Optimizing HIV pre-exposure prophylaxis among transgender women in the United States: a conceptual framework of engagement in prevention-effective adherence

Abstract Transgender women in the United States experience a disproportionate burden of HIV driven by multi-level social and structural vulnerabilities. Although oral PrEP, injectable cabotegravir, and twice-yearly lenacapavir are now available, PrEP use remains suboptimal. We conducted a qualitative analysis of 18 semi-structured life history calendar interviews conducted between February and June 2022 with transgender women in the eastern and southern United States who were indicated for PrEP and had varied PrEP histories. We generated a conceptual framework of prevention-effective adherence based on findings. Two bidirectional domains, capacity to safely engage with the healthcare system and compatibility between PrEP and individual values and preferences, shaped prevention-effective adherence. Influencing both domains were distal factors, including stigmas, identity-based oppression and marginalization, and sociostructural context. Unlike models that categorize barriers using existing frameworks, our inductively derived framework specifies how factors relate to each other, centers prevention-effective adherence rather than discrete cascade steps, and situates PrEP engagement in the life course. Our findings illuminate modifiable factors, including cost, availability of gender-affirming care, and access to evidence-based HIV/STI information, to improve and optimize PrEP engagement among transgender women in the United States.