HIV/HAART-associated oxidative stress is detectable by metabonomics

Abstract

Chronic human immunodeficiency virus (HIV) infection, separately and in combination with highly active antiretroviral therapy (HAART) is closely associated with oxidative stress (OS). Most studies demonstrating redox imbalances in HIV-infected individuals have done so using conventional biochemical methodologies. The limited simultaneous detection of multiple OS markers within one sample is a major drawback of these methodologies and can be addressed through the use of metabonomics. HIV-metabonomic studies utilizing biofluids from HAART cohorts as the investigative source, are on the increase. Data from many of these studies identified metabolic markers indicative of HIV-induced OS, usually as an outcome of an untargeted metabonomics study. Untargeted studies cast a wide net for any and all detectable metabolites in complex mixtures. Given the prevalence of OS during HIV infection and antiviral treatment, it is perhaps not surprising that indicators of this malady would become evident during metabolite identification. At times, targeted studies for specific (non-OS) metabolites would also yield OS markers as an outcome. This review examines the findings of these studies by first providing the necessary background information on OS and the main ways in which free radicals/reactive oxygen species (ROS) produced during OS, cause biomolecular damage. This is followed by information on the biomarkers which come about as a result of free radical damage and the techniques used for assaying these stress indicators. The established links between elevated ROS and lowered antioxidants during HIV infection and the subsequent use of HAART is then presented followed by a review of the OS markers detected in HIV metabonomic studies to date. We identify gaps in HIV/HAART-associated OS research and finally suggest how these research gaps can be addressed through metabonomic analysis, specifically targeting the multiple markers of HIV-induced OS.

Plasma Metabolic Signature and Abnormalities in HIV-Infected Individuals on Long-Term Successful Antiretroviral Therapy

“…Also, specific ceramides are increased in PLHIV and are known to track 4-hydroxynonenal (4-HNE) [17]. Higher levels of methionine sulfone and ceramides are indicators of increased oxidative stress, which was observed in earlier studies [5]. A recent study from the Netherlands that analyzed targeted metabolites of biogenic amine, lipids, oxylipins, and oxidative stress showed minimal change after one year of ART [10].…”

“…The metabolic side effects of the ARV drugs mainly on the lipid profile has been extensively studied [3,4]. Previous studies showed that metabolic abnormalities are common in PLHIV both in untreated and treated conditions (reviewed in Reference [5]). Factors like host immune response, opportunistic infections, ART drugs, and HIV itself could be responsible for the metabolic derangement during HIV infection.…”

Selenium, Selenoproteins and Viral Infection

“…However, the cellular and molecular mechanism for this unequal response remains elusive. Although efficient at controlling viral load and restoring immune function, HIV antiretroviral therapies, especially the protease and reverse transcriptase inhibitors, have been shown to induce oxidative stress [50,140]. Interestingly, a long time treatment (more than 2 years) with antiretroviral therapy improves selenium levels as compared with HIV-infected patients not receiving the treatment [141].…”

Beneficial and Detrimental Effects of Antiretroviral Therapy on HIV-Associated Immunosenescence

“…Besides inhibiting mtDNA replication, NRTIs can also directly damage mitochondrial enzymes, enhancing the generation of ROS production [127]. Indeed, an increase in oxidative stress has been frequently associated with antiretroviral treatment in HIV patients [128-130]. Several studies have demonstrated that the increase in ROS production mediated by HAART favours the onset of ageing-associated diseases [131-133].…”