Islatravir update: treatment studies to use a lower dose but PrEP research discontinued in favour of MK-8537
On 29 September 2022, MSD/Merck announced that studies using the investigational NRTTI islatravir as HIV treatment will continue, but using a new lower dose. 
This will hopefully overcome the reduction in total lymphocyte and CD4 counts that led to most islatravir studies being stopped at the end of 2021. [2, 3, 4]
The earlier unexpected effect is now being explained by an accumulation of intracellular concentrations of islatravir triphosphate that will hopefully be avoided by using a reduced dose.
New studies will include:
- Phase 3 studies using once-daily oral islatravir plus doravirine as initial ART and as a switch therapy.
- Phase 2 research into once-weekly oral islatravir in combination with once-weekly oral lenacapavir (being developed by Gilead).
However, dose reductions are not appropriate for the longer-acting formulations of islatravir, including a monthly oral tablet and an annual implant that were both being studied as PrEP.
Instead, the company is planning to continue long-acting PrEP studies using MK-8527, a second NRTTI at an earlier stage of development, in the hope that it might have a different side effect profile and that this might not be a class effect.
- Merck press release. Merck to initiate new phase 3 clinical program with lower dose of daily oral islatravir in combination with doravirine for treatment of people with HIV-1 infection. (29 September 2022).
- Selected islatravir studies stop enrolment: further complications with important investigational drugs. HTB (6 December 2021).
- MSD/Merck stop once-weekly NNRTI MK-8507: islatravir studies continue with closer monitoring. HTB (November 2021).
- FDA further limit use of islatravir in ongoing studies. HTB (20 December 2021).