Qualitative serum organic acid profiles of HIV-infected individuals not on antiretroviral treatment

Abstract

The first application of gas chromatography mass spectrometry (GC-MS) metabolomics to the analysis of organic acid profiles in sera of asymptomatic HIV-infected individuals (n = 18) compared to uninfected controls (n = 21), is reported here. Several organic acids are well-established diagnostic biomarkers of mitochondrial dysfunction, making the analysis of the organic acid metabolome well suited to monitoring the progressive disruption of mitochondrial structure and function during HIV infection. Using a multifaceted analyticalbioinformatics procedure, at least 10 of these metabolites could be linked to (1) disrupted mitochondrial metabolism, (2) changes in lipid metabolism and (3) oxidative stress, all of which are aberrations caused by HIV infection. Because of the role of the mitochondria in apoptosis, higher levels of this type of cell death in infected (compared to uninfected) individuals was used to support GC-MS data. This study demonstrates that mass spectrometry metabolomics detects biomarkers of mitochondrial dysfunction which could potentially be developed into indicators of HIV infection, perhaps also to monitor disease progression and the response to antiretroviral treatment (ART).

The Th1/Th2/Th17 cytokine profile of HIV-infected individuals: A multivariate cytokinomics approach

“…This could mean that for the chronic phase of HIV infection cytokine changes are subtle and increase or become more distinct with disease progression. Whether this is a consistent characteristic of disease progression -from chronic HIV infection to full-blown AIDS -as similarly observed for our metabonomics findings [28] will have to be addressed by more comprehensive investigations.…”

Metabonomic analysis of HIV-infected biofluids

“…Whilst the above-mentioned investigations were mainly untargeted (entire metabolome analysed), Williams et al a targeted GC-MS metabonomics approach to characterize for the first time, organic acid changes in the serum of treatment naive patients. The organic acid metabolome was investigated because these metabolites are associated with mitochondrial dysfunction, a pathological consequence of HIV infection which was also confirmed through the detection of apoptosis 8 and cytokine production. 60 Organic acids having a role in mitochondrial metabolism, lipid metabolism and oxidative stress pathways were mostly elevated in infected patient sera.…”

Nanoflow-Nanospray Mass Spectrometry Metabolomics Reveals Disruption of the Urinary Metabolite Profiles of HIV-Positive Patients on Combination Antiretroviral Therapy

“…Other studies analysing blood samples from cART-naïve HIV patients report disrupted lipid and carbohydrate metabolism and changes in organic acids associated with oxidative stress and disturbed mitochondrial metabolism. 8,21 In the current study, 12 metabolites were detected which decreased in the urine of HIV-positive patients on cART. Of these, four were bile acids which, depending on the metabolite and after adjusting for confounding variables, were detected at between 2 and 80 times lower levels in the urine from both cART groups (Table 3).…”