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.
Highlights
Mucosa-associated lymphoid tissues, such as the gut-associated lymphoid tissue (GALT), harbor approximately 40%–60% of lymphocytes in the human body
There is an abundance of lymphoid aggregates in the gut submucosa and memory CD4+CCR5+ T cells in gut epithelial cells [11]. Because these cells are highly susceptible to human immunodeficiency virus type 1 (HIV) infection even without activation, they are likely to be the prime site of HIV infection and replication [9,11]
Based on the results of that field study, we conducted this cross-sectional study to clarify the impact of HIV infection and antiretroviral therapy (ART) on the immune profile and microbial translocation status of children aged over 2 years who have an immune status considered to be relatively mature and stable [9,19,20]
Summary
Mucosa-associated lymphoid tissues, such as the gut-associated lymphoid tissue (GALT), harbor approximately 40%–60% of lymphocytes in the human body. In the early stages of HIV infection, the remarkable destruction of CD4+ T (CD4+) cells, the type 17 helper T-cell (Th17) subset, occurs in GALT [1,2,3], resulting in the decline in the immune and mechanical barrier functions of the gut mucosa. There is an abundance of lymphoid aggregates in the gut submucosa and memory CD4+CCR5+ T cells in gut epithelial cells [11] Because these cells are highly susceptible to HIV infection even without activation, they are likely to be the prime site of HIV infection and replication [9,11]. Based on the results of that field study, we conducted this cross-sectional study to clarify the impact of HIV infection and ART on the immune profile and microbial translocation status of children aged over 2 years who have an immune status considered to be relatively mature and stable [9,19,20]
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