As 2019 draws to a close, TheBodyPro takes stock of the year's most noteworthy developments in HIV. And not just any developments: We're looking specifically at those with the largest impact for people who provide HIV care and services in the U.S. In this series, veteran clinician-researcher David Alain Wohl, M.D., guides us through the new research and other important moments of 2019 that have the greatest potential to alter the HIV clinical landscape in the months and years to come.
Where once there was just one blue PrEP pill, now there are two. In October 2019, the U.S. Food and Drug Administration (FDA) approved emtricitabine/tenofovir alafenamide (FTC/TAF, Descovy) as PrEP for those at risk of acquiring HIV-1 by any route other than vaginal sex. (We will get to that last part in a second.) The approval comes seven years after emtricitabine/tenofovir disoproxil fumarate (FTC/TDF, Truvada) became the first PrEP drug.
This approval follows the reporting of results from the DISCOVER trial, a randomized, double-blind trial of FTC/TDF versus FTC/TAF involving 5,399 men who have sex with men (MSM) and transgender women (TW) in North America and Europe. Preliminary 48-week data were presented at CROI 2019 and made a splash by showing that that FTC/TAF was non-inferior to FTC/TDF in preventing new infections.
Moreover, the number of incident infections was really low despite the level of HIV risk required for study entry: Out of over 5,300 people, there were 22 infections overall (7 for FTC/TAF and 17 for FTC/TDF), and five of those people (1 in the FTC/TAF arm, 4 in the FTC/TDF arm) were probably already living with HIV at baseline before starting the study product. Measurements of drug levels suggest suboptimal adherence for most who became HIV-infected. Furthermore, in a week 96 analysis presented at the European AIDS Conference, only one additional infection occurred; this was in the FTC/TAF arm.
As expected, bone and renal parameters favored TAF. At 96 weeks, median weight gains were greater for FTC/TAF (1.7 kg) compared to FTC/TDF (0.5 kg).
The Bottom Line on FTC/TAF as a New PrEP Regimen
There is little doubt that FTC/TAF is effective as PrEP. The few cases of incident HIV in the DISCOVER trial may have some wondering if a comparison with FTC/TDF can be made, but the baseline HIV infections and ongoing high rate of STIs in both arms suggest that the study population was at-risk and yet was protected by both agents. Given similar efficacy and the renal and bone benefits, TAF should be favored -- with the only clinical downside being slightly greater weight gain.
That there are scant data on use of FTC/TAF as PrEP in cisgender women is a problem -- and, thus, is the reason for the limitation on the FDA approval to non-vaginal sex. PrEP studies are tough to do, and a PrEP trial in cis-women would be nearly impossible in the U.S: As we saw with DISCOVER, incidence rates are low, so large numbers of high-risk cis-women would be needed. Importantly, however, the FDA indication does not preclude use of FTC/TAF as PrEP in women who could become infected via routes other than vaginal sex.
Expanded access to PrEP is necessary, and while toxicity concerns are only one of many reasons some defer or drop PrEP, a safer way to deliver tenofovir can only help. Yet, advances in medicinal chemistry, including long-acting PrEP formulations, are only part of the solution to the problem of getting more people who are at risk of HIV infection on PrEP.
The cost of this new drug has been raised as a deterrent, and for some it is. But, even if FTC/TAF -- or FTC/TDF, for that matter -- was absolutely free (slogan idea: PrEP for All), the proportion of at-risk people taking PrEP would be unlikely to climb anywhere near the 1.4 million that the Centers for Disease Control and Prevention estimates are candidates for biomedical HIV prevention.
Free drugs do nothing to solve the question of how people without health insurance can cover ancillary expenses, such as prescriber visits and even minimal laboratory testing. Further, there is ample data demonstrating that many of those who are at risk for HIV underestimate their potential for acquiring the virus, and don't perceive themselves to need PrEP. Other work clearly outlines not only challenges in getting people with an indication for PrEP to initiate it, but also to remain on it. That so many who start PrEP discontinue it tells us we have much more to learn about how best to apply effective biomedical interventions to socially complex behaviors.
In the coming year, we will see more trials of new and novel PrEP medications. Eventually, these products will offer a greater breadth of choices for people at risk of HIV infection -– much like the panoply of medications and devices available to prevent unwanted pregnancy. But what we also need to see is end-user data. To date, HIV prevention has mostly taken a "Look at what we've got; what do you think?" rather than a "What do you want?" approach. If we can design sneakers and headphones that people covet and are loyal to, then why not PrEP?
The young man who has sex with men in Atlanta; the cis-woman with the roaming boyfriend in Philadelphia; the teen who injects heroin in Kentucky: What do they want PrEP to look like? Where would they like to get it, and from whom? How do communities (in all their various and evolving forms) come to not only accept PrEP, but to promote it? How, in a system full of holes through which so many fall, do we make HIV prevention fully accessible?
Warehouses full of TAF/FTC, TDF/FTC -- and, in the future, additional oral or injected PrEP drugs -- will not get us much further in protecting those who are at risk without the research to answer these questions.