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Relationship Between Anemia and Systemic Inflammation in People Living With HIV and Tuberculosis: A Sub-Analysis of the CADIRIS Clinical Trial.

ABSTRACT: People with HIV (PWH) are at increased risk of developing active tuberculosis (TB), and anemia is a common complication in both conditions. Anemia in TB patients has been linked to immune activation, levels of inflammatory biomarkers in blood, and risk for HIV disease progression and death. In this study we show that anemia was associated with a more pronounced inflammatory profile in HIV-TB coinfected persons in a cohort of 159 individuals with advanced HIV disease (CD4 count < 100 cells/µL) recruited as part of a randomized clinical trial (NCT00988780). A panel of plasma biomarkers was assessed on plasma obtained prior to combination antiretroviral therapy (cART) initiation. We performed a series of multidimensional analyses including clinical variables and concentrations of inflammatory biomarkers to profile systemic inflammation of PWH with and without anemia. We observed that TB participants presented with moderately lower levels of hemoglobin than non-TB participants. These participants also presented a higher Degree of Inflammatory Perturbation (DIP) score, related to increased levels of IFN-γ and TNF. The DIP was associated with TB coinfection and anemia before cART initiation. Future mechanistic studies are warranted to assess the determinants of such associations and the implications on treatment outcomes.

SUBMITTER: Araujo-Pereira M

PROVIDER: S-EPMC9260499 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Relationship Between Anemia and Systemic Inflammation in People Living With HIV and Tuberculosis: A Sub-Analysis of the CADIRIS Clinical Trial.

Araújo-Pereira Mariana M Barreto-Duarte Beatriz B Arriaga María B MB Musselwhite Laura W LW Vinhaes Caian L CL Belaunzaran-Zamudio Pablo F PF Rupert Adam A Montaner Luis J LJ Lederman Michael M MM Sereti Irini I Madero Juan G Sierra JGS Andrade Bruno B BB

Frontiers in immunology 20220623

People with HIV (PWH) are at increased risk of developing active tuberculosis (TB), and anemia is a common complication in both conditions. Anemia in TB patients has been linked to immune activation, levels of inflammatory biomarkers in blood, and risk for HIV disease progression and death. In this study we show that anemia was associated with a more pronounced inflammatory profile in HIV-TB coinfected persons in a cohort of 159 individuals with advanced HIV disease (CD4 count < 100 cells/µL) re ...[more]

PMID: 35812431

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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.

Project description:IntroductionTuberculosis (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.DiscussionWe 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.ConclusionsA 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.

Project description:BackgroundAnemia is the most frequent hematologic abnormality among people living with human immunodeficiency virus (HIV) (PLWHIV) and is associated with HIV disease progression and higher risk of mortality of the patients. However, there is a wide variation of the prevalence of anemia among PLWHIV in different clinical settings. We aimed to obtain more precise estimates of prevalence of anemia and severity of anemia among PLWHIV, which may be important for patients, caregivers, researchers and health policy-makers.MethodsWe systematically searched PubMed, EMBASE, Web of Science, and Cochrane Library for original articles reporting the prevalence of anemia defined using age and sex-specific hemoglobin levels according to World Health Organization criteria among PLWHIV from inception to August 31, 2021. We used DerSimonian-Laird random-effects meta-analyses to obtain pooled prevalence and 95% confidence intervals (CIs) of anemia and severity of anemia among PLWHIV. A univariable meta-regression has been conducted to assess the association between anemia prevalence and study characteristics, including study design, median year of sampling, geographical region, World Bank Income level, and proportion of antiretroviral therapy (ART).FindingsWe included 63 observational studies covering 110,113 PLWHIV. The pooled prevalence of anemia was 39.7% (95% CI: 31.4%-48.0%) for children living with HIV aged <15 years, 46.6% (95% CI: 41.9%-51.4%) for adults (men and non-pregnant women) living with HIV aged ≥15 years, and 48.6% (95% CI: 41.6%-55.6%) for pregnant women living with HIV. Among adults living with HIV, the pooled prevalence of severity of anemia was 21.6% (95% CI: 19.9%-23.3%), 22.6% (95% CI: 14.8%-30.4%), and 6.2% (95% CI: 4.4%-8.1%) for mild, moderate and severe anemia, respectively. Compared with East Africa, anemia prevalence among adults living with HIV was higher in Southern Africa (p = 0.033).InterpretationAnemia is prevalent among PLWHIV. Thus, policies, strategies, and programs should be considered to identify the predictors of anemia among PLWHIV to reduce the burden of anemia among patients in the ART era.

Dataset Information

Relationship Between Anemia and Systemic Inflammation in People Living With HIV and Tuberculosis: A Sub-Analysis of the CADIRIS Clinical Trial.

Publications

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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