Research Projects

Chronic HIV-1 infection leads to a dysregulation of the immune system, with Regulatory T cells (Treg) declining at different rates than other CD4+ T cell subsets. This selective persistence makes Treg potential candidates for an enriched HIV-1 reservoir that could promote viral rebound upon interruption or failure of therapy. However, the existence of these latent reservoirs is a major roadblock in HIV cure research. Currently, techniques like PCR and functional assays fail to estimate exact reservoir size, distribution, and dynamics. The insufficiency in Treg purified from patients' blood samples complicates investigating Treg reservoirs in HIV pathogenesis. This study proposes to accurately quantify the relative fraction of intact or rebound competent proviral load from Treg cells and compare it with other CD4+ subsets using the recently developed technology IPDA (Intact Provral DNA Assay). This new scalable tool will help characterize HIV-1 provirus with genetic integrity at a single cell resolution even from a relatively rare population like Treg. The study also aims to quantify subset-specific decay dynamics of intact and defective viral reservoirs from patients receiving Anti-Retroviral Therapy (ART). The study will evaluate gene expression dynamics within Tregs across HIV-1 disease progression, both in ART-naïve and treatment-receiving conditions. A follow-up component will analyze these signatures and epigenetic stability longitudinally to understand ART-mediated restoration within Treg compartment. The study will also investigate the metabolic activity of Treg as a function of altered gene expression and draw correlations between them.