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Title: Microbial translocation in children with HIV in Uganda
Author: Fitzgerald, F. C. S.
ISNI:       0000 0004 7225 2039
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2017
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Background: There are >100000 new HIV infections in children each year, nearly 90% of which are in Africa. Untreated HIV results in activation across all axes of the immune system and this immune activation is linked to poor outcome. This study aimed to investigate microbial translocation (the crossing of microbial products such as bacterial DNA and components of bacterial cell walls from the gut into the blood stream) as a potential driver of immune activation and poor outcome in African children with HIV. Method: The study included HIV-infected children initiating treatment with antiretroviral therapy (ART) in the clinical trial CHAPAS-3 in Uganda (ISRCTN69078957). ART naïve and ART-experienced children from urban (Kampala) and rural (Gulu) settings were included with age-matched HIV uninfected controls from urban communities. Plasma was collected at 3 time points from HIV infected children and a one-off plasma sample from HIV uninfected controls. Cell pellet samples from HIV-infected children in the urban setting and baseline were also available. Microbial translocation was assessed using broad range 16S rDNA polymerase chain reactions (PCR) with next generation sequencing (NGS) and a panel of specific bacterial PCRs. Intestinal barrier function was assessed using Intestinal fatty acid binding protein (I-FABP). Results: In total, 305 children were included: 119 ART naïve (median age 2.8 years, interquartile range (IQR) 1.7-4, median baseline CD4% 20, IQR 14-24); 22 ART experienced children (median age 6.5 years IQR 5.9-9.2, median baseline CD4% 34, IQR 31-39) (urban site); 55 ART-naïve children (rural site)(median age 2 IQR 1.7-3.5, median baseline CD4% 30, IQR 22-41) and 109 age-matched HIV-uninfected controls. For the HIV-infected groups, immune recovery was good. Most molecular assays including broad range PCR were negative or very low at all time points and across all groups. No relationship was seen between molecular assay results and clinical events including invasive infections in the HIV-infected group. I-FABP was significantly higher in control groups than HIV infected (urban) groups at baseline, and the rural group was also higher. I-FABP increased in both urban HIV-infected groups over time. Conclusion: In this longitudinal study, there was no convincing relationship between markers of microbial translocation and clinical progress in HIV infected children from Uganda after ART initiation. Levels of translocation were low and similar in HIV-uninfected controls. I-FABP may be a marker of a healthy gut in this setting. Microbial translocation does not play a pivotal role in driving immune activation in this setting.
Supervisor: Klein, N. ; Harris, K. ; Gibb, D. M. ; Prendergast, A. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available