Generation and characterization of iPSC models from HIV-1-positive individuals with divergent clinical outcomes

The clinical outcome of human immunodeficiency virus type-1 (HIV-1) infection varies greatly among individuals, ranging from rapid disease progression to natural viral suppression. While viral and environmental factors contribute, host genetics are considered major determinants of disease trajectory. To enable mechanistic studies of host factors underlying disease outcomes, we generated 50 induced pluripotent stem cell (iPSC) lines from 18 participants of the Multicenter AIDS Cohort Study (MACS), spanning a spectrum of clinical trajectories. Reprogrammed MACS lines are confirmed to be HIV-1 negative and Sendai vector-free. We validate their pluripotency and demonstrate robust differentiation into macrophages capable of productive HIV-1 infection. These MACS-iPSC lines offer a genetically diverse resource to model HIV-1 infection in vitro, where clinical progression is known. Crucially, their capacity to differentiate into HIV-1 target cells and other disease-relevant lineages makes them a powerful tool to uncover host determinants of HIV-1 pathogenesis and advance targeted treatment and curative strategies.