{"doi":"10.1371/journal.pcbi.1004677","title":"Residual Viremia in Treated HIV+ Individuals","abstract":null,"journal":"PLOS Computational Biology","year":2016,"id":626162,"datarank":0.6496100010429497,"base_score":4.330733340286331,"endowment":4.330733340286331,"self_citation_contribution":0.6496100010429497,"citation_network_contribution":0.0,"self_endowment_contribution":0.6496100010429497,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":75,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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":291274,"name":"Alan S. Perelson","orcid":"0000-0002-2455-0002","position":1,"is_corresponding":false},{"id":434152,"name":"Jessica M. Conway","orcid":"0000-0003-1474-4230","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Residual Viremia in Treated HIV+ Individuals","abstract":"Antiretroviral therapy (ART) effectively controls HIV infection, suppressing HIV viral loads. However, some residual virus remains, below the level of detection, in HIV-infected patients on ART. The source of this viremia is an area of debate: does it derive primarily from activation of infected cells in the latent reservoir, or from ongoing viral replication? Observations seem to be contradictory: there is evidence of short term evolution, implying that there must be ongoing viral replication, and viral strains should thus evolve. However, phylogenetic analyses, and rare emergent drug resistance, suggest no long-term viral evolution, implying that virus derived from activated latent cells must dominate. We use simple deterministic and stochastic models to gain insight into residual viremia dynamics in HIV-infected patients. Our modeling relies on two underlying assumptions for patients on suppressive ART: that latent cell activation drives viral dynamics and that the reproductive ratio of treated infection is less than 1. Nonetheless, the contribution of viral replication to residual viremia in patients on ART may be non-negligible. However, even if the portion of viremia attributable to viral replication is significant, our model predicts (1) that latent reservoir re-seeding remains negligible, and (2) some short-term viral evolution is permitted, but long-term evolution can still be limited: stochastic analysis of our model shows that de novo emergence of drug resistance is rare. Thus, our simple models reconcile the seemingly contradictory observations on residual viremia and, with relatively few parameters, recapitulates HIV viral dynamics observed in patients on suppressive therapy.","is_dataset_classified":null,"base_score":4.330733340286331,"endowment":4.330733340286331,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26735135","pmcid":"PMC4703306","openalex_id":"https://openalex.org/W2231521459","authors":[],"funders":[{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI028433","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01-AI028433","title":null},{"funder_name":"NIH HHS","grant_id":"R01-OD011095","title":null},{"funder_name":"NIH HHS","grant_id":"R01 OD011095","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01OD011095-28","title":"Modeling Viral and T Lymphocyte Dynamics"},{"funder_name":"National Institutes of Health","grant_id":"5R01AI028433-25","title":"Immune System Modeling/HIV"}],"total_grants":6,"fwci":5.5985,"citation_percentile":0.96183937,"influential_citations":0,"citation_trend":[{"year":2016,"count":7},{"year":2017,"count":15},{"year":2018,"count":6},{"year":2019,"count":5},{"year":2020,"count":8},{"year":2021,"count":6},{"year":2022,"count":4},{"year":2023,"count":7},{"year":2024,"count":8},{"year":2025,"count":6},{"year":2026,"count":3}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1004677&type=printable","host_type":"journal"},{"url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1004677&type=printable","host_type":"publisher"},{"url":"http://dx.plos.org/10.1371/journal.pcbi.1004677","host_type":"publisher"},{"url":"https://doi.org/10.1371/journal.pcbi.1004677","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/26735135","host_type":"repository"},{"url":"https://www.osti.gov/biblio/1236042","host_type":"repository"},{"url":"https://doaj.org/article/d90516b04f38473f877c5d2e772930f2","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4703306","host_type":"repository"},{"url":"https://www.osti.gov/servlets/purl/1236042","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC4703306","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC4703306?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1371/journal.pcbi.1004677","host_type":""},{"url":"https://dx.doi.org/10.1371/journal.pcbi.1004677","host_type":""}],"fields_of_study":["HIV Research and Treatment","HIV/AIDS Research and Interventions","HIV/AIDS drug development and treatment","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":["Humans","Models, Biological","RNA, Viral","Viremia","Virus Replication","HIV-1","HIV Infections","Computational Biology","Viral Load","Anti-Retroviral Agents"],"keywords":["Viremia","Viral load","Viral replication","Virology","Viral evolution","Biology","Residual","Immunology","Virus","Genetics","Genome","Gene","QH301-705.5","Computational Biology","HIV Infections","Virus Replication","Models, Biological","Anti-Retroviral Agents","HIV-1","Humans","RNA, Viral","Biology (General)","Research Article"],"sdg_mappings":[{"sdg_number":2,"sdg_label":"2. 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