Drug-Drug Interaction Study in Trans Women Living With HIV
- Conditions
- HivTransgenderism
- Interventions
- Registration Number
- NCT05663892
- Lead Sponsor
- Maple Leaf Research
- Brief Summary
Introduction: Transgender (trans) women have been found to be at higher risk of and to be disproportionally affected by HIV. Trans women with HIV have also been found to have low usage and adherence rates to antiretroviral therapy (ART). Both healthcare providers and trans women, themselves, have expressed concerns of drug-drug interactions (DDIs) between ART drugs and feminizing hormones, which have in turn been shown to contribute to low rates of ART usage amongst trans women with HIV. The objective of this DDI study is to investigate the pharmacokinetic effects of the common feminizing hormone regimens (oral estradiol with an anti-androgen (pharmaceutical and/or surgical and/or medical) on the antiretroviral combination bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) and vice versa.
Methods and Analysis: Participants will be assigned to three groups: group 1 will include 15 trans women with HIV who are taking feminizing hormones and ART (investigational group); group 2 will include 15 premenopausal cis women with HIV taking ART (ART control group); group 3 will include 15 trans women without HIV taking feminizing hormones (hormone control group). Women with HIV will have to be virally suppressed for at least three months and they will have to already be taking B/F/TAF or have their current ART regimen switched to B/F/TAF at baseline. Trans women participants will be required to be on 2 mg oral estradiol or higher and an anti-androgen (pharmaceutical, medical or surgical). Plasma ART drug concentrations will be sampled at the 2-month visit and compared among trans women with HIV on feminizing hormones and premenopausal cis women with HIV. Serum estradiol and total testosterone concentrations will be sampled at the baseline and month 2 visits and compared among trans women with and without HIV. If successful, this trial will serve to provide empirical evidence regarding a lack of, or presence of DDIs between B/F/TAF and feminizing hormones.
Dissemination: The findings will be disseminated through publication in peer-reviewed journals as well as presented at national and international conferences and community groups.
- Detailed Description
Introduction: Transgender (trans) women have been found to be at higher risk of and to be disproportionally affected by HIV for multiple biologic and social reasons. Trans women living with HIV have also been found to have low usage and adherence rates to antiretroviral therapy (ART). Both healthcare providers and trans women, themselves, have expressed concerns of drug-drug interactions (DDIs) between ART drugs and feminizing hormones, which have in turn been shown to contribute to low rates of ART usage amongst trans women living with HIV. The objective of this DDI study is to investigate the pharmacokinetic effects of the common feminizing hormone regimens (oral estradiol with an anti-androgen (pharmaceutical and/or surgical and/or medical)) on the antiretroviral combination bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) and vice versa.
Methods and analysis: Participants will be assigned to three groups: group 1 will include 15 trans women living with HIV who are taking feminizing hormones and ART (investigational group); group 2 will include 15 premenopausal cis women living with HIV taking ART (ART control group); group 3 will include 15 trans women living without HIV taking feminizing hormones (hormone control group). Women living with HIV will have to be virally suppressed for at least three months and they will have to already be taking B/F/TAF or have their current ART regimen switched to B/F/TAF at baseline. Trans women participants will be required to be on 2 mg oral estradiol or higher and an anti-androgen (pharmaceutical, medical or surgical). Plasma ART drug concentrations will be sampled at the 2-month visit and compared among trans women living with HIV on feminizing hormones and premenopausal cis women living with HIV. Serum estradiol and total testosterone concentrations will be sampled at the baseline and month 2 visits and compared among trans women living with and without HIV. The primary endpoints are B/F/TAF pharmacokinetic parameters (Cmin, Cmax and AUC) between trans and cis women living with HIV at month 2 and the estradiol concentrations (Cmin, C4h, Cmax and AUC) and the proportions of the month 2 C4h that are within target (200 to 735 pmol/L) between trans women living with and without HIV at month 2. Other endpoints will include the mean estradiol and testosterone concentrations at baseline and the difference between baseline and month 2 estradiol pre-dose and C4h, satisfaction with feminizing hormones, HIV viral load, adherence, adverse events, patient-reported outcomes (i.e., symptoms), satisfaction with ART regimen and health status. If successful, this trial will serve to provide empirical evidence regarding a lack of, or presence of DDIs between B/F/TAF and feminizing hormones.
