{"doi":"10.1093/infdis/jiag045","title":"Dynamics of Intact and Defective Human Immunodeficiency Virus Type 1 (HIV-1) Proviruses During Decades of Suppressive Antiretroviral Treatment in Young Adults With Perinatal HIV","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:sec>\n                    <jats:title>Background</jats:title>\n                    <jats:p>Understanding HIV-1 reservoir dynamics during long-term antiretroviral therapy (ART) in youth with perinatal Human Immunodeficiency Virus Type-1 (HIV-1) is essential for ART-free remission strategies.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods</jats:title>\n                    <jats:p>We quantified intact and defective HIV proviruses in 201 peripheral blood mononuclear cell samples (PBMCs) from participants ages 17.6–21.2 years in the Pediatric HIV/AIDS Cohort Study (PHACS) Adolescent Master Protocol. Participants were classified as early-suppressed (ES, &amp;lt;1 year of age at virologic suppression [VS]) or late-suppressed (LS, 1–5 years of age at VS) and had maintained VS for up to 20 years.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Results</jats:title>\n                    <jats:p>Twenty-six participants (11 ES and 15 LS) were evaluated. Early-suppressed participants exhibited significantly lower intact HIV reservoirs compared with LS participants, with 67% of ES samples below detection limits (2.0 copies/106 PBMCs). By 5 years of VS, the ES participants had significantly lower mean intact proviral load (2.0 vs 6.6 copies/106 PBMCs) than LS participants, largely driven by faster clearance of intact proviruses in the first 5 years of VS. Among LS participants, females had larger intact reservoirs than males (mean: 12.5 vs 4.1 intact copies/106 PBMCs) and exhibited greater increases in defective proviruses over time.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions</jats:title>\n                    <jats:p>Achieving VS by 1 year of age in perinatal HIV infection results in substantially smaller HIV intact reservoirs by age 5, with effects sustained through young adulthood. Additionally, sex-based differences, larger intact reservoirs and increases in defective proviruses in females, underscore the need for tailored ART-free remission and cure strategies for this population.</jats:p>\n                  </jats:sec>","journal":"The Journal of Infectious Diseases","year":2026,"id":610638,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"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":382511,"name":"Kunjal Patel","orcid":"0000-0003-0002-681X","position":1,"is_corresponding":false},{"id":520356,"name":"Wendy Yu","orcid":"0000-0001-5967-2352","position":2,"is_corresponding":false},{"id":576179,"name":"Joseph Szewczyk","orcid":"0000-0003-0540-3274","position":3,"is_corresponding":false},{"id":543049,"name":"Adit Dhummakupt","orcid":null,"position":4,"is_corresponding":false},{"id":443829,"name":"Sandra Burchett","orcid":"0000-0002-7106-9262","position":5,"is_corresponding":false},{"id":1570043,"name":"Russell B Van Dyke","orcid":null,"position":6,"is_corresponding":false},{"id":385139,"name":"Deborah Persaud","orcid":"0000-0001-5195-8743","position":7,"is_corresponding":false},{"id":922771,"name":"Priya Khetan","orcid":"0000-0001-5688-2071","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Dynamics of Intact and Defective Human Immunodeficiency Virus Type 1 (HIV-1) Proviruses During Decades of Suppressive Antiretroviral Treatment in Young Adults With Perinatal HIV","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:sec>\n                    <jats:title>Background</jats:title>\n                    <jats:p>Understanding HIV-1 reservoir dynamics during long-term antiretroviral therapy (ART) in youth with perinatal Human Immunodeficiency Virus Type-1 (HIV-1) is essential for ART-free remission strategies.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods</jats:title>\n                    <jats:p>We quantified intact and defective HIV proviruses in 201 peripheral blood mononuclear cell samples (PBMCs) from participants ages 17.6–21.2 years in the Pediatric HIV/AIDS Cohort Study (PHACS) Adolescent Master Protocol. Participants were classified as early-suppressed (ES, &amp;lt;1 year of age at virologic suppression [VS]) or late-suppressed (LS, 1–5 years of age at VS) and had maintained VS for up to 20 years.