{"doi":"10.1186/s12879-024-08985-y","title":"Role of thymosin α1 in restoring immune response in immunological nonresponders living with HIV","abstract":"<jats:title>Abstract</jats:title><jats:sec>\n                <jats:title>Background</jats:title>\n                <jats:p>Immunological nonresponders (INRs) living with HIV are at increased risk of co-infection and multiple tumors, with no effective strategy currently available to restore their T-cell immune response. This study aimed to explore the safety and efficacy of thymosin α1 in reconstituting the immune response in INRs.</jats:p>\n              </jats:sec><jats:sec>\n                <jats:title>Methods</jats:title>\n                <jats:p>INRs with CD4 + T cell counts between 100 and 350 cells/μL were enrolled and received two-staged 1.6 mg thymosin α1 subcutaneous injections for 24 weeks (daily in the first 2 weeks and biweekly in the subsequent 22 weeks) while continuing antiretroviral therapy. T cell counts and subsets, the expression of PD-1 and TIM-3 on T cells, and signal joint T cell receptor excision circles (sjTREC) at week 24 were evaluated as endpoints.</jats:p>\n              </jats:sec><jats:sec>\n                <jats:title>Results</jats:title>\n                <jats:p>Twenty three INRs were screened for eligibility, and 20 received treatment. The majority were male (19/20), with a median age of 48.1 years (interquartile range: 40.5–57.0) and had received antiretroviral therapy for 5.0 (3.0, 7.3) years. Multiple comparisons indicated that CD4 + T cell count and sjTREC increased after initiation of treatment, although no significant differences were observed at week 24 compared to baseline. Greatly, levels of CD4 + T cell proportion (17.2% vs. 29.1%, <jats:italic>P</jats:italic> &lt; 0.001), naïve CD4 + and CD8 + T cell proportion (17.2% vs. 41.1%, <jats:italic>P</jats:italic> &lt; 0.001; 13.8% vs. 26.6%, <jats:italic>P</jats:italic> = 0.008) significantly increased. Meanwhile, the proportion of CD4 + central memory T cells of HIV latent hosts (42.7% vs. 10.3%, <jats:italic>P</jats:italic> &lt; 0.001) significantly decreased. Moreover, the expression of PD-1 on CD4 + T cells (14.1% vs. 6.5%, <jats:italic>P</jats:italic> &lt; 0.001) and CD8 + T cells (8.5% vs. 4.1%, <jats:italic>P</jats:italic> &lt; 0.001) decreased, but the expression of TIM-3 on T cellsremained unaltered at week 24. No severe adverse events were reported and HIV viral loads kept stable throughout the study.</jats:p>\n              </jats:sec><jats:sec>\n                <jats:title>Conclusions</jats:title>\n                <jats:p>Thymosin α1 enhance CD4 + T cell count and thymic output albeit as a trend rather than an endpoint. Importantly, it improves immunosenescence and decreases immune exhaustion, warranting further investigation.</jats:p>\n              </jats:sec><jats:sec>\n                <jats:title>Trial registration</jats:title>\n                <jats:p>This single-arm prospective study was registered with ClinicalTrials.gov (NCT04963712) on July 15, 2021.</jats:p>\n              </jats:sec>","journal":"BMC Infectious Diseases","year":2024,"id":621918,"datarank":0.3958585994422889,"base_score":2.639057329615259,"endowment":2.639057329615259,"self_citation_contribution":0.3958585994422889,"citation_network_contribution":0.0,"self_endowment_contribution":0.3958585994422889,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"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":1606228,"name":"Jiangrong Wang","orcid":null,"position":1,"is_corresponding":false},{"id":1606229,"name":"Jingna Xun","orcid":null,"position":2,"is_corresponding":false},{"id":1422401,"name":"Xinyu Zhang","orcid":"0000-0002-0809-3817","position":3,"is_corresponding":false},{"id":1064426,"name":"Li Liu","orcid":"0000-0001-6126-2635","position":4,"is_corresponding":false},{"id":1606230,"name":"Zichen Song","orcid":null,"position":5,"is_corresponding":false},{"id":1556240,"name":"Renfang Zhang","orcid":null,"position":6,"is_corresponding":false},{"id":252214,"name":"Jun Chen","orcid":"0000-0002-1273-5624","position":7,"is_corresponding":false},{"id":767293,"name":"Hongzhou Lu","orcid":"0000-0002-8308-5534","position":8,"is_corresponding":false},{"id":1606227,"name":"Chaoyu Chen","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Role of thymosin α1 in restoring immune response in immunological nonresponders living with HIV","abstract":"<jats:title>Abstract</jats:title><jats:sec>\n                <jats:title>Background</jats:title>\n                <jats:p>Immunological nonresponders (INRs) living with HIV are at increased risk of co-infection and multiple tumors, with no effective strategy currently available to restore their T-cell immune response. This study aimed to explore the safety and efficacy of thymosin α1 in reconstituting the immune response in INRs.