{"doi":"10.1128/jvi.76.3.968-979.2002","title":"Viral Dynamics during Structured Treatment Interruptions of Chronic Human Immunodeficiency Virus Type 1 Infection","abstract":"<jats:title>ABSTRACT</jats:title><jats:p>Although antiviral agents which block human immunodeficiency virus (HIV) replication can result in long-term suppression of viral loads to undetectable levels in plasma, long-term therapy fails to eradicate virus, which generally rebounds after a single treatment interruption. Multiple structured treatment interruptions (STIs) have been suggested as a possible strategy that may boost HIV-specific immune responses and control viral replication. We analyze viral dynamics during four consecutive STI cycles in 12 chronically infected patients with a history (&gt;2 years) of viral suppression under highly active antiretroviral therapy. We fitted a simple model of viral rebound to the viral load data from each patient by using a novel statistical approach that allows us to overcome problems of estimating viral dynamics parameters when there are many viral load measurements below the limit of detection. There is an approximate halving of the average viral growth rate between the first and fourth STI cycles, yet the average time between treatment interruption and detection of viral loads in the plasma is approximately the same in the first and fourth interruptions. We hypothesize that reseeding of viral reservoirs during treatment interruptions can account for this discrepancy, although factors such as stochastic effects and the strength of HIV-specific immune responses may also affect the time to viral rebound. We also demonstrate spontaneous drops in viral load in later STIs, which reflect fluctuations in the rates of viral production and/or clearance that may be caused by a complex interaction between virus and target cells and/or immune responses.</jats:p>","journal":"Journal of Virology","year":2002,"id":592924,"datarank":3.5373337923466854,"base_score":4.174387269895637,"endowment":4.174387269895637,"self_citation_contribution":0.6261580904843456,"citation_network_contribution":2.91117570186234,"self_endowment_contribution":0.6261580904843456,"citer_contribution":2.91117570186234,"corpus_percentile":null,"corpus_rank":null,"citation_count":64,"citer_count":56,"citers_with_citation_signal":48,"citers_with_endowment":48,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":31312,"name":"Javier Martinez-Picado","orcid":null,"position":1,"is_corresponding":false},{"id":1517368,"name":"Lidia Ruiz","orcid":null,"position":2,"is_corresponding":false},{"id":97919,"name":"Bonaventura Clotet","orcid":"0000-0003-3232-4598","position":3,"is_corresponding":false},{"id":1517369,"name":"Andrew J. Leigh Brown","orcid":null,"position":4,"is_corresponding":false},{"id":443173,"name":"Simon D. W. Frost","orcid":"0000-0002-5207-9879","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Viral Dynamics during Structured Treatment Interruptions of Chronic Human Immunodeficiency Virus Type 1 Infection","abstract":"<jats:title>ABSTRACT</jats:title><jats:p>Although antiviral agents which block human immunodeficiency virus (HIV) replication can result in long-term suppression of viral loads to undetectable levels in plasma, long-term therapy fails to eradicate virus, which generally rebounds after a single treatment interruption. Multiple structured treatment interruptions (STIs) have been suggested as a possible strategy that may boost HIV-specific immune responses and control viral replication. We analyze viral dynamics during four consecutive STI cycles in 12 chronically infected patients with a history (&gt;2 years) of viral suppression under highly active antiretroviral therapy. We fitted a simple model of viral rebound to the viral load data from each patient by using a novel statistical approach that allows us to overcome problems of estimating viral dynamics parameters when there are many viral load measurements below the limit of detection. There is an approximate halving of the average viral growth rate between the first and fourth STI cycles, yet the average time between treatment interruption and detection of viral loads in the plasma is approximately the same in the first and fourth interruptions. We hypothesize that reseeding of viral reservoirs during treatment interruptions can account for this discrepancy, although factors such as stochastic effects and the strength of HIV-specific immune responses may also affect the time to viral rebound. We also demonstrate spontaneous drops in viral load in later STIs, which reflect fluctuations in the rates of viral production and/or clearance that may be caused by a complex interaction between virus and target cells and/or immune responses.</jats:p>","is_dataset_classified":null,"base_score":4.174387269895637,"endowment":4.174387269895637,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"11773372","pmcid":null,"openalex_id":"https://openalex.org/W2102326449","authors":[],"funders":[{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI047745","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R21 AI047745","title":null},{"funder_name":"FIC NIH HHS","grant_id":"TW00767","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R56 AI047745","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"AI47745","title":null}],"total_grants":5,"fwci":2.9018,"citation_percentile":0.91887991,"influential_citations":0,"citation_trend":[{"year":2012,"count":2},{"year":2013,"count":1},{"year":2014,"count":2},{"year":2016,"count":1},{"year":2017,"count":2},{"year":2018,"count":2},{"year":2019,"count":1},{"year":2021,"count":1},{"year":2024,"count":3},{"year":2026,"count":1}],"oa_status":"green","license":"other-oa","oa_locations":[{"url":"https://www.research.ed.ac.uk/en/publications/0c385893-c29e-4f2e-91f0-2e7833aa8d9f","host_type":"repository"},{"url":"https://www.research.ed.ac.uk/en/publications/0c385893-c29e-4f2e-91f0-2e7833aa8d9f","host_type":"repository"},{"url":"https://journals.asm.org/doi/pdf/10.1128/JVI.76.3.968-979.2002","host_type":"publisher"},{"url":"https://doi.org/10.1128/jvi.76.3.968-979.2002","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/11773372","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/135793","host_type":"repository"}],"fields_of_study":["HIV Research and Treatment","HIV/AIDS Research and Interventions","HIV/AIDS drug development and treatment","Antiretroviral Therapy, Highly Active","Drug Administration Schedule","HIV Infections","HIV-1","Humans","Models, Biological","Models, Statistical","Prospective Studies","Viral Load"],"mesh_terms":["Drug Administration Schedule","Humans","Models, Biological","Prospective Studies","Models, Statistical","HIV-1","HIV Infections","Viral Load","Antiretroviral Therapy, Highly Active"],"keywords":["Viral load","Viral replication","Biology","Virus","Immune system","Virology","Immunology","Viral shedding","Viral disease","Drug holiday","Human immunodeficiency virus (HIV)"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-26T16:13:52.287587Z","pmid":null,"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":[]}