{"doi":"10.1142/9789811286421_0045","title":"Lymphocyte Count Derived Polygenic Score and Interindividual Variability in CD4 T-cell Recovery in Response to Antiretroviral Therapy","abstract":"Access to safe and effective antiretroviral therapy (ART) is a cornerstone in the global response to the HIV pandemic. Among people living with HIV, there is considerable interindividual variability in absolute CD4 T-cell recovery following initiation of virally suppressive ART. The contribution of host genetics to this variability is not well understood. We explored the contribution of a polygenic score which was derived from large, publicly available summary statistics for absolute lymphocyte count from individuals in the general population (PGSlymph) due to a lack of publicly available summary statistics for CD4 T-cell count. We explored associations with baseline CD4 T-cell count prior to ART initiation (n=4959) and change from baseline to week 48 on ART (n=3274) among treatment-naïve participants in prospective, randomized ART studies of the AIDS Clinical Trials Group. We separately examined an African-ancestry-derived and a European-ancestry-derived PGSlymph, and evaluated their performance across all participants, and also in the African and European ancestral groups separately. Multivariate models that included PGSlymph, baseline plasma HIV-1 RNA, age, sex, and 15 principal components (PCs) of genetic similarity explained ∼26-27% of variability in baseline CD4 T-cell count, but PGSlymph accounted for <1% of this variability. Models that also included baseline CD4 T-cell count explained ∼7-9% of variability in CD4 T-cell count increase on ART, but PGSlymph accounted for <1% of this variability. In univariate analyses, PGSlymph was not significantly associated with baseline or change in CD4 T-cell count. Among individuals of African ancestry, the African PGSlymph term in the multivariate model was significantly associated with change in CD4 T-cell count while not significant in the univariate model. When applied to lymphocyte count in a general medical biobank population (Penn Medicine BioBank), PGSlymph explained ∼6-10% of variability in multivariate models (including age, sex, and PCs) but only ∼1% in univariate models. In summary, a lymphocyte count PGS derived from the general population was not consistently associated with CD4 T-cell recovery on ART. Nonetheless, adjusting for clinical covariates is quite important when estimating such polygenic effects.","journal":"PubMed","year":2023,"id":415095,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9494,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT00013520","NCT00050895","NCT00118898"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":432073,"name":"Scott Dudek","orcid":"0000-0003-2904-3824","position":1,"is_corresponding":false},{"id":920716,"name":"Karl Keat","orcid":"0000-0002-0945-5816","position":2,"is_corresponding":false},{"id":98505,"name":"Yuki Bradford","orcid":null,"position":3,"is_corresponding":false},{"id":42538,"name":"Zinhle Cindi","orcid":null,"position":4,"is_corresponding":false},{"id":351140,"name":"Eric S. Daar","orcid":"0000-0003-1880-7331","position":5,"is_corresponding":false},{"id":298225,"name":"Roy M. Gulick","orcid":"0000-0002-1431-8912","position":6,"is_corresponding":false},{"id":259558,"name":"Sharon A. Riddler","orcid":"0000-0002-2545-7037","position":7,"is_corresponding":false},{"id":428567,"name":"Jeffrey L. Lennox","orcid":"0000-0002-2064-5565","position":8,"is_corresponding":false},{"id":351141,"name":"Phumla Sinxadi","orcid":"0000-0002-1312-3523","position":9,"is_corresponding":false},{"id":292655,"name":"David W. Haas","orcid":"0000-0002-5813-1594","position":10,"is_corresponding":false},{"id":22049,"name":"Marylyn D. Ritchie","orcid":"0000-0002-1208-1720","position":11,"is_corresponding":false},{"id":1165601,"name":"Kathleen M. Cardone","orcid":null,"position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T01:22:08.814145Z","pmid":"38160309","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":[]}