March/April 2016 

An emerging long-acting nuke

Researchers with the pharmaceutical company Merck have developed a new nucleoside analogue (commonly called a nuke) code-named MK-8591. The chemical shorthand for this drug is EFdA.

This new nuke has potent anti-HIV activity in lab experiments with HIV and cells. It works in part by interfering with an enzyme called reverse transcriptase, which is needed by HIV to successfully infect cells.

Animal studies suggest that the drug persists inside them, so phase I human studies were done to explore and understand this possibility.

In the phase I study (in humans), different doses of MK-8591 were taken orally—10, 30 or 100 mg once weekly for three weeks. According to Merck scientists, the drug is reportedly “well tolerated.” It lowers HIV viral load by about 1.64 log.

Merck has created long-acting injectable formulations of this drug. Experiments on rats suggest that a single injection of these formulations could provide high levels of MK-8591 in the blood for up to six months. Merck plans to test these formulations in people, perhaps administered every six months. If developed, MK-8591 may have potential as another form of pre-exposure prophylaxis (PrEP) or as treatment (when combined with other long-acting agents).

—Sean R. Hosein


Grobler J, Friedman E, Barrett SE, et al. Long-acting oral and parenteral dosing of MK-8591 for HIV treatment or prophylaxis. Conference on Retroviruses and Opportunistic Infections, 22-25 February 2016, Boston, MA. Abstract 98.