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Pharmacokinetics of on demand, single dose tenofovir rectal douche for HIV Pre-Exposure Prophylaxis in young men (ATN 163)
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BACKGROUND: A behaviorally-congruent, on-demand rectal tenofovir (TFV) douche as pre-exposure prophylaxis (PrEP) to prevent HIV acquisition via receptive anal intercourse (RAI) would fill a critical gap in PrEP product availability. We previously reported pharmacokinetics (PK) of a single TFV douche in adult cisgender men (DREAM-01), median age 38 (range: 25, 64). Here we report ATN 163 describing the PK of the same TFV douche in young cisgender men, age 18-24, at risk of HIV via RAI.
METHODS: Participants enrolled at a single site between January and August 2022. One 125 mL douche containing 660 mg TFV was rectally administered. We collected blood at 1, 6, 24, and 72 hours post-dose with sparsely sampled rectal swabs and tissue biopsies at 1, 24, and 72 hours. TFV and TFV diphosphate (TFV-DP) concentrations were quantified using validated liquid chromatographic-tandem mass spectrometric assays. PK analysis was performed for TFV/TFV-DP. We compared ATN 163 to DREAM-01 using Mann-Whitney U tests.
RESULTS: Eight male (62.5% White and 37.5% Black) participants not on PrEP were enrolled, with a median (range) age of 21 (18, 24) years. Median weight and BMI were 182.6 (146.1, 258.5) pounds and 27.0 (22.7, 36.2), respectively. Estimated GFR (CKD-Epi) was 143 (129, 156) mL/min. TFV and TFV-DP concentrations in plasma and rectal samples (Figure 1) were not significantly different from DREAM-01 (all p values > 0.11). All PBMC TFV-DP concentrations were non-quantifiable. We observed no significant differences in plasma TFV Tmax, Cmax, T1/2, and AUClast comparing ATN 163 and DREAM-01 (all p values > 0.53). No adverse events were attributed to the TFV douche.
CONCLUSIONS: The TFV douche was well tolerated and demonstrated similar plasma and rectal PK between younger and older adults. This warrants inclusion of young men in future clinical investigations of the rectal TFV douche without dose adjustment.
METHODS: Participants enrolled at a single site between January and August 2022. One 125 mL douche containing 660 mg TFV was rectally administered. We collected blood at 1, 6, 24, and 72 hours post-dose with sparsely sampled rectal swabs and tissue biopsies at 1, 24, and 72 hours. TFV and TFV diphosphate (TFV-DP) concentrations were quantified using validated liquid chromatographic-tandem mass spectrometric assays. PK analysis was performed for TFV/TFV-DP. We compared ATN 163 to DREAM-01 using Mann-Whitney U tests.
RESULTS: Eight male (62.5% White and 37.5% Black) participants not on PrEP were enrolled, with a median (range) age of 21 (18, 24) years. Median weight and BMI were 182.6 (146.1, 258.5) pounds and 27.0 (22.7, 36.2), respectively. Estimated GFR (CKD-Epi) was 143 (129, 156) mL/min. TFV and TFV-DP concentrations in plasma and rectal samples (Figure 1) were not significantly different from DREAM-01 (all p values > 0.11). All PBMC TFV-DP concentrations were non-quantifiable. We observed no significant differences in plasma TFV Tmax, Cmax, T1/2, and AUClast comparing ATN 163 and DREAM-01 (all p values > 0.53). No adverse events were attributed to the TFV douche.
CONCLUSIONS: The TFV douche was well tolerated and demonstrated similar plasma and rectal PK between younger and older adults. This warrants inclusion of young men in future clinical investigations of the rectal TFV douche without dose adjustment.