CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

Herein, we report the impact of MHT on the PK parameters of F/TDF in trans men using oral daily PrEP. Methods: iMACT was a PK study evaluating the potential drug-drug interactions (DDI) between MHT and oral PrEP among trans men in Thailand. Trans men who had not undergone oophorectomy were enrolled between May and October 2022. MHT (testosterone enanthate 200 mg intramuscular) was administered at baseline and every 2 weeks until week 12, while oral daily F/TDF-based PrEP (200/300 mg) was initiated at week 6 and prescribed until the end of study at week 16. PK sampling was conducted at week 12 (PrEP with MHT) and 16 (PrEP without MHT). Plasma FTC and tenofovir (TFV); and intracellular TFV-diphosphate (TFV-DP) and FTC triphosphate (FTC-TP) concentrations in peripheral blood mononuclear cells (PBMCs), rectal, and cervical tissues were assessed. Results: 19/20 participants completed the PK visits and were included in this analysis. Median (IQR) age and body mass index were 34 (28-39) years and 22.1 (21.3-24.7) kg/m 2 , respectively. The geometric mean ratios (GMRs) (90%CI) of area under the concentration-time curve from 0 to 24 hours (AUC0-24) and maximum concentration (C max ) at week 12 and 16 (reference) were as follows: TFV, 1.03 (0.96-1.11, p=0.55) and 1.17 (1.03-1.32, p=0.08); and FTC, 1.05 (1.00-1.09, p=0.12) and 1.09 (1.00-1.18, p=0.17). Median pre-dose TFV-DP and FTC-TP concentrations were not significantly different between week 12 and 16 in PBMCs (C24 TFV-DP, 83.6 [72.0-102.3] vs 81.3 [36.1-100.8] fmol/10 6 cells, p=0.19; and C24 FTC-TP, 3433.5 [2692.9-4635.5] vs 4008.6 [2608.3-5025.2] fmol/10 6 cells, p=0.47), rectal tissue (TFV-DP, 211.7 [82.4-517.7] vs 61 [33.1 388.7] fmol/mg, p=0.65; and FTC-TP, 8.33 [4.9-11.9] vs 5.23 [4.4-7.2], fmol/mg, p=0.11), and cervical tissue (TDF-DP, 8.7 [4.0-12.4] vs 5.9 [2.8-9.1] fmol/mg, p=0.51; and FTC-TP, 30.3 [5.1-143.0] vs 34.0 [29.0-153.8] fmol/mg, p=0.28). Conclusion: Plasma levels of TFV and FTC, and intracellular concentrations of TFV-DP and FTC-TP in PBMCs, rectal and cervical tissue, were comparable when F/TDF-based PrEP was administered with and without MHT, suggesting no clinically significant DDI from MHT towards F/TDF-based PrEP. The figure, table, or graphic for this abstract has been removed. 1146 Potential Drug Interactions From Hormone Therapy Toward F/TAF-Based PrEP in Trans Men: iMACT Study Akarin Hiransuthikul 1 , Narukjaporn Thammajaruk 2 , Stephen Kerr 1 , Rena Janamnuaysook 2 , Siriporn Nonenoy 2 , Piranun Hongchookiat 2 , Rapee Trichavaroj 2 , Yardpiroon Tawon 3 , Jakkrapatara Boonruang 2 , Nipat Teeratakulpisarn 2 , Tim R. Cressey 3 , Peter L. Anderson 4 , Nittaya Phanuphak 2 , for the iMACT Study Team 1 Chulalongkorn University, Bangkok, Thailand, 2 Institute of HIV Research and Innovation (IHRI), Bangkok, Thailand, 3 Chiang Mai University, Chiang Mai, Thailand, 4 University of Colorado Anschutz Medical Campus, Aurora, CO, USA Background: We previously reported that plasma total testosterone concentrations were comparable in trans men receiving oral daily PrEP with masculinizing hormone therapy (MHT). Herein, we report the impact of MHT on the PK parameters of oral daily F/TAF-based PrEP. Methods: iMACT was a PK study evaluating the potential drug-drug interactions between MHT and oral daily PrEP among trans men Thailand. Trans men who had not undergone oophorectomy were enrolled between May and October 2022. MHT, testosterone enanthate 200 mg intramuscular, was administered at baseline and every 2 weeks until week 12, while oral daily F/ TAF-based PrEP (200/25 mg) was prescribed from week 6 until the end of study at week 16. PK sampling was performed at 12 (PrEP with MHT) and 16 (PrEP without MHT) to assess plasma FTC, TAF, and tenofovir (TFV); and intracellular TFV-diphosphate (TFV-DP) and FTC triphosphate (FTC-TP) concentrations in peripheral blood mononuclear cells (PBMCs), rectal, and cervical tissues. Results: Among 20 participants, median (interquartile range [IQR]) age and body mass index were 27.5 (22.5-33) years and 23.8 (20.5-25.2) kg/ m 2 , respectively. The geometric mean ratios (GMRs) (90%CI) of area under the concentration-time curve from 0 to 24 hours (AUC 0-24 ) and maximum concentration (C max ) at week 12 and 16 (reference) were: TAF, 0.99 (0.80-1.21, p=0.93) and 1.00 (0.69-1.44, p=0.99); TFV, 1.03 (0.94-1.14, p=0.63) and 0.97 (0.84-1.43, p=0.64); and FTC, 1.02 (0.99-1.05, p=0.48) and 0.97 (0.85-1.12, p=0.80). There were no statistically significant differences in median TFV-DP and FTC-TP concentrations in PBMCs (C24 TFV-DP, 564.2 [IQR: 280.7-927.4] vs 631.9 [IQR: 347.1-727] fmol/10 6 cells, p=0.77; and C24 FTC-TP, 3341.2 [IQR: 2522.7-5352.9] vs 3888.3 [IQR: 2096.9-5592.5] fmol/10 6 cells, p=0.60) and rectal tissue (TFV-DP, 53.4 [30.3-185.4] vs 65.3 [32.8-92.3] fmol/mg, p=0.51;

