11 mg dose selected for once-monthly MK-8527 for phase 3 PrEP studies

24 February 2026. Related: Early access, Conference reports, HIV prevention and transmission, CROI 33 (Retrovirus) 2026.

Simon Collins, HIV i-Base

A second study presented at CROI 2026 reported on the studies that led to selecting the 11 mg dose of MK-8527 (the successor compound to islatravir) that will be used in a once-monthly oral formulation in phase 3 PrEP studies. [1]

This was decided based on PK results using doses from 6 mg to 12 mg from five phase 1 studies and one phase 2 study.

These studies predicted that an 11 mg dose would exceed the efficacy threshold in more than 95% of participants at four time points: 30 minutes after the 1st dose, 31 days after the 1st dose, 31 days at steady state, and 38 days at steady state. Protective levels are also achieved within an hour.

This dose is predicted to also cover exposure during pregnancy (when levels are predicted to be 10% to 30% lower), in people with mild renal impairment (eGFR >60 mL/min) and in people weighing >35 kg (increased weight reduces exposure). Protection extends for an additional week if the monthly dose is late.

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Although the 11 mg dose was already reported in HTB in July 2025mr it is good to see the research that supported this decision. [2]

CROI 2026 also included a PrEP study showing that islatravir did not protect macaques against virus with the M184V mutation. This is important becasue islatravir is very similar to MK-8527. [3]

Although important to report, this is not expected to change the approach to the development as PrEP. 

Reference

1. Mapoor Y et al. MK-8527 Phase III Dose Selection for Monthly Oral HIV-1 Preexposure Prophylaxis. CROI 2026, Denver. Oral abstract 126.
2. IAS 2025: Once-monthly oral PrEP using MK-8527: the drug that could stop HIV. HTB (23 February 2025).
   https://i-base.info/htb/51874
3. Islatravir PrEP doesn’t protect against M184V mutation in macaque study. HTB (23 February 2025).
   https://i-base.info/htb/53297