The metabolic consequences of HIV/TB co-infection
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ABSTRACT:
ORGANISM(S): Homo sapiens (human)
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PROVIDER: S-BSST1084 | biostudies-other |
REPOSITORIES: biostudies-other
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Project description: Not available
| S-BSST1397 | biostudies-other
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:BACKGROUND:Current 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. METHODS:Four 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. RESULTS:The 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. CONCLUSIONS:By 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:In 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.Data 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.118,989 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).Comprehensive 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-other
Project description:Background:Antiretroviral therapy (ART) for persons with HIV infection prevents tuberculosis (TB) disease. Additionally, sequential ART after initiation of TB treatment improves outcomes. We examined ART use, retention in care, and viral suppression (VS) before, during, and 3 years following TB treatment for an inner-city cohort in the United States. Methods:Retrospective cohort study among persons treated for culture-confirmed TB between 2008 and 2015 at an inner-city hospital. Results:Among 274 persons with culture-confirmed TB, 96 (35%) had HIV co-infection, including 23 (24%) new HIV diagnoses and 73 (76%) previous diagnoses. Among those with known HIV prior to TB, the median time of known HIV was 6 years, and only 10 (14%) were on ART at the time of TB diagnosis. The median CD4 at TB diagnosis was 87 cells/uL. Seventy-four (81%) patients received ART during treatment for TB, and 47 (52%) has VS at the end of TB treatment. Only 32% of patients had continuous VS 3 years after completing TB treatment. There were 3 TB recurrences and 3 deaths post-TB treatment; none of these patients had retention or VS after TB treatment. Conclusions:Among persons with active TB co-infected with HIV, we found that the majority had known HIV and were not on ART prior to TB diagnosis, and retention in care and VS post-TB treatment were very low. Strengthening the HIV care continuum is needed to improve HIV outcomes and further reduce rates of active TB/HIV co-infection in our and similar settings.
| S-EPMC5890473 | biostudies-literature
Project description:Systemic immune activation is critical to the pathogenesis of HIV-1 disease, and is accentuated in HIV/TB co-infected patients. The contribution of immune activation at sites of HIV/TB co-infection to viral activity, CD4 T cell count, and productive HIV-1 infection remain unclear. In this study, we measured markers of immune activation both in pleural fluid and plasma, and in T cells in pleural fluid mononuclear cell (PFMC) and peripheral blood mononuclear cell (PBMC) in HIV/TB co-infected subjects. The relationship between soluble and T cell activation markers with viral load in pleural fluid and blood CD4 T cell count were assessed. The T cell phenotype and activation status of HIV-1 p24 + T cells in PFMC and PBMC from HIV/TB patients were determined. We found that T cell and macrophage-specific and non-specific soluble markers of immune activation, sCD27, sCD163, IL1Ra, and sCD14, were higher in pleural fluid as compared to plasma from HIV/TB co-infected subjects, and higher as compared to pleural fluid from TB mono-infected subjects. Intestinal fatty acid-binding protein, a marker of intestinal tract damage, in plasma from HIV/TB co-infected patients was not different than that in HIV+ subjects. Expression of HLADR and CD38 double positive (HLADR/CD38) on CD4 T cells, and CD69+ on CD8 T cells correlated with pleural fluid viral load, and inversely with blood CD4 T cell count. Higher expression of HLADR/CD38 and CCR5 on CD4 T cells, and HLADR/CD38 and CD69 on CD8 T cells in PFMC were limited to effector memory populations. HIV-1 p24+ CD8 negative (includes CD4 + and double negative T cells) effector memory T cells in PFMC had higher expression of HLADR/CD38, Ki67, and CCR5 compared to HIV-1 p24- CD8 negative PFMC. Cumulatively, these data indicate that sites of HIV/TB co-infection are the source of intense immune activation.
| S-EPMC5117743 | biostudies-literature
Project description:Granule-associated killing molecules released from cytotoxic T lymphocytes participate as a crucial step in immunity against tuberculosis (TB), but the role of coordinated production remains controversial. Coordinated release of effector molecules in vitro after stimulating peripheral blood mononuclear cells (PBMCs) of active TB or HIV/TB coinfection patients with PPD, purified protein derivative of tuberculin and avirulent Mtb, H37Ra, an attenuated strain were investigated in association with clinical outcomes. Perforin, granzyme-B, granulysin and IFN-? were measured using ELISA. Before anti-TB treatment, PBMCs of TB stimulated with PPD or H37Ra released higher perforin, granzyme-B, and granulysin levels than in HIV/TB and released significantly higher IFN-? (p = 0.045, p = 0.022). Granulysin positively correlated with perforin in TB (p = 0.042, r = 0.385), HIV/TB coinfection (p = 0.003, r = 0.941) after PPD stimulation, and after H37Ra stimulation in TB (p = 0.005, r = 0.549), but negatively correlated with granzyme B in TB (p = 0.042, r = -0.386), HIV/TB coinfection (p = 0.042, r = 0.754) were noted. After anti-TB treatment, increased levels of perforin, granulysin and IFN-? in TB or HIV/TB upon PPD or H37Ra stimulation, and decreased granzyme-B levels after PPD (p = 0.003) or H37Ra (p = 0.028) stimulation in TB were observed. These results suggest that granulysin may act synergistic with perforin and IFN-? in TB, indicating its crucial function in host immunity to tuberculosis. Future studies with larger numbers of patients ought to be conducted in the future.
