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Principal Investigator: Luis J Montaner
Organization: WISTAR INSTITUTE
Fiscal Year: 2024
Award: $5,736,593
Funding agency: National Institute of Allergy and Infectious Diseases
Summary
Current HIV curative strategies have proven insufficient to eradicate viral reservoirs or prevent viral rebound after
antiretroviral therapy (ART) cessation. The unifying hypothesis for the BEAT-HIV Collaboratory is that
through a better mechanistic understanding of HIV latent reservoirs and host factors governing viral
control and reactivation, long-term viral remission or eradication of HIV will be achieved by combination
immunotherapy inclusive of bNAbs, adoptively transferred immune cells, and nanoparticle therapies.
We will test this hypothesis by pursuing three highly interconnected research focus areas. The first aim will seek
to understand epigenetic status of intact proviruses, extrinsic/intrinsic factors affecting proviral reactivation and
expression, and novel host mechanisms for post-treatment control of HIV. The second aim will develop
strategies for long-term control in the absence of ART by use of DNA-delivered anti-HIV bNAbs and eCD4Ig in
combination with optimized tissue-based CD8 T-cell- and NK cell-mediated responses. The third aim will
develop a combination nanotherapy and immunotherapy strategy to eradicate viral reservoirs. All aims will be
supported by a clinical biorepository (blood and tissue), CD34+ or patient-derived xenograft humanized mice,
non-human primate (NHP) models, and a clinical trial development group as a link to the ACTG. Community
engagement will advance education and a socio-behavioral sciences and ethics focus by leveraging a >25-year
relationship with the local HIV community thereby ensuring partnership with stakeholders. Central administration
of resources will ensure achievement of high impact milestones, study team communications, and yearly goal-
oriented resource allocation and/or redistribution as informed by advances in the field. As an established
Collaboratory, we bring together diverse expertise, innovation, and industry partners to develop and test novel
strategies to advance an HIV cure and/or durable viral control in the absence of ART under a single common
multi-investigator, multi-industry team. Studies within the three interconnected aims together with a strong
community engagement plan will lay the groundwork for future clinical trials that will integrate new knowledge
gained by the BEAT HIV-1 Collaboratory to eradicate or functionally cure HIV infection.
Terms: <AACTG><ACTG><AIDS Virus><AIDS clinical trial group><Achievement><Achievement Attainment><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Address><Adoptive Transfer><Affect><After Care><After-Treatment><Aftercare><Area><Basic Research><Basic Science><Behavioral Sciences><Binding><Blood><Blood Reticuloendothelial System><Body Tissues><C-C CKR-5><C-C CKR-5 Gene><C-C Chemokine Receptor Type 5><C-C Chemokine Receptor Type 5 Gene><CC Chemokine Receptor 5><CC-CKR-5><CC-CKR-5 Gene><CC-CKR5><CCCKR5><CCCKR5 Gene><CCR-5><CCR-5 Gene><CCR5><CCR5 Protein><CCR5 Receptors><CCR5 gene><CD195 Antigen><CD195 Antigen Gene><CD34><CD34 gene><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><CHEMR13><CHEMR13 Gene><CKR-5><CKR-5 Gene><CKR5><CKR5 Gene><CKR5 Receptors><CMKBR5><CMKBR5 Gene><COVID-19><CV-19><Cancer Treatment><Cell Body><Cells><Chemokine (C-C Motif) Receptor 5><Chemokine (C-C) Receptor 5><Chemokine (C-C) Receptor 5 Gene><Clinical><Clinical Data><Clinical Trials><Collaborations><Combination immunotherapy><Communication><Communities><Coronavirus Infectious Disease 2019><Cytotoxic cell><DNA><Deoxyribonucleic Acid><Development><Disease remission><Education><Educational aspects><Ensure><Epigenetic><Epigenetic Change><Epigenetic Mechanism><Epigenetic Process><Ethics><Foundations><Future><Goals><HIV><HIV Infections><HIV-1><HIV-1 Fusion Co-Receptor><HIV-1 Fusion Co-Receptor Gene><HIV-I><HIV1><HPCA1><HTLV-III Infections><HTLV-III-LAV Infections><Host Factor><Host Factor Protein><Human Immunodeficiency Virus Type 1><Human Immunodeficiency Viruses><Human T-Lymphotropic Virus Type III Infections><Human immunodeficiency virus 1><Immune><Immune mediated therapy><Immunes><Immunologically Directed Therapy><Immunotherapeutic agent><Immunotherapy><Industry><Infection><Institution><Integration Host Factors><Interruption><Intervention><Intervention Strategies><Intrinsic factor><Investigators><K lymphocyte><Knowledge><LAV-HTLV-III><Lead><Link><Lymphadenopathy-Associated Virus><Maintenance><Malignant Neoplasm Therapy><Malignant Neoplasm Treatment><Mediating><Mission><Modeling><Molecular Interaction><NK Cells><Natural Killer Cells><PDX model><Patient derived xenograft><Pb element><Persons><Proviruses><Remission><Reproducibility><Research><Research Personnel><Research Resources><Researchers><Resource Allocation><Resources><SHIV><Scientist><Series><Social Behavior><T8 Cells><T8 Lymphocytes><Testing><Therapeutic><Tissues><Viral><Viral reservoir><Viremia><Virus Integration><Virus reservoir><Virus-HIV><acquired immunodeficiency syndrome clinical trial group><anti-cancer therapy><antiretroviral therapy><antiretroviral treatment><biobank><biorepository><cancer therapy><cancer-directed therapy><chimeric antigen receptor><collaboratory><combinatorial immunotherapy><community engagement><coronavirus disease 2019><coronavirus disease-19><coronavirus infectious disease-19><delivery vector><delivery vehicle><design><designing><develop therapy><developmental><dual immunotherapy><engagement with communities><epigenetically><ethical><heavy metal Pb><heavy metal lead><humanized mice><humanized mouse><immune drugs><immune therapeutic approach><immune therapeutic interventions><immune therapeutic regimens><immune therapeutic strategy><immune therapy><immune-based therapeutics><immune-based therapies><immune-based treatments><immuno therapy><immunologic therapeutics><immunotherapeutics><immunotherapy agent><in vivo><industrial partnership><industry partner><industry partnership><innovate><innovation><innovative><insight><interest><intervention development><interventional strategy><knowledge base><latency/reactivation><latent HIV reservoir><latent HIV-1 reservoir><latent HIV1 reservoir><nano therapy><nanoparticle therapy><nanotherapy><new approaches><non-human primate><nonhuman primate><novel><novel approaches><novel strategies><novel strategy><patient derived xenograft model><post treatment><pressure><prevent><preventing><reactivation from latency><response><simian HIV><simian human immunodeficiency virus><sociobehavior><sociobehavioral><therapeutic nanoparticles><therapy development><treatment development><viraemia><viral integration><viral rebound><viral sepsis><virus rebound><virusemia>