Abstract
Transgender individuals, whose gender identity differs from their assigned sex at birth, often undergo pharmacotherapy, including hormone therapy (HT), as part of their gender-affirming care. This pharmacotherapy, particularly when combined with antiretroviral therapy (ART) for transgender individuals living with HIV, raises concerns about drug-drug interactions (DDIs). These interactions can alter treatments' efficacy and lead to adverse health outcomes, making understanding their nature and extent critical. Despite the importance of identifying and managing DDIs in this population, limited comprehensive data are available. This systematic review aims to collate and synthesize existing evidence from clinical studies and case reports on DDIs in transgender patients, with a specific focus on those receiving ART for HIV. A comprehensive literature search was conducted across multiple databases, including PubMed, Cochrane Library, and Scopus, following a predefined protocol registered with PROSPERO. Studies reporting DDIs in transgender patients undergoing any form of pharmacotherapy were included, and data extraction and quality assessment were performed independently by two reviewers. The review found that while pharmacokinetic (PK) changes due to DDIs occur, they are often not clinically significant, suggesting that HT and ART can generally be co-administered safely in transgender individuals. However, specific interactions, such as those involving efavirenz-based ART, may require careful monitoring and individualized treatment adjustments. The findings highlight the need for tailored approaches in managing DDIs to optimize treatment efficacy and safety in transgender patients. In conclusion, this review underscores the importance of further research into DDIs in transgender populations, particularly those on ART, to better inform clinical practice and improve patient care. Understanding these interactions is vital to ensuring optimal treatment outcomes and enhancing the quality of life for transgender individuals.