RF-4 Assays, Tools
Assay Optimization, Development, and Imaging: Optimizing virologic, immunologic, and imaging methods to assess efficacy of HIV/SIV cure interventions
We hypothesize that development of a comprehensive panel of viral and immune biomarkers through use of clinical trial samples and CNS imaging will lead to identification of a biomarker profile predictive of sustained HIV remission that would avert the need for ART interruption to detect HIV remission
Specific Aims
Aim 1: Quantifying HIV-1 Proviral Reservoirs
We will establish the Intact Proviral DNA Assay (IPDA) to quantify intact and defective HIV-1 proviral reservoirs in perinatal infections, across different HIV-1 subtypes, and examine their decay dynamics as a measure of efficacy of HIV-1 remission and cure interventions.
Aim 3: Immune and Inflammatory Signatures of HIV-1 Persistence and Control
We will identify immune (humoral, Natural Killer cell, myeloid, cytotoxic T cell) and inflammatory signatures of HIV-1 persistence in perinatal infection, and biomarkers associated with reservoir control and viral rebound.
Aim 2: Characterizing Proviral Reservoirs and their Susceptibility to Reactivation
We will develop a reproducible pipeline to comprehensively characterize the inducibility and composition of the replication-intact HIV-1 proviral reservoir and its selection/elimination during cure interventions.
Aim 4: Visualizing S(H)IV/HIV
We will assess virus-specific PET imaging technologies to detect HIV/SIV active replication/ persistence in lymphoid and gut tissues and in the CNS following early effective long-term ART and upon Analytic Treatment Interruption.
Innovation and Current Research Milestones
Expansion of the IPDA, a multiplex droplet digital PCR that is precise and simultaneously measures intact, 3’, and 5’ defective proviruses, to non-subtype B HIV-1
Creation of multiple new benchmarks and biomarkers to monitor HIV-1 elimination, including a new inducibility index, biomarkers of reservoir size and reactivation potential, and correlates of control and elimination that may be unique to pediatric infection
Use of cutting-edge methods and techniques, such as systems serology for deep HIV-specific antibody (Ab) profiling, multi-parameter flow cytometry, epigenetic profiling (NOMe-seq) and single-cell RNA-seq
Application of state-of-the-art PET-CT imaging technologies to monitor viral replication, undetectable in blood, during experimental treatment in the SHIV-infected infant macaque cure model
Cross-disciplinary collaborations with experts in HIV-1 reservoirs in adults, bioinformatics, mathematical modelers, and pediatric/adolescent HIV-1 domestically and internationally, as well as in the infant macaque cure model
Program Directors
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Johns Hopkins University School of Medicine
Johns Hopkins Bloomberg School of Public Health
Departments of Molecular Microbiology & Immunology and International Health
Chief, Division of Infectious Diseases
Chair, IMPAACT HIV Cure Scientific Committee
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University of Miami