Considerations for PrEP in Transgender Persons

PrEP Choice for Transgender Individuals
Currently, 2 options exist for continuous pre-exposure prophylaxis (PrEP): oral tenofovir (TFV)-based PrEP with either emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) or FTC/tenofovir alafenamide or long-acting injectable cabotegravir (CAB). Long-acting CAB is not yet available in France or the rest of Europe, but it should be approved within a few months. In addition, there are data to support the use of FTC/TDF on demand in men who have sex with men at risk for acquiring HIV through anal sex.

Considerations for Transgender Women
When we evaluate PrEP options for transgender women, it is important to know whether they have had gender-affirming surgery and what type of sex they are having.

In my opinion, if they have not had vaginoplasty surgery and are at risk of exposure from anal sex only, they can take oral FTC/TDF either daily or on demand. However, if they have had vaginoplasty surgery, they should use either continuous PrEP with FTC/TDF or long-acting CAB, as on-demand oral PrEP is not recommended by the WHO in this situation because of insufficient data to support its use in diverse gender populations.

Another consideration: Long-acting CAB is recommended for gluteal injection only. If using injectable PrEP, it is important to know whether a transgender woman has silicone prosthetic buttocks. If PrEP is injected into the silicone, it will collect inside the silicone and not penetrate body tissues. For these patients, oral TFV-based PrEP may be the best option.

Considerations for Transgender Men
In transgender men, long-acting CAB or oral FTC/TDF can be used, although we don’t know exactly how effective PrEP is in this population because of the lack of efficacy data in transgender men. We do know that transgender men who have not had surgery and are at risk of HIV acquisition from vaginal sex should not take on-demand PrEP. The Department of Health and Human Services currently recommends taking daily oral FTC/TDF for 20 days to be protected from vaginal HIV exposure, as studies have shown that cisgender women needed more doses of TFV-based PrEP to achieve effective drug concentrations in vaginal tissue.

Drug Interactions With Gender-Affirming Hormones
The iBrEATHe study, which enrolled 24 transgender men and 24 transgender women without HIV, showed that blood estradiol levels or testosterone levels were not affected after 1 month of daily oral PrEP. In addition, clinically significant drug–drug interactions are not expected between any of the current PrEP options and gender-affirming hormone therapies. Hormone levels also can be monitored, and doses can be adjusted for desired laboratory and clinical effects.

PrEP Adherence
An important factor to address when we want to initiate PrEP in the transgender setting—either men or women—is that they face a lot of stigma. When I see a transgender woman in my outpatient clinic, I take stigma into consideration, as stigma is strongly related to adherence. Studies report a lower rate of PrEP adherence in transgender women that is associated with stigma and the way they think they are perceived by society.

We know that the socioeconomic challenges faced by transgender individuals also negatively affect adherence, so we must provide strong support to enhance PrEP adherence, because it is the key for PrEP efficacy. These barriers should be addressed during the initial PrEP consultation and at each follow-up visit.

Your Thoughts?
In your practice, which mode of PrEP delivery is most interesting to transgender individuals? Answer the polling question and join the conversation by posting a comment.