Moving forward to ‘put people first’

In recent years, there has been recognition of the living/lived experiences and rights of trans and gender diverse people globally. In some countries, there have been legislative strides supporting the rights of trans and gender diverse people exemplifying progress. For example, Bill C-16 was enacted in Canada in 2017; the bill extends protection under the Canadian Human Rights Act to include all forms of gender expression and gender identity, subsequently enhancing access medical and healthcare services for trans and gender diverse people. However, this progress is not uniform as evident by the legislative landscape in the United States; as of early 2024, 23 states have enacted limitations or bans on access to gender-affirming health care for adolescents and/or young adults. The majority of these states also impose professional or civil penalties for health care professionals who provide gender-affirming care to minors.1 In the United Kingdom, progress has been mixed with the Gender Recognition Act of 2004 allowing trans people to change their legal name and sex, but draconian processes for gender-affirming surgery still apply and non-binary and intersex individuals are not conferred the same rights. In March 2024, England's National Health Service (NHS) released an updated policy prohibiting use of puberty suppressing hormones as a routine treatment option for treatment of children and young people with gender incongruence/gender dysphoria.2 Other nations including Norway, Finland and Sweden have also recently updated guidelines to restrict the use of hormone therapy and transition-related surgery in youth to clinical research settings against guidance of major medical associations including the American Academy of Medicine, the American Psychiatric Association, the American Academy of Child and Adolescent Psychiatry and the World Professional Organization For Transgender Health.3 Amid this complicated backdrop, we are proud to announce the release of this special themed issue on trans and gender diverse populations to celebrate Pride Month 2024. The British Journal of Clinical Pharmacology is committed to demonstrating allyship with trans and gender diverse communities through this special issue. Our content critically reviews advancements in trans care, including optimization of gender-affirming hormone therapy (GAHT) and sexually transmitted and blood-borne infections (STBBI) including HIV preventative and treatment strategies and the prospective trajectory of this field. Aligning with this year's International AIDS Conference 2024 theme of 'Put people first!', the first article in this issue by Underhill et al4 underscores the pivotal role of community-based research. The authors detail the partnership with trans and gender diverse community leaders and involvement and training of trans and gender diverse people as frontline research assistants who are instrumental in the success of research with these communities. As previously discussed by Gross et al,5 optimizing clinical trial enrolment diversity is critical in order to ensure that trial results will be adequately representative of patient populations who may benefit from the studied interventions. Schonrock et al6 report an increase in the number of newly registered drug or biologic trials that recognized trans people and/or trans health within study eligibility criteria over the last 15 years, with trans women and men being eligible for more than 80% and 60% of inclusive trials, respectively. Most of the inclusive trials focused on HIV treatment or prevention; while these findings are encouraging, the authors urge that increased effort should be made to prioritize trans and gender diverse people in mental health, pain management and cancer prevention and treatment trials. Walker et al7 further explore some of the challenges regarding recruitment of the trans community into early phase trials, including potential exclusion of trans people due to overly restrictive definitions of healthy volunteers, use of appropriate biological reference ranges, and data management systems which may only record biological sex or gender with binary options. The authors provide strategies on how to improve recruitment and retention of trans and gender diverse people into phase 1 studies, enhance retention and accurately and safely collect data. Clinicians and researchers need to be aware of how to adapt and improve institutional systems in order to reduce barriers and optimize care and research. Access to GAHT is essential to many trans and gender diverse people, but concerns about possible negative interactions between antiretrovirals and GAHT may lead to under-prescribing of ARVs and/or GAHT, both of which are life-saving. Lacombe-Duncan et al8 present a protocol assessing potential drug interactions between GAHT and bictegravir/emtricitabine/tenofovir alafenamide, a first-line ARV regimen in trans women with HIV. This protocol is novel in that two control groups are included: trans women without HIV taking GAHT and cis women of reproductive age with HIV taking bictegravir/emtricitabine/tenofovir alafenamide. Scientific evidence indicates that trans women taking GAHT have biometric laboratory values closer to standard values of their identified gender vs. sex at birth.9 Furthermore, the trans gender community historically has taken offence to being compared to cis men. Therefore, this study protocol is contemporary and affirming in its design and serves as a template for designing future drug interaction studies in the transgender population. The study by Patel et al10 and the comprehensive review paper by Senneker11 on relevant drug interactions between ARVs and GAHT provide and summarize evidence that most modern ARV and PrEP regimens can be safely prescribed without negative impact on GAHT concentrations and vice versa. The case presented by Suchak et al12 illustrates the challenges of managing multi-directional drug interactions in a patient with multiple comorbidities and highlights the importance of an integrated team approach to consolidate care and avoid mismanagement of GAHT. GAHT can alter individual physiologic parameters and may impact laboratory monitoring parameters or disease risk estimates, particularly for clinical calculators that require a sex/gender variable, such as estimation of creatinine clearance, Framingham risk score or the FRAX score. Tanaudommongkon et al13 previously developed a population pharmacokinetic model of tenofovir disoproxil fumarate/emtricitabine for PrEP in trans women on GAHT, but further research in this area is needed. In particular, the pharmacokinetic impacts of GAHT in adolescents are not well explored. The paper by Cirrincione14 summarizes key pharmacologic considerations in this population, including maturational changes in drug-metabolizing enzymes and drug transporter systems during adolescence, as well as the physiologic effects of GAHT during this stage of development; these changes have important implications for treatment safety and effectiveness. Most pharmacological research to date in trans populations has primarily focused on trans women, and research on trans men is urgently required. Goodridge15 discusses important pharmacokinetic and research considerations in trans men in order to address the research gap in this important but often-overlooked population. This special issue marks the commencement of our sustained commitment to the trans and gender diverse people and their providers. The contributing authors have highlighted important insights on conducting successful research with trans and gender diverse people and provided valuable information on community-based research, of gender-affirming medications, and potential drug–drug interactions, information that is essential for improving clinical care. With the anniversary of the Stonewall Inn Riot on June 28, and in keeping with the International AIDS Conference 2024 theme of 'Put people first', we encourage readers to contemplate what research, clinical, programming and policy initiatives are necessary in their region to optimize health and clinical care, uphold social justice and advance legal rights of trans and gender diverse people. We encourage further research in this area and welcome ongoing contributions to the Virtual Issue on Pharmacological Considerations for Trans and Gender Diverse Populations. The authors have no conflicts of interest to disclose. Data sharing is not applicable to this article as no new data were created or analysed in this study.

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