An ongoing dialogue on HIV/AIDS, infectious diseases,
December 8th, 2024
Who’s Going to Get Lenacapavir for HIV Prevention?
At the International AIDS Conference this past summer, Dr. Linda-Gail Bekker brought down the house presenting the results of the PURPOSE 1 trial of twice-yearly injectable lenacapavir for prevention of HIV in women. The results — zero infections out of over 2000 participants — demonstrated clear superiority over oral PrEP with TDF/FTC. The study simultaneously appeared in the New England Journal of Medicine; always wonderful timing when that happens.
Now, with a similar study design (without the TAF/FTC arm), we have the results of PURPOSE 2, which tested lenacapavir for HIV prevention in men who have sex with men and people who are gender diverse. Again, the injectable approach significantly beat out oral PrEP, with only two infections occurring among nearly 2000 lenacapavir recipients, around a 10-fold lower rate than in the TDF/FTC arm.
These studies highlight one of the great joys of HIV medicine, in that occasionally we get a study result that’s so dramatic it makes everyone in the field wake up and go wow. To jog your memory, here are five previous 5 wow-moments, at least in my opinion:
- Zidovudine during pregnancy markedly reduces mother-to-child transmission.
- Triple therapy with protease-inhibitor/dual NRTI-based ART improves survival — a lot.
- Integrase inhibitor–based salvage treatment gives nearly everyone a chance at viral suppression, even those with multi-drug resistance.
- Pre-exposure prophylaxis works for prevention of HIV in people at high risk for HIV.
- Suppressive HIV treatment is 100% effective for prevention of HIV transmission.
After each of these studies appeared, everything changed — and changed fast. Guideline writers scrambled to update their recommendations, and HIV treaters, clinical researchers, and community activists strongly advocated for changes to the standard of care.
Will the spectacular results of the PURPOSE 1 and 2 trials meet with the same rapid change in guidelines and rapid adoption? There are reasons to think they will, and reasons to think they won’t.
On the favorable side are, obviously, the incredibly good results — so good that many media reports incorrectly cited these twice-yearly injections as a “vaccine”. Hey, quick fact check, it’s not a vaccine!
(Though parenthetically, one does speculate that something this effective will make HIV vaccine research even harder than it is already. How can one demonstrate better protection with a vaccine than seen in the PURPOSE studies?)
The contrarians will cite the current high cost of lenacapavir as treatment, especially compared to generic TDF/FTC, which CostPlus drugs now lists at $32 for a 3-month supply, and many government-sponsored programs will pay for entirely.
Plus, we have the cabotegravir experience in the “real world”, a sobering reminder that efficacy does not equal effectiveness — or at least not if the breakthrough treatment isn’t put into practice. Remember, cabotegravir was also significantly more effective than TDF/FTC in two blinded clinical trials, demonstrated 100% efficacy in women (if one excludes the participants with HIV at baseline), and has been FDA approved for HIV prevention since December 2021.
And our use of cabotegravir so far in the USA? Based on a recently published CDC report of national prescription trends for PrEP, it was around 3% of those on PrEP in 2023; someone who works on PrEP implementation research told me that it’s only a bit higher today. And its adoption in the parts of the world with the highest HIV incidence is, sadly, essentially zero.
FDA approval of lenacapavir for PrEP is pretty much a sure thing, and expected some time in 2025. Who will get it for HIV prevention promises to be one of the more fascinating stories in HIV medicine over the next couple of years. Stay tuned.
6 Responses to “Who’s Going to Get Lenacapavir for HIV Prevention?”
Leave a Reply
Paul E. Sax, MD
Contributing Editor
NEJM Journal Watch
Infectious Diseases
Biography | Disclosures | Summaries
Learn more about HIV and ID Observations.
NEJM Journal Watch — Recent Infectious Disease Articles- Observations from ID and Beyond: Who's Going to Get Lenacapavir for HIV Prevention?
- Can We Shorten the Duration of Antibiotic Treatment for Bacteremia?
- Rifampin and Gentamicin for Staphylococcal Prosthetic Valve Endocarditis: Strictly Necessary?
- Gauging Risk for Liver Cancer: Hepatitis B Viral Load Might Be a Clue
- A Fungus New to New York City
Happy Holidays, Paul. This is such a great column. Please keep it up!
I can predict who’s going to get it, or at least the order. First will be people with great insurance (not a large group); then those living in states that decide to fund the best available prevention. Finally (and I hope not too long from approval), people in countries where they need it the most.
Love the 5 “wow-moments” and the clarifying micro-lesson about the difference between efficacy and effectiveness. Just to point to a few of the highlights from another great article…
I can see early attempts by insurance companies to avoid paying for LEN. They’ll ask for documentation that “the patient has failed PrEP with generic FTC/TDF.” People will then point out the absurdity of that condition, and they’ll have to come up with something else!
Why does Lenacapavir cost $44,000 a year?
For sure Lenacapavir is effective for the purpose of prevention, but remember: 01 year if Lencapavir is the aproximate cost of more than 100.000 condoms, that prevents HIV, pregnancy and almost all sexuallly transmites diseases. Is Lenacapavir really cost-effective?