The metabolic consequences of HIV/TB co-infection

Abstract

Background The synergy between the human immunodeficiency virus (HIV) and Mycobacterium tuberculosis during co-infection of a host is well known. While this synergy is known to be driven by immunological deterioration, the metabolic mechanisms that contribute to the associated disease burden experienced during HIV/tuberculosis (TB) co-infection remain poorly understood. Furthermore, while anti-HIV treatments suppress viral replication, these therapeutics give rise to host metabolic disruption and adaptations beyond that induced by only infection or disease. Methods In this study, the serum metabolic profiles of healthy controls, untreated HIV-negative TB-positive patients, untreated HIV/TB co-infected patients, and HIV/TB co-infected patients on antiretroviral therapy (ART), were measured using two-dimensional gas chromatography time-of-flight mass spectrometry. Since no global metabolic profile for HIV/TB co-infection and the effect of ART has been published to date, this pilot study aimed to elucidate the general areas of metabolism affected during such conditions. Results HIV/TB co-infection induced significant changes to the host’s lipid and protein metabolism, with additional microbial product translocation from the gut to the blood. The results suggest that HIV augments TB synergistically, at least in part, contributing to increased inflammation, oxidative stress, ART-induced mitochondrial damage, and its detrimental effects on gut health, which in turn, affects energy availability. ART reverses these trends to some extent in HIV/TB co-infected patients but not to that of healthy controls. Conclusion This study generated several new hypotheses that could direct future metabolic studies, which could be combined with other research techniques or methodologies to further elucidate the underlying mechanisms of these changes.

A Novel Humanized Mouse Model for HIV and Tuberculosis Co-infection Studies

“…The fatty acids alterations reflected the changes of mitochondrial function and β-oxidation, and this also is also evidenced by the reduction of L-carnitine, a metabolite necessary for the uptake of large chain fatty acids by the mitochondria 78 . We recall here that lipid-related metabolites have been reported to be decreased in humans co-infected with HIV and Mtb 79 . It has been reported that Mtb can alter lipid metabolism in macrophages, reducing the rate of ATP production, while at the same time, increasing their dependence on exogenous rather than endogenous fatty acids 80 .…”

“…We recall here that lipid-related metabolites have been reported to be decreased in humans coinfected with HIV and Mtb 79 . It has been reported that Mtb can alter lipid metabolism in macrophages, reducing the rate of ATP production, while at the same time, increasing their dependence on exogenous rather than endogenous fatty acids 80 .…”

Plasma metabolomic profile is near-normal in people with HIV on long-term suppressive antiretroviral therapy

“…PCA and PLS-DA multivariate analysis showed no relevant results for any platforms used. Previous metabolomic studies have shown a clear separation between PWH and HC groups ( Hewer et al., 2006 ; Herbert et al., 2023 ), even for PWH on long-term successful antiretroviral therapy ( Babu et al., 2019 ), in which alterations in amino-acid levels, energetics, and lipids have been found. However, PWH did not achieve a CD4/CD8 ratio >1 in most studies, which could contribute to the differences observed in these studies in contrast to ours.…”

HIV–TB Coinfection: Current Therapeutic Approaches and Drug Interactions

“…The inhibition of IFN-γ due to elevated ALA levels from HIV infection demonstrates the synergistic behavior between HIV and Mtb in coinfection [ 58 ]. Although treatment with ART has been successful in restoring normal levels of some metabolites, it continues to induce mitochondrial damage, contributing to metabolic dysfunction and decreased energy stores [ 59 ]. Further research on the metabolism of HIV– Mtb co-infection as metabolite targeting through nutritional therapy in Mtb –HIV may be of therapeutic significance [ 58 ] ( Figure 4 ).…”