Microbial Translocation Does Not Drive Immune Activation in Ugandan Children Infected With HIV

被引：9

作者：

Fitzgerald, Felicity C. ^{[1
]}

Lhomme, Edouard ^{[6
,7
,8
]}

Harris, Kathryn ^{[3
]}

Kenny, Julia ^{[1
,18
]}

Doyle, Ronan ^{[3
]}

Kityo, Cissy ^{[9
]}

Shaw, Liam P. ^{[1
]}

Abongomera, George ^{[10
]}

Musiime, Victor ^{[9
]}

Cook, Adrian ^{[4
,17
]}

Brown, Julianne R. ^{[3
]}

Brooks, Anthony ^{[2
]}

Owen-Powell, Ellen ^{[4
,17
]}

Gibb, Diana M. ^{[4
,17
]}

Prendergast, Andrew J. ^{[5
,11
]}

Walker, A. Sarah ^{[4
,17
]}

Thiebaut, Rodolphe ^{[6
,7
,8
]}

Klein, Nigel ^{[1
,18
]}

Chintu, Chifumbe ^{[12
]}

Mulenga, Veronica ^{[12
]}

Kabamba, Desiree ^{[12
]}

Kavindele, Dorothy ^{[12
]}

Chabala, Chishala ^{[12
]}

Mwenechanya, Musaku ^{[12
]}

Kapasa, Monica ^{[12
]}

Zulu, Caroline C. ^{[12
]}

Kalumbi, Mox ^{[12
]}

Chambula, Elias ^{[12
]}

Lungu, Joyce ^{[12
]}

Liusha, Marjory N. ^{[12
]}

Zangata, Dorothy ^{[12
]}

Masuka, Dorica ^{[12
]}

Chambula, Elias ^{[12
]}

Chanshi, Shadreck ^{[12
]}

Chipoya, Terence ^{[12
]}

Zulu, Semy ^{[12
]}

Chola, Daniel ^{[12
]}

Chanda, Betty ^{[12
]}

Malama, Steven ^{[12
]}

Chama, Chama ^{[12
]}

Mulambo, Sylvia ^{[12
]}

Mwanza, Mpala ^{[12
]}

Asiimwe, R. Alice ^{[13
]}

Tukei, J. Vicent ^{[13
]}

Korutaro, Violet ^{[13
]}

Komunyena, Justine ^{[13
]}

Sebuliba, Isaac ^{[13
]}

Kisekka, Muzamil ^{[13
]}

Nansubuga, Carolyn ^{[13
]}

Mpanga, N. Justine ^{[13
]}

机构：

[1] Queen Mary Univ London, Infect Immun & Inflammat Programme, London, England

[2] Queen Mary Univ London, Univ Coll London UCL Genom, UCL Great Ormond St GOS Inst Child Hlth, London, England

[3] Queen Mary Univ London, GOS Natl Hlth Serv Fdn Trust, Camelia Botnar Labs, Microbiol Virol & Infect Prevent & Control, London, England

[4] Queen Mary Univ London, UCL, Med Res Council Clin Trials Unit, London, England

[5] Queen Mary Univ London, Blizard Inst, London, England

[6] Univ Bordeaux, ISPED, Bordeaux Populat Hlth Res Ctr, INSERM,UMR 1219, Bordeaux, France

[7] INRIA Res Ctr, Stat Syst Biol & Translat Med SISTM Team, Creteil, France

[8] Vaccine Res Inst VRI, Creteil, France

[9] Joint Clin Res Ctr, Kampala, Uganda

[10] Joint Clin Res Ctr, Gulu, Uganda

[11] Zvitambo Inst Maternal & Child Hlth Res, Harare, Zimbabwe

[12] Univ Teaching Hosp, Lusaka, Zambia

[13] Mulago Hosp, Baylor Ctr Excellence, Kampala, Uganda

[14] TASO Gulu, Gulu, Uganda

[15] Gulu Reg Referral Hosp, Gulu, Uganda

[16] Ctr Infect Dis Res, Lusaka, Zambia

[17] UCL, MRC Clin Trials Unit, London, England

[18] Inst Child Hlth, London, England

[19] Radboud Univ Nijmegen, Med Ctr, Nijmegen, Netherlands

[20] Univ Cape Town, Rondebosch, South Africa

来源：

JOURNAL OF INFECTIOUS DISEASES | 2019年 / 219卷 / 01期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

HIV; children; microbial translocation; immune activation; sequencing; pediatrics; Africa; T-CELL-ACTIVATION; DISEASE PROGRESSION; MACROPHAGE ACTIVATION; PLASMA-LEVELS; MORTALITY; RECOVERY; RECONSTITUTION; INFLAMMATION; ASSOCIATIONS; INDIVIDUALS;

D O I：

10.1093/infdis/jiy495

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：89 / 100

页数：12

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