</jats:p>\n              </jats:sec><jats:sec>\n                <jats:title>Methods</jats:title>\n                <jats:p>INRs with CD4 + T cell counts between 100 and 350 cells/μL were enrolled and received two-staged 1.6 mg thymosin α1 subcutaneous injections for 24 weeks (daily in the first 2 weeks and biweekly in the subsequent 22 weeks) while continuing antiretroviral therapy. T cell counts and subsets, the expression of PD-1 and TIM-3 on T cells, and signal joint T cell receptor excision circles (sjTREC) at week 24 were evaluated as endpoints.</jats:p>\n              </jats:sec><jats:sec>\n                <jats:title>Results</jats:title>\n                <jats:p>Twenty three INRs were screened for eligibility, and 20 received treatment. The majority were male (19/20), with a median age of 48.1 years (interquartile range: 40.5–57.0) and had received antiretroviral therapy for 5.0 (3.0, 7.3) years. Multiple comparisons indicated that CD4 + T cell count and sjTREC increased after initiation of treatment, although no significant differences were observed at week 24 compared to baseline. Greatly, levels of CD4 + T cell proportion (17.2% vs. 29.1%, <jats:italic>P</jats:italic> &lt; 0.001), naïve CD4 + and CD8 + T cell proportion (17.2% vs. 41.1%, <jats:italic>P</jats:italic> &lt; 0.001; 13.8% vs. 26.6%, <jats:italic>P</jats:italic> = 0.008) significantly increased. Meanwhile, the proportion of CD4 + central memory T cells of HIV latent hosts (42.7% vs. 10.3%, <jats:italic>P</jats:italic> &lt; 0.001) significantly decreased. Moreover, the expression of PD-1 on CD4 + T cells (14.1% vs. 6.5%, <jats:italic>P</jats:italic> &lt; 0.001) and CD8 + T cells (8.5% vs. 4.1%, <jats:italic>P</jats:italic> &lt; 0.001) decreased, but the expression of TIM-3 on T cellsremained unaltered at week 24. No severe adverse events were reported and HIV viral loads kept stable throughout the study.</jats:p>\n              </jats:sec><jats:sec>\n                <jats:title>Conclusions</jats:title>\n                <jats:p>Thymosin α1 enhance CD4 + T cell count and thymic output albeit as a trend rather than an endpoint. Importantly, it improves immunosenescence and decreases immune exhaustion, warranting further investigation.</jats:p>\n              </jats:sec><jats:sec>\n                <jats:title>Trial registration</jats:title>\n                <jats:p>This single-arm prospective study was registered with ClinicalTrials.gov (NCT04963712) on July 15, 2021.</jats:p>\n              </jats:sec>","is_dataset_classified":null,"base_score":2.639057329615259,"endowment":2.639057329615259,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"38233816","pmcid":"PMC10792804","openalex_id":"https://openalex.org/W4390947257","authors":[],"funders":[{"funder_name":"National Natural Science Foundation Project","grant_id":"82072281","title":null}],"total_grants":1,"fwci":2.0304,"citation_percentile":0.8646507,"influential_citations":0,"citation_trend":[{"year":2024,"count":1},{"year":2025,"count":9},{"year":2026,"count":3}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://bmcinfectdis.biomedcentral.com/counter/pdf/10.1186/s12879-024-08985-y","host_type":"journal"},{"url":"https://bmcinfectdis.biomedcentral.com/counter/pdf/10.1186/s12879-024-08985-y","host_type":"publisher"},{"url":"https://link.springer.com/content/pdf/10.1186/s12879-024-08985-y.pdf","host_type":"publisher"},{"url":"https://link.springer.com/article/10.1186/s12879-024-08985-y/fulltext.html","host_type":"publisher"},{"url":"https://doi.org/10.1186/s12879-024-08985-y","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/38233816","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10792804","host_type":"repository"},{"url":"https://doaj.org/article/a9684320c4e14e90a9efad6a8daef003","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10792804/pdf/12879_2024_Article_8985.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC10792804","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC10792804?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["T-cell and B-cell Immunology","HIV Research and Treatment","Immune Cell Function and Interaction"],"mesh_terms":["Hepatitis A Virus Cellular Receptor 2","Thymalfasin","Adult","Female","Humans","Immunity","Male","Middle Aged","Prospective Studies","CD4-Positive T-Lymphocytes","HIV Infections","CD4 Lymphocyte Count","Programmed Cell Death 1 Receptor"],"keywords":["Interquartile range","Medicine","CD8","Thymosin","Immune system","Internal medicine","T cell","Immunology","Medical microbiology","Gastroenterology","HIV","Immune response","Thymosin α1","Thymic Output","Immunological Nonresponders"],"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":"2026-08-03T16:51:37.091055Z","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":[]}