Relationship Between Anemia and Systemic Inflammation in People Living With HIV and Tuberculosis: A Sub-Analysis of the CADIRIS Clinical Trial.
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SUBMITTER: Araujo-Pereira M
PROVIDER: S-EPMC9260499 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Tuberculosis (TB) is associated with systemic inflammation and anemia, which are aggravated in persons living with HIV (PLWH). Here, we characterized the dynamics of hemoglobin levels in PLWH coinfected with TB undergoing antitubercular therapy (ATT). We also examined the relationships between anemia and systemic inflammatory disturbance as well as the association between persistent anemia and unfavorable clinical outcomes. Data on several blood biochemical parameters and on blood cell counts were retrospectively analyzed in a cohort of 256 TB/HIV patients from Brazil during 180 days of ATT. Multidimensional statistical analyses were employed to profile systemic inflammation of patients stratified by anemia status (hemoglobin levels <12 g/dL for female and <13.5 g/dL for male individuals) prior to treatment and to perform prediction of unfavorable outcomes, such as treatment failure, loss to follow up and death. We found that 101 (63.63%) of patients with anemia at pre-ATT persisted with such condition until day 180. Such individuals exhibited heightened degree of inflammatory perturbation (DIP), which in turn was inversely correlated with hemoglobin levels. Recovery from anemia was associated with increased pre-ATT albumin levels whereas persistent anemia was related to higher total protein levels in serum. Multivariable regression analysis revealed that lower baseline hemoglobin levels was the major determinant of the unfavorable outcomes. Our findings demonstrate that persistent anemia in PLWH during the course of ATT is closely related with chronic inflammatory perturbation. Early intervention to promote recovery from anemia may improve ATT outcomes.
| S-EPMC7541849 | biostudies-literature
Project description:BackgroundTuberculosis (TB) is an infectious morbidity that commonly occurs in people living with HIV (PWH) and increases the progression of HIV disease, as well as the risk of death. Simple markers of progression are much needed to identify those at highest risk for poor outcome. This study aimed to assess how baseline severity of anaemia and associated inflammatory profiles impact death and the incidence of TB in a cohort of PWH who received TB preventive therapy (TPT).MethodsThis study is a secondary posthoc analysis of the AIDS Clinical Trials Group A5274 REMEMBER clinical trial (NCT0138008), an open-label randomised clinical trial of antiretroviral-naïve PWH with CD4 <50 cells/μL, performed from October 31, 2011 to June 9, 2014, from 18 outpatient research clinics in 10 low- and middle-income countries (Malawi, South Africa, Haiti, Kenya, Zambia, India, Brazil, Zimbabwe, Peru, and Uganda) who initiated antiretroviral therapy and either isoniazid TPT or 4-drug empiric TB therapy. Plasma concentrations of several soluble inflammatory biomarkers were measured prior to the commencement of antiretroviral and anti-TB therapies, and participants were followed up for at least 48 weeks. Incident TB or death during this period were primary outcomes. We performed multidimensional analyses, logistic regression analyses, survival curves, and Bayesian network analyses to delineate associations between anaemia, laboratory parameters, and clinical outcomes.FindingsOf all 269 participants, 76.2% (n = 205) were anaemic, and 31.2% (n = 84) had severe anaemia. PWH with moderate/severe anaemia exhibited a pronounced systemic pro-inflammatory profile compared to those with mild or without anaemia, hallmarked by a substantial increase in IL-6 plasma concentrations. Moderate/severe anaemia was also associated with incident TB incidence (aOR: 3.59, 95% CI: 1.32-9.76, p = 0.012) and death (aOR: 3.63, 95% CI: 1.07-12.33, p = 0.039).InterpretationOur findings suggest that PWH with moderate/severe anaemia display a distinct pro-inflammatory profile. The presence of moderate/severe anaemia pre-ART was independently associated with the development of TB and death. PWH with anaemia should be monitored closely to minimise the occurrence of unfavourable outcomes.FundingNational Institutes of Health.
| S-EPMC10242630 | biostudies-literature
Project description:Many randomized and cohort studies have reported a survival benefit with cotrimoxazole prophylaxis without detecting a difference in tuberculosis (TB) incidence by cotrimoxazole status. However, several in vitro studies have reported that cotrimoxazole possesses anti-TB activity. We sought to compare TB incidence and TB diagnostic yield by cotrimoxazole use among participants in a well characterized cohort of HIV-infected adults living in a high TB prevalence region.We analyzed prospective data from a long-term longitudinal cohort of adults receiving HIV care and TB investigations in Soweto, South Africa. Using longitudinal analysis, we compared total and laboratory confirmed TB incidence by cotrimoxazole status as well as all-cause mortality. In addition, we compared TB culture results by cotrimoxazole status.In a multivariable analysis, adjusted for sex, body mass index, WHO clinical stage, time-updated CD4 count, and antiretroviral therapy status, we observed an association between cotrimoxazole and an increase in TB incidence (hazard ratio 1.7, 95% CI: 1.2, 2.2). However, when restricted to laboratory-confirmed TB, there was no association between cotrimoxazole and TB incidence (hazard ratio: 0.97, 95% CI: 0.39, 2.4). In TB cases, we found no difference in the proportion of positive sputum cultures or days to culture positivity by cotrimoxazole status. Cotrimoxazole was associated with a reduction in mortality.In this cohort with a mortality benefit from cotrimoxazole, we found an increased risk of all TB among individuals using cotrimoxazole, likely a result of residual confounding, but no association between use of cotrimoxazole and laboratory-confirmed TB. Cotrimoxazole did not compromise TB diagnosis.
