Switching from the initial preexposure prophylaxis (PrEP) pill emtricitabine/tenofovir disoproxil fumarate (F/TDF) to the recently licensed emtricitabine/tenofovir alafenamide (F/TAF) could prevent 25 cases of end-stage renal disease and more than 2000 fractures over 5 years, according to a cost-effectiveness analysis by researchers at Massachusetts General Hospital and the Yale School of Public Health [1,2]. But the higher cost of F/TAF than a probably imminent generic F/TDF may be too steep to justify those safety gains, the researchers argued in their cost analysis.
In a poster presented at CROI  and an article simultaneously published in Annals of Internal Medicine , Rochelle Walensky and colleagues estimated "the greatest possible clinical benefits and economic savings" with F/TAF, as well as the highest price payers should be willing to tolerate for F/TAF over generic F/TDF.
Sold as Truvada, F/TDF became the only licensed PrEP pill in 2012. F/TAF got licensed for PrEP in 2019 and proved virologically noninferior to F/TDF, while upsetting kidney and bone markers less, in the DISCOVER trial [3,4].
The Mass General-Yale team used published data to estimate fractures, end-stage renal disease cases, quality-adjusted life years (QALYs), costs, and cost-effectiveness of F/TAF. They claimed to "tip the scales" in favor of F/TAF in portraying its potential bone and kidney advantages in the best possible light. For example, they assumed that all fractures resulting from F/TDF use would require surgery and all cases of severe kidney disease would be irreversible and require dialysis.
Setting societal "willingness to pay" thresholds at $50,000, $100,000, and $150,000, the researchers projected maximum justifiable prices for F/TAF. Then they estimated the number of people in the United States who could get F/TDF or F/TAF if the entire US HIV prevention budget--more than $900 million--went only to pay for PrEP.
In an analysis limited to US men who have sex with men (MSM), using F/TDF rather than F/TAF for 5 years would lead to 25 excess cases of end-stage renal disease, the researchers calculated, and to 2101 excess fractures. Total 5-year QALYs for MSM would be similar for F/TAF (618,030) and F/TDF (617,340). But 5-year costs would stand almost twice higher with F/TAF ($10.3 billion) than F/TDF ($5.3 billion). The incremental cost-effectiveness ratio (ICER, change in cost/change in QALYs) of switching all PrEP users to F/TAF would be $7.2 million/QALY.
If society were willing to pay no more than $100,000 per QALY, the investigators reckoned that the "maximum justifiable price markup" of F/TAF over F/TDF would be $370 in the total population and $670 in an older-than-55 population.
F/TAF carries an annual price tag of $16,000 if used daily. With the US HIV prevention budget set at $900.8 million, the Mass General-Yale group calculated that F/TAF would allow no more than 54,300 people in the United States to get PrEP. That number amounts to 11% of an estimated 492,000 US MSM. If all PrEP users switched to a generic PrEP that costs 50% of F/TAF, PrEP coverage would double. PrEP coverage would quadruple if generic F/TDF came in at a 75% discount compared with F/TAF.
In their article  the researchers concede their analysis rests on daily dosing of F/TAF. Using PrEP only before and after sex has proved as effective as daily PrEP  and would cost considerably less.
But focused on the results as they stand, the researchers proposed that "the imminent availability of generic F/TDF represents an extraordinary opportunity to expand PrEP coverage among the most price-sensitive members of the HIV at-risk population.”