The Journal of infectious diseases · 2025
Anal Sex and Tenofovir Douche Sequence Impacts Colorectal Distribution of HIV Surrogate and Douche: DREAM-02.
Клиническое исследование I фазыСтатьяНазвание и аннотация: Перевод в очереди
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Zheng Ruohui, Fuchs Edward J, Nimmagadda Sridhar, Rohan Lisa C, Wang Lin, Bertagnolli Lynn N, Massih Sandra, Caffo Brian S, Hendrix Craig W
Аннотация
BACKGROUND: Men who have sex with men are at high risk of human immunodeficiency virus (HIV) acquisition through unprotected receptive anal intercourse (RAI). Behaviorally congruent HIV preexposure prophylaxis (PrEP) has long been advocated by individuals who find adherence challenging or prefer minimizing systemic drug concentrations. We developed an event-driven, behaviorally congruent rectal tenofovir douche as a PrEP option for RAI and demonstrated product safety/acceptability in a previous clinical study. Here, our goal was to compare colorectal distribution of an HIV surrogate and tenofovir douche when the tenofovir douche preceded or followed simulated RAI (sRAI).
METHODS: Five participants completed 2 paired study visits. At visit one, participants received an 111indium-diethylenetriaminepentaacetic acid-labelled tenofovir douche prior to sRAI using 99mTc-sulfur colloid in autologous semen as HIV surrogate. At visit two, the radiolabeled tenofovir douche was administered following radiolabeled sRAI. Colorectal distribution of both douche and HIV surrogate radioisotopes were assessed using single-photon emission computed tomography/transmission computed tomography. Systemic permeability was assessed by plasma TFV concentrations.
RESULTS: Colorectal distribution of the douche was not different between sequences. Conversely, the majority of HIV surrogate was within the rectosigmoid when the douche was administered prior to sRAI, but the distribution extended into descending colon when the douche was administered following sRAI. Regardless of sequence, an early plasma TFV peak 20 minutes after dosing was observed.
CONCLUSIONS: Douching following RAI may increase HIV distribution in the colon with uncertain impact on HIV acquisition risk. The early plasma TFV suggests even more rapid time to protection than reported in prior studies.
CLINICAL TRIALS REGISTRATION: NCT04195776.
METHODS: Five participants completed 2 paired study visits. At visit one, participants received an 111indium-diethylenetriaminepentaacetic acid-labelled tenofovir douche prior to sRAI using 99mTc-sulfur colloid in autologous semen as HIV surrogate. At visit two, the radiolabeled tenofovir douche was administered following radiolabeled sRAI. Colorectal distribution of both douche and HIV surrogate radioisotopes were assessed using single-photon emission computed tomography/transmission computed tomography. Systemic permeability was assessed by plasma TFV concentrations.
RESULTS: Colorectal distribution of the douche was not different between sequences. Conversely, the majority of HIV surrogate was within the rectosigmoid when the douche was administered prior to sRAI, but the distribution extended into descending colon when the douche was administered following sRAI. Regardless of sequence, an early plasma TFV peak 20 minutes after dosing was observed.
CONCLUSIONS: Douching following RAI may increase HIV distribution in the colon with uncertain impact on HIV acquisition risk. The early plasma TFV suggests even more rapid time to protection than reported in prior studies.
CLINICAL TRIALS REGISTRATION: NCT04195776.