Dataset Information

A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Trial of Radiopaque Islatravir-Eluting Subdermal Implants for Pre-exposure Prophylaxis Against HIV-1 Infection.

ABSTRACT:

Background

Islatravir (MK-8591) is a deoxyadenosine analogue in development for the treatment and prevention of HIV-1 infection. An islatravir-eluting implant could provide an additional option for PrEP.

Setting

Previous data support a threshold islatravir triphosphate concentration for PrEP of 0.05 pmol/10 6 cells in peripheral blood mononuclear cells (PBMCs). Prototype islatravir-eluting implants were previously studied to establish general tolerability and pharmacokinetics (PK) of islatravir relative to the threshold level.

Methods

In this randomized, double-blind, placebo-controlled, phase 1 trial, a next-generation radiopaque islatravir-eluting implant (48 mg, 52 mg, or 56 mg) or placebo implant was placed for a duration of 12 weeks in participants at low risk of HIV infection. Safety and tolerability, as well as PK for islatravir parent and islatravir triphosphate from plasma and PBMCs, were assessed throughout placement and 8 weeks after removal.

Results

In total, 36 participants (8 active and 4 placebo per dose arm) were enrolled and completed the study. Implants were generally well tolerated, with no discontinuations due to an adverse event (AE), and no clear dose-dependence in implant-related AEs. No clinically meaningful relationships were observed for changes in laboratory values, vital signs, or electrocardiogram assessments. Mean islatravir triphosphate levels at day 85 (0.101-0.561 pmol/10 6 cells) were above the PK threshold for all dose levels.

Conclusion

Islatravir administered via a subdermal implant has the potential to be an effective and well tolerated method for administering PrEP to individuals at risk of acquiring HIV-1.

SUBMITTER: Matthews RP

PROVIDER: S-EPMC9936965 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Trial of Radiopaque Islatravir-Eluting Subdermal Implants for Pre-exposure Prophylaxis Against HIV-1 Infection.

Matthews Randolph P RP Zang Xiaowei X Barrett Stephanie E SE Koynov Athanas A Goodey Adrian A Heimbach Tycho T Weissler Vanessa L VL Leyssens Carlien C Reynders Tom T Xu Zhiqing Z Rottey Sylvie S Vargo Ryan R Robertson Michael N MN Stoch S Aubrey SA Iwamoto Marian M

Journal of acquired immune deficiency syndromes (1999) 20221129 4

<h4>Background</h4>Islatravir (MK-8591) is a deoxyadenosine analog in development for the treatment and prevention of HIV-1 infection. An islatravir-eluting implant could provide an additional option for pre-exposure prophylaxis (PrEP).<h4>Setting</h4>Previous data support a threshold islatravir triphosphate concentration for PrEP of 0.05 pmol/10 6 cells in peripheral blood mononuclear cells. Prototype islatravir-eluting implants were previously studied to establish general tolerability and phar ...[more]

PMID: 36450129

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Dataset Information

A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Trial of Radiopaque Islatravir-Eluting Subdermal Implants for Pre-exposure Prophylaxis Against HIV-1 Infection.

Background

Setting

Methods

Results

Conclusion

Publications

A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Trial of Radiopaque Islatravir-Eluting Subdermal Implants for Pre-exposure Prophylaxis Against HIV-1 Infection.

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