Innovations in the Quantitative Virus Outgrowth Assay and Its Use in Clinical Trials
Overview
Affiliations
A robust measure of the size of the latent HIV reservoir is essential to quantifying the effect of interventions designed to deplete the pool of reactivatable, replication competent proviruses. In addition to the ability to measure a biologically relevant parameter, any assay designed to be used in a clinical trial needs to be reproducible and scalable. The need to quantify the number of resting CD4+ T cells capable of releasing infectious virus has led to the development of the quantitative viral outgrowth assay (VOA). The assay as originally described has a number of features that limit its scalability for use in clinical trials; however recent developments reducing the time and manpower requirements of the assay, while importantly improving reproducibility mean that it is becoming much more practical for it to enter into more widespread use. This review describes the background to VOA development and the practical issues that they present in utilising them in clinical trials. It describes the innovations that have made their usage more practical and the limitations that still exist.
Wonderlich E, Reece M, Kulpa D Methods Mol Biol. 2022; 2407:315-331.
PMID: 34985673 DOI: 10.1007/978-1-0716-1871-4_21.
Inter-Laboratory Reproducibility of Inducible HIV-1 Reservoir Quantification by TILDA.
Lungu C, Procopio F, Overmars R, Beerkens R, Voermans J, Rao S Viruses. 2020; 12(9).
PMID: 32887284 PMC: 7552071. DOI: 10.3390/v12090973.
Key Players in HIV-1 Transcriptional Regulation: Targets for a Functional Cure.
Mori L, Valente S Viruses. 2020; 12(5).
PMID: 32403278 PMC: 7291152. DOI: 10.3390/v12050529.
What's Hot in HIV in 2019-A Basic and Translational Science Summary for Clinicians From IDWeek 2019.
Titanji B, Kelley C Open Forum Infect Dis. 2020; 7(3):ofaa053.
PMID: 32154324 PMC: 7052744. DOI: 10.1093/ofid/ofaa053.
Wonderlich E, Subramanian K, Cox B, Wiegand A, Lackman-Smith C, Bale M PLoS Pathog. 2019; 15(10):e1008074.
PMID: 31609991 PMC: 6812841. DOI: 10.1371/journal.ppat.1008074.