Study to Determine Interaction Between the Use of Feminizing Hormone Therapy and Antiretroviral Agents Concomitantly Among Transgender Women

Study Overview
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Brief Summary
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Objective To determine pharmacokinetic (PK) DDI between GAHT and ARVs used as PrEP and ART among TGW To evaluate ARV adherence among TGW

Detailed Description
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GAHT will be initiated on week 0. ARVs, either PrEP or ART, will be initiated on week 3. GAHT will then be withheld on week 5, and restart at week 8. GAHT: Oral estradiol valerate 2 mg once daily and cyproterone acetate 25 mg once daily, which are the treatment of choice for GAHT in the TRC-ARC's Tangerine Community Health Center, will be provided to all participants. PrEP and ART regimen: Generic fixed-dose combination of TDF 300 mg and FTC 200 mg will be used for PrEP and a generic fixed-dose combination of TDF 300 mg, FTC 200 mg and efavirenz 600 mg will be used for ART as recommended in the 2017 Thailand National Guidelines on HIV/AIDS Treatment and Prevention.

Official Title
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The Thai Red Cross AIDS Research Centre

Conditions
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PrEP and ART

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Thai nationality Age 18-40 years old Male-to-female transgender individual PrEP/ART naïve Body mass index 18.5-25 kg/m2 Calculated creatinine clearance (CrCl) ≥60 mL/min, as estimated by the Cockcroft- Gault equation Alanine aminotransferase (ALT) ≤2.5 x ULN Have signed the informed consent form Exclusion Criteria: Known history of allergy to hormonal or ARV component to be used in the study Male-to-female transgender who underwent orchiectomy Any of the following in HIV-infected participants CD4 < 350 cells/mm3 History of psychiatric disorder that may be worsening by taking EFV Previous use of injectable GAHT in the past 6 months Current use of any of the following medication: Anticonvulsant: Phenytoin, carbamazepine or phenobarbitol Ergot-containing agents: dihydroergotamine, ergotamine or other ergot derivatives Sedatives: Midazolam or triazolam Herbs: Gingko biloba, St John's wort or milk thistle Anti-infective agents: Erythromycin, clarithromycin, ketoconazole, itraconazole, rifampicin or rifabutin Alcohol or drug use that, in the opinion of the investigator, would interfere with completion of study procedures

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| GAHT and PrEP<br>HIV-negative TGW will have HIV testing using the 4th generation immunoassays/nucleic acid testing (NAT) in acute HIV testing algorithm currently used at the Thai Red Cross Anonymous Clinic at week 5, 8, and 15. Creatinine clearance will be performed at week 15. | |
| GAHT and ART<br>HIV-positive TGW on ART will have their plasma HIV RNA measured at the same day ART is initiated and at week 15 (12 weeks after ART provision). CD4 count will be measure at week 15. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric mean (%CV) area under the plasma concentration time curve from 0 to 24 hours (AUC0-24) of estradiol |  | Measured at week 3 and week 5 of the study period | 
| Geometric mean (%CV) area under the plasma concentration time curve from 0 to 24 hours (AUC0-24) of tenofovir |  | Measured at week 5 and week 8 of the study period | 
| Geometric mean (%CV) maximum plasma concentration (Cmax) of estradiol |  | Measured at week 3 and week 5 of the study period | 
| Geometric mean (%CV) maximum plasma concentration (Cmax) of tenofovir |  | Measured at week 5 and week 8 of the study period | 
| Geometric mean (%CV) trough plasma concentration (C24) of estradiol |  | Measured at week 3 and week 5 of the study period | 
| Geometric mean (%CV) trough plasma concentration (C24) of tenofovir |  | Measured at week 5 and week 8 of the study period | 
| Geometric mean (%CV) half-life (t1/2) of estradiol |  | Measured at week 3 and week 5 of the study period | 
| Geometric mean (%CV) half-life (t1/2) of tenofovir |  | Measured at week 5 and week 8 of the study period |