Akarin Hiransuthikul, Narukjaporn Thammajaruk, Stephen Kerr, Rena Janamnuaysook, Siriporn Nonenoy, Piranun Hongchookiat, Rapee Trichavaroj, Yardpiroon Tawon, Jakkrapatara Boonruang, Nipat Teeratakulpisarn, Tim R. Cressey, Peter L. Anderson, Nittaya Phanuphak, the iMACT study team
{"title":"在变性男性中探索男性化激素疗法与口服暴露前预防（F/TDF 和 F/TAF）之间潜在的药物相互作用（iMACT 研究）：在泰国进行的随机、开放标签药代动力学研究","authors":"Akarin Hiransuthikul, Narukjaporn Thammajaruk, Stephen Kerr, Rena Janamnuaysook, Siriporn Nonenoy, Piranun Hongchookiat, Rapee Trichavaroj, Yardpiroon Tawon, Jakkrapatara Boonruang, Nipat Teeratakulpisarn, Tim R. Cressey, Peter L. Anderson, Nittaya Phanuphak, the iMACT study team","doi":"10.1002/jia2.26445","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Introduction</h3>\n \n <p>Concerns regarding potential drug−drug interactions (DDIs) between hormone therapy and pre-exposure prophylaxis (PrEP) may hinder PrEP use among transgender persons. Transgender men have often been overlooked in biomedical HIV research, and potential DDIs between masculinizing hormone therapy (MHT) and PrEP have not been addressed. We aimed to assess the potential DDIs between MHT and daily oral PrEP among transgender men.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Transgender men without HIV who never underwent oophorectomy were enrolled between May and October 2022. Participants were randomly assigned to receive emtricitabine-tenofovir disoproxil fumarate (F/TDF) or emtricitabine-tenofovir alafenamide (F/TAF) for daily oral PrEP. Intramuscular testosterone enanthate 200 mg was administered every 2 weeks from baseline to week 12, while oral PrEP was initiated at week 6 and continued until week 16. Pharmacokinetic (PK) sampling was conducted at weeks 4 and 12 to assess the impact of PrEP on MHT and at weeks 12 and 16 to evaluate the impact of MHT on PrEP. Plasma total testosterone, TAF, tenofovir (TFV) and FTC; tenofovir-diphosphate (TFV-DP) and emtricitabine-triphosphate (FTC-TP) concentrations in peripheral blood mononuclear cells (PBMCs) were measured in all participants. Cervical and rectal tissues were obtained in a subset of 20 participants (10 per group) to measure TDF-DP and FTC-TP.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Thirty-nine participants (19 F/TDF and 20 F/TAF) completed the PK visits. No significant changes in the PK parameters of plasma total testosterone, TFV, FTC and TAF (for F/TAF group); urine TFV and FTC; and PBMC and rectal tissue TFV-DP and FTC-TP were observed when MHT and PrEP were administered together. Both TFV-DP and FTC-TP concentrations in cervical tissue were significantly lower when MHT was co-administered with F/TAF (TFV-DP: median [IQR] of 12.9 [6.78–14.56] fmol/mg at weeks 12 vs. 20.63 [7.47–53.43] fmol/mg at week 16, <i>p</i> = 0.04; and FTC-TP: 67.05 [27.24–77.24] fmol/mg vs. 120.43 [65.98–245.76] fmol/mg, <i>p</i> = 0.02).</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Our findings across multiple anatomical compartments suggest that oral PrEP should not affect the effectiveness of MHT and that F/TDF-based PrEP should be effective when taken with MHT. However, further research is needed to assess the effectiveness of TAF-based PrEP in transgender men.</p>\n </section>\n \n <section>\n \n <h3> Clinical Trial Number</h3>\n \n <p>NCT04593680.</p>\n </section>\n </div>","PeriodicalId":201,"journal":{"name":"Journal of the International AIDS Society","volume":"28 4","pages":""},"PeriodicalIF":4.6000,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jia2.26445","citationCount":"0","resultStr":"{\"title\":\"Exploring potential drug−drug interactions between masculinizing hormone therapy and oral pre-exposure prophylaxis (F/TDF and F/TAF) among transgender men (iMACT study): a randomized, open-label pharmacokinetic study in Thailand\",\"authors\":\"Akarin Hiransuthikul, Narukjaporn Thammajaruk, Stephen Kerr, Rena Janamnuaysook, Siriporn Nonenoy, Piranun Hongchookiat, Rapee Trichavaroj, Yardpiroon Tawon, Jakkrapatara Boonruang, Nipat Teeratakulpisarn, Tim R. Cressey, Peter L. Anderson, Nittaya Phanuphak, the iMACT study team\",\"doi\":\"10.1002/jia2.26445\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Introduction</h3>\\n \\n <p>Concerns regarding potential drug−drug interactions (DDIs) between hormone therapy and pre-exposure prophylaxis (PrEP) may hinder PrEP use among transgender persons. Transgender men have often been overlooked in biomedical HIV research, and potential DDIs between masculinizing hormone therapy (MHT) and PrEP have not been addressed. We aimed to assess the potential DDIs between MHT and daily oral PrEP among transgender men.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Transgender men without HIV who never underwent oophorectomy were enrolled between May and October 2022. Participants were randomly assigned to receive emtricitabine-tenofovir disoproxil fumarate (F/TDF) or emtricitabine-tenofovir alafenamide (F/TAF) for daily oral PrEP. Intramuscular testosterone enanthate 200 mg was administered every 2 weeks from baseline to week 12, while oral PrEP was initiated at week 6 and continued until week 16. Pharmacokinetic (PK) sampling was conducted at weeks 4 and 12 to assess the impact of PrEP on MHT and at weeks 12 and 16 to evaluate the impact of MHT on PrEP. Plasma total testosterone, TAF, tenofovir (TFV) and FTC; tenofovir-diphosphate (TFV-DP) and emtricitabine-triphosphate (FTC-TP) concentrations in peripheral blood mononuclear cells (PBMCs) were measured in all participants. Cervical and rectal tissues were obtained in a subset of 20 participants (10 per group) to measure TDF-DP and FTC-TP.