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Disparities","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006545","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>We assessed the effect of untreated HIV infection as well as different antiretroviral therapy (ART) on the metabolome\/lipidome.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgab663","type":"journal-article","created":{"date-parts":[[2021,9,9]],"date-time":"2021-09-09T08:04:00Z","timestamp":1631174640000},"page":"119-135","source":"Crossref","is-referenced-by-count":10,"title":["Distinct Lipidomic Signatures in People Living With HIV: Combined Analysis of ACTG 5260s and MACS\/WIHS"],"prefix":"10.1210","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1894-6040","authenticated-orcid":false,"given":"Jennifer","family":"Jao","sequence":"first","affiliation":[{"name":"Northwestern University Feinberg School of Medicine, Department of Pediatrics, Division of Pediatric Infectious Diseases, Department of Medicine, Division of Adult Infectious Diseases, Chicago, Illinois 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren C","family":"Balmert","sequence":"additional","affiliation":[{"name":"Northwestern University Feinberg School of Medicine, Department of Preventive Medicine, Division of Biostatistics, Chicago, Illinois 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Sun","sequence":"additional","affiliation":[{"name":"Ann and Robert H. Lurie Children\u2019s Hospital of Chicago, Department of Pediatrics, Division of Pediatric Infectious Diseases, Chicago, Illinois 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace A","family":"McComsey","sequence":"additional","affiliation":[{"name":"University Hospitals Cleveland Medical Center and Case Western Reserve University, Department of Pediatrics, Department of Medicine, Cleveland, Ohio 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd T","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Johns Hopkins University , Baltimore, Maryland 21218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phyllis C","family":"Tien","sequence":"additional","affiliation":[{"name":"University of California, San Francisco, Department of Medicine and Department of Veterans Affairs Medical Center, Division of Infectious 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