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

Felicity Fitzgerald (1) , Edouard Lhomme (2, 3) , Kathryn Harris (4) , Julia Kenny (1) , Ronan Doyle (4) , Cissy Kityo (5) , Liam P. Shaw (1) , George Abongomera (5) , Victor Musiime (5) , Adrian Cook (1) , Julianne R Brown (4) , Anthony Brooks (1) , Ellen Owen-Powell (1) , Diana M. Gibb (1) , Andrew J. Prendergast (6) , Ann Sarah Walker (1) , Rodolphe Thiébaut (2, 3) , Nigel Klein (1)

1 UCL - University College of London [London]
2 SISTM - Statistics In System biology and Translational Medicine
3 BPH - Bordeaux population health
4 GOSH - Great Ormond Street Hospital for Children [London]
5 Joint Clinical Research Centre
6 QMUL - Queen Mary University of London

Objective: Immune activation is associated with morbidity/mortality in HIV-infection despite antiretroviral therapy (ART). We investigated whether microbial translocation drives immune activation in HIV-infected Ugandan children. Methods: Nineteen markers of immune activation/inflammation were measured over 96 weeks in HIV-infected Ugandan children in CHAPAS-3 (ISRCTN69078957) and HIV-uninfected age-matched controls. Microbial translocation was assessed using molecular techniques including next-generation sequencing. Results: Of 249 children included, 120 were HIV-infected ART-naive and 22 ART-experienced (median (IQR) age 2.8(1.7-4.0) and 6.5(5.9-9.2) years; median baseline CD4% 20(14-24) and 35(31-39)). 107 were HIV-uninfected controls. Median (IQR) CD4% increase was 17(12-22) at week-96 in ART-naive children, and viral load was<100 copies/mL in 76%/91% ART-naive/experienced. Immune activation decreased with ART. Children could be divided by immune activation markers into clusters: cluster-1 (majority HIV-uninfected); cluster-2 (mixed HIV-uninfected/ART-naive/ART-experienced); and cluster-3 (majority ART-naive). Immune activation was low in cluster-1, decreased in cluster-3, and persisted in cluster-2. Blood microbial DNA levels were negative/very low across groups, with no difference between clusters except Enterobacteriaceae (higher in cluster-1,p<0.0001). Conclusion: Immune activation decreased with ART, with marker-clustering indicating different activation patterns by HIV/ART status. Levels of bacterial DNA in blood were low regardless of HIV/ART/immune activation status. Microbial translocation did not drive immune activation in this setting.

Mots clés: SISTM; HIV; Children; Microbial translocation; Immune activation; Sequencing; Pediatrics; Africa.

Domaines: Santé publique et épidémiologie

Felicity Fitzgerald, Edouard Lhomme, Kathryn Harris, Julia Kenny, Ronan Doyle, et al.. Microbial Translocation Does Not Drive Immune Activation in Ugandan Children Infected With HIV. Journal of Infectious Diseases, 2019, 219 (1), pp.89-100. ⟨10.1093/infdis/jiy495⟩. ⟨hal-03160724v2⟩