Connecting rare cell states with HIV-1 susceptibility in single CD4+ T cells

A. SPECIFIC AIMSThe Third Coast Center for AIDS Research will continue to follow the advice of the transformational Chicago architect, Daniel Burnham. Our“big plan” is to continue catalyzing impactful cross-institutional and cross-disciplinary collaborationslocally,and across CFARs. Our innovative initiatives have been realized with nimble and opportunisticstrategic planning thatmakesthe whole of our HIV research more than the sum of its parts. Wewill continue toenhanceinformation exchange, networkingand infrastructure, including data and computational resources,that will fuelincreasing innovation, more productive collaborations,and continuing contributions of each scientific Core to the following Overall aimsthat build on our solid foundation.Aim 1: To initiate and facilitateadditionalinnovativecollaborationsthat willslow, and eventually stop,the HIV epidemicby improvingcare continuums for prevention and HIV suppression.Teams of behavioraland social scientists, public healthprofessionals,and biomedical researcherswilldesign and implementtranslationalresearchengagingvulnerablepopulationsat risk for HIV acquisition, and thoselivingwith HIV,to enhance continuums of care for preventionandviral suppression.This builds on our strengths in research with young men who have sex with men (YMSM), trans-gender women (TGW), and Black/African American communities. We will continue workingclosely with the Chicago and Illinois Departments of Public Health, and other CFARs, on“Ending the HIV Epidemic”(EtHE).This will include providing unique access for researchers to public health data, continuing/expanding our implementation science initiatives,andexpandingcollaborative research with community organizationsthat willenhanceresearchonpre-exposure prophylaxis (PrEP), antiretroviral treatment (ART) as prevention,and social determinants of HIV risk.New immuno-and chemo-prevention approachesand risk network-based responseswill also be prioritized.All Cores and the Innovation and Implementation for Impact on EtHE (I3EtHE) Scientific Working Group (SWG) will enable this.Aim 2: To advance novelinterventions for aging-related illnesses(non-AIDS complications)that occur prematurely despite suppression of HIV viremia.Vibrant new collaborationsarebuildingon our nation-leading observational cohorts of those at-risk and living with HIVto innovateon understanding and intervening in premature aging and its manifestationsas complicationsin persons living withwell-treatedHIVthrough a spectrum of research from defining causative mechanisms to clinical phenotypingthat will aiddrug development / repurposing.Unique advantages includebi-directionally beneficial collaborations with experts inaging mechanisms and aging-related diseases,the ability to research early warningsof premature aging among YMSMas well as older participantson ART, and novel concepts and technologies. This ispossible due to CFAR-enabled support from our two universities, a newNHLBI K12 programteaming CFARwith heart, lung, and sleep experts, as well as collaborations, accomplishments and networks of all scientificCores.Aim 3: To accelerate discoveryandempower development oftransformativeimprovements inHIVpreventionandtreatment, includingsustainingremission after stopping ART. Our expanding team of researchersfocused on discovering and developing new diagnostics and interventionswill continuegenerating innovativeideas bybuilding on strengths in imaging, virology, engineering, and clinical / translational research. Resources in data/computationalscience, ?wearables?, person-centered outcomes measures,quan