CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

612

Safety and PK/PD of a Tenofovir Rectal Douche Administered in Different Sequences, DREAM-03 Ruohui Zheng 1 , Ken Ho 2 , Edward J. Fuchs 1 , Alex Carballo-Diéguez 3 , Lisa C. Rohan 2 , Rebecca Giguere 3 , Rhonda M. Brand 2 , Stacey Edick 2 , Rahul P. Bakshi 1 , Teresa L. Parsons 1 , Cindy E. Jacobson 4 , Christina Bagia 2 , Lin Wang 2 , Mark Marzinke 1 , Craig W. Hendrix 1 1 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 2 University of Pittsburgh, Pittsburgh, PA, USA, 3 New York State Psychiatric Institute, New York, NY, USA, 4 Magee–Womens Research Institute, Pittsburgh, PA, USA Background: On-demand and behaviorally congruent forms of HIV pre exposure prophylaxis (PrEP) have long been requested by communities at risk of HIV, especially men who have sex with men (MSM). Previously in DREAM-01, we reported safety, acceptability, and pharmacokinetics/pharmacodynamics (PK/ PD) of three single-dose tenofovir (TFV) rectal douche formulations in MSM and identified a lead formulation. Given that MSM report using multiple douches for cleanliness prior to receptive anal intercourse, DREAM-03 sought to report safety and PK/PD outcomes when using multiple TFV douches with and without water douches. Methods: TFV douche products that consisted of 660 mg TFV in 125 mL hypo osmolar saline were tested in three sequences: (A) three TFV douches, (B) one TFV douche then two tap water douches, and (C) two tap water douches then one TFV douche. We collected blood over 168 hours post-dose and rectal swabs/ tissue biopsies over 72 hours. TFV and TFV diphosphate (TFV-DP) concentrations were quantified using validated methods. Anti-HIV effect was evaluated using an ex vivo colonic explant HIV challenge method with biopsies collected over 6 hours post-dose. An HIV p24 assay was used to quantify viral replication. Results among different sequences were compared using Wilcoxon signed-rank tests. Results: Nine male participants were enrolled, with a median (range) age of 38 (29, 52) years and a median weight of 77 (64, 113) kg. No grade >2 study related adverse events were reported. Plasma TFV concentrations at 4 and 6 hours were significantly higher (4.9- and 6.5-fold, respectively) in sequence A than those in sequence B (Figure 1A). A trend of higher TFV-DP concentrations in rectal mucosal mononuclear cells (MMCs) at 24 and 72 hours in sequences A (12.0- and 3.5-fold, respectively) and C (5.1- and 4.2-fold, respectively) than those in sequence B were also observed (Figure 1B). Compared to pre-drug baseline, HIV replication after ex vivo HIV challenge demonstrated a concentration-response relationship with 2.8 log, 2.2 log 10 , and 2.2 log 10 maximal effects for sequences A, B, and C, respectively. Conclusion: Our result demonstrates that administering three TFV rectal douches are well tolerated. In addition, using non-medicated douches after a TFV douche may likely reduce both systemic and local TFV exposures, and may subsequently compromise anti-HIV effect of the TFV douche. Our study suggests that after non-medicated douches, a TFV douche should be used to provide better protection against HIV.

Conclusion: 10-day digital pill adherence was a significant predictor of TFV-DP in PBMC. TFV-DP was higher in PWH on b/ART, which may enhance virologic effect, dose forgiveness, and/or side effects. TFV-DP in DBS and PBMC were moderately correlated, which may be due in part to TFV-DP in PBMC being more susceptible to recent non-adherence given the shorter half-life in PBMC vs. DBS (2 vs. 17 days). Further investigation of other factors contributing to variability in TFV-DP in PBMCs is warranted.

611

Adherence Markers for Doxy-PEP in Plasma and Urine Richard Haaland 1 , Jeffrey Fountain 1 , Chuong Dinh 1 , Tiancheng Edwards 1 , Deborah Omoyege 2 , Christopher Conway-Washington 2 , Colleen Kelley 3 , Walid Heneine 1 1 Centers for Disease Control and Prevention, Atlanta, GA, USA, 2 Emory Vaccine Center, Atlanta, GA, USA, 3 Emory Center for AIDS Research, Atlanta, GA, USA Background: Clinical trials of Doxy-PEP demonstrated high efficacy in preventing bacterial sexually transmitted infections (STIs) among men who have sex with men but not in women. Low Doxy-PEP efficacy observed among women may be related to poor adherence highlighting the importance of objective adherence monitoring in future trials and implementation studies. We examined doxycycline (DOXY) concentrations in urine and plasma, two specimen types commonly collected for STI testing, following a single oral DOXY dose to identify objective adherence markers of Doxy-PEP dosing. Methods: Eleven male and 9 female participants provided blood and urine up to 7 days after receiving a 200 mg oral DOXY dose. DOXY was measured in plasma and urine by liquid chromatography-mass spectrometry with a lower limit of quantification of 10 ng/mL. DOXY concentrations are reported as median and interquartile range. Adherence indicators were identified as the 10th percentile concentration at each time point. Results: Plasma DOXY concentrations peaked 2 hours after dosing and declined to 0.487 µg/mL (0.402 – 0.682 µg/mL) 24 hours after dosing. Plasma DOXY remained measurable in all participants 96 hours after dosing (0.043 µg/mL; 0.032 – 0.067 µg/mL) but became undetectable in 13 of 16 participants by 7 days post dose. Urine DOXY concentrations were significantly greater than those in plasma with a urine to plasma ratio of 38:1 (9:1 – 103:1; p < 0.001). Urine DOXY concentrations also peaked 2 hours after dosing and declined to 13.1 µg/ mL (6.8 – 28.5 µg/mL) 24 hours after dosing but remained measurable in 15 of 16 participants 7 days after dosing at 0.202 µg/mL (0.137 – 0.318 µg/mL). DOXY adherence indicators for plasma were determined to be 0.30 and 0.03 µg/mL at 1 and 4 days after dosing, respectively, while urine adherence indicators were determined to be 3.00, 0.35 and 0.07 µg/mL at 1, 4 and 7 days after dosing, respectively. Concentrations were not significantly different between male and female participants at each time point. Conclusion: We identified adherence measures after a single DOXY dose within a pharmacologic tail of 4 and 7 days in plasma and urine, respectively. The data will inform and enable adherence testing in clinical studies to better assess Doxy-PEP efficacy.

Poster Abstracts

613

Early Identification of ART Missed Doses: Baseline Data From the RETAIN Study Lauren Jennings 1 , Chantel Schreuder 1 , Richard Madimabe 1 , Campbell McDuling 2 , Tebogo Mosina 1 , Lora Sabin 3 , Catherine Orrell 1 1 Desmond Tutu HIV Foundation, Cape Town, South Africa, 2 University of Cape Town, Cape Town, South Africa, 3 Boston University, Boston, MA, USA Background: We present baseline data from "Improving RETention and viral load outcomes for people taking Antiretroviral therapy through early IdentificatioN of missed doses (RETAIN)", a cohort study exploring detailed adherence metrics [viral load (VL), electronic adherence monitoring (EAM);

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