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FDA approves Descovy, an updated version of Truvada—but not for PrEP

, by Liz Highleyman

DescovyThe U.S. Food and Drug Administration this week approved Descovy, Gilead Sciences’ latest combination pill containing emtricitabine and an updated version of tenofovir. The new tenofovir alafenamide, or TAF, is easier on the kidneys and bones than its predecessor, tenofovir disoproxil fumarate (TDF).

Descovy offers a new option for antiretroviral treatment, but it was not approved for HIV prevention—and it is not yet clear whether it will work as well for PrEP as Truvada, which contains TDF and emtricitabine. Daily Truvada remains the only FDA-approved PrEP regimen.

“Emtricitabine and TAF is not known to work for PrEP, and may work poorly because of low penetration of the drug into rectal and vaginal tissues,” Robert Grant, MD, from the UCSF Gladstone Institutes and San Francisco AIDS Foundation told BETA. “Emtricitabine and TDF is quite safe for PrEP and is known to work when used.”

Tenofovir is one of the most widely used antiretrovirals and is generally considered safe and well tolerated, but the TDF formulation (sold as Viread and also as an ingredient in the Atripla, Complera, and Stribild combination pills) can cause bone loss soon after starting treatment and impaired kidney function in susceptible people.

TAF is a pro-drug that delivers the active agent, tenofovir diphosphate, to HIV-infected cells more efficiently than TDF. TAF produces high drug levels in T-cells with smaller doses, which means lower concentrations in the blood and less drug exposure for the bones, kidneys, and other organs and tissues.

Descovy is a once-daily pill that contains emtricitabine and TAF—similar to Truvada, but with 25 mg of TAF replacing 300 mg of TDF. It should be taken with at least one other antiretroviral drug, such as an HIV integrase inhibitor, protease inhibitor, or NNRTI. Descovy is the third approved TAF-containing combination pill, after Genvoya (with elvitegravir and cobicistat) and Odefsey (with rilpivirine).

Approval of Descovy was based on Phase 3 clinical trials showing that a TAF-containing regimen worked as well as TDF-containing regimens in people starting treatment for the first time and in treatment-experienced people who switched from TDF- to TAF-containing combinations. At least 90% of people taking either type of regimen achieved or maintained undetectable viral load at 48 weeks, but those on TAF had less hip and spine bone loss and more favorable kidney function lab tests.

At the recent Conference on Retroviruses and Opportunistic Infections (CROI), Joel Gallant, MD, from the Southwest Care Center in Santa Fe reported that Descovy suppressed HIV replication as well as Truvada when used in combination regimens with various third drugs. In addition, people who switched from Truvada to Descovy saw improvements in their kidney function and bone density.

What About PrEP?

Given the kidney and bone health benefits of TAF, some have suggested that Descovy might potentially be a good alternative to Truvada for PrEP. But there is not yet enough research to show whether TAF will prevent HIV as well as Truvada, which reduces the risk of infection by more than 90% when taken consistently.

While doctors are allowed to prescribe Descovy “off-label” for non-approved uses, researchers and advocates cautioned against substituting it for Truvada as PrEP until clinical trials are done.

“While Descovy has been approved for the treatment of HIV infection, we know absolutely nothing about whether this drug works for PrEP,” said Jim Pickett, director of prevention advocacy and gay men’s health at the AIDS Foundation of Chicago. “Descovy as PrEP is a data-free zone and we should not make any assumptions. Individuals and providers should not use Descovy for PrEP until—if and when—we get positive results from human trials, which are in the early planning stages right now.”

Two studies presented at CROI offered conflicting evidence about how well TAF as PrEP could potentially work for people.

Gerardo Garcia-Lerma, PhD, from the Centers for Disease Control and Prevention and colleagues—the team that previously did much of the animal research showing that Truvada is effective for PrEP—tested whether the drugs in Descovy could prevent rectal infection in monkeys exposed to a multiple doses of an HIV-like virus.

They found that none of the six monkeys pre-treated with TAF and emtricitabine were infected after 19 rectal exposures, while all monkeys given a placebo became infected after one to ten exposures.

But an early human study—designed to test drug levels and safety, not effectiveness—suggests there is reason for caution about TAF for PrEP.

Katy Garrett, PharmD, from the University of North Carolina at Chapel Hill and colleagues from Gilead found that tenofovir levels were lower in vaginal and rectal tissue and fluid samples from healthy HIV-negative women who took TAF compared to those who took TDF. Levels in female genital tissue were about two-fold lower, while levels in rectal tissue were about ten-fold lower.

We know that the effectiveness of Truvada for HIV prevention is strongly associated with having high enough tenofovir levels as measured in the blood (or hair samples, in some studies). Yet it is still not clear whether the protective effect is due to high drug levels in the blood, in exposed genital or rectal tissues, or perhaps in vulnerable cells themselves.

Both Garcia-Lerma and Garrett emphasized that TAF should not be used for HIV prevention until human trials are completed, and advocates sounded a similar note of caution about substituting Descovy for Truvada as PrEP.

“Truvada has proven to be an exceptionally safe drug for PrEP for most people, but the prospect of an even safer drug is good news,” said David Evans, director of treatment advocacy at Project Inform. “We know right now that Truvada is pretty forgiving—even four doses per week for people using it for anal sex is highly protective. We don’t know that yet about TAF. Recent data showed that although it was highly effective in monkeys, less of the drug concentrates in human rectal cells than TDF. What that will mean for efficacy is going to require studies, which we hope will begin in the coming months.”

“We are pleased with the FDA approval of Descovy, as we are with any advances that could make PrEP medications easier and more accessible,” Steve Gibson, director of sexual health services at Strut, told BETA. “We still recommend daily Truvada for PrEP, as this is the only approved medication that has been proven safe and effective at preventing HIV infections.”

Liz Highleyman is a freelance medical writer and editor-in-chief of HIVandHepatitis.com.

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