Metabolic Insights into HIV/TB Co-infection: An Untargeted Urinary Metabolomics Approach
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ORGANISM(S): Homo sapiens (human)
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PROVIDER: S-BSST1397 | biostudies-other |
REPOSITORIES: biostudies-other
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Project description:IntroductionAmid the global health crisis, HIV/TB co-infection presents significant challenges, amplifying the burden on patients and healthcare systems alike. Metabolomics offers an innovative window into the metabolic disruptions caused by co-infection, potentially improving diagnosis and treatment monitoring.AimThis study uses untargeted metabolomics to investigate the urinary metabolic signature of HIV/TB co-infection, enhancing understanding of the metabolic interplay between these infections.MethodsUrine samples from South African adults, categorised into four groups - healthy controls, TB-positive, HIV-positive, and HIV/TB co-infected - were analysed using GCxGC-TOFMS. Metabolites showing significant differences among groups were identified through Kruskal-Wallis and Wilcoxon rank sum tests.ResultsVarious metabolites (n = 23) were modulated across the spectrum of health and disease states represented in the cohorts. The metabolomic profiles reflect a pronounced disruption in biochemical pathways involved in energy production, amino acid metabolism, gut microbiome, and the immune response, suggesting a bidirectional exacerbation between HIV and TB. While both diseases independently perturb the host's metabolism, their co-infection leads to a unique metabolic phenotype, indicative of an intricate interplay rather than a simple additive effect.ConclusionMetabolic profiling revealed a unique metabolic landscape shaped by HIV/TB co-infection. The findings highlight the potential of urinary differential metabolites for co-infection, offering a non-invasive tool for enhancing diagnostic precision and tailoring therapeutic interventions. Future research should focus on expanding sample sizes and integrating longitudinal analyses to build upon these foundational insights, paving the way for metabolomic applications in combating these concurrent pandemics.
| S-EPMC11252185 | biostudies-literature
Project description: Not available
| S-BSST1402 | biostudies-other
Project description: Not available
| S-BSST1084 | biostudies-other
Project description:IntroductionThe human immunodeficiency virus (HIV) and tuberculosis (TB) co-infection presents significant challenges due to the complex interplay between these diseases, leading to exacerbated metabolic disturbances. Understanding these metabolic profiles is crucial for improving diagnostic and therapeutic approaches.ObjectiveThis study aimed to characterise the urinary acylcarnitine and amino acid profiles, including 5-hydroxyindoleacetic acid (5-HIAA), in patients co-infected with HIV and TB using targeted liquid chromatography mass spectrometry (LC-MS) metabolomics.MethodsUrine samples, categorised into HIV, TB, HIV/TB co-infected, and healthy controls, were analysed using HPLC-MS/MS. Statistical analyses included one-way ANOVA and a Kruskal-Wallis test to determine significant differences in the acylcarnitine and amino acid profiles between groups.ResultsThe study revealed significant metabolic alterations, especially in TB and co-infected groups. Elevated levels of medium-chain acylcarnitines indicated increased fatty acid oxidation, commonly associated with cachexia in TB. Altered amino acid profiles suggested disruptions in protein and glucose metabolism, indicating a shift towards diabetes-like metabolic states. Notably, TB was identified as a primary driver of these changes, affecting protein turnover, and impacting energy metabolism in co-infected patients.ConclusionThe metabolic profiling of HIV/TB co-infection highlights the profound impact of TB on metabolic pathways, which may exacerbate the clinical complexities of co-infection. Understanding these metabolic disruptions can guide the development of targeted treatments and improve management strategies, ultimately enhancing the clinical outcomes for these patients. Further research is required to validate these findings and explore their implications in larger, diverse populations.
| S-EPMC11297823 | biostudies-literature
Project description:BackgroundThe 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.MethodsIn 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.ResultsHIV/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.ConclusionThis 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.
