Sex Hormone Therapy and Tenofovir Diphosphate Concentration in Dried Blood Spots: Primary Results of the Interactions Between Antiretrovirals And Transgender Hormones Study

Abstract

Background Pilot studies showed lower tenofovir plasma concentrations during PrEP use among transgender women (TGW) using feminizing hormones compared with cisgender men (CGM). Tenofovir diphosphate (TFV-DP) concentrations in TGW and transgender men (TGM) using gender affirming hormones and on directly observed dosing of PrEP have not been studied. Methods TGM and TGW on at least 6 months of stable sex hormone therapy containing testosterone or estradiol (respectively) were enrolled in a 4-week study of directly observed dosing of daily oral co-formulated emtricitabine and tenofovir disoproxil fumarate (FTC/TDF). TFV-DP in dried blood spots and sex hormones in serum were measured at weekly intervals. TFV-DP was compared with 2 and 4 week samples from DOT-DBS (NCT02022657). Results From May 2017 to June 2018, 24 TGM and 24 TGW were enrolled; one TGM withdrew prior to 4 weeks of PrEP. Ethnicity (non-exclusive) was 27 (57%) white, 10 (21%) black, and 15 (32%) latinx. The median age was 31 (IQR 28 to 40). Of TGW, 9 (38%) took spironolactone in addition to estradiol. Testosterone (total and free) and estradiol concentrations were comparable before and after 4 weeks of PrEP use in TGM and TGW respectively. Historical controls comprised of 17 cisgender women (CGW) and 15 CGM. TFV-DP concentrations at week 4 were comparable between TGW and TGM (mean difference -6%; 95% CI -21% to 12%; P=0.47), comparable between TGW and CGM (mean difference -12%; 95% CI -27% to 7%; P=0.21) and were lower among TGM compared with CGW (mean difference -23%; 95% CI -36% to -7%; P=0.007). All persons in all groups were projected to reach the TFV-DP threshold that has been associated with high protection from HIV. There were no associations between serum estradiol or free testosterone concentrations and TFV-DP. Conclusion CGM, TGM, and TGW had comparable TFV-DP concentrations in DBS after 4 weeks of directly observed daily FTC/TDF PrEP use. Serum hormone concentrations were not affected by FTC/TDF PrEP use.

Global scoping review of HIV prevention research with transgender people: Transcending from trans‐subsumed to trans‐centred research

“…Three recent trans-centred studies reported that the use of feminizing hormones was associated with reduced PrEP concentrations in blood, suggesting that the reduced efficacy of oral PrEP is not merely the result of lower adherence amongst transgender women [47][48][49]. Another recent study assessing the drug interactions between sex hormone therapy and oral PrEP showed that tenofovir concentrations were comparable between transgender women and cisgender men, but not between transgender men and cisgender women, although all participants were projected to reach protective PrEP levels [50]. Furthermore, a secondary analysis of iPrEx trial data showed that significant differences in baseline characteristics between transgender women and cisgender MSM (e.g.…”

Southern African guidelines on the safe, easy and effective use of pre-exposure prophylaxis: 2020

“…Transgender women on feminising hormonal treatment were thought to be in danger of drug–drug interactions with reduced efficacy of PrEP; however, a recent study has shown this is not the case. 45 …”

“…Transgender women on feminising hormonal treatment were thought to be in danger of drug-drug interactions with reduced efficacy of PrEP; however, a recent study has shown this is not the case. 45 Tenofovir disoproxil fumarate is largely eliminated by the kidneys. There are few drug interactions of note, but TDF should be used with caution with medications that cause renal toxicity (see Table 3).…”

HIV incidence and risk factors among transgender women and cisgender men who have sex with men in two cities of China: a prospective cohort study

“…In addition, transgender women are still a very hidden population in China, thus, intervention delivery through social media, including mobile apps may also needed [ 28 ]. In addition to traditional interventions such as health education and condom use, newer strategies such as pre-exposure prophylaxis should also consider to include transgender women [ 55 , 56 ] to ensure that this population in China are not left behind.…”