Safety Profiles of FDA-Approved PrEP Agents

Segment Description: Infectious disease experts provide insights into the currently available FDA agents approved for PrEP therapy and discuss their safety profile.

Interview Transcript (modified slightly for readability):

Joseph Eron, MD: Ian, do you want to talk about what we have for PrEP [pre-exposure prophylaxis] right now? Then maybe we can talk about what is coming or has just recently been approved.

Ian Frank, MD: There are 2 FDA products for PrEP. Both include tenofovir and emtricitabine. The older form of tenofovir, tenofovir disoproxil fumarate, and emtricitabine, that’s Truvada®. And the newer form tenofovir alafenamide plus emtricitabine, that is Descovy®. The newer formulation is a little safer, less renal toxicity potential; fewer problems with decreasing bone mineral density. And the products are equally effective in a head-to-head trial.

It’s important for the audience to understand that PrEP is really effective when people adhere to it. In an early study with tenofovir disoproxil fumarate, TDF and FTC [emtricitabine], if men who have sex with men took 4 or more doses a week, nobody got infected. PrEP may not be as effective in women as it is in men, and women may need to adhere at higher rates than men who have sex with men, because of the different ways these drugs enter tissues and the concentration in mucosal tissues where people may get exposed. We can’t say that PrEP is as effective in women at lower levels who are adhering at lower levels.

Joseph Eron, MD: Julia, with the newer form and the TAF-FTC [tenofovir alafenamide emtricitabine—emtricitabine] versus TDF-FTC [tenofovir disoproxil fumarate–emtricitabine], how should we think about those alternatives in terms of cost or effectiveness? Do you have ideas here?

Julia Marcus, PhD, MPH: Yes, as Ian mentioned, they are equally effective — TAF-FTC [tenofovir alafenamide emtricitabine–emtricitabine] and TDF-FTC [tenofovir disoproxil fumarate–emtricitabine]. However, that was a trial done only in men who had sex with men, and a handful of transsexual women. The FDA approval for TAF-FTC [tenofovir alafenamide emtricitabine–emtricitabine] excluded people at risk of HIV through receptive vaginal sex. In terms of safety we can think about renal and bone health. But there were also some adverse effects associated with TAF-FTC [tenofovir alafenamide emtricitabine–emtricitabine] that I think are worth considering, including increased cholesterol and weight gain compared with TDF-FTC [tenofovir disoproxil fumarate–emtricitabine]. So they really are both extremely safe drugs with very few people stopping the medication.

Joseph Eron, MD: That’s really important.

Julia Marcus, PhD, MPH: We’re talking about biomarkers, really.

Joseph Eron, MD: We’re talking about biomarkers at this point.

Julia Marcus, PhD, MPH: They’re not really clinically significant differences. And the cost issue is really relevant here. They’re very expensive medications and TDF-FTC [tenofovir disoproxil fumarate—emtricitabine] is about to go generic later this year, so there’s an opportunity here to maintain people on TDF-FTC [tenofovir disoproxil fumarate–emtricitabine] and then switch them to generics, at a cost of approximately $24,000 a year for PrEP. I think it could make a huge difference once the cost begins to go down on generics.

Joseph Eron, MD: Sure. Allison, I’m curious to understand adolescents. Do you worry more about the bone effects? I know they haven’t really been studied in younger adolescents. TDF-FTC [tenofovir disoproxil fumarate—emtricitabine] has an indication I guess in younger adolescents.

Allison Agwu, MD, ScM: Yes, a TDF-FTC [tenofovir disoproxil fumarate—emtricitabine], such as Truvada as you noted, was studied down to age 15. There were 2 studies: the ATN 113 and then with older ages, ATN 110. The results showed some of the same bone effects that we’re seeing. But nobody knows what that’s going to mean long term.

But I’ll tell you, if you’re preventing HIV infection in these young people, you have to balance that as well. I think your point is well taken in terms of what’s clinically meaningful.

Joseph Eron, MD: There is certainly a difference between TAF [tenofovir alafenamide emtricitabine] and TDF [tenofovir disoproxil fumarate] in terms of bone, and it’s a sensitive time in adolescence of bone deposition. I’m not advocating 1 way or the other. I’m just saying that that’s probably something we need to think about.

Allison Agwu, MD, ScM: I agree. It’s certainly a part of the conversation you have, as well as the cost issues. I think these issues are going to be important. With respect to the cost issues, I believe there are some assistant programs that are available.

Joseph Eron, MD: One of the things we were discussing earlier is the difference between the South and the other 3 regions. As well as the differences state by state in terms of Medicaid, which affects testing and affects the expansion of care for people with HIV. We live in red states. Colleen, do you want to comment?