| S-EPMC10436461 | biostudies-literature
Project description:BackgroundTB and HIV co-epidemic is a major public health problem in many parts of the world, particularly in developing counties. We aimed to summarize the prevalence of TB and HIV co-infection in mainland China, using meta-analysis based on systematic review of published articles.MethodsWe systematically reviewed published studies, from the MEDLINE and Chinese BioMedical Literature Databases, on the prevalence of HIV infection among TB patients and on the prevalence of TB among HIV/AIDS population until 15 April 2010, and quantitatively summarized the estimates using meta-analysis.ResultsIn total, 29 studies were included in this review, with consistently homogeneous results. TB patients, for whom the summary prevalence of HIV infection was 0.9% (0.6%-1.4%) in mainland China, were found to be a potential target population for HIV screening. The prevalence of TB among HIV/AIDS population was 7.2% (4.2%-12.3%), but this was much higher when the analyses were restricted to AIDS patients (22.8%). Significantly higher prevalence was observed for males and hospital-based studies.ConclusionsOur analyses indicated that the prevalence of HIV/TB co-infection in China deserves special attention, screening of TB among HIV/AIDS populations should be attached more importance, which would be much more helpful for treatment of both diseases.
| S-EPMC2873981 | biostudies-literature
Project description:Tuberculosis (TB) and Human Immunodeficiency Virus (HIV) infections have been identified to form a deadly synergy that is posing serious threats to human health and economic development particularly in Sub-Saharan Africa (SSA). Six years into the end TB strategy, it is imperative to assess HIV detection rate among TB patients in order to determine the prevalence as well as establish the temporal trend of the co-morbidity in the Eastern region of Ghana where the magnitude of HIV and TB/HIV co-morbidity have consistently been noted to be high. The study reviewed records of 840 TB patients retrospectively from January 1, 2009 to December 31, 2018 in Suhum Municipal. Socio-demographic characteristics and clinical data of study participants were extracted from the Municipal TB registers using an excel spread sheet. Data were exported into STATA version 16.0 for analysis with statistical significance set at p-value ≤0.05. Of the 840 TB patients, 793 (94.4%) were screened for HIV, with 18.6% (95% CI: 0.16-0.21) yielding positive results. A sharp increase in the trend of the co-infection was observed from 6 (14.6%) in 2009 to 21 (36.8%) in 2010. The highest (40.4%) co-infection prevalence was recorded in 2011. The study recorded an overall decreasing trend of the co-infection. Case detection rate for HIV among persons living with TB was high. TB/HIV co-infection rate in Suhum Municipal is high and occurs more often among females and persons aged 30 years to 49 years. A fairly stable prevalence trend of TB/HIV co-infection rate was also identified. In conclusion, ongoing integrated TB/HIV activities are showing good results and therefore need to be sustained.
| S-EPMC10021621 | biostudies-literature
Project description:BackgroundCurrent diagnostics are inadequate to meet the challenges presented by co-infection with Mycobacterium tuberculosis (Mtb) and HIV, the leading cause of death for HIV-infected individuals. Improved characterization of Mtb/HIV coinfection as a distinct disease state may lead to better identification and treatment of affected individuals.MethodsFour previously-published TB and HIV co-infection related datasets were used to train and validate multinomial machine learning classifiers that simultaneously predict TB and HIV status. Classifier predictive performance was measured using leave-one-out cross validation on the training set and blind predictive performance on multiple test sets using area under the ROC curve (AUC) as the performance metric. Linear modelling of signature gene expression was applied to systematically classify genes as TB-only, HIV-only or combined TB/HIV.ResultsThe optimal signature discovered was a 10-gene random forest multinomial signature that robustly discriminated active tuberculosis (TB) from other non-TB disease states with improved performance compared with previously published signatures (AUC: 0.87), and specifically discriminated active TB/HIV co-infection from all other conditions (AUC: 0.88). Signature genes exhibited a variety of transcriptional patterns including both TB-only and HIV-only response genes and genes with expression patterns driven by interactions between HIV and TB infection states, including the CD8+ T-cell receptor LAG3 and the apoptosis-related gene CERKL.ConclusionsBy explicitly including distinct disease states within the machine learning analysis framework, we developed a compact and highly diagnostic signature that simultaneously discriminates multiple disease states associated with Mtb/HIV co-infection. Examination of the expression patterns of signature genes suggests mechanisms underlying the unique inflammatory conditions associated with active TB in the presence of HIV. In particular, we observed that dysregulation of CD8+ effector T-cell and NK-cell associated genes may be an important feature of Mtb/HIV co-infection.
