SBIR-STTR Award

Public Health Problem Modern antiretroviral therapy (ART) combinations greatly improve survival of HIV infected individuals and reduce HIV transmission. However, there are still 38 million people living with HIV (PWH) worldwide and of those 1.8 million are children under the age of 15, highlighting the imperative need for curative therapies. In limited resource areas, where pediatric HIV is most common, the use of new assays that require less blood volumes, lower cost and less labor-intensive methods are necessary to facilitate clinical trials aimed at reducing the size of the latent reservoir and/or to achieve a cure or ART-free remission. The ultimate value of the SBIR Phase I project will demonstrate the ability of our technology to characterize and quantify the pediatric HIV-1 reservoir, which remains a critical unmet need in the HIV cure field. Issues with Current Solutions & How Product Meets Unmet Needs RNAamp allows direct detection of RNA, which provides the most accurate measure of the HIV replication competent reservoir. The assay is proven to be faster and have better reliability and quantification than HIV reservoir assays based on QVOA, RT-qPCR, RT-ddPCR, iSCA and IPDA. RNA target amplification and detection is accomplished by oligonucleotide-templated photoreduction using short, sequence-specific profluorophore and catalytic probes. Reproducibility is outstanding (4% variance between replicates) and Limit of Detection (LoD) is 1 HIV-infected cells/1 x 106 PBMCs or 1-10 RNA copies/mL, using a standard blood draw (10-30 mL). Jan Biotech's RNAamp quick, direct RNA test, with its use of small blood samples, ease of sample preparation, reliability and sensitivity, quantitative ability and short time to result, is ideally suited for characterization and quantification of the rebound-competent pediatric HIV reservoir. of Approach Jan Biotech has developed an assay with a prediction accuracy of 0.92 for time to rebound after treatment interruption for early/acute-treated adult participants. The assay, RNAamp, utilizes nonezymatic, chemical amplification of cell-associated HIV RNA targets to provide quick, sensitive, and quantitative measurement of the HIV reservoir. No other assay, including QVOA, IPDA, iSCA, RT-qPCR, or RT-ddPCR, provided a prediction accuracy of greater than 0.2 for the same adult participants. This proposal is to develop RNAamp for cross- subtype (i.e., non-B subtype) HIV reservoir detection, specifically for pediatric testing, for which the use of small samples easily tested by RNAamp is crucial. Pediatric HIV-infected individuals are typically treated during early HIV infection, often treated at birth, and physician-monitored or spontaneous treatment interruption is more frequent in this population. Pediatric treatment efficacy and treatment interruption clinical trials typically include non-B subtype HIV-infected participants. Collaborators and Unique Resources Jan Biotech, Inc., with expertise in molecular diagnostic development, will consult with Jonathan Li, MD, MMSc Assistant Professor of Medicine, Harvard Medical School, in a AIDS Clinical Trials Group (ACTG) study and Harris Gelbard, MD, PhD, University of Rochester Medical School. Phase I Specific Aims Specific Aim 1: Develop HIV-1 cross-subtype (CS) RNAamp multiplexed assay Specific Aim 2: Correlate CS-RNAamp to Pol RT-qPCR using non-B subtype HIV-infected cells Specific Aim 3: Pediatric human sample testing using CS-RNAamp HIV reservoir characterization Market after Phase II Completion Both Gilead and Merck are commercially interested in the technology. Regulatory approval will be sought for commercialization.

Public Health Relevance Statement:
Project Narrative - Relevance to Public Health Modern antiretroviral therapy (ART) combinations greatly improve survival of HIV infected individuals and reduce HIV transmission. However, there are still 38 million people living with HIV (PWH) worldwide and of those 1.8 million are children under the age of 15, highlighting the imperative need for curative therapies. In limited resource areas, where pediatric HIV is most common, the use of new assays that require less blood volumes, lower cost and less labor intensive methods are necessary to facilitate clinical trials aimed at reducing the size of the latent reservoir and/or to achieve a cure or ART-free remission.