and FTC-TP, 7.6 [6.4-14.7] vs 7.7 [5.6-11.1] fmol/mg, p=0.51) between the two visits. However, both TFV-DP and FTC-TP concentrations in cervical tissue were significantly lower at week 12 than 16 (TFV-DP, 12.90 [6.8-14.6] vs 20.6 [7.5 53.4] fmol/mg, p=0.04; and FTC-TP, 67.1 [27.2-77.2] vs 120.4 [66.0-245.8] fmol/ mg, p=0.02). Conclusion: Plasma TAF, TFV, and FTC; and intracellular TFV-DP and FTC-TP levels in PBMCs and rectal tissue were comparable when F/TAF-based PrEP was co-administered with MHT. However, TFV-DP and FTC-TP concentrations trended significantly lower in cervical tissue. The figure, table, or graphic for this abstract has been removed. 1147 One-Year Declines in Bone Mineral Density Among Young Women in Uganda Using TDF-Based PrEP and DMPA Renee Heffron 1 , Timothy Muwonge 2 , Katherine K. Thomas 3 , Kidist Zewdie 3 , Timothy Ssebuliba 2 , Gabrielle Stein 3 , Susan Morrison 3 , Josephine Badaru 2 , Agnes Nakyanzi 2 , Felix Bambia 2 , Kenneth K. Mugwanya 3 , Christina Wyatt 4 , Michael T. Yin 5 , Flavia Kiweewa Matovu 6 , Andrew Mujugira 2 1 University of Alabama at Birmingham, Birmingham, AL, USA, 2 Infectious Diseases Institute, Kampala, Uganda, 3 University of Washington, Seattle, WA, USA, 4 Duke University, Durham, NC, USA, 5 Columbia University, New York, NY, USA, 6 Makerere University–Johns Hopkins University Research Collaboration, Kampala, Uganda Background: Injectable depot medroxyprogesterone acetate (DMPA) is the most common contraceptive choice among young women in Uganda and nearby countries, where HIV burden is also high and HIV PrEP may be offered. DMPA and TDF-based PrEP have been associated with reductions in bone mineral density (BMD) when used consistently over multiple years. For young women who have not yet reached peak bone mass and choose to use DMPA, it is unknown whether concurrent PrEP use exacerbates declines in BMD. Methods: We conducted a 2-year prospective observational study with women ages 16-25 years in Kampala, Uganda, who desired prevention for pregnancy and HIV. Women were provided either condoms or injectable DMPA for contraception and either condoms or FTC/TDF as oral PrEP for HIV prevention, according to their choices. Annual dual x-ray absorptiometry (DXA) scans were performed to measure BMD. We used tenofovir-diphosphate (TFV-DP) quantification in dried blood spots and delivery of DMPA injections to determine exposure to each agent. Linear regression models estimated the difference in % BMD change from baseline to month 12 for women using oral PrEP and DMPA versus women using either agent individually or neither agent. Results: Of 499 enrolled women with median age 20 years (IQR 18-21) and normal baseline distribution of BMD z-scores, discontinuation and re-starting of contraceptive and PrEP use was common during follow-up. Women using neither agent (n=39) experienced BMD growth of 2.01% at lumbar spine, 1.22% at hip, 0.10% at femoral neck. Women with consistent use of both agents during 1 year (n=22) experienced an average BMD loss of 1.04% in the lumbar spine and hip and 1.77% in femoral neck. These losses were statistically different relative to women who used neither agent: difference in % BMD change of -3.05% at the lumbar spine (95% CI -4.77%, -1.33%, p=0.001), -2.26% in total hip (95% CI -3.38%, -0.69%, p=0.006), and approached significance at the femoral neck (-1.87%, -3.84%, 0.11%, p=0.067). When examining exposure to each agent independent of the other (Table), we observed some significant declines but in smaller magnitude. Conclusion: Despite limited sample size, we observed a trend for women with concurrent DMPA and PrEP use to have 1-3% lower BMD than unexposed women after 12 months. Given participant ages and exposure time, this difference may be clinically significant and further work is need to quantify the impact of longer concurrent exposure to TDF-based PrEP and DMPA.

Poster Abstracts

CROI 2024 373