Islatravir (MK-8591) implant sustains HIV PrEP protection for more than one year
Simon Collins, HIV i-Base
IAS 2019 included the first results that a small implant with a slow-release formulation of the newly-named islatravir (MK-8591) might sustain drug levels for over a year.
This was a double-blind placebo-controlled phase 1 trial, using two doses of an islatravir (54 mg or 62 mg) or placebo implant (six active plus 2 placebo per arm). Modelling from previous phase 1 and animal studies established a target threshold concentration of 0.05 pmol/106 TP in PBMCs.
The prototype implants used in the study used the same polymer as the companys’ contraceptive etonogestrel implant and are a similar size (4 cm x 2 mm)
The implants were removed after 12 weeks, with PK sampling continuing for a further four weeks for free drug and intracellular triphosphate levels. These levels remained above this target with both active implants.
PK results and predicted durability of effect are included in Table 1. This modelled protection for 8-10 months and 12-16 months for the 54 mg and 62 mg implants respectively. The 54 mg implant included some mean minimum PK levels that dropped below the minimum target threshold: all results were above this threshold with the higher dose implant.
Safety results were good with the implants reported as tolerable, with no serious adverse events or early discontinuations. At least one side effect was reported by all participants, including those receiving placebo implants, with low grade pain linked to either placement or removal. Although numbers were small, mild skin redness might have been dose-related (33% vs 83%).
The 62 mg dose is being taken forward in next studies.
Table 1: PK and predicted durability with islatravir implants for PrEP
|54 mg||62 mg|
|Geometric Mean at day 85 (%GCV) (pmol/106cells)||0.135 (27.3)||0.272 (45.2)|
|Estimated mean C at one year (pmol/106 cells)*||0.02||0.08|
|Projected duration for protection: range (months)||8-10||12-16|
* Target threshold 0.05 pmol/106 cells.
In animals studies the effectiveness of islatravir was comparable to that seen with TDF/FTC PrEP.
Given the effectiveness of oral PrEP is closely related to adherence to oral pills, a slow release implant could both broaden access to PrEP and increase efficacy on a population level.
This will depend on efficacy studies which have not yet started.
Slow-release removable implants are already widely used in some countries as contraceptive options for women.
Actually, the use of a subcutaneous cotton strip for PrEP could easily produce a cult following as popular as piercings or tattoos.
- Matthews RP et al. First-in-human trial of MK-8591-eluting implants demonstrates concentrations suitable for HIV prophylaxis for at least one year. 10th IAS Conference on HIV Science (IAS 2019), 21-24 July 2019, Mexico City. Late breaker post abstract TUAC0401LB.