Metabonomic analysis of HIV-infected biofluids

Abstract

Monitoring the progression of HIV infection to full-blown acquired immune deficiency syndrome (AIDS) and assessing responses to treatment will benefit greatly from the identification of novel biological markers especially since existing clinical indicators of disease are not infallible. Nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS) are powerful methodologies used in metabonomic analyses for an approximation of HIV-induced changes to the phenotype of an infected individual. Although early in its application to HIV/AIDS, (biofluid) metabonomics has already identified metabolic pathways influenced by both HIV and/or its treatment. To date, biofluid NMR and MS data show that the virus and highly active antiretroviral treatment (HAART) mainly influence carbohydrate and lipid metabolism, suggesting that infected individuals are susceptible to very specific metabolic complications. A number of well-defined biofluid metabonomic studies clearly distinguished HIV negative, positive and treatment experienced patient profiles from one another. While many of the virus or treatment affected metabolites have been identified, the metabonomics measurements were mostly qualitative. The identities of the molecules were not always validated neither were the statistical models used to distinguish between groups. Assigning particular metabolic changes to specific drug regimens using metabonomics also remains to be done. Studies exist where identified metabolites have been linked to various disease states suggesting great potential for the use of metabonomics in disease prognostics. This review therefore examines the field of metabonomics in the context of HIV/AIDS, comments on metabolites routinely detected as being affected by the pathogen or treatment, explains what existing data suggest and makes recommendations on future research.

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).…”

“…The use of a discovery-based untargeted metabolomics approach may help to further elucidate mechanisms of action, metabolism and toxicity associated with the use of cART. 8 This analytical approach allows the profiling of a wide range of metabolites in a patient's biofluids, such as urine and blood, and therefore has great potential for the discovery of biomarkers of pharmaceutical efficacy and toxicity in HIV infection. To date, the effect of cART exposure on urinary metabolite profiles has not been studied using trace analytical methods, yet analysis of this biofluid may provide a useful non-invasive screen for pharmaceutical efficacy and toxic side effects arising from exposure to combinations of NRTIs and PIs.…”

UPLC-MS Metabonomics Reveals Perturbed Metabolites in HIV-Infected Sera

“…Alterations in the metabolism of carbohydrates (e.g glucose, [12]) and lipids [13,14] have been identified very early in AIDS research as key metabolites affected during HIV infection. These early observations were however, made using laborious conventional rather than metabonomics methodologies [15].…”

“…Because metabolites are (i) the end products of all enzymatic/chemical reactions occurring in the body, (ii) altered by infection and treatment, (iii) detectable through analytical techniques and (iv) informative regarding an individual's physiological state [16], these molecules are being revisited for their role as biomarkers of HIV infection (see studies highlighted in [15). To date, accurate and reliable markers for the diagnosis of HIV infection, monitoring of disease progression and assessing the success of therapeutic interventions are still lacking [17].…”

Mid-ATR-FTIR Spectroscopic Profiling of HIV/AIDS Sera for Novel Systems Diagnostics in Global Health

“…Several spectroscopic techniques have been employed to obtain metabolic profiles that distinguish diseased from healthy biofluids (Derenne et al, 2012;Edelstein, 2011;Graça et al, 2013;Johnston et al, 2010;Serkova and Niemann, 2006;Sitole et al, 2013). Previous studies from our group described the potential of both nuclear magnetic resonance (NMR) spectroscopy (Hewer et al, 2006;Philippeos et al, 2009) and mass spectrometry (MS) (Williams et al, 2012) in HIV/AIDS metabolomics.…”