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J Acquir Immune Defic Syndr. 2014 May 1;66(1):16-24. doi: 10.1097/QAI.0000000000000096.

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

Author information

1
*Department of Microbiology and Immunology, Miami Center for AIDS Research, University of Miami Miller School of Medicine, Miami, FL; †Department of Public Health Sciences, Division of Biostatistics, University of Miami Miller School of Medicine, Miami, FL; and ‡Department of Clinical Research, Tuberculosis Research Center, Indian Council of Medical Research, Chennai, India (Sudheesh Pilakka-Kanthikeel is now with the Department of Immunology, Herbert-Wertheim College of Medicine, Florida International University, Miami, FL).

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.

PMID:
24378729
PMCID:
PMC4386670
DOI:
10.1097/QAI.0000000000000096
[Indexed for MEDLINE]
Free PMC Article

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