Co-occurring factors that heighten transgender women's vulnerability to suboptimal ART adherence in India - SUMMARY Background: In India, HIV prevalence is highest among transgender women (TGW) or Hijras. Although HIV can be managed with ongoing antiretroviral therapy (ART), achieving maximal benefit necessitates engagement with the healthcare system and requires excellent adherence, which has shown to be challenging in India despite ART being free. Studies have shown that TGW in India experience high rates of individual (e.g., drug and alcohol use, depression), interpersonal (e.g., victimization, discrimination), and structural (e.g., poverty, housing instability, clinic access) challenges. While limited evidence suggests that these co-occurring syndemic factors are associated with suboptimal adherence and viral suppression among TGW in other settings, little is known about whether and how these factors influence ART adherence and viral suppression among TGW in India. Moreover, while TGW experience high rates of discrimination and familial rejection based on their gender identity, which may be compounded for TGW living with HIV, many TGW in India counteract this familial and societal rejection by forming their own family units comprised of other TGW. Based on research in other settings, this social support might buffer the detrimental effect syndemic factors may have on ART adherence. Environment: We will leverage an established, 16-year research collaboration between the PI’s mentors and Humsafar Trust (HST), the largest NGO focused on sexual and gender minority health in India – with research sites in both Mumbai and New Delhi, India's two biggest cities with 12.5 and 16.8 million people, respectively. Approach: The study aims to understand patterns and high-risk groups underlying suboptimal ART adherence and unsuppressed viral load related to substance use, stigma, and other syndemic factors among TGW in Mumbai and New Delhi, India and to assess potential buffering mechanisms for future intervention targets. To this end, we propose to: (1) conduct qualitative interviews with TGW (n=30) and clinical and social service providers (n=10) to assess the individual, interpersonal and structural level syndemic factors impacting ART adherence and unsuppressed viral load; and (2) to characterize patterns of multilevel syndemic factors and identify high-risk profiles of 150 TGW living with HIV in Mumbai and New Delhi. We will conduct a quantitative assessment and use Latent Class Analysis (LCA) to determine the patterns of the multilevel barriers that arise in Aim 1, and fit a multilevel model to better understand the relationships between the identified syndemic classes and unsuppressed viral load (via plasma viral load testing) and ART adherence (via self-report). Findings from this R36 doctoral dissertation award will provide preliminary data, using qualitative and LCA syndemic risk profiles, to support the submission of a larger NIH grant to design and pilot test an adaptive, multi-component (e.g., possibly including substance use treatment, resilience coping, skill-building) intervention to improve HIV care continuum outcomes among TGW living with HIV in India.