Distinct Lipidomic Signatures in People Living with HIV: Combined Analysis of ACTG 5260s and MACS/WIHS

Jennifer Jao*, Lauren C. Balmert, Shan Sun, Grace A. McComsey, Todd T. Brown, Phyllis C. Tien, Judith S. Currier, James H. Stein, Yunping Qiu, Derek Leroith, Irwin J. Kurland

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)119-135
Number of pages17
JournalJournal of Clinical Endocrinology and Metabolism
Volume107
Issue number1
DOIs
StatePublished - Jan 1 2022

Keywords

  • HIV
  • lipidomics
  • lipogenesis
  • metabolomics

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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