A Phase 1 Clinical Trial to Assess the Safety and Pharmacokinetics of a Tenofovir Alafenamide/Elvitegravir Insert Administered Rectally for HIV Prevention.
J Infect Dis
; 230(3): 696-705, 2024 Sep 23.
Article
en En
| MEDLINE
| ID: mdl-38655842
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, 20â mg/16â 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 72â 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 2.4â ng/mL and TFV 4.4â ng/mL. Rectal tissue EVG peaked at 2 hours (median, 2 inserts = 9â ng/mg) but declined to below limit of quantification in the majority of samples at 24 hours, whereas tenofovir diphosphate (TFV-DP) remained high >2000â 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 72â hours. Clinical Trials Registration . NCT04047420.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Administración Rectal
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Adenina
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Infecciones por VIH
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Quinolonas
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Fármacos Anti-VIH
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Alanina
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Tenofovir
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Infect Dis
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos