MK-8527 – a new translocation inhibitor
HIV nucleoside reverse transcriptase translocation inhibitors (NRTTI) are a new class of drugs designed to interfere with HIV-infected cells at several points in the viral life cycle. The first translocation inhibitor was islatravir, which is still in clinical trials. At high doses, islatravir was found to significantly depress lymphocyte levels. It is being tested at much lower doses and this problem has not recurred. An analogue of islatravir is MK-8527. It is taken orally once daily and does not have potential to cause many drug interactions. It is being considered for once-weekly and perhaps once-monthly dosing.
MK-8527 has been tested for preliminary safety in adults in single doses of 1, 3 and 10 mg in one study (study A). In another study (study B), lower doses were tested (1, 0.5 and 0.25 mg).
All 37 participants had not previously received HIV treatment and had a viral load that ranged between 2,000 and 720,000 copies/mL.
Results
In study A, doses of 3 and 10 mg caused a significant decrease in viral load of about 1.5 logs.
In study B, overall, there was a decrease of more than 1 log in viral load and this was maintained for 10 days after dosing.
The drug was well tolerated. Although 12 people reported headache and other symptoms, these were judged not to be related to MK-8527.
No serious adverse effects were reported, no changes to electrocardiograms were found and no one died.
Further studies are planned with this novel compound.
—Sean R. Hosein
REFERENCES:
- Gillespie G, Carstens RP, Zang X, et al. Safety and Pharmacokinetics of MK-8527, a Novel nRTTI, in Adults without HIV. Conference on Retroviruses and Opportunistic Infections, March 3-6, 2024. Abstract 129.
- Carstens RP, Kapoor Y, Vargo R, et al. Single Dose Administration of MK-8527, a Novel nRTTI, in Adults With HIV-1. Conference on Retroviruses and Opportunistic Infections, March 3-6, 2024. Abstract 115.