{"doi":"10.1210/clinem/dgab663","title":"Distinct Lipidomic Signatures in People Living With HIV: Combined Analysis of ACTG 5260s and MACS/WIHS","abstract":"CONTEXT: Disentangling contributions of HIV from antiretroviral therapy (ART) and understanding the effects of different ART on metabolic complications in persons living with HIV (PLHIV) has been challenging. OBJECTIVE: We assessed the effect of untreated HIV infection as well as different antiretroviral therapy (ART) on the metabolome/lipidome. METHODS: Widely targeted plasma metabolomic and lipidomic profiling was performed on HIV-seronegative individuals and people living with HIV (PLHIV) before and after initiating ART (tenofovir/emtricitabine plus atazanavir/ritonavir [ATV/r] or darunavir/ritonavir [DRV/r] or raltegravir [RAL]). Orthogonal partial least squares discriminant analysis was used to assess metabolites/lipid subspecies that discriminated between groups. Graphical lasso estimated group-specific metabolite/lipid subspecies networks associated with the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Correlations between inflammatory markers and metabolites/lipid subspecies were visualized using heat maps. RESULTS: Of 435 participants, 218 were PLHIV. Compared to HIV-seronegative individuals, ART-naive PLHIV exhibited higher levels of saturated triacylglycerols/triglycerides (TAGs) and 3-hydroxy-kynurenine, lower levels of unsaturated TAGs and N-acetyl-tryptophan, and a sparser and less heterogeneous network of metabolites/lipid subspecies associated with HOMA-IR. PLHIV on RAL vs ATV/r or DRV/r had lower saturated and unsaturated TAGs. Positive correlations were found between medium-long chain acylcarnitines (C14-C6 ACs), palmitate, and HOMA-IR for RAL but not ATV/r or DRV/r. Stronger correlations were seen for TAGs with interleukin 6 and high-sensitivity C-reactive protein after RAL vs ATV/r or DRV/r initiation; these correlations were absent in ART-naive PLHIV. CONCLUSION: Alterations in the metabolome/lipidome suggest increased lipogenesis for ART-naive PLHIV vs HIV-seronegative individuals, increased TAG turnover for RAL vs ATV/r or DRV/r, and increased inflammation associated with this altered metabolome/lipidome after initiating ART. Future studies are needed to understand cardiometabolic consequences of lipogenesis and inflammation in PLHIV.","journal":"The Journal of Clinical Endocrinology & Metabolism","year":2021,"id":195033,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8341,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":373367,"name":"Lauren C. Balmert","orcid":"0000-0001-5476-4514","position":1,"is_corresponding":false},{"id":765700,"name":"Shan Sun","orcid":"0000-0002-9807-626X","position":2,"is_corresponding":false},{"id":247284,"name":"Grace A. McComsey","orcid":"0000-0003-2690-8888","position":3,"is_corresponding":false},{"id":109430,"name":"Todd T. Brown","orcid":"0000-0001-8599-278X","position":4,"is_corresponding":false},{"id":150354,"name":"Phyllis C. Tien","orcid":null,"position":5,"is_corresponding":false},{"id":396976,"name":"Judith S. Currier","orcid":"0000-0003-4279-4737","position":6,"is_corresponding":false},{"id":381245,"name":"James H. Stein","orcid":"0000-0002-2770-8223","position":7,"is_corresponding":false},{"id":266141,"name":"Yunping Qiu","orcid":"0000-0003-1039-5264","position":8,"is_corresponding":false},{"id":442216,"name":"Derek LeRoith","orcid":"0000-0003-0565-1753","position":9,"is_corresponding":false},{"id":266142,"name":"Irwin J. Kurland","orcid":"0000-0002-9633-1917","position":10,"is_corresponding":false},{"id":296936,"name":"Jennifer Jao","orcid":null,"position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-18T23:50:03.719152Z","pmid":"34498048","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":[]}