Oral Abstract Submission
Anthony Mills, MD
Chief Medical Officer
Men’s Health Foundation
Los Angeles, CA
Disclosure: Bristol Myers Squibb: Grant/Research Support
Gilead Sciences: Consultant, Grant/Research Support
Merck: Consultant, Grant/Research Support
ViiV Healthcare: Consultant, Grant/Research Support
Laura Salazar, MD
St Joseph Heritage Healthcare
Newport Beach, CA
Disclosure: Gilead sciences: Scientific Research Study Investigator, Advisor or Review Panel member, Speaker's Bureau
ViiV: Scientific Research Study Investigator, Advisor or Review Panel member, Speaker's Bureau
Peter Shalit, MD, PhD
Disclosure: Gilead Sciences: Advisor or Review Panel member, Research Grant or Support
Janssen: Advisor or Review Panel member, Research Grant or Support
Merck: Grant/Research Support, Advisor or Review Panel member
ViiV Healthcare: Advisor or Review Panel member, Research Grant or Support
Susanne Doblecki-Lewis, MD, MSPH
Associate Professor of Clinical Medicine
University of Miami
Disclosure: Gilead Sciences: Advisory Board, Grant/Research Support
Roche Diagnostics: Advisory Board
Background : In the DISCOVER PrEP trial, emtricitabine/tenofovir alafenamide (F/TAF) was non-inferior to emtricitabine/tenofovir disoproxil fumarate (F/TDF) for HIV prevention. Here, we report on the renal outcomes of F/TAF and F/TDF among all DISCOVER participants and in those on baseline F/TDF PrEP who were randomized to F/TAF.
Methods : 5387 men who have sex with men (MSM) and transgender women (TGW) at risk for HIV were randomized 1:1 to receive blinded F/TDF or F/TAF taken once daily (full cohort). Of these, 905 were on F/TDF PrEP at enrollment, of whom 465 were randomized to F/TAF. Renal function and safety assessments included urinalysis (UA), estimated glomerular filtration rate (eGFRCG), urine protein:creatinine (Cr) ratio (UPCR), markers of proximal tubular function (β2-microglobulin:Cr ratio [β2M:Cr] and retinol binding protein:Cr ratio [RBP:Cr]) and investigator-reported renal adverse events (AEs). Week 48 data are presented.
Results : In the full cohort, F/TAF was associated with more favorable changes in eGFRCG, β2M:Cr, and RBP:Cr compared to F/TDF (Table 1). Treatment-emergent proteinuria by UA was more common with F/TDF than F/TAF (24.3% vs 21.3% p=0.009), as were treatment-emergent elevations in UPCR > 200mg/g (35 [1.5%] vs. 16 [0.7%], p=0.005). Compared to F/TDF, participants taking F/TAF had numerically fewer study drug-related renal AEs, severe study drug-related renal AEs, and discontinuations due to renal AEs (Table 2). Proximal renal tubulopathy (Fanconi syndrome) was reported in one participant in the F/TDF arm and none in the F/TAF arm. In participants on F/TDF PrEP at enrollment who were randomized to F/TAF, statistically significant increases in eGFRCG were apparent as early as week 4 (Table 1 and Figure 1), as were decreases in tubular proteinuria (Table 1). Renal biomarker changes in PrEP-naïve participants mirrored those in the full cohort.
Through 48 weeks, MSM and TGW taking F/TAF for PrEP had significantly better measures of renal function and fewer study-drug related renal AEs compared to those taking F/TDF; switching from F/TDF to F/TAF was associated with improvements in eGFRCG and tubular function biomarkers. F/TAF for PrEP is effective and has a superior renal safety profile compared to F/TDF.