CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

694 GLOMERULAR FILTRATION RATE RECOVERY AFTER A SWITCH FROM TDF TO TAF OR ABC Rosanne Verwijs 1 , Ingeborg Wijting 1 , Marjo van Kasteren 2 , Jan G. Hollander 3 , Inge Derdelinckx 4 , Guido van den Berk 5 , Saskia Vrouenraets 6 , Mark Claassen 7 , Wouter Bierman 8 , Casper Rokx 1 , Bart Rijnders 1 1 Erasmus University Medical Center, Rotterdam, Netherlands, 2 Elisabeth– TweeSteden Ziekenhuis, Tilburg, Netherlands, 3 Maasstad Hospital, Rotterdam, Netherlands, 4 University Hospitals Leuven, Leuven, Belgium, 5 OLVG, Amsterdam, Netherlands, 6 Slotervaart MC, Amsterdam, Netherlands, 7 Rijnstate Hospital, Arnhem, Netherlands, 8 University Medical Center Groningen, Groningen, Netherlands Background: Tenofovir-disoproxil fumarate (TDF) containing cART can be associated with an accelerated decline of the estimated glomerular filtration rate (eGFR). Limited data are available on the extent of the reversibility of this eGFR decline and whether using T-alafenamide (TAF) is non-inferior to abacavir (ABC) regarding eGFR recovery after TDF discontinuation. Methods: The BACTAF-studies are 2 multicenter studies; an ongoing prospective randomized study (NCT02957864) and a retrospective cohort study. Both have similar goals; 1. Evaluate the reversibility of TDF-associated eGFR decline and 2. Compare the eGFR recovery in pts switching to TAF or ABC. Pts were included if they had switched from TDF to TAF or ABC for a significant eGFR-decline, defined as a decline of >3mL/min/yr during ≥5yrs of TDF use or an eGFR decline >25% or an eGFR<70mL/min with eGFR>90mL/min at TDF initiation. Pts with detectable HIV-RNA, diabetes, history of cardiovascular disease, uncontrolled hypertension, use of >1 antihypertensive drug, use of potentially nephrotoxic medication, ABC resistance, HBV/HCV coinfection or another diagnosed kidney disease that may partially explain the eGFR-decline were excluded to increase the likelihood of TDF-relatedness of the eGFR decline. An eGFR recovery of >50% at week 48 after TDF discontinuation was considered successful and defined the primary endpoint. Results: Of the 215 pts included, 114 switched to TAF and 101 to ABC. eGFR had declined by a mean of 5.1mL/min/yr and 6.7 mL/min/yr during a median of 7 and 5yrs of TDF use respectively. The mean eGFR was 73mL/min at TAF and 67mL/min at ABC initiation, and 22% and 33% had an eGFR<60 mL/min. Week 48 eGFR results were available for 187 pts and showed significant increases by 6.7mL/min with TAF and 6.5mL/min with ABC (p<0.001 compared to baseline for both, p>0.1 for TAF versus ABC). A >50% eGFR recovery was observed in 28/100 (28%) and 23/85 (27%) respectively (p>0.1). In 23 of 46 patients with w48 results available and eGFR<60 at TDF discontinuation, a recovery to >60ml/min was observed. Overall, more pts discontinued ABC than TAF (11% vs 2%, p=0.008) and this was mostly driven by discontinuations for drug-related AE (10% vs 2%, p=0.014). HIV-RNA remained suppressed in all but 2 pts. Conclusion: Although a modest improvement in eGFR was observed after TDF discontinuation, few patients recovered >50% of their eGFR. The recovery rate in patients that switched to TAF and ABC was comparable. 695 SUBCLINICAL TUBULAR IMPAIRMENT IS COMMON IN ART-TREATED HIV+ PATIENTS IN UGANDA Cecilia Costa 1 , Silvia Scabini 1 , Arvind Kaimal 2 , William Kasozi 2 , Jessica Cusato 1 , Olive Mbabazi 2 , John Bosco Kafufu 2 , Erisa S. Mwaka 2 , Giovanni Di Perri 1 , Mohammed Lamorde 2 , Andrea Calcagno 1 , Barbara Castelnuovo 2

693 EVOLUTION AND REVERSIBILITY OF RENAL FUNCTION AFTER SWITCH FROM TDF TO TAF REGIMENS Roberta Gagliardini 1 , Patrizia Lorenzini 1 , Alessandro Cozzi-Lepri 2 , Nicola Gianotti 3 , Loredana Sarmati 4 , Stefano Rusconi 5 , Emanuela Messina 3 , Amedeo Capetti 5 , Annalisa Saracino 6 , Giordano Madeddu 7 , Antonella D’Arminio Monforte 8 , Andrea Antinori 1 , for the Icona Foundation Study Group 1 Lazzaro Spallanzani National Institute for Infectious Diseases, Rome, Italy, 2 University College London, London, UK, 3 San Raffaele Scientific Institute, Milan, Italy, 4 University of Rome Tor Vergata, Rome, Italy, 5 ASST Fatebenefratelli, Milan, Italy, 6 University of Bari, Bari, Italy, 7 University of Sassari, Sassari, Italy, 8 University of Milan, Milan, Italy Background: Tenofovir alafenamide (TAF) benefits over Tenofovir disoproxil fumarate (TDF) on renal function has been consistently demonstrated mainly as change of renal filtrate in randomized clinical trials. However, a recent meta- analysis has shown a significant advantage of TAF (in term of discontinuations for renal events) only if combined with a boosted third drug. Aim of the study was to evaluate size of improvement and reversibility of renal function in patients (pts) previously exposed to TDF who switched to TAF. Methods: HIV+ pts from the Icona Foundation Cohort switching from a TDF- to a TAF-containing regimen, maintaining the same third drug were included. Outcomes: a) difference in estimated glomerular filtration rate (eGFR, by CKD-EPI formula) at 3-6 months (the later measurement); b) proportion of pts with recovery of eGFR to the baseline before TDF introduction (± 5%); c) change of eGFR category in CKD (from G2 60-89 ml/min/1.73 m2 to G1≥90). T-test for paired and unpaired samples was used to analyze eGFR change and Poisson regression analysis for predictors for all the two categorical outcomes. Results: 947 pts were included: 504 in unboosted regimen (75% NNRTI as third drug, 25% INI), 443 in boosted one (21% PI, 79% INI); 793 (84%) males, median age 44 (36-52) years, eGFR 93 (81-105) ml/min/1.73 m2 at baseline (BL, time of switch to TAF), eGFR 109 (98-118) before TDF introduction, TDF exposure 3 (2-5) years. Mean change in eGFR after 3-6 months (data available for 627 pts) was +1.2 ml/min/1.73 m2 in the overall population (p=0.007), and +1.7 and +0.6 in unboosted and boosted, respectively (p=0.19). An eGFR recovery to pre-TDF values was observed in 302/896 (33.7%) pts; higher eGFR pre-TDF was associated to a lower probability of recovery, while higher CD8 values and being on a unboosted regimen predicted greater probability of recovery (Table 1). A change from G2 to G1 eGFR category in CKD was observed in 96/394 (24.4%), the use of booster did not seem to affect this outcome (Table 1). Conclusion: After switching from TDF to TAF, only a small even statistically significant improvement in eGFR was observed and a complete recovery of renal filtrate or a transition to normal CKD category occurred in less than half of cases over a median of 1 year of observation. Unboosted regimens seem to be associated with a higher probability of regaining renal filtrate. These data may be useful for selecting in which patients to maintain TDF without jeopardizing renal function.

Poster Abstracts

CROI 2019 266