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

On-demand topical products could be an important tool for HIV prevention. We evaluated the safety, pharmacokinetics, and ex vivo pharmacodynamics of a tenofovir alafenamide/elvitegravir (TAF/EVG; 16 mg/20 mg) insert administered rectally. MTN-039 was a Phase 1, open-label, single-arm, 2-dose study....

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Published in:The Journal of infectious diseases 2024-04
Main Authors: Riddler, Sharon A, Kelly, Clifton W, Hoesley, Craig J, Ho, Ken S, Piper, Jeanna M, Edick, Stacey, Heard, Faye, Doncel, Gustavo F, Johnson, Sherri, Anderson, Peter L, Brand, Rhonda M, Kunjara Na Ayudhya, Ratiya Pamela, Bauermeister, José A, Hillier, Sharon L, Hendrix, Craig W
Format: Article
Language:English
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Summary:On-demand topical products could be an important tool for HIV prevention. We evaluated the safety, pharmacokinetics, and ex vivo pharmacodynamics of a tenofovir alafenamide/elvitegravir (TAF/EVG; 16 mg/20 mg) insert administered rectally. MTN-039 was a Phase 1, open-label, single-arm, 2-dose study. Blood, rectal fluid (RF), and rectal tissue (RT) were collected over 72 hours (hr) following rectal administration of one and two TAF/EVG inserts for each participant. ClinicalTrials.gov Identifier: NCT04047420. 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. RT EVG peaked at 2-hr (median 2 inserts= 9 ng/mg) but declined to BLQ in the majority of samples at 24-hr, whereas TFV-DP remained high >2,000 fmol/million cells for 72-hr with 2 inserts. Compared to baseline, median cumulative log10 HIV p24 antigen of ex vivo rectal tissue HIV infection was reduced at each timepoint for both 1 and 2 inserts (p
ISSN:0022-1899
1537-6613
1537-6613
DOI:10.1093/infdis/jiae211