FTC exposure higher in young transgender men than cisgender controls
14 October 2020. Related: Conference reports, PK and drug interactions, HIV prevention and transmission, PK Workshop 21st 2020.
Mark Mascolini for NATAP and Virology Education
By two measures, transgender men (TM) had somewhat higher plasma emtricitabine (FTC) exposure than historical cisgender men taking FTC as part of TDF/FTC preexposure prophylaxis (PrEP). [1]
And TM had higher FTC exposure than transgender women (TW). TW had 25% higher tenofovir (TFV) troughs (Ctau) than historical cisgender women.
Transgender people run a higher risk of HIV infection in the United States than the general population, noted University of Colorado, Aurora researchers who conducted this study with colleagues from other centres. But relatively little is known about the pharmacokinetics of PrEP constituents TFV and FTC in TM or TW because those groups have not been well represented in PrEP trials.And the potential impact of cross-sex hormone therapy (csHT) on PrEP remains inadequately studied. As a result, effectiveness of PrEP remains poorly understood in these groups at high risk for HIV infection.
To address these issues, researchers from the University of Colorado, Aurora, and colleagues conducted a TFV/FTC pharmacokinetic study in TM and TW and compared results to those in historical cisgender controls. Participating HIV negative TM and TW were receiving a stable csHT dose and had not taken tenofovir disoproxil fumarate (TDF)/FTC PrEP within 3 months. All TM and TW participants were between the ages of 15 and 24.
Enrollees took daily observed TDF/FTC for 4 weeks. Intensive pharmacokinetic sampling after an overnight fast was conducted 2-3 weeks after first dosing. Researchers compared results to those in 9 cisgender men and 10 cisgender women without HIV and with a median age of 30.5 years who followed the same protocol in the Cell-PrEP study. [2]
The transgender group included 24 TW and 23 TM with a median age of 21 years (range: 16 to 24) and median creatinine clearance of 146 mL/min (range: 69 to 197) for TW and 115 mL/min (range: 75 to 243) for TM. Three quarters of participants (76%) were white, 22% Hispanic, and 13% black. Among 24 TW, 12 used oral or sublingual estrogen and 12 used intramuscular estrogen.
Eighteen of 23 TM had intramuscular testosterone injections and 5 had subcutaneous injections.TFV area under the concentration-time curve (AUCtau) was similar for TW and TM (geometric mean 2628 and 2770 ng*h/mL), as was TFV trough concentration (Ctau) (57.3 and 55.3 ng/mL). Compared with TM, TW had 20% lower FTC exposure (AUCtau 10,706 vs 13,445 vs ng*h/mL, p=0.0005) and 24% lower FTC maximum concentration (Cmax 1665 vs 2191 ng/mL p=0.004) but similar FTC troughs.
TW had 25% higher TFV Ctau than Cell-PrEP cisgender women (57.3 vs 45.7 ng/mL, P = 0.049) but a similar TFV Cmax and AUCtau. FTC concentrations did not differ significantly between TW and cisgender control women.
TM did not differ much from Cell-PrEP cisgender men in TFV or FTC Ctau, but TM had 20% higher TFV AUCtau than control men (2770 vs 2301 ng*h/mL, p=0.039), 36% higher FTC Cmax (2191 vs 1608 ng/mL, p=0.001), and 33% higher FTC AUCtau (13,445 vs 10,125 ng*h/mL, p<0.0001).The University of Colorado team concluded that daily PrEP with TDF/FTC should continue to be recommended for transgender adolescents and young adults who run a risk of HIV infection.
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This study is important for providing PK data for transgender people who as a group are likely to use and depend on PrEP as an option to protect against HIV.
The study reported plasma levels of these NRTIs, as surrogate markers for TFV-DP and FTC-TP intracellular levels in genital tissue.
Daily dosing is still recommended as the higher plasma levels in transmen is not likely to translate to protective levels needed in genital tissue.
- Yager J, Brooks K, Brothers J, et al. Steady-state plasma TFV/FTC among adolescent transgender men and women receiving directly observed daily TDF/FTC. International Workshop on Clinical Pharmacology of HIV, Hepatitis, and Other Antiviral Drugs Virtual Meeting, September 28-30, 2020. Abstract 1.
- ClinicalTrials.gov. Evaluation of the cellular pharmacology of tenofovir and emtricitabine according to HIV infection status. ClinicalTrials.gov identifier NCT01040091. https://clinicaltrials.gov/ct2/show/NCT01040091