麻豆传媒

MEXICO CITY -- Despite not showing statistically significant superiority for HIV infection prevention in the so-called DISCOVER trial, tenofovir alafenamide (TAF) may still wind up as the preferred companion to emtricitabine for pre-exposure prophylaxis (PrEP), a researcher said here.

In a secondary analysis of DISCOVER results -- main findings of which were reported last spring -- TAF showed pharmacokinetic properties that, at least in principle, should make it a better choice than the previous standard, tenofovir difumarate (TDF), said Christoph Spinner, MD, of Technische Universität of Munich in Germany.

The primary outcome in DISCOVER was that seven patients in the TAF group developed HIV infections versus 15 on TDF, both in combination with emtricitabine. The difference was not statistically significant for superiority in the 5,400-patient trial. Nevertheless, Spinner and colleagues sought to understand whether differences between the drugs could explain the numerically lower rate with TAF.

At a press conference at the , Spinner said that TAF remains in the system longer than TDF may widen the window in which infections can be prevented. That in turn may widen the window in which the drug is actively defending against infection.

Participants in DISCOVER were randomized to receive a daily regimen of emtricitabine/TAF at a dose of 200 mg/25 mg or emtricitabine/TDF at a dose of 200 mg/300 mg. Participants were followed for up to 96 weeks, and their adherence to the regimens were measured through pill counts and how much of the drug was detected in their blood.

There were no differences in HIV risk, sexually transmitted infection, or adherence by pill count or self-report.

Spinner said that tenofovir levels in peripheral blood mononuclear cells and in dried blood spots from samples taken at week 4 were higher than the presumed protective threshold in 98% of the TAF patients tested compared with 65% of the TDF patients.

The median duration of protection after the last dose of tenofovir at steady state was also 60% longer for patients taking the emtricitabine/TAF regimen compared with those on emtricitabine/TDF, Spinner said.

Additionally, low concentration of tenofovir in peripheral blood was associated with an increased risk of acquiring HIV, and concentrations tended to be lower with TDF.

'TAF has advantageous pharmacokinetic parameters for HIV prevention compared to TDF including a more rapid, higher, and longer sustained duration of tenofovir levels above the protective threshold," Spinner said, "and may explain the differences in HIV transmission rates seen in the trial."

"Dr. Spinner's study tells us that in prevention, taking emtricitabine/TAF or emtricitabine/TDF gives us options for PrEP," press conference moderator Brenda Crabtree-Ramirez, MD, of Mexico's National Institute of Science, Medicine and Nutrition based here, told 麻豆传媒.

"Although in the DISCOVER study there was no difference in the incidence of HIV in the short term, we can't be sure what the long-term outcomes will be. The findings that patients had greater concentrations of TAF in their blood might indicate that in the long-term TAF might be better, but right now it is risky to say that there is greater efficacy in the TAF group. In the long-term will will see how these differences make a difference in outcome," said Crabtree-Ramirez. "As for, now it is really wait and see."

Matthew Spinelli, MD, of the University of California San Francisco, told 麻豆传媒 that cost is the major problem with TAF. "It is a more expensive drug than TDF, and TDF will soon become generic," he said.

"Despite the findings in the DISCOVER substudy, I still think we need more time to determine if there is a substantial difference in treatment with these tenofovir agents," he said. "Right now I would only use TAF if I had a patients with frank chronic kidney disease."