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

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