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Thirty-nine participants (19 F/TDF and 20 F/TAF) completed the PK visits. No significant changes in the PK parameters of plasma total testosterone, TFV, FTC and TAF (for F/TAF group); urine TFV and FTC; and PBMC and rectal tissue TFV-DP and FTC-TP were observed when MHT and PrEP were administered together. Both TFV-DP and FTC-TP concentrations in cervical tissue were significantly lower when MHT was co-administered with F/TAF (TFV-DP: median [IQR] of 12.9 [6.78–14.56] fmol/mg at weeks 12 vs. 20.63 [7.47–53.43] fmol/mg at week 16, <i>p</i> = 0.04; and FTC-TP: 67.05 [27.24–77.24] fmol/mg vs. 120.43 [65.98–245.76] fmol/mg, <i>p</i> = 0.02).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>Our findings across multiple anatomical compartments suggest that oral PrEP should not affect the effectiveness of MHT and that F/TDF-based PrEP should be effective when taken with MHT. However, further research is needed to assess the effectiveness of TAF-based PrEP in transgender men.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Clinical Trial Number</h3>\\n \\n <p>NCT04593680.</p>\\n </section>\\n </div>\",\"PeriodicalId\":201,\"journal\":{\"name\":\"Journal of the International AIDS Society\",\"volume\":\"28 4\",\"pages\":\"\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2025-04-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jia2.26445\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of the International AIDS Society\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/jia2.26445\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the International AIDS Society","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jia2.26445","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Exploring potential drug−drug interactions between masculinizing hormone therapy and oral pre-exposure prophylaxis (F/TDF and F/TAF) among transgender men (iMACT study): a randomized, open-label pharmacokinetic study in Thailand
Introduction
Concerns regarding potential drug−drug interactions (DDIs) between hormone therapy and pre-exposure prophylaxis (PrEP) may hinder PrEP use among transgender persons. Transgender men have often been overlooked in biomedical HIV research, and potential DDIs between masculinizing hormone therapy (MHT) and PrEP have not been addressed. We aimed to assess the potential DDIs between MHT and daily oral PrEP among transgender men.
Methods
Transgender men without HIV who never underwent oophorectomy were enrolled between May and October 2022. Participants were randomly assigned to receive emtricitabine-tenofovir disoproxil fumarate (F/TDF) or emtricitabine-tenofovir alafenamide (F/TAF) for daily oral PrEP. Intramuscular testosterone enanthate 200 mg was administered every 2 weeks from baseline to week 12, while oral PrEP was initiated at week 6 and continued until week 16. Pharmacokinetic (PK) sampling was conducted at weeks 4 and 12 to assess the impact of PrEP on MHT and at weeks 12 and 16 to evaluate the impact of MHT on PrEP. Plasma total testosterone, TAF, tenofovir (TFV) and FTC; tenofovir-diphosphate (TFV-DP) and emtricitabine-triphosphate (FTC-TP) concentrations in peripheral blood mononuclear cells (PBMCs) were measured in all participants. Cervical and rectal tissues were obtained in a subset of 20 participants (10 per group) to measure TDF-DP and FTC-TP.
Results
Thirty-nine participants (19 F/TDF and 20 F/TAF) completed the PK visits. No significant changes in the PK parameters of plasma total testosterone, TFV, FTC and TAF (for F/TAF group); urine TFV and FTC; and PBMC and rectal tissue TFV-DP and FTC-TP were observed when MHT and PrEP were administered together. Both TFV-DP and FTC-TP concentrations in cervical tissue were significantly lower when MHT was co-administered with F/TAF (TFV-DP: median [IQR] of 12.9 [6.78–14.56] fmol/mg at weeks 12 vs. 20.63 [7.47–53.43] fmol/mg at week 16, p = 0.04; and FTC-TP: 67.05 [27.24–77.24] fmol/mg vs. 120.43 [65.98–245.76] fmol/mg, p = 0.02).
Conclusions
Our findings across multiple anatomical compartments suggest that oral PrEP should not affect the effectiveness of MHT and that F/TDF-based PrEP should be effective when taken with MHT. However, further research is needed to assess the effectiveness of TAF-based PrEP in transgender men.
期刊介绍：
The Journal of the International AIDS Society (JIAS) is a peer-reviewed and Open Access journal for the generation and dissemination of evidence from a wide range of disciplines: basic and biomedical sciences; behavioural sciences; epidemiology; clinical sciences; health economics and health policy; operations research and implementation sciences; and social sciences and humanities. Submission of HIV research carried out in low- and middle-income countries is strongly encouraged.
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