| S-EPMC3885446 | biostudies-other
Project description:In this study we performed data-independet mass-spectrometry analysis of blood plasma collected from a cohort consisting of people living with HIV-1, people living with HIV-2, and HIV seronegative individuals. The data was used to infer signs of damage to a wide array of tissues and cell types.
2024-02-16 | PXD045155 | Pride
Project description:BACKGROUND:Although both chronic lung disease and HIV are inflammatory diseases common in sub-Saharan Africa, the relationship between systemic inflammation and lung function among people living with HIV (PLWH) in sub-Saharan Africa is not well described. METHODS:We measured lung function (using spirometry) and serum high sensitivity C-reactive protein, interleukin 6 (IL-6), soluble CD14 (sCD14), and soluble CD163 (sCD163) in 125 PLWH on stable antiretroviral therapy (ART) and 109 age- and sex-similar HIV-uninfected control subjects in rural Uganda. We modeled the relationship between lung function and systemic inflammation using linear regression, stratified by HIV serostatus, controlled for age, sex, height, tobacco, and biomass exposure. RESULTS:Half of subjects [46% (107/234)] were women, and the median age was 52 years (interquartile range: 48-55). Most PLWH [92% (115/125)] were virologically suppressed on first-line ART. Median CD4 count was 472 cells/mm. In multivariable linear regression models stratified by HIV serostatus, an interquartile range increase in IL-6 and sCD163 were each inversely associated with lung function (mL, 95% confidence interval) among PLWH [IL-6: forced expiratory volume in 1 second (FEV1) -18.1 (-29.1 to -7.1), forced vital capacity (FVC) -17.1 (-28.2 to -5.9); sCD163: FVC -14.3 (-26.9 to -1.7)]. High sensitivity C-reactive protein (>3 vs. <1 mg/L) was inversely associated with lung function among both PLWH and HIV-uninfected control subjects [PLWH: FEV1 -39.3 (-61.7 to -16.9), FVC -44.0 (-48.4 to -6.4); HIV-uninfected: FEV1 -37.9 (-63.2 to -12.6), FVC -58.0 (-88.4 to -27.5)]. sCD14 was not associated with lung function, and all interaction terms were insignificant. CONCLUSIONS:Macrophage activation and systemic inflammation are associated with lower lung function among PLWH on stable ART in rural Uganda. Future work should focus on underlying mechanisms and public health implications.
| S-EPMC6037568 | biostudies-literature
Project description:Purpose of reviewPeople living with HIV (PLWH) are commonly coinfected with Mycobacterium tuberculosis, particularly in high-transmission resource-limited regions. Despite expanded access to antiretroviral therapy and tuberculosis (TB) treatment, TB remains the leading cause of death among PLWH. This review discusses recent advances in the management of TB in PLWH and examines emerging therapeutic approaches to improve outcomes of HIV-associated TB.Recent findingsThree recent key developments have transformed the management of HIV-associated TB. First, the scaling-up of rapid point-of-care urine-based tests for screening and diagnosis of TB in PLWH has facilitated early case detection and treatment. Second, increasing the availability of potent new and repurposed drugs to treat drug-resistant TB has generated optimism about the treatment and outcome of multidrug-resistant and extensively drug-resistant TB. Third, expanded access to the integrase inhibitor dolutegravir to treat HIV in resource-limited regions has simplified the management of TB/HIV coinfected patients and minimized serious adverse events.SummaryWhile it is unequivocal that substantial progress has been made in early detection and treatment of HIV-associated TB, significant therapeutic challenges persist. To optimize the management and outcomes of TB in HIV, therapeutic approaches that target the pathogen as well as enhance the host response should be explored.
