Although tenofovir alafenamide coformulated with emtricitabine (TAF/FTC or F/TAF; Descovy®, Gilead Sciences, Inc) has a marginally more benign side effect profile compared with tenofovir disoproxil fumarate coformulated with emtricitabine (TDF/FTC or F/TDF; Truvada®, Gilead Sciences, Inc), the additional cost of the newer HIV pre-exposure prophylaxis (PrEP) is not justifiable, especially since a generic alternative to TDF/FTC will soon be available and likely decrease the cost of this formulation, according to a cost-analysis paper published in Annals of Internal Medicine and presented at the Conference on Retroviruses and Opportunistic Infections virtual meeting held in March 2020.1,2

In many countries, analysis are routinely considered when making treatment recommendations; this has not been the case in the United States. However, in 2018 PrEP and other antiretroviral treatments were among the top 5 therapeutic classes in nondiscounted spending for medicine, and thus the consideration of cost is has begun to emerge.3 Since 2012 when the Department of Health and Human Services guidelines first included an antiretroviral cost table, a section on cost considerations has been included.3

Because TDF/FTC, which was approved by the Food and Drug Administration (FDA) in 2012, is expected to lose its patent protection, generic versions are expected to become commercially available in late 2020 and early 2021 and thus substantially decrease in cost.  Given that cost is a key barrier in scaling up PrEP, researchers sought to identify the highest possible price premium that TAF/FTC, which was approved by the FDA in October 2019, could command over generic TDF/FTC over a 5-year period.

To maximize the benefits of TAF/FTC, researchers intentionally portrayed the bone and renal safety benefits of TAF/FTC in the most favorable light possible, and assumed that it has no side effects, thus excluding potential risks for increased weight gain. In addition, they skewed the study as much as possible against TDF/FTC. Thus, they assumed that every fracture caused by TDF/FTC was a hip fracture (because this is the most expensive to address surgically), and the decline in kidney function seen in people on TDF/FTC was not reversible.

Though the model was stratified by age, researchers also performed a subanalysis of solely people aged > 55 years because both bone mineral loss and kidney dysfunction are more common in older people.

Although the total population of people who received PrEP was 132,340 in 2018, the model included 93.4% of this population who were men who have sex with men (MSM), because TAF/FTC is currently only approved for use in MSM and transgender women. Researchers noted that data was not available on AIDSVu for the number of transgender women who receive PrEP.

The analysis estimated that switching from TDF/FTC to TAF/FTC averted a maximum of 2101 fractures and 25 cases of end-stage renal disease over a 5-year period. Assuming TAF/FTC current costs at $16,600 per year and a 50% discount for generic TDF/FTC at $8300 per year, switching all patients to TAF/FTC would increase total expenditures for HIV PrEP by $5 billion ($40,210 per person).

The incremental cost-effectiveness ratio (ICER) of switching all patients receiving PrEP to TAF/FTC exceeded $7 million per quality-adjusted life-years (QALY). The ICER of switching all patients who receive PrEP aged > 55 years was lower, but exceeded $3 million per QALY. “Relaxing any of the pessimistic assumptions regarding the renal and bone safety of [TDF/FTC] …only makes [TAF/FTC] even less cost-effective,” noted the researchers.

Using a societal willingness-to-pay threshold of $100,000 per QALY, the maximum fair price of TAF/FTC would be increased to $370 compared with generic TDF/FTC in the total population and $670 over generic TDF/FTC in the population aged > 55 years.

At the current price of TAF/FTC ($16,000) and a fixed HIV prevention budget in the United States of $900.8 million, TAF/FTC would allow for no more than 54,300 people to receive PrEP, 11% of the estimated 492,000 MSM. Researchers noted that this coverage level could be doubled (quadrupled), by switching to a generic TDF/FTC alternative priced at a 50% (75%) discount to the branded option.

Since its approval in October 2019, TAF/FTC has captured 25% of the market for PrEP prescriptions in the United States, and the manufacturer expects 40% to 45% of individuals receiving PrEP to have been switched to TAF/FTC before generic TDF/FTC becomes available, stated the researchers.

“In the presence of a generic [TDF/FTC] option, branded [TAF/FTC’s] price cannot be justified by its modest benefits,” said senior author A. David Paltiel, PhD, professor at the Yale School of Public Health, in a press release.4 “If branded [TAF/FTC] succeeds in driving out its generic competitor, PrEP expansion in the US could grind to a halt and the new drug could end up causing more avoidable HIV transmissions than it prevents.”

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This “study highlights the outsized cost of [TAF/FTC] compared with potential clinical benefits once [TDF/FTC] is generic and makes it clear that shifting to [TAF/FTC] as first-line PrEP for all cannot be universally recommended,” concluded Carlos del Rio, MD, and Wendy S. Armstrong, MD, from Emory University School of Medicine in Atlanta, Georgia, in an editorial commentary.3

References

1. Walensky RP, Horn T, McCann NC, Freedberg KA, Paltiel AD. Comparative pricing of branded tenofovir alafenamide-emtricitabine relative to generic tenofovir disoproxil fumarate-emtricitabine for HIV preexposure prophylaxis: a cost-effectiveness analysis [published online March 10, 2020]. Ann Intern Med. doi:10.7326/M19-3478

2. Walensky RP, Horn T, McCann NC, Freedberg KA, Paltiel AD. F/TAF vs F/TDF for PrEP: how much is “better” worth? Presented at: CROI 2020; March 8-11, 2020; Boston, MA. Abstract 1089.

3. Del Rio C, Armstrong WS. How much are we willing to pay for preexposure prophylaxis in the United States? [published online March 10, 2020]. Ann Intern Med. doi:10.7326/M20-0799

4. Expensive new drug could undermine HIV prevention efforts [press release]. New Haven, CT: Yale School of Public Health, Office of Public Relations. Published March 9, 2020. https://publichealth.yale.edu/communications/news-article/23020/ Accessed April 12, 2020.