乌鸦传媒

At the 2019 Conference on Retroviruses and Opportunistic Infections (CROI) meeting, the DISCOVER trial showed that emtricitabine/tenofovir alafenamide (F/TAF, Descovy) was noninferior to F/tenofovir disoproxil fumarate (TDF, Truvada) in preventing HIV infection at 48 weeks. Findings presented at the virtual showed similar efficacy at 96 weeks, as well as possibly superior safety for F/TAF. These data could help clinicians and PrEP users decide whether to switch to F/TAF; and still another option generic F/TDF, may be coming later this year.

In this exclusive 乌鸦传媒 video, , of Beth Israel Deaconess Medical Center in Boston, discusses the question of cost in determining what physicians should recommend for their patients.

Following is a transcript of his remarks:

I was going to talk today about a piece that a group wrote for the Annals of Internal Medicine in February of this year that related to the question about use of tenofovir alafenamide vs tenofovir disoproxil fumarate or TAF vs TDF based regimens for daily pre-exposure prophylaxis in HIV. And the background for this is that there's been a robust evidence for using TDF/FTC as daily prep for multiple populations including FDA approval and guidance for many years. And in October of 2019, there was FDA approval of daily use of TAF/FTC for prep. And this has been the result of the DISCOVER study, which was a large non-inferiority study that was amongst several thousand MSM and transgender women comparing the efficacy and safety of daily TAF/FTC vs TDF/FTC.

And the study showed that TAF/FTC for prep was non-inferior, meaning it was as protective as TDF/FTC, which was a great result in terms of new PrEP options for the population study. And the question really has been about is one or the other regimen safer? And in that study DISCOVER they found that there was a slight improvement relative to TDF in renal and bone biomarkers for people who were randomized to use the TAF regimen. People randomized to use the TDF regimen had slight increases in their overall body weight and also some poor lipid profiles including more people being prescribed statins over the course of the study group randomized to TAF.

So the reason we wrote this piece in the Annals of Internal Medicine was to try and summarize all of this for frontline clinicians who may be thinking about what's the appropriate recommendation for patients that they may see in clinic. And, initially we heard a lot of anecdotal reports from colleagues that a lot of people were taking the results of the DISCOVER study, which had been presented in abstract form at CROI in 2019 and also the International AIDS Society Conference. And we're talking about making switches from TDF to TAF based on some of the reports on the slight improvements in renal and bone markers. But as we dug into some of the data presented to the FDA in October, we thought it would be important to point out that in fact there wasn't really a safety difference that made one or the other option better for all people who may be opting for PrEP use. But in fact there were differences in the safety profiles and that TAF seemed to be better for people who might have renal and bone conditions or be at risk for adverse outcomes. But that people who were more concerned about their body weight or cardiovascular preventative health in terms of liquid profiles, then sticking with TDF might be a better option. So we really wanted to point out that there wasn't a safer option, but there were just differences in the safety profiles.

This is all really relevant because there will be availability of generic TDF/FTC starting in the fall of this year and then probably be able to pull generics off the market in early 2021 and we pull the generics, we wanted to point out that the price would probably drop substantially for TDF/FTC vs TAF/FTC. And so the cost effectiveness greatly improved with the use of a generic formulation when those multiples hit the market.

And given that the access to PrEP in this country has been affected quite substantially by cost limitations, we thought it was really important to highlight for society that en mass switch from TDF to TAF based regimens would not necessarily be cost effective. And in fact, since we put this piece in the Annals of Internal Medicine, there was another piece in the same journal by Rochelle Walensky and her group in March of this year, which was time to be presented around CROI. And they found that the cost-effectiveness of switching people to TAF/FTC versus TDF/FTC is really not there. And in fact the amount of money you'd have to pay to improve one quality adjusted life here, which is a metric of cost effectiveness, would be somewhere between three and $7 million depending on the baseline condition and comorbidities of an individual patient. And that in fact the most that we should pay as a society for using TAF vs TDF is about $300 or $400 per year per person.

So all this is to say that as clinicians to think about TAF vs TDF PrEP, it really seems like on a societal level, a large scale switching doesn't make good sense. And some from the New York City Department of Health, Demetre Daskalakis, who was a co-author on our paper, have put out statements on behalf of their public health guidance suggesting that TDF/FTC remained the first line PrEP for most people for whom it's indicated with a small percentage of people with renal and bone issues, having TAF/FTC as a great backup option. So we just thought it'd be really helpful for clinicians who may not be as familiar with all the nuances of the DISCOVER study and the FDA approval and some of the data around cost effectiveness, in terms of thinking about which are the best options for their patients. And that's really what we wanted to convey.

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