| S-EPMC9608335 | biostudies-literature
Project description:In people living with HIV (PLWHIV), coinfection with cytomegalovirus (CMV) has been associated with inflammation, immunological ageing, and increased risk of severe non-AIDS related comorbidity. The effect of CMV-specific immune responses on systemic inflammation, immune activation and T-cell senescence was evaluated in 53 PLWHIV treated with combination antiretroviral therapy (cART). Activated-, terminally differentiated-, naïve-, and senescent T-cells were assessed by flow cytometry, and plasma levels of CMV IgG, interleukin-6, tumor necrosis factor-α, high-sensitivity C-reactive protein and soluble-CD14 were measured. In PLWHIV, expression of interleukin-2, tumor necrosis factor-α and interferon-γ was measured by intracellular-cytokine-staining after stimulation of T-cells with CMV-pp65, CMV-IE1, and CMV-gB. Increased CMV-specific T-cell responses were associated with a higher ratio of terminally differentiated/naïve CD8+ T-cells and with increased proportions of senescent CD8+ T-cells, but not with systemic inflammation or sCD14. Increased CMV-specific CD4+ T-cell responses were associated with increased proportions of activated CD8+ T-cells. In PLWHIV with expansion of CMV-specific T-cells or increased T-cell senescence, CMV-specific polyfunctionality was maintained. That the magnitude of the CMV-specific T-cell response was associated with a senescent immune phenotype, suggests that a dysregulated immune response against CMV may contribute to the immunological ageing often described in PLWHIV despite stable cART.
| S-EPMC5830877 | biostudies-literature
Project description:INTRODUCTION:Tuberculosis (TB) is a leading cause of mortality among people living with HIV (PLHIV). An invigorated global END TB Strategy seeks to increase efforts in scaling up TB preventive therapy (TPT) as a central intervention for HIV programmes in an effort to contribute to a 90% reduction in TB incidence and 95% reduction in mortality by 2035. TPT in PLHIV should be part of a comprehensive approach to reduce TB transmission, illness and death that also includes TB active case-finding and prompt, effective and timely initiation of anti-TB therapy among PLHIV. However, the use and implementation of preventive strategies has remained deplorably inadequate and today TB prevention among PLHIV has become an urgent priority globally. DISCUSSION:We present a summary of the current and novel TPT regimens, including current evidence of use with antiretroviral regimens (ART). We review challenges and opportunities to scale-up TB prevention within HIV programmes, including the use of differentiated care approaches and demand creation for effective TB/HIV services delivery. TB preventive vaccines and diagnostics, including optimal algorithms, while important topics, are outside of the focus of this commentary. CONCLUSIONS:A number of new tools and strategies to make TPT a standard of care in HIV programmes have become available. The new TPT regimens are safe and effective and can be used with current ART, with attention being paid to potential drug-drug interactions between rifamycins and some classes of antiretrovirals. More research and development is needed to optimize TPT for small children, pregnant women and drug-resistant TB (DR-TB). Effective programmatic scale-up can be supported through context-adapted demand creation strategies and the inclusion of TPT in client-centred services, such as differentiated service delivery (DSD) models. Robust collaboration between the HIV and TB programmes represents a unique opportunity to ensure that TB, a preventable and curable condition, is no longer the number one cause of death in PLHIV.
| S-EPMC6947976 | biostudies-literature
Project description:Hepatotoxicity is frequently reported as an adverse reaction during the treatment of tuberculosis. The aim of this study was to determine the incidence of hepatotoxicity and to identify predictive factors for developing hepatotoxicity after people living with HIV/AIDS (PLWHA) start treatment for tuberculosis. This was a prospective cohort study with PLWHA who were monitored during the first 60 days of tuberculosis treatment in Pernambuco, Brazil. Hepatotoxicity was considered increased levels of aminotransferase, namely those that rose to three times higher than the level before initiating tuberculosis treatment, these levels being associated with symptoms of hepatitis. We conducted a multivariate logistic regression analysis and the magnitude of the associations was expressed by the odds ratio with a confidence interval of 95%. Hepatotoxicity was observed in 53 (30.6%) of the 173 patients who started tuberculosis treatment. The final multivariate logistic regression model demonstrated that the use of fluconazole, malnutrition and the subject being classified as a phenotypically slow acetylator increased the risk of hepatotoxicity significantly. The incidence of hepatotoxicity during treatment for tuberculosis in PLWHA was high. Those classified as phenotypically slow acetylators and as malnourished should be targeted for specific care to reduce the risk of hepatotoxicity during treatment for tuberculosis. The use of fluconazole should be avoided during tuberculosis treatment in PLWHA.
| S-EPMC4917242 | biostudies-literature
Project description:An unprecedented number of new tuberculosis (TB) medications are currently in development, and there will be great pressure to deploy these new drugs among all populations after their efficacy is demonstrated. People living with HIV experience a large burden of TB and have a particularly pressing need for TB treatments that are shorter and less toxic. In addition, all people living with HIV now require antiretroviral therapy during TB treatment. A roadmap of the research, programmatic, and regulatory considerations includes the following: (1) inclusion of people living with HIV early in clinical trials for treatment and prevention using new TB medications, (2) prioritization of key studies of HIV-TB drug interactions and interactions between new TB agents, and (3) optimization of clinical trial infrastructure, laboratory capacity, and drug susceptibility testing.
| S-EPMC3361323 | biostudies-literature