7/30/2018

Interactions between Feminizing Hormones and PrEP among Transgender Women

The iFACT Study clarified some of the confusion regarding interactions between Truvada for PrEP and feminizing hormone replacement therapy in transgender women. Hopefully, this will help overcome the reluctance of some transgender women to take PrEP. The iFACT Study concluded:
1. Truvada does not lower levels of feminizing hormones in transgender women.
2. Daily adherence for PrEP is key for transgender women taking estradiol since femiinizing estradiol may impact PrEP efficacy.
Tenofovir levels in the blood were reduced by 13% in trans-women who used estradiol, but remained above the level shown to confer protection, investigators from the Thai Red Cross AIDS Research Centre said.

Some prior studies have shown that blood concentrations of Truvada in trans women were lower than expected. This could occur either because feminizing hormones interact in a way that reduces drug levels or because trans women have poorer adherence. The latter may occur because trans women are worried that PrEP could affect their hormone therapy, which they prioritise over HIV prevention. Previous work by the same group found that some trans women living with HIV are hesitant to use antiretroviral therapy or do not take it as prescribed because of concerns about drug interactions with their hormone therapy. The same may be true of PrEP acceptance among transgender women. An analysis of data from the pivotal iPrEx trial showed that Truvada PrEP appears to work well for transgender women, but only if they use it consistently. Studies of cisgender women suggest that they may need to take PrEP more consistently than men to achieve a similar level of protection.

At AIDS 2018, a pharmacokinetic study of potential drug-drug interactions between feminizing hormone therapy and PrEP. The iFACT study enrolled 20 HIV-negative trans women who still had intact testicles and had not received injectable hormones within the past six months. They were in their early- to mid-twenties and had normal body weight and kidney function. At the start of the study, the participants started a feminizing hormone therapy regimen of estradiol valerate (2 mg/day) plus the androgen blocker cyproterone acetate (25 mg/day). The research team stressed that feminizing hormone regimens vary in different countries and that these results are applicable only to this particular regimen. At week 3, the women started taking Truvada. At week 5, they stopped the hormone regimen so the researchers could compare PrEP drug levels on and off hormones, resuming at week 8. They then continued on both hormones and PrEP through week 15.

The iFACT study showed that concurrent use of hormone therapy and PrEP did not affect hormone levels. Comparing levels at week 3 (before starting PrEP) and week 5 (while on PrEP), the researchers saw no significant differences in maximum estradiol levels, estradiol levels 24 hours after dosing, estradiol half-life or area under the curve, a measure of total drug exposure over 24 hours. They also saw no changes in testosterone concentrations. They therefore concluded that PrEP did not significantly affect levels of feminizing hormones. However, looking at the effect of feminizing hormones on tenofovir, they found that tenofovir levels at 24 hours after dosing and tenofovir total exposure was about 13% lower in the presence of estradiol. The study did not measure emtricitabine levels. This difference was statistically significant, but the study team emphasized that its clinical implications for PrEP efficacy are not clear. Even with this reduction, the mean tenofovir level was still above the target level shown to confer protection in previous studies. They also noted that it is not known whether this difference in blood levels correlates with tenofovir levels in rectal tissue, where HIV exposure typically occurs.

The authors concluded that their results provide reassurance that transgender women can use PrEP without fear that it will decrease hormones to a suboptimal level.”

Reference: Hiransuthikul A et al. Drug-drug interactions between the use of feminizing hormone therapy and pre-exposure prophylaxis among transgender women: the iFACT study. 22nd International AIDS Conference (AIDS 2018), Amsterdam, abstract TUPDX0107LB, 2018.

Source: Reporting from Amsterdam for PRN News: Bill Valenti, MD