiation were similar in the two ART groups [Figure A]. In the first 6 months of ART, eGFR changes per year (95% CI) were -8% (-6, -9) and -15% (-9, -21) in the TDF group and 8% (4, 10) and 14% (7, 21) in the other NRTI group, for persons with baseline eGFR 60-89 and <60mL/min, respectively. Compared to NRTI users, TDF users with eGFR<90mL/min had faster loss of renal function during the initial 6 months of ART [Figure B, C]. From 6 to 12 months, TDF users with reduced kidney function at baseline experienced significant renal recovery (eGFR 60-89: 16%/yr [95% CI: 11, 20]; eGFR<60: 60%/yr [95% CI: 37, 82]) whereas NRTI users did not (eGFR 60-89: -6%/yr [95% CI: -13, 1]; eGFR<60: -6%/yr [95% CI: -22, 10]). Consistent patterns were observed among individuals who stayed on therapy for at least 1 year. Conclusions: In this large study among HIV+ patients in care in North America, TDF was associated with short-term eGFR decline and subsequent recovery among those with reduced kidney function at baseline (eGFR<90mL/min). Investigation into whether this acute eGFR decline is associated with longer-term risk of ESRD is underway.

Poster Abstracts

685 Associations of Tenofovir Disoproxil FumarateWith Urine Biomarkers of Kidney Damage

Vasantha Jotwani 1 ; Rebecca Scherzer 1 ; Michelle Estrella 2 ; Lisa Jacobson 3 ; MalloryWitt 4 ; Frank J. Palella 5 ; Bernard J. Macatangay 6 ; Chirag Parikh 7 ; Joachim Ix 8 ; Michael Shlipak 1 1 Univ of California San Francisco, San Francisco, CA, USA; 2 Johns Hopkins Univ Sch of Med, Baltimore, MD, USA; 3 Johns Hopkins Univ, Baltimore, MD, USA; 4 Harbor-Univ of California Los Angeles Med Cntr, Torrance, CA, USA; 5 Northwestern Univ, Chicago, IL, USA; 6 Univ of Pittsburgh Sch of Med, Pittsburgh, PA, USA; 7 Yale Univ Sch of Med, New Haven, CT, USA; 8 Univ of California San Diego, San Diego, CA, USA Background: Tenofovir disoproxil fumarate (TDF) is widely prescribed for the treatment of HIV, but has been associated with the development of kidney disease. We hypothesized that TDF exposure would be associated with novel biomarkers of kidney tubular injury and fibrosis. Methods: This cross-sectional study of 884 HIV-infected men from the Multicenter AIDS Cohort Study evaluated associations of cumulative exposure to TDF and other antiretroviral medications (ARVs) with four urine biomarkers: interleukin-18 (IL-18) and kidney injury molecule-1 (KIM-1), proximal tubular injury markers; pro-collagen type III

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CROI 2016