In a recent study supported by the National Institutes of Health and Gilead Science, a large number of transgender women living with HIV in Los Angeles, CA, reported non-adherence to prescribed antiretroviral therapy (ART), hormone therapy (HT), or both. Roughly 40% of the women surveyed specifically cited concern over possible ART-HT drug-drug interactions as a factor for not taking these medications as prescribed. Unfortunately, there is comparatively little research into this and other unique health issues faced by trans women.
Trans Women at Risk
Transgender women are at a 50-fold higher risk of HIV infection than the general population. In the US, the number of transgender people who received a new HIV diagnosis in 2013 was more than three times the national average, and data between 2009 and 2014 indicated that 84% of transgender individuals diagnosed with HIV were women. An estimated 22% of trans women in the US and 19% globally are currently living with HIV. Trans women of color are the most vulnerable — half of all transgender people diagnosed with HIV in the US are Black. The reasons for this come down to the fact that a number of intersecting HIV risk factors are more common among transgender people and are directly related to transphobia and marginalization, including unemployment, homelessness, incarceration, sex work, mental health issues, social exclusion, and a lack of access to healthcare, condoms, and pre-exposure prophylaxis (PrEP).
Adherence to ART is crucial for preventing negative health outcomes for people with HIV. Proper use of ART can also lead to durable viral suppression, substantially reducing the risk of transmission. In the US, only 59% of HIV-positive transgender individuals reported having access to ART, compared to 82% of cisgender patients. This disparity is due to more than financial reasons, as transgender patients struggle to find culturally competent providers. Some 19% of transgender people report being denied care based on their gender identity, leading many to be wary of medical providers in general.
The recent Los Angeles study reflects the discordance between trans women and their health care providers, indicating that sub-optimal provider engagement and communication is a major reason for why what little data attesting to the safety of ART-HT is not reaching patients. Despite so many women on both HT and ART reporting concerns, only 49% discussing possible drug-drug interactions with their health care team. Additionally, 34% of the HIV-positive women surveyed also reported using unsupervised hormone therapies, which carry higher risks of adversely impacting ART effectiveness and possible drug-drug interactions.
Limited Data on Trans Health
With the exception of clinical trials related to medical transitioning, clinical research of specific health concerns of transgender patients is sparse. Furthermore, transgender study participants often have their data aggregated by birth sex rather than together as part of an important subpopulation with distinct physiological considerations. In the case of HIV, research that does exist focuses on behavioral interventions for prevention rather than on potential unique medical issues.
Even when trans inclusion is intended, study materials and surveys may not ask the right questions to accurately determine a person's transgender status. For example, early iPrEx — a large PrEP study originally designed for men who have sex with men — data reported only 1% of its enrollees were women. However, a more thorough self-interview later found that as many as 14% of the cohort fell under the trans umbrella. This research gap is also seen in large epidemiological studies, partly due to the fact that many federal, state, and local agencies do not collect trans-specific data.
While some drug-drug interactions have been reported for certain types of HT and ART, this is largely based on the exogenous estrogens found in hormonal contraception as used by cis women. Some ART drugs do lower the concentration of certain components of hormonal contraception, reducing their effectiveness. Likewise, certain ART drugs are less effective when combined with HT. However, there have been no published studies on drug-drug interactions with ART and the two most commonly prescribed anti-androgens, spironolactone and finasteride.
Luckily, research that has been done is promising for transgender individuals currently living with or at risk of HIV. The largest study of PrEP that included trans women has found it to be safe and effective with no negative impact on feminizing hormone therapies. Additionally, previous research has found that HIV-positive trans women who received hormone prescriptions from their HIV primary care provider were much more likely to be currently taking ART and to have an undetectable viral load. Evidence also suggests that estrogen has a protective effect against HIV. Likewise, spironolactone may inhibit HIV infection.
Additionally, there have been recent efforts to combat the research gap. Last year, the California HIV/AID Research Program awarded $9.4 million in grants to research programs specifically designed for transgender people of all genders. Among these is the first PrEP demonstration project in the US to focus exclusively on transgender populations. One of the stated goals of this study is to look for possible interactions with HT.
Part of a Bigger Problem
Marginalization specific to transgender identities isn't the only reason why there is so little clinical research available to aid in the treatment of trans women with HIV. American medical research continues to struggle to include patients who are not cisgender men and much fundamental research has been conducted with only (usually white) male patients involved. This research gap has persisted despite the NIH mandate for the inclusion of women and minorities as participants in clinical research being passed over two decades ago. This factor may contribute to why women are more likely to have adverse drug interactions. Likewise, women in general — both cis and trans — are less likely to adhere to PrEP and the the complex reasons of why this may happen have not yet been fully explored.
Until all groups historically excluded or poorly represented in clinical research are afforded the same consideration, inclusion, and respect, this lack of individualized care will continue to reinforce widespread health disparities.