Abstract Body

In DISCOVER, a multinational, double-blind, randomized controlled trial, F/TAF compared to F/TDF demonstrated noninferior efficacy for HIV prevention and improved bone mineral density (BMD) and renal safety biomarkers at week (W) 48. We now report W96 safety outcomes.

We evaluated renal and lipid parameters and weight changes in participants on F/TAF vs F/TDF through W96. BMD was evaluated in a substudy and also examined in younger participants (age <25 yrs) who are still accruing bone mass. We also examined glomerular function, proteinuria, and biomarkers of proximal tubular injury (PTI; β2M/Cr, RBP/Cr) in participants ≥50 yrs of age and those with moderate renal impairment (eGFR 60‒<90 mL/min).

Among 5387 participants evaluated, unlike those on F/TDF (n=2693), F/TAF users had significantly increased BMD, with the magnitude of between-group differences increasing between W48 to W96 (Table 1). Participants <25 yrs had greater declines in BMD on F/TDF with a greater magnitude of difference between groups than those ≥25 yrs. Overall, F/TAF users had increases in eGFR and declines in UPCR and PTI biomarkers. Older participants on F/TDF had a greater magnitude of decline in eGFR and a greater increase in UPCR and PTI markers compared to younger F/TDF users. Similarly, those with eGFR 60‒<90 mL/min had greater statistically significant changes in PTI markers, if on TDF, compared with those with eGFR ≥90 mL/min. Those on F/TAF had stable lipids through W96, whereas those on F/TDF had decreases in lipids at W48 and W96. Those on F/TDF had a smaller weight increase than those on F/TAF through W96 (Table 1).

These DISCOVER data allow for the largest single-variable comparison of the two tenofovir prodrugs without underlying HIV infection and in the absence of third antiretroviral agents. Overall, those on F/TAF had increased BMD compared to declines in those on F/TDF, with more pronounced differences in younger participants. Older participants on F/TDF and those with impaired renal function had more adverse impact on renal biomarkers. Lipid and weight changes were consistent with the known lipid-lowering and weight suppressive effects of TDF, respectively. F/TAF is a safe, longer-term option for PrEP, with certain subgroups experiencing a greater magnitude of benefit in BMD and renal biomarkers.