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AMSTERDAM – Transgender women who were taking feminizing hormone therapy and pre-exposure prophylaxis (PrEP) to prevent HIV infection showed a small but possibly important decline in serum levels of tenofovir, one of the two ingredients in the PrEP formulation, researchers reported here.

After 8 weeks, tenofovir levels were 13% lower among transgender women who received by feminizing hormones and the combination of tenofovir and emtricitabine (Truvada) which make up the PrEP pill (P=0.009), reported Akarin Hiransuthikul, MD, lead investigator of the iFACT study and a researcher with the Thai Red Cross AIDS Researcher Centre, Bangkok.

At a press conference at the 22nd International AIDS Conference, Hiransuthikul said, "While it is great that our studies have found this previously unknown drug-drug interaction with feminizing hormone therapy, there are still key questions that need to be answered: Does this interaction occur in target tissues such as those in the rectum? And does this 13% reduction in blood concentration of tenofovir mean anything clinically to the effectiveness of PrEP?"

Press conference moderator Linda-Gail Bekker, MD, president of the International AIDS Society, and professor of medicine at the Desmond Tutu HIV Foundation, Cape Town, South Africa, said she was not sure that a 13% reduction was unimportant. "I think that when you are talking about rectal exposure there may not be much of a difference," she said, "but when these transgender women complete their transition then the difference in vaginal exposure could be important. I think that most modelers will suggest that a 13% reduction in levels is not going to be clinically significant."

"This is a small study but it is important to the trans community who have real questions about this," she told MedPage Today. "It is important that the trans community knows we are doing research in this area."

Hiransuthikul noted that the level of estradiol valerate taken by the participants was not significantly affected by PrEP medication. "This means that you can use PrEP without the fear that it will decrease the hormone levels in your body," he said. Testosterone levels also did not vary, he said.

"We know that PrEP is effective in preventing HIV transmission, but there have been studies that show that the blood level of PrEP appeared to be lower in transgender women than in non-transgender people," Hiransuthikul said. The reason for the lower levels could have been due to a drug-drug interaction; non compliance with PrEP or transgender women may have prioritized hormone drugs over PrEP.

That question led to the formation of iFACT, he said, which is investigating the possible drug-drug interaction between hormones and antiretroviral drugs, with the current report looking at the use of PrEP. He noted that the study might not be applicable to all areas because feminizing hormone therapies for transgender women differ across regions and countries.

To determine the impact of the drug-drug interaction, the researchers enrolled 20 transgender women who had never undergone orchiectomy and had not received injectable feminizing hormone therapy in the past 6 months. They were enrolled in the 8-week trial between January and March 2018, Hiransuthikul reported.

During the first 3 weeks of the study, the participants received only feminizing hormone therapy. From weeks 3 to 5 and weeks 8 to 15 they received both hormonal therapy and PrEP; only PrEP was given during weeks 5 to 8.