{"doi":"10.1093/infdis/jiaa089","title":"Assessing the Suitability of Next-Generation Viral Outgrowth Assays to Measure Human Immunodeficiency Virus 1 Latent Reservoir Size","abstract":"BACKGROUND: Evaluations of human immunodeficiency virus (HIV) curative interventions require reliable and efficient quantification of replication-competent latent reservoirs. The \"classic\" quantitative viral outgrowth assay (QVOA) has been regarded as the reference standard, although prohibitively resource and labor intensive. We compared 6 \"next-generation\" viral outgrowth assays, using polymerase chain reaction or ultrasensitive p24 to assess their suitability as scalable proxies for QVOA. METHODS: Next-generation QVOAs were compared with classic QVOA using single leukapheresis-derived samples from 5 antiretroviral therapy-suppressed HIV-infected participants and 1 HIV-uninfected control; each laboratory tested blinded batches of 3 frozen and 1 fresh sample. Markov chain Monte Carlo methods estimated extra-Poisson variation at aliquot, batch, and laboratory levels. Models also estimated the effect of testing frozen versus fresh samples. RESULTS: Next-generation QVOAs had similar estimates of variation to QVOA. Assays with ultrasensitive readout reported higher infectious units per million values than classic QVOA. Within-batch testing had 2.5-fold extra-Poisson variation (95% credible interval [CI], 2.1-3.5-fold) for next-generation assays. Between-laboratory variation increased extra-Poisson variation to 3.4-fold (95% CI, 2.6-5.4-fold). Frozen storage did not substantially alter infectious units per million values (-18%; 95% CI, -52% to 39%). CONCLUSIONS: The data offer cautious support for use of next-generation QVOAs as proxies for more laborious QVOA, while providing greater sensitivities and dynamic ranges. Measurement of latent reservoirs in eradication strategies would benefit from high throughput and scalable assays.","journal":"The Journal of Infectious Diseases","year":2020,"id":76729,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9474,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":399934,"name":"Daniel I. S. Rosenbloom","orcid":"0000-0003-1413-3907","position":1,"is_corresponding":false},{"id":239681,"name":"Peter Bacchetti","orcid":"0000-0002-9323-2972","position":2,"is_corresponding":false},{"id":370429,"name":"Xutao Deng","orcid":null,"position":3,"is_corresponding":false},{"id":344321,"name":"Melanie Dimapasoc","orcid":"0000-0003-0328-315X","position":4,"is_corresponding":false},{"id":399935,"name":"Sheila M. Keating","orcid":"0000-0002-8324-3694","position":5,"is_corresponding":false},{"id":324937,"name":"Sonia Bakkour","orcid":null,"position":6,"is_corresponding":false},{"id":58755,"name":"Douglas D. Richman","orcid":"0000-0003-0962-9254","position":7,"is_corresponding":false},{"id":258969,"name":"John W. Mellors","orcid":"0000-0002-3737-9742","position":8,"is_corresponding":false},{"id":71691,"name":"Steven G. Deeks","orcid":"0000-0001-6371-747X","position":9,"is_corresponding":false},{"id":239683,"name":"Jun Lai","orcid":"0009-0008-6435-2888","position":10,"is_corresponding":false},{"id":239682,"name":"Subul Beg","orcid":"0000-0003-1862-6012","position":11,"is_corresponding":false},{"id":228714,"name":"Janet D. Siliciano","orcid":"0000-0001-6712-3775","position":12,"is_corresponding":false},{"id":399936,"name":"Amélie Pagliuzza","orcid":"0000-0001-8124-2607","position":13,"is_corresponding":false},{"id":235294,"name":"Nicolas Chomont","orcid":"0000-0001-9747-5018","position":14,"is_corresponding":false},{"id":401060,"name":"Carol Lackman-Smith","orcid":null,"position":15,"is_corresponding":false},{"id":399937,"name":"Roger G. Ptak","orcid":"0000-0002-8492-3085","position":16,"is_corresponding":false},{"id":36841,"name":"Michael P. Busch","orcid":"0000-0002-1446-125X","position":17,"is_corresponding":false},{"id":246884,"name":"Mars Stone","orcid":"0000-0001-5619-2767","position":0,"is_corresponding":true}],"reference_count":25,"raw_metadata":null,"created_at":"2026-07-18T21:48:27.511277Z","pmid":"32147687","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}