Examining Metabolite Profile Changes of People Living With HIV on ART

HIV/AIDS therapy pills on pink background
Researchers worked to identify changes in plasma metabolites in those with HIV and to study the differences in plasma metabolite profiles after the initiation of antiretroviral therapy.

People living with HIV who underwent treatment with antiretroviral therapy (ART) were found to have altered plasma metabolite profiles, according to the results of a study published in Open Forum Infectious Diseases.

Data from the Malaysian HIV and Aging (MHIVA; n=121) study and healthy control group participants (n=70) were analyzed for plasma metabolite profiles.

Among the HIV group, 71 had fast immune recovery and 50 had impaired recovery. These cohorts were 61% and 39% men who had been on ART for a median of 6 (interquartile range [IQR], 4-11) and 7 (IQR, 5-11) years with a current CD4 count of 751 (IQR, 578-877) and 428 (IQR, 264-537) cells/µL, respectively.

A principal component analysis identified a clear separation of the metabolite profiles among people living with HIV and control group participants.

The most important metabolites were indole-3-propionate and tryptophan; both metabolites were lower among the HIV cohort. Among the low immune recovery subset, kynurenic acid and tryptophan betaine differed significantly.

In total, 44 unique metabolites differed on the basis of HIV status (all P <.02), 13 differed between the slow immune recovery cohort and control group participants, 11 between the fast immune recovery cohort and control group participants, and 20 were shared by the HIV cohorts.

There was a correlation between cysteine and CD4 concentration (R, 0.3; P =.005); cysteine was 1.51 times higher among the individuals who had fast immune recovery (P <.0001).

Compared with control group participants, participants with HIV on ART demonstrated more affected glycine and serine metabolism pathways with a 16.7-fold (P =5.1´1015) and 12.3-fold (P =3.2´109) enrichment, respectively.

Bile acid biosynthesis was 4.7-fold enriched among people living with HIV with fast immune recovery (P =.008), but it was not enriched among those with slow immune recovery.

This study was limited by its cross-sectional design. It remains unclear whether the metabolite alterations were due to HIV infection or ART.

These data indicated that people living with HIV on ART had an altered metabolite profile and changes in bile acid composition, which may indicate microbial dysbiosis.


Nyström S, Govender M, Hwei YS, Kamarulzaman A, Rajasuriar R, Larsson M. HIV infected individuals on ART with impaired immune recovery have altered plasma metabolite profiles. Open Forum Infect Dis. Published online June 3, 2021. doi:10.1093/ofid/ofab288