ART decreases estradiol, but does not impact hormone therapy efficacy, in transgender women
Estradiol pharmacokinetic parameters were significantly decreased in the presence of ART among transgender women who are HIV-positive, according to data from a recent study.
“Through our community-led test and treat project and the Tangerine Community Health Center, we have had a great opportunity to see many transgender women clients who came to our health care facility for STIs, HIV and gender-affirmative hormones services, among other things” Akarin Hiransuthikul, MD, of PREVENTION, Thai Red Cross AIDS Research Centre, told Healio. “This is where we began to notice that many transgender women have concerns about taking feminizing hormone therapy and PrEP or ART together.”
“Unfortunately, and surprisingly, we had no answer to those questions,” Hiransuthikul added. “That led us to this study.”
To assess possible drug-drug interactions between feminizing hormone therapy (FHT) and ART, Hiransuthikul and colleagues measured intensive pharmacokinetic parameters of blood tenofovir, efavirenz and estradiol (E2) in 20 transgender women newly diagnosed with HIV.
The researchers prescribed FHT – in this case, estradiol valerate 2 mg and cyproterone acetate 25 mg – at baseline. Patients remained on FHT until week 5 and began the treatment again at week 8. ART (tenofovir disoproxil fumarate 300 mg, emtricitabine 200 mg and efavirenz 600 mg) was started at week 3.
Intensive E2 PK were measured at weeks 3 (without ART) and 5 (with ART), and intensive TFV and EFV PK were measured at weeks 5 (with FHT) and 8 (without FHT).
According to Hiransuthikul, the study demonstrated that blood concentration of E2 was significantly reduced, by 36%, in the presence of tenofovir/emtricitabine/efavirenz. Blood tenofovir and efavirenz concentrations were decreased by 17% and 9%, respectively, in the presence of FHT, but the 90% CI “suggested a clinically significant interaction only with tenofovir.” The researchers did not see an increase in bioavailable testosterone levels in the presence of tenofovir/emtricitabine/efavirenz.
The results from Hiransuthikul and colleagues differ from an aspect of the iFACT study that demonstrated no significant changes in E2 levels in the presence of daily tenofovir/emtricitabine-based pre-exposure prophylaxis, or PrEP. The current study revealed a significant decrease in E2 levels in the presence of ART.
“We hypothesize that the drug-drug interaction between FHT and tenofovir/emtricitabine/efavirenz involves altered drug metabolism, most likely from the induction of the CYP system, particularly CYP3A4, and uridine diphosphate glucuronosyltransferase enzyme mechanism by efavirenz, subsequently reducing E2 levels,” the researchers wrote.
Hiransuthikul noted that the study’s aim was to examine drug-drug interactions from a pharmacokinetic perspective, not a clinical perspective. In addition, the ART regimen used in the study was the first-line recommendation for use in resource-limited settings.
“We hope that the findings in our study would urge the consideration of using integrase strand transfer inhibitor-based regimens among transgender women in resource-limited settings,” Hiransuthikul concluded. “The take-home message for counseling transgender women who are HIV-positive is that although efavirenz-based ART significantly affects E2 level, it does not affect the ability of FHT to suppress bioavailable testosterone to the target levels. At the same time, increased dosing of FHT may further negatively impact tenofovir and efavirenz levels.” – by Caitlyn Stulpin
Disclosures: Hiransuthikul reports no relevant financial disclosures.