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F/TAF and F/TDF Efficacy and Safety as PrEP for 96 Weeks
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"Longer-term safety of F/TAF and F/TDF for HIV PrEP: DISCOVER trial week-96 results"
CROI 2020, March 8-11, 2020, Boston
Mark Mascolini
Data through 96 weeks of the DISCOVER comparison of emtricitabine/tenofovir alafenamide (F/TAF) and F/tenofovir disoproxil fumarate (TDF) yielded no surprises: As at week 48, F/TAF remained noninferior to F/TDF in preventing HIV infection, while bone and kidney markers favored F/TAF and lipid changes leaned toward F/TDF [1]. But the 96-week wrap-up merits attention as the largest TAF-TDF comparison in people without HIV. The data could help clinicians and PrEP users now relying on F/TDF to decide whether to switch to F/TAF or to wait for a generic F/TDF, which could come to market later in 2020 [2].
DISCOVER is an ongoing phase 3 trial that randomized cisgender men and transgender women who have sex with men to daily F/TAF or F/TDF, if they had a high risk for HIV infection. When all participants finished week 48 and half made it to week 96, an interim analysis found that F/TAF is noninferior to F/TDF in warding off HIV infection, that both two-in-one pills are well tolerated, and that F/TAF produced friendlier kidney and bone signals.
Among the 2694 participants originally randomized to F/TAF, 2187 (81%) were taking the prophylactic pill at week 96; among the 2693 people randomized to F/TDF, 2218 (82%) continued using it for 96 weeks. Both groups had a median baseline age of 34, and 84% were white. A little over 15% in each group were taking F/TDF PrEP when they entered DISCOVER.
At week 96 there were 8 HIV infections in the F/TAF arm for an incidence of 0.16 per 100 person-years. Fifteen people randomized to F/TDF became infected with HIV for an incidence of 0.30 per 100 person-years. Statistical analysis at week 96 calculated an incidence rate ratio (IRR) of 0.54 leaning in favor of F/TAF and confirming the continued noninferiority of F/TAF to F/TDF in preventing HIV infection (upper bound of the IRR 95% confidence interval 1.26, below the prestipulated 1.62 noninferiority margin).
An overall 96-week safety summary showed similar results for the two agents. Study drug-related serious adverse event rates were 0.1% for F/TAF and 0.2% for F/TDF. Only 1% stopped F/TAF and 2% stopped F/TDF because of adverse events.
Both spine and hip bone mineral density (BMD) continued to improve from week 48 to week 96 in F/TAF users, while spine BMD continued to wane in F/TDF users and hip BMD stayed stable. After 96 weeks 4% taking F/TAF and 16% taking F/TDF had a 5% or greater drop in spine BMD, a significant difference (P < 0.001). On the other end of the spectrum, 10% taking F/TAF and 4% taking F/TDF had a 5% or greater gain in spine BMD (P = 0.047).
Six people stopped F/TDF and 2 stopped F/TAF because of kidney function readings. Fanconi syndrome emerged in one F/TDF user and in no one taking F/TAF. Triglycerides, total cholesterol, LDL cholesterol, as well as HDL cholesterol fell more through 96 weeks with F/TDF than with F/TAF. The total-to-HDL cholesterol ratio stayed flat with F/TDF while edging up by a median 0.1 with F/TAF, but this difference was not significant (P = 0.18).
Body mass index hardly changed through 96 weeks in either group, while weight rose a median 1.7 kg with F/TAF and a median 0.5 kg with F/TDF, a significant difference (P < 0.001). The researchers observed that the weight gain with F/TAF matched that of the placebo group in the original PrEP study, iPrEx.
Reference
1. Ogbuagu O, Podzamczer D, Salazar LC, et al. Longer-term safety of F/TAF and F/TDF for HIV PrEP: DISCOVER trial week-96 results. Conference on Retroviruses and Opportunistic Infections (CROI). March 8-11, 2020. Boston. Abstract 92.
2. Krakower DS, Daskalakis DC, Feinberg J, Marcus JL. Tenofovir alafenamide for HIV preexposure prophylaxis: what can we DISCOVER about its true value? Ann Intern Med. 2020 Jan 14. doi: 10.7326/M19-3337.
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