A 12 week longitudinal study of microbial translocation and systemic inflammation in undernourished HIV-infected Zambians initiating antiretroviral therapyReport as inadecuate




A 12 week longitudinal study of microbial translocation and systemic inflammation in undernourished HIV-infected Zambians initiating antiretroviral therapy - Download this document for free, or read online. Document in PDF available to download.

BMC Infectious Diseases

, 14:521

HIV and co-infections

Abstract

BackgroundUndernourished, HIV-infected adults in sub-Saharan Africa have high levels of systemic inflammation, which is a risk factor for mortality and other adverse health outcomes. We hypothesized that microbial translocation, due to the deleterious effects of HIV and poor nutrition on intestinal defenses and mucosal integrity, contributes to heightened systemic inflammation in this population, and reductions in inflammation on antiretroviral therapy ART accompany reductions in translocation.

MethodsHIV-infected, Zambian adults with a body mass index <18.5 kg-m were recruited for a pilot study to assess the relationships between microbial translocation and systemic inflammation over the first 12 weeks of ART. To assess microbial translocation we measured serum lipopolysaccharide binding protein LBP, endotoxin core IgG and IgM, and soluble CD14, and to assess intestinal permeability we measured the urinary excretion of an oral lactulose dose normalized to urinary creatinine Lac-Cr ratio. Linear mixed models were used to assess within-patient changes in these markers relative to serum C-reactive protein CRP, tumor necrosis factor-α receptor 1 TNF-α R1, and soluble CD163 over 12 weeks, in addition to relationships between variables independent of time point and adjusted for age, sex, and CD4+ count.

ResultsThirty-three participants had data from recruitment and at 12 weeks: 55% were male, median age was 36 years, and median baseline CD4+ count was 224 cells-μl. Over the first 12 weeks of ART, there were significant decreases in serum levels of LBP median change -8.7 μg-ml, p = 0.01, TNF-α receptor 1 -0.31 ng-ml, p < 0.01, and CRP -3.5 mg-l, p = 0.02. The change in soluble CD14 level over 12 weeks was positively associated with the change in CRP p < 0.01 and soluble CD163 p < 0.01. Pooling data at baseline and 12 weeks, serum LBP was positively associated with CRP p = 0.01, while endotoxin core IgM was inversely associated with CRP p = 0.01 and TNF-α receptor 1 p = 0.04. The Lac-Cr ratio was not associated with any serum biomarkers.

ConclusionsIn undernourished HIV-infected adults in Zambia, biomarkers of increased microbial translocation are associated with high levels of systemic inflammation before and after initiation of ART, suggesting that impaired gut immune defenses contribute to innate immune activation in this population.

KeywordsHIV infection Antiretroviral therapy Microbial translocation Nutrition Sub-Saharan Africa Inflammation Electronic supplementary materialThe online version of this article doi:10.1186-1471-2334-14-521 contains supplementary material, which is available to authorized users.

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Author: Ashley Canipe - Takondwa Chidumayo - Meridith Blevins - Michael Bestawros - Jay Bala - Paul Kelly - Suzanne Filteau - Bryan

Source: https://link.springer.com/



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