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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Microbial translocation does not drive immune activation in ugandan children infected with HIV
Journal of Infectious Diseases, Volume 219, No. 1, Year 2019
Notification
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Description
Objective 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. Methods 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. Results 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). Conclusion 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. Clinical Trials Registration ISRCTN69078957. © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC6284549/bin/jiy495_suppl_supplementary_material.docx
Authors & Co-Authors
Fitzgerald, Felicity C.
United Kingdom, London
Ucl Great Ormond Street Institute of Child Health
Lhomme, Edouard
France, Bordeaux
Bordeaux Population Health Research Center Bph
France, Bordeaux
Inria Research Centre
France, Creteil
Vaccine Research Institute Vri
Harris, Kathryn Ann
United Kingdom, Wakefield
Nhs England
Kenny, Julia M.
United Kingdom, London
Ucl Great Ormond Street Institute of Child Health
Doyle, Ronan M.
United Kingdom, Wakefield
Nhs England
Kityo, Cissy Mutuluuza
Uganda, Kampala
Joint Clinical Research Center Uganda
Shaw, Liam P.
United Kingdom, London
Ucl Great Ormond Street Institute of Child Health
Abongomera, George
Uganda, Mbarara
Joint Clinical Research Centre
Musiime, Victor
Uganda, Kampala
Joint Clinical Research Center Uganda
Cook, Adrian D.
United Kingdom, London
Medical Research Council
Brown, Julianne Rose
United Kingdom, Wakefield
Nhs England
Brooks, Anthony
United Kingdom, London
University College London
Owen-Powell, Ellen
United Kingdom, London
Medical Research Council
Gibb, Diana M.
United Kingdom, London
Medical Research Council
Prendergast, Andrew J.
United Kingdom, London
Queen Mary University of London
Zimbabwe, Harare
Zvitambo Institute for Maternal and Child Health Research
Sarah Walker, A.
United Kingdom, London
Medical Research Council
Thíébaut, Rodolphe
France, Bordeaux
Bordeaux Population Health Research Center Bph
France, Bordeaux
Inria Research Centre
France, Creteil
Vaccine Research Institute Vri
Klein, Nigel J.
United Kingdom, London
Ucl Great Ormond Street Institute of Child Health
Chintu, Chifumbe Z.
Unknown Affiliation
Mulenga, Veronica
Unknown Affiliation
Kabamba, Desiré
Unknown Affiliation
Kavindele, Dorothy
Unknown Affiliation
Chabala, Chishala
Unknown Affiliation
Mwenechanya, Musaku
Unknown Affiliation
Kapasa, Monica Lulu
Unknown Affiliation
Zulu, Caroline C.
Unknown Affiliation
Kalumbi, Mox Malama
Unknown Affiliation
Chambula, Elias
Unknown Affiliation
Lungu, Joyce Chipili
Unknown Affiliation
Liusha, Marjory N.
Unknown Affiliation
Zangata, Dorothy
Unknown Affiliation
Masuka, Dorica
Unknown Affiliation
Chanshi, Shadreck
Unknown Affiliation
Chipoya, Terence
Unknown Affiliation
Zulu, Semy
Unknown Affiliation
Chola, Daniel
Unknown Affiliation
Chanda, Betty
Unknown Affiliation
Malama, Steven
Unknown Affiliation
Chama, Chama
Unknown Affiliation
Mulambo, Sylvia
Unknown Affiliation
Mwanza, Mpala
Unknown Affiliation
Asiimwe, R. Alice
Unknown Affiliation
Tukei, J. Vicent
Unknown Affiliation
Korutaro, Violet
Unknown Affiliation
Komunyena, Justine
Unknown Affiliation
Sebuliba, Isaac
Unknown Affiliation
Kisekka, Muzamil Nsibuka
Unknown Affiliation
Nansubuga, Carolyn
Unknown Affiliation
Mpanga, N. Justine
Unknown Affiliation
Matovu, Moses
Unknown Affiliation
Okello, Charles
Unknown Affiliation
Kesande, Sharon
Unknown Affiliation
Namutebi, Gladys
Unknown Affiliation
Tumuheirirwe, E. Glorius
Unknown Affiliation
Nagawa, Immaculate
Unknown Affiliation
Nakimera, Sarah
Unknown Affiliation
Onen, Geoffrey
Unknown Affiliation
Kabasita, Fatuma
Unknown Affiliation
Sunday, Fred
Unknown Affiliation
Isabirye, Dick
Unknown Affiliation
Mirembe, Grace
Unknown Affiliation
Kaudha, Elizabeth
Unknown Affiliation
Drasiku, Amos
Unknown Affiliation
Bainomuhwezi, Bernard
Unknown Affiliation
Wavamunno, Priscilla
Unknown Affiliation
Odongo, Florence
Unknown Affiliation
Lukowe, Constance
Unknown Affiliation
Namala, Winnie S.
Unknown Affiliation
Sseremba, Daniel
Unknown Affiliation
Balaba, Alison
Unknown Affiliation
Kwaga, Alice
Unknown Affiliation
Kayiwa, Joshua
Unknown Affiliation
Odera, Matthew
Unknown Affiliation
Oronon, Paul
Unknown Affiliation
Bagurukira, Edith
Unknown Affiliation
Mwesigwa, Phyllis
Unknown Affiliation
Apugulu, Philip
Unknown Affiliation
Mugarura, Lincoln
Unknown Affiliation
David Williams, Eram
Unknown Affiliation
Odoch, Denis
Unknown Affiliation
Nankya, Immaculate L.
Unknown Affiliation
Ndashimyeeva, Emmanuel
Unknown Affiliation
Nabulime, Eva
Unknown Affiliation
Abach, James
Unknown Affiliation
Agings Odong, Willy
Unknown Affiliation
Arach, Beatrice
Unknown Affiliation
Claren Aciro, Irene
Unknown Affiliation
Omongin, Joseph
Unknown Affiliation
Amone, Geoffrey
Unknown Affiliation
Okello, Peter
Unknown Affiliation
Aleti, Philliam
Unknown Affiliation
Otim, Edward
Unknown Affiliation
Kidega, Patrick
Unknown Affiliation
Achol, Emmanuel
Unknown Affiliation
Mwape, Innocent
Unknown Affiliation
Zulu, Joshua
Unknown Affiliation
Chipili, Gabriel
Unknown Affiliation
Chibesa, Linda
Unknown Affiliation
Walker, Anne Sarah
Unknown Affiliation
Thomason, Margaret J.
Unknown Affiliation
Ferrier, Alexander
Unknown Affiliation
Baptiste, David
Unknown Affiliation
Male, Charlotte
Unknown Affiliation
Spyer, Moira J.
Unknown Affiliation
Burger, David Marinus
Unknown Affiliation
Fillekes, Quirine
Unknown Affiliation
Colbers, Angela P.H.
Unknown Affiliation
McIlleron, Helen Margaret
Unknown Affiliation
Chomba, Elwyn Nachanya
Unknown Affiliation
Ramos, José Tomás
Unknown Affiliation
Akol, Zainab
Unknown Affiliation
Elyanu, Peter J.
Unknown Affiliation
Statistics
Citations: 11
Authors: 112
Affiliations: 11
Identifiers
Doi:
10.1093/infdis/jiy495
ISSN:
00221899
Research Areas
Genetics And Genomics
Infectious Diseases
Maternal And Child Health
Study Design
Randomised Control Trial