A5065310725- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- HIV/AIDS Research and Interventions
- Immune Cell Function and Interaction
- Hepatitis C virus research
- Cytomegalovirus and herpesvirus research
- Hemoglobinopathies and Related Disorders
- Metabolomics and Mass Spectrometry Studies
- Erythropoietin and Anemia Treatment
- Parvovirus B19 Infection Studies
- Viral-associated cancers and disorders
- Animal Virus Infections Studies
- Signaling Pathways in Disease
- Polyomavirus and related diseases
- Blood groups and transfusion
- Iron Metabolism and Disorders
- HIV, Drug Use, Sexual Risk
- HIV-related health complications and treatments
University of California, Los Angeles
2020-2025
Pacific Research Institute
2020
Vitalant
2020
Blood Systems Research Institute
2016-2019
UCLA Health
2019
Abstract HIV is difficult to eradicate due the persistence of a long-lived reservoir latently infected cells. Previous studies have shown that natural killer cells are important inhibiting infection, but it unclear whether administration can reduce rebound viremia when anti-retroviral therapy discontinued. Here we show allogeneic human peripheral blood delays viral following interruption in humanized mice with HIV-1. Utilizing genetically barcoded virus technology, these efficiently reduced...
"Shock and kill" strategies focus on purging the latent HIV-1 reservoir by treating infected individuals with therapeutics that activate virus subsequently eliminating cells. We have previously reported induction of non-canonical nuclear factor κB (NF-κB) signaling through a class small-molecule antagonists known as Smac mimetics can reverse latency. Here, we describe development Ciapavir (SBI-0953294), molecule specifically optimized for latency reversal was found to be more efficacious...
Significance Since the start of HIV/AIDS epidemic, approximately 32 million people have died from infection. Although antiretroviral therapy slows disease progression by preventing virus replication, it does not eliminate latently infected cells, which can resupply active virus, necessitating lifelong treatment. Latency-reversing agents (LRAs), such as protein kinase C (PKC) modulators, present a strategy to cure activating and enabling immunological clearance latent viral reservoirs. A...
Abstract The HIV reservoir consists of infected cells in which the HIV-1 genome persists as provirus despite effective antiretroviral therapy (ART). Studies exploring cure therapies often measure intact proviral DNA levels, time to rebound after ART interruption, or ex vivo stimulation assays latently cells. This study utilizes barcoded analyze humanized mice. Using bulk PCR and deep sequencing methodologies, we retrieve 890 viral RNA barcodes 504 linked 15,305 integration sites at single...
HIV latency prevents cure of infection with antiretroviral therapy (ART) alone. One strategy for eliminating latently infected cells involves the induction viral protein expression via latency-reversing agents (LRAs), allowing killing host by cytopathic effects or immune effector mechanisms. Here, we combine a barcoded approach and humanized mouse model to study designed, synthetic kinase C modulating LRA on rebound. We show that administration this compound during ART results in delay...
Quantitative viral outgrowth assays (QVOA) use limiting dilutions of CD4+ T cells to measure the size latent HIV-1 reservoir, a major obstacle curing HIV-1. Efforts reduce reservoir require that can reliably quantify its in blood and tissues. Although QVOA is regarded as "gold standard" for measurement, little known about accuracy precision or how cell storage conditions laboratory-specific practices affect results. Owing this lack knowledge, confidence intervals around estimates-as well...
Abstract Background Evaluations of human immunodeficiency virus (HIV) curative interventions require reliable and efficient quantification replication-competent latent reservoirs. The “classic” quantitative viral outgrowth assay (QVOA) has been regarded as the reference standard, although prohibitively resource labor intensive. We compared 6 “next-generation” assays, using polymerase chain reaction or ultrasensitive p24 to assess their suitability scalable proxies for QVOA. Methods...
Latency reversing agents (LRAs) such as protein kinase C (PKC) modulators can reduce rebound-competent HIV reservoirs in small animal models. Furthermore, administration of natural killer (NK) cells following LRA treatment improves this reservoir reduction. It is currently unknown why the combination a PKC modulator and NK so potent whether exposure to may augment cell function some way.
Understanding the effect of delayed processing whole blood on plasma ferritin will inform feasibility both routine testing in donors and clinical research study design.Whole tubes drawn from 16 were held at 4°C centrifuged 24-hour intervals to assess concentration up 5 days after draw. Intraindividual variation over time was measured 21 healthy samples collected weekly for 4 weeks then 12 weeks.No significant observed stored draw (p = 0.32). The estimated loss 4.75% within reported 5% assay....
People with sickle cell disease (SCD) are reported to have low rates of HIV infection, slower progression AIDS and lower HIV-associated mortality compared the general population. Mechanisms potential resistance in SCD incompletely understood. We retrospectively reviewed Transfusion Safety Study compare status between people other congenital anemias who were routinely exposed blood products during high-risk period before screening implementation. Non-SCD anemia diagnosis was associated a...
Author(s): Stone, M; Rosenbloom, D; Bacchetti, P; Deng, X; Busch, Dimapasoc, Keating, S; Richman, Mellors, J; Deeks, Siliciano, Chomont, N; Ptak, R
ABSTRACT Quantitative viral outgrowth assays (QVOA) use limiting dilutions of CD4+ T cells to measure the size latent HIV-1 reservoir, a major obstacle curing HIV-1. Efforts reduce reservoir require that can reliably quantify its in blood and tissues. Although QVOA is regarded as “gold standard” for measurement, little known about accuracy precision or how cell storage conditions laboratory-specific practices affect results. Owing this lack knowledge, confidence intervals around estimates –...
Author(s): Bakkour, S; Keating, SM; Deng, X; Stone, M; Worlock, A; Deeks, Bacchetti, P; Dimapasoc, Lau, J; Montalvo, L; Hauenstein, Richman, D; Busch, MP