CROI 2021: Dosing for once-weekly oral ART: islatravir plus MK-8507 studies due to start in 2021
12 March 2021. Related: Conference reports, Antiretrovirals, CROI 28 (virtual) 2021.
Simon Collins, HIV i-Base
CROI 2021 included several studies on a once-weekly oral combinations using islatravir and a new NNRTI MK-8501. 
A single 20 mg once-weekly dose of islatravir was shown to produce intracellular concentrations that is similar to steady-state using the 0.75 mg daily dose. After 14 days, islatravir levels were still five-fold above the inhibitory quotient for lamivudine resistant HIV, showing this would also have some flexibility it a single dose was later or missed. 
The study modelling for dosing MK-8507 was based on real world simulations in combination with islatravir and assuming 80% adherence. The study reported that the three doses studies – 100 mg, 200 mg and 400 mg – should all provide >90% efficacy against common NNRTI mutations including K103N and Y181C.
MK-8507 has a half-life of ~70 hours and mean viral load reductions of –1.5 log once week after a single dose were reported at Glasgow 2020. 
An oral presentation at CROI 2021 also presented additional new information about MK-8507, including activity against early NNRTIs (K103N, Y181C and G190A) – with a resistance profile similar to doravirine. 
Studies using islatravir plus MK-8507 in a dual once-weekly combination are planned to start later in 2021.
- Kandala B et al. Model-informed dose selection for islatravir/MK-8507 oral once-weekly phase 2b study. CROI 2021, 6–10 March 2021. Poster 376.
- Single doses of MK-8507 reduce viral load by mean –1.5 log and support once-weekly dosing above 80 mg. HTB (14 October 2020).
- Diamond T et al. Resistance profile of MK-8507, a novel NNRTI suitable for weekly oral HIV treatment. CROI 2021, 6–10 March 2021. Oral abstract 129.
https://www.croiconference.org/abstract/resistance-profile-of-mk-8507-a-novel-nnrti-suitable-for-weekly-oral-hiv-treatment/ (abstract and webcast)
This report was first posted on 9 March 2021.