A small study of women and men of transgender experience who used Truvada (tenofovir disoproxil fumarate/emtricitabine) to protect themselves from HIV found that the pre-exposure prophylaxis (PrEP) pill didn’t change levels of gender-affirming hormones for women or men. For trans men, however, levels of tenofovir, one of Truvada’s components, were lower than they were in cisgender women.

Still, whether the drop matters is unclear. No one acquired HIV during the four-week study, and all participants were projected to reach “highly protective” drug levels by eight weeks.

These are the initial findings of the small Interactions Between Antiretrovirals and Transgender Hormones (I-BREATHe) trial, published in the journal Clinical Infectious Diseases.

The findings contradict earlier research that suggested that use of feminizing hormones was associated with lower concentrations of tenofovir in the blood. Again, in that study, it was unclear whether the drop in drug concentrations was significant enough to increase the risk of acquiring HIV. Understanding these interactions has been a focus for researchers in recent years, as public health officials begin to understand the extent of vulnerability to HIV among many trans people.

In this study, 24 women and 24 men of trans experience agreed to be observed daily while taking 200 milligrams of Truvada for four weeks. Participants had negative HIV tests and were over 18 years old. By four weeks, enough tenofovir has accumulated in the body to estimate PrEP drug levels. The researchers collected dried blood spots from each participant to test for levels of tenofovir and emtricitabine. These drug levels were then compared to those of cisgender PrEP users documented in a previous study.

PrEP adherence was over 99%; one person left the study after two weeks.

At the end of the four weeks, estrogen and testosterone levels remained constant, with no differences observed in levels of estradiol, estrone, total and free testosterone, dihydrotestosterone or sex hormone–binding globulin.

Tenofovir levels were comparable, if slightly lower, in transgender women compared to cisgender men (down 12%), but that change wasn’t significant. However, tenofovir concentrations dropped nearly twice as much in trans men (23%) compared with cisgender women—and that decrease was statistically significant. This remained true even when controlling for factors like age, weight and use of the androgen-blocker spirolactone as part of gender-affirming hormone therapy.

But it’s unclear whether these laboratory findings mean anything in the real world.

“These results support current recommendations for PrEP dosing using regimens that contain tenofovir disoproxil fumarate [one of the two drugs in Truvada],” wrote lead study author Robert Grant, MD, of the University of California, San Francisco, and colleagues. “Our findings also suggest that the lower concentrations of [tenofovir] in dried blood spots among transgender women in the iPrEx trial were due to less use of the medication, rather than differences in metabolism” of the drugs.

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