Uncovering metabolic shifts: An ¹H-NMR study on the dual impact of HIV/TB coinfection and ART
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ABSTRACT:
ORGANISM(S): Homo sapiens (human)
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PROVIDER: S-BSST1874 | biostudies-other |
REPOSITORIES: biostudies-other
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Project description: Not available
| S-BSST1726 | biostudies-other
Project description:Tuberculosis (TB) is a major cause of morbidity and mortality in children, and early diagnosis and treatment are crucial to reduce long-term morbidity and mortality. In this study, we explore whether urine nuclear magnetic resonance (NMR)-based metabolomics could be used to identify differences in the metabolic response of children with different diagnostic certainty of TB. We included 62 children with signs and symptoms of TB and 55 apparently healthy children. Six of the children with presumptive TB had bacteriologically confirmed TB, 52 children with unconfirmed TB, and 4 children with unlikely TB. Urine metabolic fingerprints were identified using high- and low-field proton NMR platforms and assessed with pattern recognition techniques such as principal components analysis and partial least squares discriminant analysis. We observed differences in the metabolic fingerprint of children with bacteriologically confirmed and unconfirmed TB compared to children with unlikely TB (p = 0.041 and p = 0.013, respectively). Moreover, children with unconfirmed TB with X-rays compatible with TB showed differences in the metabolic fingerprint compared to children with non-pathological X-rays (p = 0.009). Differences in the metabolic fingerprint in children with different diagnostic certainty of TB could contribute to a more accurate characterisation of TB in the paediatric population. The use of metabolomics could be useful to improve the prediction of TB progression and diagnosis in children.
| S-EPMC8184981 | biostudies-literature
Project description:HIV and M. tuberculosis are two intersecting epidemics making the search for new dual action drugs against both pathogens extremely important. Here, we report on the synthesis and suppressive activities of five dual-targeted HIV/TB compounds. These compounds are heterodimers of AZT, as anti-HIV molecules, and 5-substituted uracil derivatives, as anti-TB molecules. We found that these compounds inhibit the growth of M. tuberculosis and suppress the replication of HIV in human cell cultures and human lymphoid tissues ex vivo. We identified one particular heterodimer that inhibited both HIV and the drug-resistant TB strain MS-115 most potently. This compound demonstrated low toxicity and had no cytostatic effect on cells in culture, constituting an ideal candidate for future development and further in vivo testing.
| S-EPMC5576140 | biostudies-literature
Project description:OBJECTIVE:To identify determinants of tuberculosis (TB) case fatality including the impact of antiretroviral therapy (ART) at different CD4 thresholds for HIV-positive adult and adolescent TB patients. METHODS:Through a retrospective analysis of the electronic TB database, we identified the HIV status of newly registered patients aged ?15 years. Multivariable Cox proportional hazard models were used to determine the risk factors for TB case fatality in these patients. RESULTS:In 2009, 2010, and 2011, 25,841, 26,104, and 25,554 newly registered adult TB patients were treated in primary health care clinics in Cape Town, of whom 49.7%, 50.4%, and 50.9% were HIV positive. ART uptake increased over 3 years from 43% to 64.9%, and case fatality of the HIV-positive patients decreased from 7.0% to 5.8% (P < 0.001). Female gender, increasing age, retreatment TB, low CD4 counts, and extrapulmonary TB were associated with increased case fatality, whereas patients on ART had a substantial decrease in case fatality. The difference in case fatality between patients on ART and not on ART was most pronounced at low CD4 counts with the positive influence of ART noted up to a CD4 count threshold of 350 cells per cubic millimeter (P < 0.001). Despite improvements in ART uptake, in 2011, 21% of the patients with CD4 counts <350 cells per cubic millimeter did not start ART during TB treatment. CONCLUSION:This study showed a relatively poor uptake of ART among severely immune-compromised TB patients. Patients with CD4 counts <350 cells per cubic millimeter were shown to clearly benefit from ART during TB treatment, and ART initiation should be prioritized for this category of patients.
