CATIE News

• Earlier studies found trans women less likely to have adequate PrEP levels in blood tests
• However, a new study found effective levels of the drug among trans women and men
• Researchers concluded that previous findings may have been affected by low adherence

Clinical trials have found that a pill containing two anti-HIV drugs significantly reduces the risk of HIV infection in gay and bisexual men when used as directed. This pill contains two anti-HIV drugs, tenofovir DF (TDF) + FTC, and is sold under the brand name Truvada and in generic formulations. Using medicines to prevent HIV infection is called pre-exposure prophylaxis (PrEP).

Only one large randomized clinical trial of TDF + FTC, called iPrEX, included significant numbers of transgender women and none have included transgender men. A subgroup analysis of iPrEX found that transgender women were less likely to have protective levels of TDF + FTC in their blood than other people, particularly if they were taking gender-affirming hormones (in this case, “feminizing hormones” such as estrogen, progesterone and so on).

Three small and short studies have focused on assessing the concentration of TDF in the blood and suggested that feminizing hormones slightly reduced the amount of TDF in the blood and in cells lining the rectum. However, as mentioned, these studies were small and adherence to PrEP was not verified. (TDF levels are most commonly assessed in large clinical trials of PrEP.)

In an important development, researchers in the United States have published the results of a 47-person study in transgender women and transgender men concerning concentrations of TDF in the blood. All participants were also taking gender-affirming hormones. The dosing of PrEP was directly observed in the vast majority of cases. Over a period of four weeks the researchers found the following:

• Levels of testosterone in transgender men and estrogen in transgender women were similar before and after initiation of PrEP.
• Levels of TDF in the blood were similar in transgender women and transgender men during the study. However, when researchers compared data from the present study with data from a trial several years earlier in cisgender men and women, they found that TDF levels in transgender people and cisgender men were slightly less than in cisgender women.

Study details

In the present study, researchers recruited 24 transgender women and 24 transgender men. One of the men prematurely withdrew from the study, leaving 47 participants. The average age was 31 years and none of the participants had HIV infection. The major ethno-racial groups were as follows:

• White – 57%
• Hispanic – 32%
• Black – 21%

Hormone use

The main hormones used by participants were as follows:

Transgender women

• estradiol – taken orally by 20 people and injected by 4 people
• progesterone or medroxyprogesterone – taken orally by 4 people
• spironolactone – taken by 9 people

Transgender men

• testosterone cypionate (injected) – taken by 18 people
• testosterone enanthate (injected) – taken by 2 people
• testosterone gel (applied topically) – taken by 2 people
• testosterone (implanted) – taken by 1 person

Weight

Transgender people had similar weight (74 kg) and an average body mass index (BMI) of 26.

Adherence

In more than 98% of doses, researchers were able to directly observe adherence to PrEP (taken daily). This was mostly done via live or recorded video or in person.

Researchers analysed levels of several hormones in blood samples from participants.

TDF levels were assessed using a well-validated technique with dried blood spots on paper.

Results—Hormone levels

PrEP had no significant impact on levels of estradiol or testosterone in transgender people. None of the participants reported adverse effects due to low hormone levels. In addition, no participant felt the need to alter their levels of gender-affirming hormones during the study.

Neither estradiol, testosterone nor any other hormone affected levels of TDF in the blood.

The study lasted for four weeks. During this time, TDF levels rose steadily and reached a range that can confer protection from HIV. Based on the excellent adherence of participants, the researchers projected that TDF levels in the blood would rise further, reaching highly protective levels.

Side effects

The combination of TDF + FTC for HIV prevention has been studied in tens of thousands of people. Side effects are generally mild and tend to resolve over time. Common side effects reported in this study, in decreasing order, were as follows:

• nausea
• diarrhea
• fatigue
• abdominal pain

No participant discontinued PrEP because of side effects.

No cases of HIV infection occurred.

Bear in mind

Researchers compared TDF levels in transgender people in the present study with TDF levels in cisgender women and gay/bisexual men collected several years ago from another study. In general, they found that TDF levels were similar in all populations, though slightly lower in transgender people, as well as in gay/bisexual men compared to cisgender women. The reasons for this are not clear.

Regarding data from iPrEX that found lower concentrations of TDF in transgender women than in gay/bisexual men, the researchers stated that their findings suggest that in iPrEX transgender women had lower levels of TDF “due to less use of the medication, rather than differences in metabolism.”

The researchers pointed out that “large cohorts of transgender men and transgender women taking PrEP have been and are being studied; HIV infections in these cohorts would be expected if PrEP were not highly effective.”

Although the present study had many strengths including its size and enrollment of transgender people, it had the following imperfections:

• it lasted for only four weeks
• researchers did not collect samples from tissues that are relevant to the sexual spread of HIV—the wet tissues of the anogenital mucosa and nearby lymph nodes
• it did not assess the newer formulation of tenofovir called TAF (tenofovir alafenamide)

An external view

Harvard University infectious disease specialist Douglas Krakower, MD, reviewed findings from the present and other studies and agreed that while transgender men and transgender women and cisgender men had similar concentrations of TDF, they were “slightly lower” than in cisgender women. He stated that “despite its limitations, the [present] study provides strong evidence that gender-affirming hormone therapy and TDF-FTC PrEP can be used together without compromising gender-affirming care or HIV prevention.”

To increase the impact of PrEP among transgender people, Dr. Krakower suggests at least the following:

• Larger observational studies are needed “to confirm that PrEP provides near-complete protection against HIV acquisition among transgender persons as it does for other populations, which could further increase confidence in PrEP.”
• Researchers “need to ensure that studies of future PrEP modalities (for example, long-acting PrEP) are inclusive and welcoming to diverse transgender populations, to increase the likelihood that PrEP will meet the unique needs of multiple groups, including people who do not identify with the binary conceptualization of gender (for example, gender nonconforming or genderqueer).”
• Further interventions “to reduce transgender stigma in healthcare settings are needed, so that transgender people can feel comfortable accessing PrEP as part of patient-centred and gender-affirming health care. If researchers and clinicians can develop and deliver PrEP in ways that meet the needs of transgender populations, then PrEP can be a cornerstone in the effective and equitable response to HIV that we need.”

––Sean R. Hosein

Resources

Oral pre-exposure prophylaxis (PrEP) – CATIE fact sheet

PrEP for understudied populations: Exploring questions about efficacy and safety – Prevention in Focus

How does PrEP prevent HIV? – CATIE video

PrEP Q&A

Canadian guidelines on HIV pre-exposure prophylaxis and nonoccupational postexposure prophylaxis – Biomedical HIV Prevention Working Group of the CIHR Canadian HIV Trials Network (CTN)

PrEP for trans women – PleasePrEPme.org

REFERENCES:

1. Grant RM, Pellegrini M, Defechereux PA, et al. Sex hormone therapy and tenofovir diphosphate concentration in dried blood spots: Primary results of the iBrEATHe Study. Clinical Infectious Diseases. 2020; in press.
2. Krakower DS. HIV preexposure prophylaxis: Meeting the needs of transgender populations. Clinical Infectious Diseases. 2020; in press.
3. Anderson PL, Liu AY, Castillo-Mancilla JR, et al. Intracellular tenofovir-diphosphate and emtricitabine-triphosphate in dried blood spots following directly observed therapy. Antimicrobial Agents and Chemotherapy. 2017;62(1):e01710-17.