TY - JOUR
T1 - Transgender women on oral HIV pre-exposure prophylaxis have significantly lower tenofovir and emtricitabine concentrations when also taking oestrogen when compared to cisgender men
AU - Shieh, Eugenie
AU - Marzinke, Mark A.
AU - Fuchs, Edward J.
AU - Hamlin, Allyson
AU - Bakshi, Rahul
AU - Aung, Wutyi
AU - Breakey, Jennifer
AU - Poteat, Tonia
AU - Brown, Todd
AU - Bumpus, Namandjé N.
AU - Hendrix, Craig W.
N1 - Funding Information:
We thank the study participants for their essential contributions to this clinical research. We also thank Deborah Dunn of Chase-Brexton Health Services, Baltimore, MD, for many helpful discussions regarding transgender health care and referral of many TGW study participants. Observational aspects of the study were funded, in part, by the Johns Hopkins Center for AIDS Research through a developmental research grant (P30 AI042855) and the Clinical Pharmacology Training Program grant (Dr. Shieh, T32 GM066691). In addition, this publication was made possible by the Johns Hopkins Institute for Clinical and Translational Research (ICTR), which is funded in part by a grant from the National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the Johns Hopkins ICTR, NCATS or NIH (UL1 TR001079).
Funding Information:
We thank the study participants for their essential contributions to this clinical research. We also thank Deborah Dunn of Chase‐Brexton Health Services, Baltimore, MD, for many helpful discussions regarding transgender health care and referral of many TGW study participants. Observational aspects of the study were funded, in part, by the Johns Hopkins Center for AIDS Research through a developmental research grant (P30 AI042855) and the Clinical Pharmacology Training Program grant (Dr. Shieh, T32 GM066691). In addition, this publication was made possible by the Johns Hopkins Institute for Clinical and Translational Research (ICTR), which is funded in part by a grant from the National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the Johns Hopkins ICTR, NCATS or NIH (UL1 TR001079).
Funding Information:
Craig Hendrix, Edward Fuchs, Jennifer Breakey, Mark Marzinke and Rahul Bakshi receive research support from Gilead Sciences through a contract with and managed by Johns Hopkins University School of Medicine. The other authors note no conflicts of interest.
Publisher Copyright:
© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - Introduction: Oral HIV Pre-Exposure Prophylaxis (PrEP) with tenofovir (TFV) disoproxil fumarate (TDF)/emtricitabine (FTC) is highly effective. Transgender women (TGW) have increased HIV risk, but have been underrepresented in trials. For TGW on oestrogens for gender-affirming hormone treatment (GAHT), TDF/FTC-oestrogen interactions may negatively affect HIV prevention or gender-affirming goals. Our aim was to evaluate any pharmacokinetic drug-drug interaction between GAHT and TDF/FTC. Methods: We performed a pharmacokinetic study, in an urban outpatient setting in 2016 to 2018, of the effects of GAHT on TFV, FTC and the active forms TFV diphosphate (TFV-DP) and FTC triphosphate (FTC-TP) in eight TGW and eight cisgender men (CGM). At screening, participants were HIV negative. TGW were to maintain their GAHT regimens and have plasma oestradiol concentrations >100 pg/mL. Under direct observation, participants took oral TDF/FTC daily for seven days. At the last dose, blood was collected pre-dose, one, two, four, six, eight and twenty-four hours, and colon biopsies were collected at 24 hours to measure drug concentration. TGW versus CGM concentration comparisons used non-parametric tests. Blood and colon tissue were also obtained to assess kinase expression. Results: Plasma TFV and FTC C24 (trough) concentrations in TGW were lower by 32% (p = 0.010) and 32% (p = 0.038) respectively, when compared to CGM. Plasma TFV and FTC 24-hr area under the concentration-time curve in TGW trended toward and was significantly lower by 27% (p = 0.065) and 24% (p = 0.028) respectively. Peak plasma TFV and FTC concentrations, as well as all other pharmacokinetic measures, were not statistically significant when comparing TGW to CGM. Oestradiol concentrations were not different comparing before and after TDF/FTC dosing. Plasma oestrogen concentration, renal function (estimated creatinine clearance and glomerular filtration rate), and TFV and FTC plasma concentrations (trough and area under the concentration-time curve) were all correlated. Conclusions: GAHT modestly reduces both TFV and FTC plasma concentrations. In TGW taking GAHT, it is unknown if this reduction will impact the HIV protective efficacy of a daily PrEP regimen. However, the combination of an on demand (2 + 1 + 1) PrEP regimen and GAHT may result in concentrations too low for reliable prevention of HIV infection.
AB - Introduction: Oral HIV Pre-Exposure Prophylaxis (PrEP) with tenofovir (TFV) disoproxil fumarate (TDF)/emtricitabine (FTC) is highly effective. Transgender women (TGW) have increased HIV risk, but have been underrepresented in trials. For TGW on oestrogens for gender-affirming hormone treatment (GAHT), TDF/FTC-oestrogen interactions may negatively affect HIV prevention or gender-affirming goals. Our aim was to evaluate any pharmacokinetic drug-drug interaction between GAHT and TDF/FTC. Methods: We performed a pharmacokinetic study, in an urban outpatient setting in 2016 to 2018, of the effects of GAHT on TFV, FTC and the active forms TFV diphosphate (TFV-DP) and FTC triphosphate (FTC-TP) in eight TGW and eight cisgender men (CGM). At screening, participants were HIV negative. TGW were to maintain their GAHT regimens and have plasma oestradiol concentrations >100 pg/mL. Under direct observation, participants took oral TDF/FTC daily for seven days. At the last dose, blood was collected pre-dose, one, two, four, six, eight and twenty-four hours, and colon biopsies were collected at 24 hours to measure drug concentration. TGW versus CGM concentration comparisons used non-parametric tests. Blood and colon tissue were also obtained to assess kinase expression. Results: Plasma TFV and FTC C24 (trough) concentrations in TGW were lower by 32% (p = 0.010) and 32% (p = 0.038) respectively, when compared to CGM. Plasma TFV and FTC 24-hr area under the concentration-time curve in TGW trended toward and was significantly lower by 27% (p = 0.065) and 24% (p = 0.028) respectively. Peak plasma TFV and FTC concentrations, as well as all other pharmacokinetic measures, were not statistically significant when comparing TGW to CGM. Oestradiol concentrations were not different comparing before and after TDF/FTC dosing. Plasma oestrogen concentration, renal function (estimated creatinine clearance and glomerular filtration rate), and TFV and FTC plasma concentrations (trough and area under the concentration-time curve) were all correlated. Conclusions: GAHT modestly reduces both TFV and FTC plasma concentrations. In TGW taking GAHT, it is unknown if this reduction will impact the HIV protective efficacy of a daily PrEP regimen. However, the combination of an on demand (2 + 1 + 1) PrEP regimen and GAHT may result in concentrations too low for reliable prevention of HIV infection.
KW - HIV pre-exposure prophylaxis
KW - drug-drug interaction
KW - emtricitabine
KW - gender-affirming hormonal treatment
KW - tenofovir
KW - transgender women
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U2 - 10.1002/jia2.25405
DO - 10.1002/jia2.25405
M3 - Article
C2 - 31692269
AN - SCOPUS:85074696904
VL - 22
JO - Journal of the International AIDS Society
JF - Journal of the International AIDS Society
SN - 1758-2652
IS - 11
M1 - e25405
ER -