| S-EPMC4161924 | biostudies-literature
Project description:IntroductionSwaziland's severe HIV epidemic inspired an early national response since the late 1980s, and regular reporting of program outcomes since the onset of a national antiretroviral treatment (ART) program in 2004. We assessed effectiveness outcomes and mortality trends in relation to ART, HIV testing and counseling (HTC), tuberculosis (TB) and prevention of mother to child transmission (PMTCT).MethodsData triangulated include intervention coverage and outcomes according to program registries (2001-2010), hospital admissions and deaths disaggregated by age and sex (2001-2010) and population mortality estimates from the 1997 and 2007 censuses and the 2007 demographic and health survey.ResultsBy 2010, ART reached 70% of the estimated number of people living with HIV/AIDS with CD4<350/mm(3), with progressively improving patient retention and survival. As of 2010, 88% of health facilities providing antenatal care offered comprehensive PMTCT services. The HTC program recorded a halving in the proportion of adults tested who were HIV-infected; similarly HIV infection rates among HIV-exposed babies halved from 2007 to 2010. Case fatality rates among hospital patients diagnosed with HIV/AIDS started to decrease from 2005-6 in adults and especially in children, contrasting with stable case fatality for other causes including TB. All-cause child in-patient case fatality rates started to decrease from 2005-6. TB case notifications as well as rates of HIV/TB co-infection among notified TB patients continued a steady increase through 2010, while coverage of HIV testing and CPT for co-infected patients increased to above 80%.ConclusionAgainst a background of high, but stable HIV prevalence and decreasing HIV incidence, we documented early evidence of a mortality decline associated with the expanded national HIV response since 2004. Attribution of impact to specific interventions (versus natural epidemic dynamics) will require additional data from future household surveys, and improved routine (program, surveillance, and hospital) data at district level.
| S-EPMC3724860 | biostudies-literature
Project description:SettingA high proportion of individuals with multidrug-resistant tuberculosis (MDR-TB) develop permanent hearing loss due to ototoxicity caused by injectable aminoglycosides (AGs). The prevalence of AG-induced hearing loss is greatest in tuberculosis (TB) and human immunodeficiency virus (HIV) endemic countries in sub-Saharan Africa. However, whether HIV coinfection is associated with a higher incidence of AG-induced hearing loss during MDR-TB treatment is controversial.ObjectiveTo evaluate the impact of HIV coinfection on AG-induced hearing loss among individuals with MDR-TB in sub-Saharan Africa.DesignThis was a meta-analysis of articles published in PubMed, Embase, Scopus, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Cochrane Review, and reference lists using search terms 'hearing loss', 'aminoglycoside', and 'sub-Saharan Africa'.ResultsEight studies conducted in South Africa, Botswana and Namibia and published between 2012 and 2016 were included. As the included studies were homogeneous (χ2 = 8.84, df = 7), a fixed-effects model was used. Individuals with MDR-TB and HIV coinfection had a 22% higher risk of developing AG-induced hearing loss than non-HIV-infected individuals (pooled relative risk 1.22, 95%CI 1.10-1.36) during MDR-TB treatment.ConclusionThis finding is critical for TB programs with regard to the expansion of injectable-sparing regimens. Our findings lend credibility to using injectable-sparing regimens and more frequent hearing monitoring, particularly in resource-limited settings for HIV-coinfected individuals.
| S-EPMC6002855 | biostudies-literature
Project description: Not available
| S-BSST1084 | biostudies-other
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:BACKGROUND:Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), affecting approximately one third of the world's population. Development of an adequate immune response will determine disease progression or progress to chronic infection. Risk of developing TB among human immunodeficiency virus (HIV)-coinfected patients (HIV-TB) is 20-30 times higher than those without HIV infection, and a synergistic interplay between these two pathogens accelerates the decline in immunological functions. TB treatment in HIV-TB coinfected persons is challenging and it has a prolonged duration, mainly due to the immune system failure to provide an adequate support for the therapy. Therefore, we aimed to study the role of the hormone 7-oxo-dehydroepiandrosterone (7-OD) as a modulator of anti-tuberculosis immune responses in the context of HIV-TB coinfection. METHODS:A cross-sectional study was conducted among HIV-TB patients and healthy donors (HD). We characterized the ex vivo phenotype of CD4 + T cells and also evaluated in vitro antigen-specific responses by Mtb stimulation of peripheral blood mononuclear cells (PBMCs) in the presence or absence of 7-OD. We assessed lymphoproliferative activity, cytokine production and master transcription factor profiles. RESULTS:Our results show that HIV-TB patients were not able to generate successful anti-tubercular responses in vitro compared to HD, as reduced IFN-γ/IL-10 and IFN-γ/IL-17A ratios were observed. Interestingly, treatment with 7-OD enhanced Th1 responses by increasing Mtb-induced proliferation and the production of IFN-γ and TNF-α over IL-10 levels. Additionally, in vitro Mtb stimulation augmented the frequency of cells with a regulatory phenotype, while 7-OD reduced the proportion of these subsets and induced an increase in CD4 + T-bet+ (Th1) subpopulation, which is associated with clinical data linked to an improved disease outcome. CONCLUSIONS:We conclude that 7-OD modifies the cytokine balance and the phenotype of CD4 + T cells towards a more favorable profile for mycobacteria control. These results provide new data to delineate novel treatment approaches as co-adjuvant for the treatment of TB.
| S-EPMC6943934 | 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