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Int. J. Mol. Sci. 2016, 17(8), 1245; doi:10.3390/ijms17081245

Impact of HIV Infection and Anti-Retroviral Therapy on the Immune Profile of and Microbial Translocation in HIV-Infected Children in Vietnam

1
Department of Viral Infection and International Health, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8640, Japan
2
National Hospital of Pediatrics, Hanoi 100-000, Vietnam
3
Yakult Central Institute, Tokyo 186-8650, Japan
4
Department of Parasitology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8640, Japan
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Brian Wigdahl
Received: 3 July 2016 / Revised: 26 July 2016 / Accepted: 28 July 2016 / Published: 2 August 2016
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Abstract

CD4+ T-lymphocyte destruction, microbial translocation, and systemic immune activation are the main mechanisms of the pathogenesis of human immunodeficiency virus type 1 (HIV) infection. To investigate the impact of HIV infection and antiretroviral therapy (ART) on the immune profile of and microbial translocation in HIV-infected children, 60 HIV vertically infected children (31 without ART: HIV(+) and 29 with ART: ART(+)) and 20 HIV-uninfected children (HIV(−)) aged 2–12 years were recruited in Vietnam, and their blood samples were immunologically and bacteriologically analyzed. Among the HIV(+) children, the total CD4+-cell and their subset (type 1 helper T-cell (Th1)/Th2/Th17) counts were inversely correlated with age (all p < 0.05), whereas regulatory T-cell (Treg) counts and CD4/CD8 ratios had become lower, and the CD38+HLA (human leukocyte antigen)-DR+CD8+- (activated CD8+) cell percentage and plasma soluble CD14 (sCD14, a monocyte activation marker) levels had become higher than those of HIV(−) children by the age of 2 years; the CD4/CD8 ratio was inversely correlated with the plasma HIV RNA load and CD8+-cell activation status. Among the ART(+) children, the total CD4+-cell and Th2/Th17/Treg-subset counts and the CD4/CD8 ratio gradually increased, with estimated ART periods of normalization being 4.8–8.3 years, whereas Th1 counts and the CD8+-cell activation status normalized within 1 year of ART initiation. sCD14 levels remained high even after ART initiation. The detection frequency of bacterial 16S/23S ribosomal DNA/RNA in blood did not differ between HIV-infected and -uninfected children. Thus, in children, HIV infection caused a rapid decrease in Treg counts and the early activation of CD8+ cells and monocytes, and ART induced rapid Th1 recovery and early CD8+-cell activation normalization but had little effect on monocyte activation. The CD4/CD8 ratio could therefore be an additional marker for ART monitoring. View Full-Text
Keywords: HIV-infected children; intestinal microbial translocation; immune activation; 16S/23S ribosomal DNA HIV-infected children; intestinal microbial translocation; immune activation; 16S/23S ribosomal DNA
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Bi, X.; Ishizaki, A.; Nguyen, L.V.; Matsuda, K.; Pham, H.V.; Phan, C.T.T.; Ogata, K.; Giang, T.T.T.; Phung, T.T.B.; Nguyen, T.T.; Tokoro, M.; Pham, A.N.; Khu, D.T.K.; Ichimura, H. Impact of HIV Infection and Anti-Retroviral Therapy on the Immune Profile of and Microbial Translocation in HIV-Infected Children in Vietnam. Int. J. Mol. Sci. 2016, 17, 1245.

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