Project Terms:
21+ years old; Adult Human; adulthood; Adult; After Care; After-Treatment; post treatment; Aftercare; ages; Age; Antibodies; Base Sequence; Nucleotide Sequence; nucleic acid sequence; Biological Assay; Assay; Bioassay; Biologic Assays; Biotechnology; Biotech; Birth; Parturition; Blood; Blood Reticuloendothelial System; Blood Volume; Complementary DNA; cDNA; Calibration; Cell Count; Cell Number; Cells; Cell Body; Child; 0-11 years old; Child Youth; Children (0-21); kids; youngster; Clinical Trials; Cohort Studies; Concurrent Studies; Combined Modality Therapy; Multimodal Therapy; Multimodal Treatment; combination therapy; combined modality treatment; combined treatment; multi-modal therapy; multi-modal treatment; Fluorescence; HIV; AIDS Virus; Acquired Immune Deficiency Syndrome Virus; Acquired Immunodeficiency Syndrome Virus; Human Immunodeficiency Viruses; LAV-HTLV-III; Lymphadenopathy-Associated Virus; Virus-HIV; HIV Infections; HTLV-III Infections; HTLV-III-LAV Infections; Human T-Lymphotropic Virus Type III Infections; HIV-1; HIV-I; HIV1; Human Immunodeficiency Virus Type 1; Human immunodeficiency virus 1; Human; Modern Man; Marketing; Medicine; Methods; Modernization; Persons; United States National Institutes of Health; NIH; National Institutes of Health; Oligonucleotides; Oligo; oligos; Physicians; Public Health; Resources; Research Resources; RNA; Non-Polyadenylated RNA; RNA Gene Products; Ribonucleic Acid; medical schools; medical college; school of medicine; Specificity; CD4 Positive T Lymphocytes; CD4 Cells; CD4 T cells; CD4 helper T cell; CD4 lymphocyte; CD4+ T-Lymphocyte; CD4-Positive Lymphocytes; T4 Cells; T4 Lymphocytes; Technology; Testing; Time; Universities; Fluorescence-Activated Cell Sorting; Fluorescence Activated Cell Sorting Fractionation; Fluorescence-Activated Cell Sortings; Measures; Blood Sample; Blood specimen; improved; Acute; Clinical; Phase; Chemicals; Evaluation; pediatric; Childhood; Individual; Measurement; interest; Disease remission; Remission; Consult; consults; Performance; internal control; professor; cohort; Peripheral Blood Mononuclear Cell; PBMC; Participant; Sampling; Molecular Interaction; Binding; AACTG; ACTG; acquired immunodeficiency syndrome clinical trial group; AIDS clinical trial group; Detection; Doctor of Philosophy; Ph.D.; PhD; International; Interruption; Recombinants; Reproducibility; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Validation; validations; Monitor; transmission process; Transmission; Preparation; preparations; Characteristics; Development; developmental; antiretroviral therapy; anti-retroviral therapy; anti-retroviral treatment; antiretroviral treatment; cost; designing; design; intervention efficacy; therapeutic efficacy; therapy efficacy; Treatment Efficacy; Population; clinical relevance; clinically relevant; commercialization; bio-markers; biologic marker; biomarker; Biological Markers; pediatric HIV; pediatric human immunodeficiency virus; IMPAACT; International Maternal Pediatric Adolescent HIV/AIDS Clinical Trials; International Maternal Pediatric Adolescent AIDS Clinical Trials; amplification and detection; detection of amplification; amplification detection; curative intervention; curative therapeutic; curative therapy; curative treatments; molecular diagnostics; latent HIV-1 reservoir; latent HIV1 reservoir; latent HIV reservoir; detection limit; multiplex assay; Resource-limited setting; Low-resource area; Low-resource community; Low-resource environment; Low-resource region; Low-resource setting; Resource-constrained area; Resource-constrained community; Resource-constrained environment; Resource-constrained region; Resource-constrained setting; Resource-limited area; Resource-limited community; Resource-limited environment; Resource-limited region; Resource-poor area; Resource-poor community; Resource-poor environment; Resource-poor region; Resource-poor setting