In a commentary recently published in the Annals of Internal Medicine, four health care practitioners push back on claims that a newer drug is more effective and safer for use as pre-exposure prophylaxis (PrEP). Their commentary, “Tenofovir Alafenamide for HIV Pre-exposure Prophylaxis—What Can We DISCOVER About Its True Value?” was written to counter misinformation and pharma company spin, they tell TheBodyPro.
PrEP, which is 99% effective in preventing HIV, is available as either of two once-daily pills: tenofovir disoproxil fumarate with emtricitabine (TDF/FTC)—best known in the U.S. by the brand name Truvada—and a newer formula, tenofovir alafenamide with emtricitabine (TAF/FTC), known as Descovy. TDF/FTC has been used for PrEP for more than seven years. Last October, the U.S. Food and Drug Administration (FDA) approved TAF/FTC for PrEP in at-risk adults and adolescents—though not for cisgender women or injection-drug users, because they weren’t tested. The FDA did not state that the formulation was better than the older drug.
Nevertheless, Gilead Sciences, which manufactures both drugs, is arguing, strenuously, that the new drug is safer and more effective. But these claims are overstated, say the team of doctors who co-authored the Annals commentary:
"Robust data show the efficacy of TDF–FTC PrEP for populations affected by HIV, including men who have sex with men (MSM), transgender women, persons who inject drugs, and heterosexuals whose partners are living with HIV. The data are so compelling that the U.S. Preventive Services Task Force issued a grade A recommendation for this regimen in 2019. In contrast, the only efficacy data for TAF–FTC are from a single randomized trial, DISCOVER, that showed that TAF–FTC was noninferior to TDF–FTC as once-daily PrEP."
"The preponderance of evidence suggests that both PrEP formulations are as safe as other commonly used preventive medications, such as oral contraceptives and statins, whose small risks for harm are vastly outweighed by their benefits."
Patients generally don’t dive into the results of randomized, controlled, double-blind studies in order to make their decisions on medications. For PrEP, increasingly, people are coming to doctors asking for Descovy, not Truvada, according to the lead author of the commentary, Douglas Krakower, M.D., who is assistant professor at the Harvard Pilgrim Health Care Institute, Beth Israel Deaconess Medical Center, and Harvard Medical School.
“Several colleagues have told me they engage frequently in Truvada versus Descovy discussions where they thought Truvada would be best, but their patients demand Descovy,” Krakower says.
Behind this demand for Descovy are well-publicized, but not necessarily well-explained, lawsuits related to Truvada used as treatment (but not PrEP). Other customers believe Descovy must be better because it’s newer, according to Krakower. And often doctors don’t disagree with these patients, because Gilead has put its thumb on the scales in favor of Descovy and has been relentless in insisting to prescribers—including Krakower—that Descovy is safer and more effective.
“I get emails, online and print ads,” Krakower tells TheBodyPro. “I got a poster about PrEP with Descovy. I had outreach from Gilead with invitations to attend informational dinners about Descovy. I talked with a rep from Gilead who said the favorable safety profile of Descovy made it optimal, which is not correct. It was not a neutral presentation of data. That’s why we tried to do an objective review in our piece.”
Gilead is not alone in pushing one drug over another, including one of its own drugs. There is a long history of “detailing,” or educational outreach to influence prescribers’ behavior. Even so, Krakower said, Gilead has been especially aggressive in pushing TAF/FTC.
It is not a coincidence that TDF/FTC is going off patent later this year, which will open up the possibility of multiple generics, which would in turn drive down the price. The patent for TAF/FTC won’t expire until 2026. At the J.P. Morgan Healthcare Conference in San Francisco earlier this month, Gilead chairman and chief executive officer Dan O’Day laid bare the company’s intentions. That is, it plans to switch up to 95% of patients under treatment with Truvada to Descovy by the fourth quarter of this year, O’Day said.
Still, even if Gilead is overstating the benefits of Descovy, the data do show that Descovy is as effective as Truvada, with equally small—if different—risk of side effects. Which suggests there is no actual harm in prescribing the newer drug. Judith Feinberg, M.D., professor of behavioral medicine and psychiatry at West Virginia University School of Medicine and one of the Annals commentary co-authors, turns that logic around and looks at it through a public-health lens. “If there is no real advantage to using Descovy, then why ask public systems to pay for it?” she tells TheBodyPro.
“Most patients want what’s best for them. But the conversation should be about whether there is a clinical advantage to using one drug over another, not just cost but whether there is a clinical advantage to it.”
Feinberg continues: “We have, since FDA approval in 2012, years of real-world data from TDF/FTC for PrEP. There is so much noise about the loss of bone density for users. But bone density problems are for treatment (on Truvada), and it is a small amount. It’s statistically significant, not clinically significant.”
And if the possible problems with Truvada are statistically, but not clinically, significant—while Descovy has been shown to have some potential issues with weight gain and cholesterol—doctors should be explaining that to patients, instead of automatically shifting them en masse to the newer drug, Feinberg says.
The problem is, Feinberg points out, that like patients, doctors don’t always dig into a mountain of data from randomized, controlled, double-blind studies that could assist in having a more nuanced conversation about which drug to prescribe.
“We are all under tremendous pressure to see as many patients as possible, quickly,” she says. “It’s like an assembly line. But the time you spend with patients is the most important thing in medical care. I don’t want anyone leaving my office not fully understanding what I’m prescribing and why.”
Feinberg, Krakower and co-authors are not the only experts warning colleagues against Truvada-phobia and Descovy cheerleading. Oni Blackstock, M.D., assistant commissioner of the Bureau of HIV at the New York City Department of Health and Mental Hygiene, says multiple generic versions of TDF/FTC, presumably at a lower price, will be “good for everyone, including insurance companies and health care systems.
“But if providers switch everyone to Descovy, without any clinical reason, that increases the cost to everyone, and possibly will stigmatize TDF/FTC generics and could exacerbate inequities in who obtains PrEP,” Blackstock tells TheBodyPro.
Earlier this week, Blackstock and Demetre C. Daskalakis, M.D., deputy commissioner of the Division of Disease Control at the New York City Department of Health and Mental Hygiene (and another co-author of the Annals commentary), sent an email to everyone in their network, bottom-lining the issue. It concluded:
"Continuing to prescribe TDF/FTC will allow us to expand PrEP use. Generic TDF/FTC will likely soon come to market in the United States at a far lower price than TAF/FTC. The lower price will benefit patients and health care systems, including safety net providers for whom PrEP medicines are a significant expense. Misleading marketing and false claims perpetuated on social media have characterized TDF/FTC as less safe than TAF/FTC, threatening this incredible opportunity to scale up PrEP."