| S-EPMC6629068 | biostudies-literature
Project description:The main physiological challenge in high altitude environment is hypoxia which affects the aerobic metabolism reducing the energy supply. These changes may further progress toward extreme environment-related diseases. These are further reflected in changes in small molecular weight metabolites and metabolic pathways. In the present study, metabolic changes due to chronic environmental hypoxia were assessed using 1H NMR metabolomics by analysing the urinary metabolic profile of 70 people at sea level and 40 people at Siachen camp (3700 m) for 1 year. Multivariate statistical analysis was carried out, and PLSDA detected 15 metabolites based on VIP score > 1. ROC analysis detected cis-aconitate, Nicotinamide Mononucleotide, Tyrosine, Choline and Creatinine metabolites with a high range of sensitivity and specificity. Pathway analysis revealed 16 pathways impact > 0.05, and phenylalanine tyrosine and tryptophan biosynthesis was the most prominent altered pathway indicating metabolic remodelling to meet the energy requirements. TCA cycle, Glycine serine and Threonine metabolism, Glutathione metabolism and Cysteine alterations were other metabolic pathways affected during long-term high-altitude hypoxia exposure. Present findings will help unlock a new dimension for the potential application of NMR metabolomics to address extreme environment-related health problems, early detection and developing strategies to combat high altitude hypoxia.
| S-EPMC9156790 | biostudies-literature
Project description:BackgroundIn Cape Town, the roll-out of antiretroviral therapy (ART) has increased over the last decade with an estimated coverage of 63% of HIV- positive patients in 2013. The influence of ART on the characteristics of the population of HIV-positive patients presenting to the primary care TB programme is unknown. In this study, we examined trends in CD4 count distribution, ART usage and treatment outcomes among HIV-positive TB patients in Cape Town from 2009 to 2013.MethodsData from the electronic TB register on all newly registered drug-sensitive TB patients ≥18 years were analyzed retrospectively. Descriptive statistics were used to compare baseline characteristics, the CD4 count distribution and TB treatment outcomes both by year of treatment and ART status at the start of TB treatment. Survival analyses were used to assess the change in mortality risk during TB treatment over time, stratified by ART status at start of TB treatment.Results118,989 patients were treated over 5 years. HIV prevalence among TB patients decreased from 50.9% in 2009 to 49.0% in 2013. The absolute number of HIV-positive TB cases declined by 13.2% between 2010 and 2013. More patients entered the TB programme on ART in 2013 compared to 2009 (30.0% vs 9.9%). Among these, the CD4 count distribution showed a year by year shift to higher CD4 counts. In 2013, over 75% of ART-naïve TB patients still had a CD4 count < 350 cells/mm3. ART initiation among ART-naive patients increased from 37.0 to 77.7% and TB case fatality declined from 7.4 to 5.2% (p < 0.001). In multivariate analysis a decrease in TB mortality was most strongly associated with CD4 count (Adjusted HR 0.82 per increase of 50 cells/mm3, 95% CI: 0.81-0.83, p < 001) and the initiation of ART during TB treatment (Adjusted HR 0.39, 95% CI: 0.35-0.42, p < 0.001).ConclusionComprehensive changes in the ART and TB treatment programmes resulted in incremental increases in ART coverage for HIV-positive TB patients and a subsequent decrease in TB case fatality due to increased ART uptake in HIV-positive ART-naïve patients. However TB still remained a major presenting opportunistic infection with the majority of cases occurring at low CD4 counts.
| S-EPMC6069570 | biostudies-literature