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Immune activation is associated with increased gut microbial translocation in treatment-naive, HIV-infected children in a resource-limited setting.

ABSTRACT: BACKGROUND:Gut damage resulting in microbial translocation (MT) is considered a major cause of immune activation (IA) in HIV infection, but data in children are limited, particularly in the absence of antiretroviral therapy. METHODS:Sixty perinatally HIV-infected, antiretroviral therapy-naive children, aged 2-12 years, were evaluated for plasma levels of lipopolysaccharide, DNA sequences encoding bacterial 16 second ribosomal DNA (16S rDNA) and soluble CD14 concurrently with markers of CD4 and CD8 T-cell IA and immune exhaustion (IE), CD4 counts, and plasma viral load. At study entry, participants were classified into immune categories (ICs): IC1 (CD4% > 25), IC2 (CD4% 15-25), and IC3 (CD4% < 15). Age-matched HIV-uninfected children served as controls. Data were evaluated at study entry and at 12 months. RESULTS:Levels of MT, IA, and IE were increased in patients as compared with controls, were highest in patients in IC3 group, and did not change over 12 months. MT products lipopolysaccharide and 16S rDNA correlated with each other and each correlated with plasma viral load, soluble CD14, and T-cell IA and IE. There was a correlation of IA with IE. CD4 counts and percentage were inversely correlated with MT products and underlying CD4 activation. CONCLUSIONS:In a natural history cohort of HIV-infected children not on therapy, MT was more pronounced in the most severely immunocompromised patients and was associated with IA. Strategies to reduce MT may help to reduce IA and prevent CD4 depletion.

SUBMITTER: Pilakka-Kanthikeel S

PROVIDER: S-EPMC4386670 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Immune activation is associated with increased gut microbial translocation in treatment-naive, HIV-infected children in a resource-limited setting.

Pilakka-Kanthikeel Sudheesh S Kris Arheart A Selvaraj Anbalagan A Swaminathan Soumya S Pahwa Savita S

Journal of acquired immune deficiency syndromes (1999) 20140501 1

<h4>Background</h4>Gut damage resulting in microbial translocation (MT) is considered a major cause of immune activation (IA) in HIV infection, but data in children are limited, particularly in the absence of antiretroviral therapy.<h4>Methods</h4>Sixty perinatally HIV-infected, antiretroviral therapy-naive children, aged 2-12 years, were evaluated for plasma levels of lipopolysaccharide, DNA sequences encoding bacterial 16 second ribosomal DNA (16S rDNA) and soluble CD14 concurrently with marke ...[more]

PMID: 24378729

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Project description:ObjectiveImmune activation is associated with morbidity and mortality during human immunodeficiency virus (HIV) infection, despite receipt of antiretroviral therapy (ART). We investigated whether microbial translocation drives immune activation in HIV-infected Ugandan children.MethodsNineteen markers of immune activation and inflammation were measured over 96 weeks in HIV-infected Ugandan children in the CHAPAS-3 Trial and HIV-uninfected age-matched controls. Microbial translocation was assessed using molecular techniques, including next-generation sequencing.ResultsOf 249 children included, 142 were infected with HIV; of these, 120 were ART naive, with a median age of 2.8 years (interquartile range [IQR], 1.7-4.0 years) and a median baseline CD4+ T-cell percentage of 20% (IQR, 14%-24%), and 22 were ART experienced, with a median age of 6.5 years (IQR, 5.9-9.2 years) and a median baseline CD4+ T-cell percentage of 35% (IQR, 31%-39%). The control group comprised 107 children without HIV infection. The median increase in the CD4+ T-cell percentage was 17 percentage points (IQR, 12-22 percentage points) at week 96 among ART-naive children, and the viral load was <100 copies/mL in 76% of ART-naive children and 91% of ART-experienced children. Immune activation decreased with ART use. Children could be divided on the basis of immune activation markers into the following 3 clusters: in cluster 1, the majority of children were HIV uninfected; cluster 2 comprised a mix of HIV-uninfected children and HIV-infected ART-naive or ART-experienced children; and in cluster 3, the majority were ART naive. Immune activation was low in cluster 1, decreased in cluster 3, and persisted in cluster 2. Blood microbial DNA levels were negative or very low across groups, with no difference between clusters except for Enterobacteriaceae organisms (the level was higher in cluster 1; P < .0001).ConclusionImmune activation decreased with ART use, with marker clustering indicating different activation patterns according to HIV and ART status. Levels of bacterial DNA in blood were low regardless of HIV status, ART status, and immune activation status. Microbial translocation did not drive immune activation in this setting.Clinical trials registrationISRCTN69078957.

Project description:BackgroundCryptococcosis is an opportunistic fungal infection that primarily affects people with advanced HIV/AIDS and is an important cause of morbidity and mortality around the globe. By far the most common presentation of the disease is cryptococcal meningitis (CM), which leads to an estimated 15-20% of all HIV related deaths worldwide, 75% of which are in sub-Saharan Africa. However, to the best of our knowledge there is quite limited reviewed data on the epidemiology of cryptococcal antigenemia in a large HIV-infected population in resource limited settings.MethodsArticles published in English irrespective of the time of publication were systematically searched using comprehensive search strings from PubMed/Medline and SCOPUS. In addition, Google Scholar and Google databases were searched manually for grey literature. Two reviewers independently assessed study eligibility, extracted data, and assessed risk of bias. The pooled prevalence of cryptococcal antigenemia was determined with 95% confidence interval (CI).ResultsAmong 2941 potential citations, we have included 22 studies with a total of 8338 HIV positive individuals. The studies were reported in ten different countries during the year (2007-2018). Most of the articles reported the mean CD4 count of the participants below 100 cells/?l. The pooled prevalence of cryptococcal antigenemia at different CD4 count and ART status was at 8% (95%CI: 6-10%) (ranged between 1.7 and 33%). Body mass index (BMI) <?18.5?kg/m2, CD4 count <?100 cells, patients presenting with headache and male gender were reported by two or more articles as an important predictors of cryptococcal antigenemia.ConclusionsImplementing a targeted screening of HIV patients with low BMI, CD4 count <?100 cells, having headache and males; and treatment for asymptomatic cryptococcal disease should be considered. Additional data is needed to better define the epidemiology of cryptococcal antigenemia and its predictors in resource limited settings in order to optimize the prevention, diagnosis, and treatment strategies.

Dataset Information

Immune activation is associated with increased gut microbial translocation in treatment-naive, HIV-infected children in a resource-limited setting.

Publications

Immune activation is associated with increased gut microbial translocation in treatment-naive, HIV-infected children in a resource-limited setting.

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