CROI 2021: Islatravir dosing for once-monthly and annual PrEP: if effective this could end HIV transmission
12 March 2021. Related: Conference reports, HIV prevention and transmission, CROI 28 (virtual) 2021.
Simon Collins, HIV i-Base
Two of the first oral abstracts at CROI reported on the next stages of one of the most important pipeline compounds for HIV prevention.
Munjal Patel from Merck/MSD presented results of PK/PD analyses that defined the islatravir exposure threshold for PrEP and the 60 mg oral once monthly dose that will be used in the upcoming phase 3 studies. [1]
This was based on intracellular triphosphate (TP) levels derived from macaque studies and phase 1 studies. In a phase 2 study, the 60 mg dose resulted in observed mean islatravir-TP that was still 26-fold higher than the minimum target PK threshold of 0.05 pmol/million cells and that levels will
A second oral presentation is the same session, presented similar results for an islatravir implant that will provide PrEP cover for a year. [2]
The technical name for this device – in case it catches on – is a “radiopaque next-generation islatravir-eluting implant”. This was a double-blind phase 1 study and 36 participants (8 active, 4 placebo per dose) at low risk of HIV either had one of three doses of an islatravir implant (48 mg, 52 mg or 56 mg) for 12 weeks or a matched placebo. This is a new formulation of islatravir implant that has a different PK and dose compared to the first dosing studies. This includes barium as a safeguard to be able to track the implant if it migrates within the body.
Islatravir-TP remained above target levels throughout and PK modelling predicted and at doses of 52 mg and above would maintain target levels for at least 52 weeks.
Tolerability was generally good. Common adverse events included haematoma, red skin, tenderness, itching and induration, with little difference between the active and placebo groups and no dose-related adverse events.
Larger phase 2 studies are now planned.
comment
Although the research into islatravir for HIV prevention is still in early stages, this compound has the potential to effectively end HIV transmission.
If efficacy matches other formulations of PrEP, and there is no concern about drug resistance, these long-acting formulations need to become as accessible as aspirin including as single-dose over-the-counter. A single pill could possibly provide both PEP and PrEP cover for a month.
Islatravir PrEP could have a larger market than statins and Viagra, probably combined.
Development and regulatory decisions should understand this urgency and pricing should match affordability for global demand.
References
The weblink for this oral abstract session is:
http://www.croiwebcasts.org/s/2021croi/Oral-02
- Patel M et al. islatravir PK threshold & dose selection for monthly oral HIV-1 PrEP. CROI 2021, 6 – 10 March 2021. Oral abstract 87.
https://www.croiconference.org/abstract/islatravir-pk-threshold-dose-selection-for-monthly-oral-hiv-1-prep/ - Matthews RP et al. Next-generation islatravir implants projected to provide yearly HIV prophylaxis. CROI 2021, 6 – 10 March 2021. Oral abstract 88.
https://www.croiconference.org/abstract/next-generation-islatravir-implants-projected-to-provide-yearly-hiv-prophylaxis/
This report was first posted on 8 March 2021.