| S-EPMC7459825 | biostudies-literature
Project description:The timing of antiretroviral therapy (ART) initiation for HIV and tuberculosis (TB) co-infected patients needs to be considered carefully. CD4 cell count can be used to guide decision making about when to initiate ART. Evidence from recent randomized trials and observational studies generally supports early initiation but does not provide information about effects of initiation time on a continuous scale. In this article, we develop and apply a highly flexible structural proportional hazards model for characterizing the effect of treatment initiation time on a survival distribution. The model can be fitted using a weighted partial likelihood score function. Construction of both the score function and the weights must accommodate censoring of the treatment initiation time, the outcome, or both. The methods are applied to data on 4903 individuals with HIV/TB co-infection, derived from electronic health records in a large HIV care program in Kenya. We use a model formulation that flexibly captures the joint effects of ART initiation time and ART duration using natural cubic splines. The model is used to generate survival curves corresponding to specific treatment initiation times; and to identify optimal times for ART initiation for subgroups defined by CD4 count at time of TB diagnosis. Our findings potentially provide 'higher resolution' information about the relationship between ART timing and mortality, and about the differential effect of ART timing within CD4 subgroups.
| S-EPMC5874166 | biostudies-literature
Project description:TB and HIV co-epidemic is a major public health problem in many parts of the world. But the prevalence of TB/HIV co-infection was diversified among countries. Exploring the reasons of the diversity of TB/HIV co-infection is important for public policy, planning and development of collaborative TB/HIV activities. We aimed to summarize the prevalence of TB and HIV co-infection worldwide, using meta-analysis based on systematic review of published articles.We searched PubMed, Embase, and Web of Science for studies of the prevalence of TB/HIV co-infection. We also searched bibliographic indices, scanned reference lists, and corresponded with authors. We summarized the estimates using meta-analysis and explored potential sources of heterogeneity in the estimates by metaregression analysis.We identified 47 eligible studies with a total population of 272,466. Estimates of TB/HIV co-infection prevalence ranged from 2.93% to 72.34%; the random effects pooled prevalence of TB/HIV co-infection was 23.51% (95% CI 20.91-26.11). We noted substantial heterogeneity (Cochran's ? (2)?=?10945.31, p<0.0001; I (2)?=?99.58%, 95% CI 99.55-99.61). Prevalence of TB/HIV co-infection was 31.25%(95%CI 19.30-43.17) in African countries, 17.21%(95%CI 9.97-24.46) in Asian countries, 20.11%(95%CI 13.82-26.39) in European countries, 25.06%(95%CI 19.28-30.84) in Latin America countries and 14.84%(95%CI 10.44-19.24) in the USA. Prevalence of TB/HIV co-infection was higher in studies in which TB diagnosed by chest radiography and HIV diagnosis based on blood analyses than in those which used other diagnostic methods, and in countries with higher prevalence HIV in the general population than in countries with lower general prevalence.Our analyses suggest that it is necessary to attach importance to HIV/TB co-infection, especially screening of TB/HIV co-infection using methods with high sensitivity, specificity and predictive values in the countries with high HIV/AIDS prevalence in the general population.
| S-EPMC3669088 | biostudies-literature
Project description:INTRODUCTION:Management of concomitant use of ART and TB drugs is difficult because of the many drug-drug interactions (DDIs) between the medications. This systematic review provides an overview of the current state of knowledge about the pharmacokinetics (PK) of ART and TB treatment in children with HIV/TB co-infection, and identifies knowledge gaps. METHODS:We searched Embase and PubMed, and systematically searched abstract books of relevant conferences, following PRISMA guidelines. Studies not reporting PK parameters, investigating medicines that are not available any longer or not including children with HIV/TB co-infection were excluded. All studies were assessed for quality. RESULTS:In total, 47 studies met the inclusion criteria. No dose adjustments are necessary for efavirenz during concomitant first-line TB treatment use, but intersubject PK variability was high, especially in children <3?years of age. Super-boosted lopinavir/ritonavir (ratio 1:1) resulted in adequate lopinavir trough concentrations during rifampicin co-administration. Double-dosed raltegravir can be given with rifampicin in children >4?weeks old as well as twice-daily dolutegravir (instead of once daily) in children older than 6?years. Exposure to some TB drugs (ethambutol and rifampicin) was reduced in the setting of HIV infection, regardless of ART use. Only limited PK data of second-line TB drugs with ART in children who are HIV infected have been published. CONCLUSIONS:Whereas integrase inhibitors seem favourable in older children, there are limited options for ART in young children (<3?years) receiving rifampicin-based TB therapy. The PK of TB drugs in HIV-infected children warrants further research.
| S-EPMC7662174 | biostudies-literature