Hepatitis B virus (HBV): serological markers of infection and immunity in a cohort of South African children

Children age 6-60 months were recruited as part of the Co-infection in South-African Children (COSAC) study, in Kimberley, South Africa. HIV-negative participants (n=174) were recruited through the Kimberley Respiratory Cohort (KReC). These children were admitted to hospital with a clinical diagnosis of respiratory tract infection between July 2014 and August 2016. HIV-positive children (n=136) were recruited primarily from HIV outpatient clinics, (recruited between September 2009 and July 2016). Children had research blood samples taken at the same time as routine clinical blood tests. We tested all samples for markers of hepatitis B virus (HBV) infection and immunity. HBsAg testing was carried out in Kimberley Hospital, South Africa using the Magnetic parcel chemiluminometric immunoassay (MPCI; Advia Centaur platform). Confirmatory HBsAg testing, together with anti-HBs and anti-HBc testing, was carried out by the microbiology department at Oxford University Hospitals (OUH) NHS Foundation Trust, Oxford, UK (Architect i2000). Ethics approval for this study was obtained from the Ethics Committee of the Faculty of Health Science, University of the Free State, Bloemfontein, South Africa (HIV Study Ref: ETOVS Nr 08/09 and COSAC Study Ref: ECUFS NR 80/2014). Written consent for enrollment into the study was obtained from the child’s parent or guardian

Indications for ART Initiation in 222 children whose CD4 counts were above CD4 treatment thresholds.

<p>^a Not within the guidelines for ART initiation in children</p><p>Indications for ART Initiation in 222 children whose CD4 counts were above CD4 treatment thresholds.</p

Sex differences in CD4+ T cell count, CD4% and viral load, amongst 2,101 ART-naïve South African children.

<p>A. Absolute CD4 counts changes with age. B. CD4% changes with age. C. Viral load changes with age. In each panel, the solid lines are Loess-smoothed regression lines for female children and the dotted lines are Loess-smoothed regression lines for male children. A multivariable linear regression model, with both sex and age as covariates, shows significantly lower absolute CD4 counts in males (p = 0.005); significantly lower CD4% in males (p = 3.7x10^-7); and no significant difference in viral load between the sexes.</p

Proportion of HIV-infected children who were female in the subgroups analyzed within the Kimberley cohort.

<p>The proportion of female children in whom ART was initiated at CD4 counts higher than the CD4 thresholds compared to those in whom ART was initiated at CD4 counts lower than the CD4 thresholds differed significantly (p<0.001).</p

Study cohorts of HIV-infected South African children analyzed.

<p>Study cohorts of HIV-infected South African children analyzed.</p

Absolute CD4 count, CD4% and viral load in HIV-infected children and HIV-uninfected neonates.

<p>^<b>a</b> Mann Whitney test</p><p><u>HIV-Infected Children, n = 2,101</u>.</p

Multivariate analysis of sex differences in CD4+ T cell recovery after initiating ART.

<p>^a HR: Hazard ratio</p><p>^b 95% confidential interval range</p><p>^c aHR: adjusted hazard ratio</p><p>Multivariate analysis of sex differences in CD4+ T cell recovery after initiating ART.</p

Sex differences in immune reconstitution amongst the patients started treatment under the pre-2013 WHO guidelines.

<p>Sex differences by log rank test are shown as follows: A. Survival after ART initiation. B. CD4+ T cell percentage recovery (>35%) rate among the children who started ART aged 1–4 years old with CD4+ T cell <25%. C. Absolute CD4+ T cell count recovery (>750/ul) among children initiating ART aged ≥5 years old with absolute CD4+ T cell counts <350/ul.</p