August 15, 2017
MK-8591 -- a very interesting NRTI in early stages of development -- is notable for a very high potency, a long-half life and the potential for use both as HIV treatment and for HIV prevention.
Oral dosing might be weekly, and PrEP includes the potential for a small removable slow-release implant that would last a year.
Two interesting studies were presented at IAS 2017.
The first, in 30 HIV positive participants, reported mean viral load reductions seven days after a single dose that ranged from approximately -1.2 logs (for the tiny 0.5 mg, 1.0 mg and 2.0 mg groups) to approximately -1.6 logs (for the 10 mg and 30 mg group).12
Both plasma and intracellular drug levels were dose-related, with higher doses achieving levels approximately 1 log higher with the half-life in PBMCs ranging from 78 to 128 hours, allowing for a wide range of potential dosing schedules.
For reasons that are unclear, and against the study protocol, one participant did not begin full ART (risking drug resistance by continued monotherapy) although neither viral load nor resistance data were presented for the case.
The second study was for PrEP in 16 macaques randomised to oral MK-8591 or placebo every week for 12 weeks, and were exposed to SIV rectally every week.13
All animals receiving the placebo became infected within 1 to 4 challenges compared to none of the MK-8591 animals, even after 12 challenges with continued follow-up for a further three months. MK-8591 resulted in a 41.5-fold lower risk of infection (95% CI: 7.3 to 237.9) compared to placebo (p< 0.0001).
Mean intracellular trough concentrations of MK-8591-TP at the time of challenge were similar to levels achieved using a once-weekly 10 mg oral dose of 10mg in HIV positive human studies.
Further details of both studies are included in a separate HTB report.14
Fostemsavir is an attachment inhibitor in phase 3 studies that as a new class of HIV drug might be especially important for people who have multidrug resistance to current ARVs.
Although no new efficacy or safety results were presented at IAS 2017 -- the ongoing phase 3 study doesn't finish until 2020 -- two small drug interactions studies were presented as posters.
The first reported increases in levels of methadone or buprenorphine, with a caution for monitoring for signs of sedation, but without a routine need to dose-adjust.15
The second poster reported that fostemsavir can be safely taken with a combined oral contraceptive containing norethindrone (1.5 mg) and reduced dose ethinyl estradiol (30 ug).16
Finally, a poster was presented on a study in dogs for subcutaneous and intramuscullar injections of the new nanoformulations of investigational NNRTI elsulfavirine or its prodrug (VS-1500A) that is being developed for potential as treatment and prevention in some middle-income countries.17
Single injections of both SC and IM formulations of the prodrug maintained therapeutic drug levels for at least four weeks.
Unless stated otherwise, abstracts refer to the 9th IAS Conference on HIV Science, 23-26 July 2017, Paris.
[Note from TheBodyPRO.com: This article was originally published by HIV i-Base on Aug. 10, 2017. We have cross-posted it with their permission.]
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