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Quantitative viral outgrowth assays (QVOA) use limiting dilutions of CD4+ T cells to measure the size of the latent HIV-1 reservoir, a major obstacle to curing HIV-1. Efforts to reduce the reservoir require assays that can reliably quantify its size in blood and tissues. Although QVOA is regarded as a "gold standard" for reservoir measurement, little is known about its accuracy and precision or about how cell storage conditions or laboratory-specific practices affect results. Owing to this lack of knowledge, confidence intervals around reservoir size estimates-as well as judgments of the ability of therapeutic interventions to alter the size of the replication-competent but transcriptionally inactive latent reservoir-rely on theoretical statistical assumptions about dilution assays. To address this gap, we have carried out a Bayesian statistical analysis of QVOA reliability on 75 split samples of peripheral blood mononuclear cells (PBMC) from 5 antiretroviral therapy (ART)-suppressed participants, measured using four different QVOAs at separate labs, estimating assay precision and the effect of frozen cell storage on estimated reservoir size. We found that typical assay results are expected to differ from the true value by a factor of 1.6 to 1.9 up or down. Systematic assay differences comprised a 24-fold range between the assays with highest and lowest scales, likely reflecting differences in viral outgrowth readout and input cell stimulation protocols. We also found that controlled-rate freezing and storage of samples did not cause substantial differences in QVOA compared to use of fresh cells (95% probability of < 2-fold change), supporting continued use of frozen storage to allow transport and batched analysis of samples. Finally, we simulated an early-phase clinical trial to demonstrate that batched analysis of pre- and post-therapy samples may increase power to detect a three-fold reservoir reduction by 15 to 24 percentage points.
This article was published in the following journal.
Name: PLoS computational biology
To compare the reliability and repeatability of simplified skeletal maturity scoring (SSMS) and thumb ossification composite index (TOCI) in the assessment of skeletal maturity in adolescent idiopathi...
Infectious bursal disease virus (IBDV) and chicken anemia virus (CAV) cause relevant immunosuppressive diseases in poultry. Clinical diagnosis of these viruses is challenging given the different disea...
The Psoriasis Area and Severity Index (PASI) represents the gold standard for psoriasis severity assessments but is limited by its subjectivity and low intra- and inter-rater consistency.
Measurement of fore and pelvic limb alignment in veterinary orthopedics is significant, as it is in human medicine. The establishment of reference ranges for alignments and comparing measured ranges i...
As the burden of liver disease reaches epidemic levels, there is a high unmet medical need to develop robust, accurate and reproducible non-invasive methods to quantify liver tissue characteristics fo...
The objective of this study is to define the repeatability and reproducibility of quantifying flow-mediated dilation (FMD) of the brachial artery (BA) using the AngioDefender (AD) methodol...
The investigators aim to study the prevalence of latent tuberculosis infection (LTBI) using whole-blood interferon-r release assays, and determine the risk factors of LTBI in Korean health...
This study will assess the next generation of blood tests for latent TB infection, which may be able to indicate how treatment is working as well as in diagnosis infection.
This study aims to compare the performance of the tuberculin skin test, used for more than 50 years as a diagnostic tool for latent tuberculosis infection, with 2 blood tests which have re...
In patients receiving long term dialysis, using new generation of QuantiFERON-TB Gold Plus can have less result variability in inter-experiment and serial follow up in comparing with Quant...
A loose confederation of computer communication networks around the world. The networks that make up the Internet are connected through several backbone networks. The Internet grew out of the US Government ARPAnet project and was designed to facilitate information exchange.
The inter- and intra-relationships between various microorganisms. This can include both positive (like SYMBIOSIS) and negative (like ANTIBIOSIS) interactions. Examples include virus - bacteria and bacteria - bacteria.
Metal devices for fastening together two or more parts of dental prostheses for stabilizing or retaining them by attachment to abutment teeth. For a precision attachment for a partial denture DENTURE PRECISION ATTACHMENT is available.
Classification system for assessing impact injury severity developed and published by the American Association for Automotive Medicine. It is the system of choice for coding single injuries and is the foundation for methods assessing multiple injuries or for assessing cumulative effects of more than one injury. These include Maximum AIS (MAIS), Injury Severity Score (ISS), and Probability of Death Score (PODS).
Rapid methods of measuring the effects of an agent in a biological or chemical assay. The assay usually involves some form of automation or a way to conduct multiple assays at the same time using sample arrays.
Immunoassay - ELISA
Immunoassays are quick and accurate tests to detect specific molecules. Immunoassays rely on an antibody to bind to the specific structure of a molecule. Antibodies are proteins generated by animals in response to the invasion of a foreign molecule (anti...
AIDS and HIV
AIDS; Acquired Immune Deficiency Syndrome. HIV; Human Immunodeficiency Virus HIV infection causes AIDS. HIV infection also causes the production of anti-HIV antibodies, which forms the test for HIV in patients. People who have the HIV antibodies are ...