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Clinical Trial
. 2024 Sep 23;230(3):696-705.
doi: 10.1093/infdis/jiae211.

A Phase 1 Clinical Trial to Assess the Safety and Pharmacokinetics of a Tenofovir Alafenamide/Elvitegravir Insert Administered Rectally for HIV Prevention

Sharon A Riddler  1 , Clifton W Kelly  2 , Craig J Hoesley  3   4 , Ken S Ho  1 , Jeanna M Piper  5 , Stacey Edick  1 , Faye Heard  3 , Gustavo F Doncel  6 , Sherri Johnson  7 , Peter L Anderson  8 , Rhonda M Brand  1   9 , Ratiya Pamela Kunjara Na Ayudhya  9 , José A Bauermeister  10 , Sharon L Hillier  9   11 , Craig W Hendrix  12
Affiliations
Clinical Trial

A Phase 1 Clinical Trial to Assess the Safety and Pharmacokinetics of a Tenofovir Alafenamide/Elvitegravir Insert Administered Rectally for HIV Prevention

Sharon A Riddler et al. J Infect Dis. .

Abstract

Background: On-demand topical products could be an important tool for human immunodeficiency virus (HIV) prevention. We evaluated the safety, pharmacokinetics, and ex vivo pharmacodynamics of a tenofovir alafenamide/elvitegravir (TAF/EVG, 20 mg/16 mg) insert administered rectally.

Methods: MTN-039 was a phase 1, open-label, single-arm, 2-dose study. Blood, rectal fluid, and rectal tissue were collected over 72 hours following rectal administration of 1 and 2 TAF/EVG inserts for each participant.

Results: TAF/EVG inserts were safe and well tolerated. EVG and tenofovir (TFV) were detected in blood plasma at low concentrations: median peak concentrations after 2 inserts were EVG 2.4 ng/mL and TFV 4.4 ng/mL. Rectal tissue EVG peaked at 2 hours (median, 2 inserts = 9 ng/mg) but declined to below limit of quantification in the majority of samples at 24 hours, whereas tenofovir diphosphate (TFV-DP) remained high >2000 fmol/million cells for 72 hours with 2 inserts. Compared to baseline, median cumulative log10 HIV p24 antigen of ex vivo rectal tissue HIV infection was reduced at each time point for both 1 and 2 inserts (P < .065 and P < .039, respectively).

Discussion: Rectal administration of TAF/EVG inserts achieved high rectal tissue concentrations of EVG and TFV-DP with low systemic drug exposure and demonstrable ex vivo inhibition of HIV infection for 72 hours. Clinical Trials Registration . NCT04047420.

Keywords: HIV prevention; elvitegravir; microbicide; rectal insert; tenofovir alafenamide.

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Conflict of interest statement

Potential conflicts of interest. S. A. R. received research grants from Gilead Sciences and Merck. P. L. A. received research contracts from Gilead Sciences paid to his institution. S. L. H. received research grants and consulting fees from Merck. G. F. D. received research grants from Gilead Sciences. C. W. H. has received clinical research funding from Gilead Sciences and Merck; he is a coinventor of 2 issued US patents related to microbicides; and is founder of Prionde BioPharma, LLC, a microbicide company. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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References

    1. Baeten JM, Donnell D, Ndase P, et al. . Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med 2012; 367:399–410. - PMC - PubMed
    1. Grant RM, Lama JR, Anderson PL, et al. . Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 2010; 363:2587–99. - PMC - PubMed
    1. Landovitz RJ, Donnell D, Clement ME, et al. . Cabotegravir for HIV prevention in cisgender men and transgender women. N Engl J Med 2021; 385:595–608. - PMC - PubMed
    1. Baeten JM, Palanee-Phillips T, Brown ER, et al. . Use of a vaginal ring containing dapivirine for HIV-1 prevention in women. N Engl J Med 2016; 375:2121–32. - PMC - PubMed
    1. Brown ER, Hendrix CW, van der Straten A, et al. . Greater dapivirine release from the dapivirine vaginal ring is correlated with lower risk of HIV-1 acquisition: a secondary analysis from a randomized, placebo-controlled trial. J Int AIDS Soc 2020; 23:e25634. - PMC - PubMed

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