HIV-infected individuals on art with impaired immune recovery have altered plasma metabolite profiles
Document Type
Article
Publication Date
7-1-2021
Abstract
Background. Multiple host factors may influence immune reconstitution in HIV-infected people after the initiation of suppressive antiretroviral therapy (ART). Aberrant metabolic pathways have been reported in people with HIV (PWH) on ART. We hypothesized that alterations in plasma metabolites were associated with immune recovery following ART. Methods. In this cross-sectional study, the plasma metabolomic profiles of PWH on ART were evaluated. PWH of slow and fast immune recovery were classified by increase in CD4 T cells following 2 years of ART. Targeted plasma metabolite profiling by liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry to determine metabolite signatures for HIV recovery identified >200 metabolites. Results. Notably, indole-3-propionic acid was downregulated during HIV, possibly reflecting impaired gastrointestinal epithelium homeostasis. The most important metabolite discriminating between the PWH with fast and slow immune recovery was cysteine. Upregulated cysteine and cysteine pathways may contribute to redox-balance maintenance and T-cell function in PWH with fast immune recovery. Additionally, serine and glycine metabolism and bile acid biosynthesis were the most perturbed metabolic pathways in PWH. Conclusions. These results provide a starting point for developing biomarker candidates for immune recovery in PWH on ART and provide insight into the interplay of metabolism and immune response in HIV infection.
Keywords
Antiretroviral therapy, HIV, Immune recovery, Metabolomics
Divisions
medicinedept,ceria
Funders
Swedish Research Council European Commission [01091],ALF grants, Region Ostergotland, Sweden,Linkoping University Hospital Research Fund,Universiti Malaya [H-20001-E000001]
Publication Title
Open Forum Infectious Diseases
Volume
8
Issue
7
Publisher
Oxford University Press
Publisher Location
JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA