CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

648

Estradiol Concentrations in Trans Women on BIC/FTC/TAF Compared to Those Without HIV Alice Tseng 1 , Mona Loutfy 2 , Ashley Lacombe-Duncan 3 , Yasmeen Persad 2 , Raymond Fung 4 , Ian Armstrong 5 , Louie L. Y. Chan 6 , Quang Nguyen 7 , Suza Hranilovic 8 , Darrell H. S. Tan 8 , Roberta Halpenny 5 , Nirubini Jeyarajah 5 , Jennifer McCully 5 , V. Logan Kennedy 2 , Kimberly K. Scarsi 9 1 University Health Network, Toronto, Canada, 2 Women's College Research Institute, Toronto, Canada, 3 University of Michigan, Ann Arbor, MI, USA, 4 Michael Garron Hospital, Toronto, ON, Canda, 5 Maple Leaf Medical Clinic, Toronto, Canada, 6 Church Wellesley Health Centre, Toronto, ON, Canada, 7 Sherbourne Health Centre, Toronto, ON, Canada, 8 Unity Health Toronto (St Michael's Hospital), Toronto, ON, Canada, 9 University of Nebraska Medical Center, Omaha, NE, USA Background: Accessing feminizing hormone therapy (FHT) is essential to many trans women. Concern around drug-drug interactions between FHT and antiretroviral therapy (ART) can be a barrier to acceptance of ART for trans women with HIV. We measured serum estradiol concentrations in trans women with HIV taking FHT and BIC/FTC/TAF versus trans women without HIV taking FHT and no ART. Methods: This was a single-center, parallel group, clinical study of adult trans women with HIV taking ART and without HIV not taking ART. Participants were taking at least 2 mg/day of oral 17-beta estradiol plus an anti-androgen therapy, with no FHT medication changes for at least 3 months prior to entry. Women with HIV were on suppressive ART for at least 6 months, either taking or switched to BIC/FTC/TAF at entry. At the month 2 visit, blood was collected prior to ART and FHT dosing and then at 1, 2, 3, 4, 6, 8, and 24 hours post-dose. Estradiol concentrations were measured from serum using chemiluminescent microparticle immunoassay (CMIA). Area under the concentration-time curve (AUC) over 24 hours was calculated by noncompartmental methods. Median estradiol maximum concentration (C max ), time to C max (T max ) and AUC were compared between groups using Wilcoxon rank-sum tests. Data are reported as medians (IQRs). Results: Participants (n=25) were enrolled from November 2022 to June 2024 and the 10 participants on ART had a median age of 36.5 (30, 45.25) years compared to 29 (27, 37.5) years for the 15 control participants (p=0.173). The median oral estradiol dose was 4 mg (range 2-8 mg) overall and 4 (4, 4) for the ART group and 4 (3, 4) for the control (p=0.232). Anti-androgen therapy included spironolactone (n=12), cyproterone (n=8), orchidectomy (n=4), and hypogonadism (n=1). Estradiol C max and T max for the ART group were 357.5 pmol/L(257, 512.25) and 1.5 hours (2, 2.75), respectively and 262 pmol/L (151.5, 312) (p=0.115) and 4 hours (2, 7) (p=0.130) for controls (Figure). AUCs were not different between groups: 5827 mg*h/L (4488, 8352) for the ART group and 4808 mg*h/L (2952, 6281) for controls (p=0.235). Overall, 64% had estradiol C4h within the target of 200-750 pmol/L[80% among women on ART and 53% among those not on ART (p=0.229)]. Conclusions: Among trans women on FHT, estradiol concentrations were similar between trans women on BIC/FTC/TAF and controls. This suggests a low probability of clinically relevant drug-drug interactions between FHT and BIC/ FTC/TAF.

647

Pharmacokinetics of Twice-Daily TAF in Adults With HIV-Associated TB on BIC/FTC/TAF and Rifampicin Emmanuella C. Osuala 1 , Ivan N. Nkuhairwe 2 , Marothi P. Letsoalo 1 , Kogieleum Naidoo 1 , Rubeshan Perumal 1 , James F. Rooney 3 , Roeland Wasmann 2 , Paolo Denti 2 , Kelly E. Dooley 4 , Anushka Naidoo 1 , for the INSIGHT Study Team 1 Centre for the AIDS Programme of Research in South Africa, Durban, South Africa, 2 University of Cape Town, Cape Town, South Africa, 3 Gilead Sciences, Inc, Foster City, CA, USA, 4 Vanderbilt University Medical Center, Nashville, TN, USA Background: Tenofovir alafenamide fumarate (TAF) is a pro-drug of tenofovir (TFV) with less renal and bone toxicity than tenofovir disoproxil fumarate (TDF). However, unlike TDF, it has been shown to interact with rifampicin (RIF) in healthy volunteers. The pharmacokinetics (PK) of TAF with RIF in people with HIV (PWH) and tuberculosis (TB) have not been evaluated. Methods: A PK sub-study nested within the INSIGHT trial (NCT04734652) evaluated the plasma and intracellular PK of TFV and TFV-diphosphate (TFV-DP) in adults with HIV and TB initiated on a bictegravir(BIC)/emtricitabine(FTC)/TAF regimen dosed twice-daily (BD) until 2 weeks post RIF-based TB treatment and once-daily (QD) thereafter until 48 weeks. Plasma and dried blood spot (DBS) samples (3mm punches) were collected at weeks 4 and 12 (pre-dose, 1, 2, 4, 6, and 8-12h post-dose) during first-line TB treatment and at week 32 (pre-dose, 1, 2, 4, 6-8, and 24-25h post-dose) after TB treatment. Non-compartmental PK analyses were conducted using the PKanalix2024R1 software. Participants underwent regular clinical and safety monitoring during study follow-up visits. We report the preliminary PK data for TFV and intracellular TFV-DP when TAF is dosed with or without RIF. Results: Forty-three participants were enrolled in the PK sub-study in the BIC arm; median (IQR) age and weight were 35 (30-39) years and 57 (52-64) kg; 77% were male, and all were black. A total of 79 PK profiles were evaluable for TFV on TAF BD+RIF (20 PK profiles for TFV-DP during RIF) and 40 PK profiles for TAF QD alone (10 PK profiles for TFV-DP off RIF). Geometric mean ratio (GMR) (90% CI) AUC0-24 for TFV was 1.24 (1.06, 1.45) and 1.21 (1.03, 1.42) at weeks 4 and 12 on TAF BD with RIF relative to week 32 on QD TAF. GMR (90% CI) AUC0-24 for TFV-DP was 0.97 (0.79, 1.19) at weeks 12 versus week 32 with and without RIF, respectively (Table 1). Overall, 95% of participants achieved viral suppression at week 24 in the BIC arm. TAF BD+RIF did not result in higher TFV-DP intracellular concentrations than for QD dosing, there were no BIC/FTC/TAF related drug toxicity events in the study including no treatment discontinuations. Conclusions: Twice-daily TAF achieved sufficient exposures to overcome RIF enzyme-inducing effects in adults with HIV and TB, achieving TFV-DP intracellular concentrations above those previously reported with TDF. These data support the use of TAF in a fixed dose combination of BIC/FTC/TAF in PWH and TB.

Poster Abstracts

CROI 2025 179