Eight years after emtricitabine/tenofovir disoproxil fumarate (Truvada) as pre-exposure prophylaxis (PrEP) was established as efficacious for preventing HIV, transgender women using estradiol as feminizing hormone therapy (FHT) can now feel assured that "PrEP does not affect hormones," as Akarin Hiransuthikul, M.D., with the Thai Red Cross AIDS Research Centre put it while presenting the results of iFACT at the 22nd International AIDS Conference (AIDS 2018) in Amsterdam, the Netherlands on July 23, 2018.
"As tenofovir blood levels were observed to decrease by 13%, this decrease is within range that brings protection from HIV infection, continued Hiransuthikul. He said that it remains unclear why FHT caused this decrease of tenofovir levels in the blood, and they are continuing to explore whether these levels also drop in other parts of the body that are important for preventing HIV acquisition, such as the rectal cavity.
These findings mark a crucial point in the history of PrEP delivery among trans women, as they offer clarity for health care providers, PrEP outreach campaigns, and trans women using estradiol as FHT who, respectively, have remained concerned over the years about prescribing, promoting, and using PrEP with FHT.
Since PrEP was first approved for clinical use in the U.S. in 2012, PrEP awareness, acceptability, and use -- all of which are important indicators of PrEP initiation and uptake -- among trans women has continually been low. In one study between 2012 and 2015, only one in three trans women in Boston and Chicago were aware of PrEP, and only one in four found PrEP to be acceptable to use. No changes in the proportion of awareness were observed over these years. Furthermore, only 5% of the 300 trans women in the study reported ever taking PrEP. Similarly, in studies conducted in Brazil and Thailand, only a small portion of trans women found PrEP to be acceptable and initiated use.
This low utilization of PrEP among trans women on FHT can be attributed to several components, including provider hesitancy to prescribe, lack of promotional campaigns, and personal concerns about negative side effects of PrEP on FHT.
Some prior studies that explore health care providers' role in delivering PrEP to trans women have shown that providers have continually been hesitant to prescribe PrEP to trans women on FHT mainly due to having little-to-no scientific knowledge about how PrEP and FHT may interact inside the body. As there are currently no specific and official standard of care clinical guidelines on how to initiate and monitor PrEP with FHT among trans women from principal national and global public health agencies, such as the Centers for Disease Control and Prevention, the World Health Organization, or the World Professional Association for Transgender Health, many health care providers are deterred from prescribing these life-saving medicines altogether, while others proactively monitor physiological effects through routine blood tests.
Moreover, PrEP and FHT research on trans women has continually lagged within the HIV prevention scientific community. Because this type of research has not been prioritized, there are few public health promotional campaigns aimed at increasing PrEP awareness and use among trans women on FHT. Almost all PrEP campaigns in the U.S. are dedicated to other populations impacted by the HIV/AIDS epidemic, and trans women have been excluded from them. This, combined with the exclusive marketing of PrEP and the lack of research on interactions between PrEP and FHT, have led many trans women to view PrEP as an HIV prevention tool that does not resonate with their gender and can potentially threaten their medical gender affirmation, contributing to poor PrEP uptake in these communities. [[One recent study of PrEP acceptability among black and Latinx transwomen in Baltimore by Tonia Poteat, Ph.D., of the John Hopkins Bloomberg School of Public Health, corroborates these findings.
Indeed, previous studies have shown trans women mainly reporting concerns (and rightfully so) on potential negative side effects of PrEP on FHT. Most trans women prioritize many aspects of their gender affirmation (e.g., taking hormones) over other medications. This prioritization of FHT over PrEP and other HIV prevention methods was seen among many trans women participants in the early trials in which they were included, such as iPrEx; however, these trials were not designed specifically by, with, or for trans women.
These trials showed that "while PrEP was highly protective among trans women who were highly adherent, a good portion of trans women on FHT showed lower than expected blood levels of PrEP," said Hiransuthikul. These low blood concentrations could be the result of either an actual interaction between FHT and PrEP or low adherence to PrEP due to trans women viewing PrEP as a threat to their gender affirmation -- particularly because no studies at the time provided context for how PrEP might impact FHT.
This is what makes the iFACT study monumental: It provides evidence that we can address one of the bigger barriers to PrEP initiation and uptake for trans women on FHT.
The results of the iFACT study are promising and should galvanize the PrEP and HIV prevention scientific community to conduct further studies that are specifically designed for, by, and with trans women.
"There are still some key questions that we need to explore before we move forward with this research since we don't know if the reduction in PrEP blood level means anything, said Hiransuthikul. "We need randomized clinical controlled trials to understand how FHT impacts PrEP, as well as how PrEP may impact other types of FHT regimens besides estradiol," he added.
While the implications for HIV prevention will likely be a subject of debate without more research, this should not thwart health care providers from prescribing PrEP, and public health campaigns should promote PrEP to trans women on FHT.
According to Hiransuthikul, we need to start conveying to trans patients in a straightforward way that "PrEP does not impact hormone therapy." He noted: "[W]hile there is a reduction of PrEP, if at the end of the day you have good adherence to PrEP daily and practice safer sex, that is better. There is still protection."
For detailed information about the iFACT study design and results, view the poster here.
Arjee Restar is a trans advocate, a freelance writer, and a public health scholar from Brown and Columbia universities. She has published in The Lancet. Follow Arjee on Twitter @ArjeeRestar.