Dissemination: The findings will be disseminated through publication in peer-reviewed journals as well as presented at national and international conferences and community groups.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 45
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Investigational Population (Group 1) - Trans women living with HIV Estradiol Tablets Trans women living with HIV, taking: * Biktarvy * Oral 17(Beta)-Estradiol Comparator Population (Group 3) - Trans Women Living without HIV Estradiol Tablets Trans women living without HIV, taking: -Oral 17(Beta)-Estradiol Comparator Population (Group 2) - Cis Women Living with HIV Biktarvy 50/200/25 Tab Cis women living with HIV, taking: -Biktarvy Investigational Population (Group 1) - Trans women living with HIV Biktarvy 50/200/25 Tab Trans women living with HIV, taking: * Biktarvy * Oral 17(Beta)-Estradiol
- Primary Outcome Measures
Name Time Method BIC, FTC, and TAF area under the curve (AUC) plasma concentrations. Month 2 AUC plasma concentrations of BIC, FTC, and TAF will be compared between trans women living with HIV (group 1) and premenopausal cis women living with HIV (group 2).
2h PBMC and DBS TFV-DP and FTC-TP concentrations. Month 2 PBMC and DBS TFV-DP and FTC-TP concentrations done at 2h after ingestion of medications will be compared between trans women living with HIV (group 1) and premenopausal cis women living with HIV (group 2).
Minimum serum concentrations (Cmin) of estradiol. Month 2 Estradiol Cmin at month 2 will be compared between groups 1 and 3.
Maximum serum concentrations (Cmax) of estradiol Month 2 Estradiol Cmax at month 2 will be compared between groups 1 and 3.
Estradiol serum concentration area under the curve (AUC) Month 2 Estradiol AUC at month 2 will be compared between groups 1 and 3.
4 hour serum concentration (C4h) of estradiol Month 2 Estradiol C4h at month 2 and the proportions of the month 2 C4h that are within target (200 to 735 pmol/L) and will be compared between groups 1 and 3.
BIC, FTC, and TAF minimum plasma concentrations. Month 2 Minimum plasma concentrations (Cmin) of BIC, FTC, and TAF concentrations will be compared between trans women living with HIV (group 1) and premenopausal cis women living with HIV (group 2).
BIC, FTC, and TAF maximum plasma concentrations. Month 2 Maximum plasma concentrations (Cmax) of BIC, FTC, and TAF concentrations will be compared between trans women living with HIV (group 1) and premenopausal cis women living with HIV (group 2).
- Secondary Outcome Measures
Name Time Method Baseline estradiol pre-dose serum concentration (Cmin) and comparison to month 2 Months 0 & 2 Baseline estradiol pre-dose concentrations, and these will be compared between groups 1 and 3 and assessed to see the proportion that meets target. The baseline estradiol pre-dose concentrations will be taken on variable ART regimens for the trans women living with HIV; the month 2 estradiol pre-dose concentrations will be taken from the trans women living with HIV who are taking B/F/TAF; and the change in estradiol pre-dose concentrations from baseline to month 2 in those who switched to B/F/TAF will be compared to those who did not and to those in group 3.
Baseline estradiol C4h serum concentration and comparison to month 2 Months 0 & 2 Baseline estradiol C4h concentrations, and these will be compared between groups 1 and 3 and assessed to see the proportion that meets target. The baseline estradiol C4h concentrations will be taken on variable ART regimens for the trans women living with HIV; the month 2 estradiol C4h concentrations will be taken from the trans women living with HIV who are taking B/F/TAF; and the change in estradiol C4h concentrations from baseline to month 2 in those who switched to B/F/TAF will be compared to those who did not and to those in group 3.
Participant health status using the SF-36 Months 0, 2 & 6 Participant health status in all groups will be assessed using the SF-36 at baseline and month 2, which allows us to convert to a utility and conduct cost-effectiveness analyses in the future, if desired. The SF-36 will be repeated for Groups 1 and 2 at the 6-month visit. The SF-36 consists of eight scale scores (vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health). These eight scale scores are the weighted sums of the questions in their section and then each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. SF-36 is interpreted in ascending fashion with lower scores equating to more disability and higher scores meaning less disability. The individual scale scores and overall scale score are most often reported as a mean and standard deviation (SD).
