title: 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.
authors.affiliation: Department of Viral Infection and International Health, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8640, Japan. bixiuqio@staff.kanazawa-u.ac.jp.
authors.forename: Xiuqiong
authors.initials: X
authors.lastname: Bi
authors.affiliation: Department of Viral Infection and International Health, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8640, Japan. azumi0306@aol.com.
authors.forename: Azumi
authors.initials: A
authors.lastname: Ishizaki
authors.affiliation: National Hospital of Pediatrics, Hanoi 100-000, Vietnam. dinhlam73@yahoo.com.
authors.forename: Lam Van
authors.initials: LV
authors.lastname: Nguyen
authors.affiliation: Yakult Central Institute, Tokyo 186-8650, Japan. kazunori.matsuda@yher.be.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Matsuda
authors.affiliation: National Hospital of Pediatrics, Hanoi 100-000, Vietnam. vhnhi44@gmail.com.
authors.forename: Hung Viet
authors.initials: HV
authors.lastname: Pham
authors.affiliation: National Hospital of Pediatrics, Hanoi 100-000, Vietnam. phanthuchung@gmail.com.
authors.forename: Chung Thi Thu
authors.initials: CT
authors.lastname: Phan
authors.affiliation: Yakult Central Institute, Tokyo 186-8650, Japan. ogata@ninesigma.com.
authors.forename: Kiyohito
authors.initials: K
authors.lastname: Ogata
authors.affiliation: National Hospital of Pediatrics, Hanoi 100-000, Vietnam. huygt2006@gmail.com.
authors.forename: Thuy Thi Thanh
authors.initials: TT
authors.lastname: Giang
authors.affiliation: National Hospital of Pediatrics, Hanoi 100-000, Vietnam. phungthuy2707@yahoo.com.
authors.forename: Thuy Thi Bich
authors.initials: TT
authors.lastname: Phung
authors.affiliation: National Hospital of Pediatrics, Hanoi 100-000, Vietnam. ntuyen_nhp@yahoo.com.vn.
authors.forename: Tuyen Thi
authors.initials: TT
authors.lastname: Nguyen
authors.affiliation: Department of Parasitology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8640, Japan. tokoro@med.kanazawa-u.ac.jp.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Tokoro
authors.affiliation: National Hospital of Pediatrics, Hanoi 100-000, Vietnam. nhatan.pham@yahoo.com.
authors.forename: An Nhat
authors.initials: AN
authors.lastname: Pham
authors.affiliation: National Hospital of Pediatrics, Hanoi 100-000, Vietnam. hangdung2001@yahoo.com.
authors.forename: Dung Thi Khanh
authors.initials: DT
authors.lastname: Khu
authors.affiliation: Department of Viral Infection and International Health, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8640, Japan. ichimura@med.kanazawa-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ichimura
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D018988:Bacterial Translocation; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D008297:Male; D012336:RNA, Ribosomal, 16S / Q000097:blood / Q000235:genetics; D012338:RNA, Ribosomal, 23S / Q000097:blood / Q000235:genetics; D014744:Vietnam
chemical_list: D015415:Biomarkers; D012336:RNA, Ribosomal, 16S; D012338:RNA, Ribosomal, 23S
keywords: 16S/23S ribosomal DNA; HIV-infected children; immune activation; intestinal microbial translocation