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Results</jats:title>\n                    <jats:p>Twenty-six participants (11 ES and 15 LS) were evaluated. Early-suppressed participants exhibited significantly lower intact HIV reservoirs compared with LS participants, with 67% of ES samples below detection limits (2.0 copies/106 PBMCs). By 5 years of VS, the ES participants had significantly lower mean intact proviral load (2.0 vs 6.6 copies/106 PBMCs) than LS participants, largely driven by faster clearance of intact proviruses in the first 5 years of VS. Among LS participants, females had larger intact reservoirs than males (mean: 12.5 vs 4.1 intact copies/106 PBMCs) and exhibited greater increases in defective proviruses over time.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions</jats:title>\n                    <jats:p>Achieving VS by 1 year of age in perinatal HIV infection results in substantially smaller HIV intact reservoirs by age 5, with effects sustained through young adulthood. Additionally, sex-based differences, larger intact reservoirs and increases in defective proviruses in females, underscore the need for tailored ART-free remission and cure strategies for this population.</jats:p>\n                  </jats:sec>","is_dataset_classified":null,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"41616083","pmcid":"PMC13007499","openalex_id":"https://openalex.org/W7126152725","authors":[],"funders":[{"funder_name":"Pediatric Adolescent Virus Elimination","grant_id":"UM1AI164566","title":null},{"funder_name":"National Institutes of Health","grant_id":"AI150412, AI186792","title":null},{"funder_name":"IMPAACT Lab Center","grant_id":"UM1AI106716","title":null},{"funder_name":"IMPAACT Lab Center","grant_id":"NCT02720094 and NCT03164564","title":null},{"funder_name":"Johns Hopkins Center for AIDS Research","grant_id":"P30AI094189","title":null},{"funder_name":"Harvard T.H. 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Craniofacial Research","grant_id":"","title":null},{"funder_name":"National Institutes of Health","grant_id":"","title":null},{"funder_name":"Pediatric HIV/AIDS Cohort Study","grant_id":"","title":null},{"funder_name":"Pediatric HIV/AIDS Cohort Study (PHACS)","grant_id":"","title":null},{"funder_name":"Pediatric HIV/AIDS Cohort Study (PHACS)","grant_id":"","title":null},{"funder_name":"Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)","grant_id":"","title":null},{"funder_name":"National Institutes of Health (OD)","grant_id":"","title":null},{"funder_name":"National Institute of Dental & Craniofacial Research (NIDCR)","grant_id":"","title":null},{"funder_name":"National Institute of Allergy and Infectious Diseases (NIAID)","grant_id":"","title":null},{"funder_name":"National Institute of Neurological Disorders and Stroke (NINDS)","grant_id":"","title":null},{"funder_name":"National Institute on Deafness and Other Communication Disorders (NIDCD)","grant_id":"","title":null},{"funder_name":"National Institute of Mental Health (NIMH)","grant_id":"","title":null},{"funder_name":"National Institute on Drug Abuse (NIDA)","grant_id":"","title":null},{"funder_name":"National Cancer Institute (NCI)","grant_id":"","title":null},{"funder_name":"National Institute on Alcohol Abuse and Alcoholism (NIAAA)","grant_id":"","title":null},{"funder_name":"National Heart, Lung, and Blood Institute (NHLBI)","grant_id":"","title":null}],"total_grants":47,"fwci":14.3645,"citation_percentile":0.98159898,"influential_citations":0,"citation_trend":[{"year":2026,"count":2}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1093/infdis/jiag045","host_type":"journal"},{"url":"https://doi.org/10.1093/infdis/jiag045","host_type":"publisher"},{"url":"https://academic.oup.com/jid/advance-article-pdf/doi/10.1093/infdis/jiag045/66647504/jiag045.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/jid/article-pdf/233/6/e1396/66647504/jiag045.pdf","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41616083","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13007499/","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC13007499","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC13007499?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["HIV Research and Treatment","HIV/AIDS drug development and treatment","HIV/AIDS Research and Interventions","Humans","HIV Infections","Female","Male","Proviruses","HIV-1","Adolescent","Young Adult","Viral Load","Leukocytes, Mononuclear","Anti-HIV Agents","Cohort Studies"],"mesh_terms":["Adolescent","Female","Humans","Leukocytes, Mononuclear","Male","Proviruses","Cohort Studies","HIV-1","HIV Infections","Anti-HIV Agents","Viral Load","Young Adult"],"keywords":["Young adult","Human immunodeficiency virus (HIV)","Lentivirus","Antiretroviral treatment","Viral disease","Sida","HIV","Perinatal","Young Adults","Proviral Reservoir"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-01T10:02:50.002797Z","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":[]}