Baseline total testosterone serum concentration and comparison to month 2 Months 0 & 2 Baseline total testosterone concentrations, and these will be compared between groups 1 and 3 and assessed to see the proportion that meets target. The baseline total testosterone concentrations will be taken on variable ART regimens for the trans women living with HIV; the month 2 total testosterone concentrations will be taken from the trans women living with HIV who are taking B/F/TAF; and the change in total testosterone concentrations from baseline to month 2 in those who switched to B/F/TAF will be compared to those who did not and to those in group 3.
Proportion of patient with an undetectable HIV-RNA. Months 0, 2 & 6 Proportion of patients with an undetectable HIV-RNA (\<40 copies/mL) will be compared between groups 1 and 2 throughout the study period.
Patient reported outcomes (PROs) using the HIV Symptom Index Distress Module (HSIDM) Months 0, 1, 2 & 6 PROs will be assessed for groups 1 and 2 at all study visits using the HSIDM at baseline, months 2 and 6. However, since the scale does not mention HIV and asks about symptoms solely, group 3 participants will be asked to complete it at baseline and month 2. Participants are asked about their experience with each of 20 symptoms during the past 4 weeks using a 5-point, Likert-type scale; therefore the minimum score is 0 and and maximum is 100. A higher score would mean that the participant has had a lot of symptoms and it has bothered them a lot.
FEM-SQ questionnaire score Months 0, 2 & 6 Total score on the Feminizing Medical Gender Affirmation Satisfaction Scale (FEM-SQ), a questionnaire for measuring satisfaction with medical gender affirmation, will be compared between groups 1 and 3 throughout the study period. The FEM-SQ is a new questionnaire developed by our team through mixed-methods survey development including expert consultation and focus groups with 23 trans women (version 1), semi-structured interviews with over 10 trans women (version 2), and quantitative data collection (survey administration) with 300 trans women (version 3). For the importance sub-scale the minimum score is 0 and the maximum score is 85. For the satisfaction sub-scale the minimum score is 18 and the maximum sub score is 90 with higher scores meaning the participant is satisfied with their feminizing hormone therapy.
Frequency of BIC, FTC, and TAF related adverse events Months 1, 2 & 6 Frequency and severity of B/F/TAF related adverse effect for participants in groups 1 and 2 who have changed to B/F/TAF at each follow-up visit.
Adverse effects will be recorded using the NIAID standardized toxicity grading system (Appendix D) and will be reported as a frequency and proportion of with any adverse effect, any grade 2 or higher and any requiring stopping the treatment.ART adherence using theMedication Adherence Self-Reported Inventory (MASRI) Months 0, 1, 2 & 6 ART adherence will be assessed at each visit for groups 1 and 2 using a validated visual analogue scale (VAS) of ART use, the MASRI, over the prior month at each visit. The instructions for the VAS read: 'put a cross on the line below at the point showing your best guess about how much medication you have taken in the last month. We would be surprised if this was 100% for most people, e.g., 0% means you have taken no medication; 50% means you have taken half your medication; 100% means you have taken every single dose of medication'. The VAS ranges from 0 to 100% in 10% intervals.
Satisfaction with ART Regimens using the HIVTSQ Months 0, 2 & 6 We will be asking about satisfaction with ART regimen using the HIV Treatment Satisfaction Questionnaire (HIVTSQ). There are two versions of the HIVTSQ that have been developed. At the baseline, month 2 and month 6 visits, the 10-item HIVTSQ status version (HIVTSQs) will be used. The HIVTSQc will be used in addition to the HIVTSQs at month 6. The questionnaires are both scored out of 66, the HIVTSQs has a range from 0 to 66 with a higher score meaning that one is more satisfied with their treatment. Item number 12 is not included in the composite score, it is stand alone. The HIVTSQc ranges from -33 to +33.
Trial Locations
- Locations (1)
Maple Leaf Research
🇨🇦Toronto, Ontario, Canada