Tenofovir Douche as HIV Pre-Exposure Prophylaxis for Receptive Anal Intercourse: Safety, Acceptability, Pharmacokinetics, & Pharmacodynamics (DREAM 01).
HIV
Microbicide
Pharmacodynamics
Pharmacokinetics
Phase I
Pre-exposure prophylaxis
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
29 Nov 2023
29 Nov 2023
Historique:
received:
02
09
2023
revised:
14
11
2023
accepted:
27
11
2023
medline:
29
11
2023
pubmed:
29
11
2023
entrez:
29
11
2023
Statut:
aheadofprint
Résumé
Despite highly effective HIV pre-exposure prophylaxis (PrEP) options, no options provide on-demand, non-systemic, and behaviorally-congruent PrEP that many desire. A tenofovir-medicated rectal douche before receptive anal intercourse (RAI) may provide this option. Three tenofovir rectal douches - 220-mg iso-osmolar Product A, 660-mg iso-osmolar Product B, and 660-mg hypo-osmolar Product C - were studied in 21 HIV-negative men who have sex with men. We sampled blood and colorectal tissue to assess safety, acceptability, pharmacokinetics, and pharmacodynamics. The douches had high acceptability without toxicity. Median plasma tenofovir peak concentrations for all products were several-fold below trough concentrations associated with oral tenofovir disoproxil fumarate (TDF). Median colon tissue mucosal mononuclear cell (MMC) tenofovir-diphosphate concentrations exceeded target concentrations from 1-hour through 3-to-7-days after dosing. For 6-7-days after a single Product C dose, MMC tenofovir-diphosphate exceeded concentrations expected with steady-state oral TDF 300-mg on-demand "2-1-1" dosing. Compared to pre-drug baseline, HIV replication after ex vivo colon tissue HIV challenge demonstrated a concentration-response relationship with 1.9 log10 maximal effect. All three tenofovir douches achieved tissue tenofovir-diphosphate concentrations and colorectal antiviral effect exceeding oral TDF with lower systemic tenofovir. tenofovir douches may provide a single dose, on-demand, behaviorally-congruent PrEP option and warrant continued development.
Sections du résumé
BACKGROUND
BACKGROUND
Despite highly effective HIV pre-exposure prophylaxis (PrEP) options, no options provide on-demand, non-systemic, and behaviorally-congruent PrEP that many desire. A tenofovir-medicated rectal douche before receptive anal intercourse (RAI) may provide this option.
METHODS
METHODS
Three tenofovir rectal douches - 220-mg iso-osmolar Product A, 660-mg iso-osmolar Product B, and 660-mg hypo-osmolar Product C - were studied in 21 HIV-negative men who have sex with men. We sampled blood and colorectal tissue to assess safety, acceptability, pharmacokinetics, and pharmacodynamics.
RESULTS
RESULTS
The douches had high acceptability without toxicity. Median plasma tenofovir peak concentrations for all products were several-fold below trough concentrations associated with oral tenofovir disoproxil fumarate (TDF). Median colon tissue mucosal mononuclear cell (MMC) tenofovir-diphosphate concentrations exceeded target concentrations from 1-hour through 3-to-7-days after dosing. For 6-7-days after a single Product C dose, MMC tenofovir-diphosphate exceeded concentrations expected with steady-state oral TDF 300-mg on-demand "2-1-1" dosing. Compared to pre-drug baseline, HIV replication after ex vivo colon tissue HIV challenge demonstrated a concentration-response relationship with 1.9 log10 maximal effect.
CONCLUSIONS
CONCLUSIONS
All three tenofovir douches achieved tissue tenofovir-diphosphate concentrations and colorectal antiviral effect exceeding oral TDF with lower systemic tenofovir. tenofovir douches may provide a single dose, on-demand, behaviorally-congruent PrEP option and warrant continued development.
Identifiants
pubmed: 38019657
pii: 7454273
doi: 10.1093/infdis/jiad535
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.