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

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.

SUBMITTER: Bi X

PROVIDER: S-EPMC5000643 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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

Bi Xiuqiong X Ishizaki Azumi A Nguyen Lam Van LV Matsuda Kazunori K Pham Hung Viet HV Phan Chung Thi Thu CT Ogata Kiyohito K Giang Thuy Thi Thanh TT Phung Thuy Thi Bich TT Nguyen Tuyen Thi TT Tokoro Masaharu M Pham An Nhat AN Khu Dung Thi Khanh DT Ichimura Hiroshi H

International journal of molecular sciences 20160802 8

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 ...[more]

PMID: 27490536

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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.

Dataset Information

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

Publications

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

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