Microbial Translocation Does Not Drive Immune Activation in Ugandan Children Infected With HIV.
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
01 01 2019
01 01 2019
Historique:
received:
04
05
2018
accepted:
10
08
2018
pubmed:
15
8
2018
medline:
15
11
2019
entrez:
15
8
2018
Statut:
ppublish
Résumé
Immune 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. Nineteen 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. Of 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). Immune 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. ISRCTN69078957.
Identifiants
pubmed: 30107546
pii: 5070381
doi: 10.1093/infdis/jiy495
pmc: PMC6284549
doi:
Substances chimiques
Biomarkers
0
DNA, Bacterial
0
DNA, Ribosomal
0
Banques de données
ISRCTN
['ISRCTN69078957']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
89-100Subventions
Organisme : Medical Research Council
ID : MC_UU_12023/17
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K023535/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U122886353
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12023/26
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 108065/Z/15/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12023/26
Pays : United Kingdom
Investigateurs
Chifumbe Chintu
(C)
Veronica Mulenga
(V)
Desiree Kabamba
(D)
Dorothy Kavindele
(D)
Chishala Chabala
(C)
Musaku Mwenechanya
(M)
Monica Kapasa
(M)
Caroline C Zulu
(CC)
Mox Kalumbi
(M)
Elias Chambula
(E)
Joyce Lungu
(J)
Marjory N Liusha
(MN)
Dorothy Zangata
(D)
Dorica Masuka
(D)
Elias Chambula
(E)
Shadreck Chanshi
(S)
Terence Chipoya
(T)
Semy Zulu
(S)
Daniel Chola
(D)
Betty Chanda
(B)
Steven Malama
(S)
Chama Chama
(C)
Sylvia Mulambo
(S)
Mpala Mwanza
(M)
R Alice Asiimwe
(RA)
J Vicent Tukei
(JV)
Violet Korutaro
(V)
Justine Komunyena
(J)
Isaac Sebuliba
(I)
Muzamil Kisekka
(M)
Carolyn Nansubuga
(C)
N Justine Mpanga
(NJ)
Moses Matovu
(M)
Charles Okello
(C)
Sharon Kesande
(S)
Gladys Namutebi
(G)
E Glorius Tumuheirirwe
(EG)
Immaculate Nagawa
(I)
Sarah Nakimera
(S)
Geoffrey Onen
(G)
Fatuma Kabasita
(F)
Fred Sunday
(F)
Dick Isabirye
(D)
Cissy Kityo
(C)
Victor Musiime
(V)
Grace Mirembe
(G)
Elizabeth Kaudha
(E)
Amos Drasiku
(A)
Bernard Bainomuhwezi
(B)
Priscilla Wavamunno
(P)
Florence Odongo
(F)
Constance Lukowe
(C)
Winnie Namala
(W)
Daniel Sseremba
(D)
Alison Balaba
(A)
Alice Kwaga
(A)
Joshua Kayiwa
(J)
Matthew Odera
(M)
Paul Oronon
(P)
Edith Bagurukira
(E)
Phyllis Mwesigwa
(P)
Philip Apugulu
(P)
Lincoln Mugarura
(L)
Eram David Williams
(E)
Denis Odoch
(D)
Immaculate Nankya
(I)
Emmanuel Ndashimyeeva
(E)
Eva Nabulime
(E)
James Abach
(J)
Willy Agings Odong
(W)
Beatrice Arach
(B)
Irene Claren Aciro
(I)
Joseph Omongin
(J)
Geoffrey Amone
(G)
Peter Okello
(P)
Philliam Aleti
(P)
Edward Otim
(E)
Patrick Kidega
(P)
Emmanuel Achol
(E)
Innocent Mwape
(I)
Joshua Zulu
(J)
Gabriel Chipili
(G)
Linda Chibesa
(L)
Diana M Gibb
(DM)
A Sarah Walker
(AS)
Margaret J Thomason
(MJ)
Adrian Cook
(A)
Ellen Owen-Powell
(E)
Alex Ferrier
(A)
David Baptiste
(D)
Charlotte Male
(C)
Brendan Murphy
(B)
Moira Spyer
(M)
Julia Kenny
(J)
Nigel Klein
(N)
David Burger
(D)
Quirine Fillekes
(Q)
Angela Colbers
(A)
Helen McIlleron
(H)
Elwyn Chomba
(E)
Jose Ramos
(J)
Zainab Akol
(Z)
Peter Elyanu
(P)
Harriet Nakimuli
(H)
Julia Kenny
(J)
Diana M Gibb
(DM)
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