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Disclosure to children living with HIV (CLHIV) about their own status is associated with positive outcomes such as treatment adherence, but prior cross-sectional studies in sub-Saharan Africa report disclosure rates of50%. This study aims to assess pediatric disclosure over time. 548 CLHIV were followed from 2/2013-4/2018 in Johannesburg, South Africa. Cumulative incidence of disclosure was calculated with Kaplan-Meier analysis, and disclosure characteristics assessed with a Cox model. By end of follow-up, cumulative disclosure was 70.3% (95% confidence interval: 60.0-79.9). Median age at disclosure was 9 years (range: 3-13). Baseline predictors of disclosure included older child age and the child having a history of going hungry. Prior to disclosure, 98.0% of caregivers who disclosed had conversed with their child about their illness or an HIV-related topic, or their child had asked about HIV, versus 88.6% of caregivers who never disclosed. While many children did not receive disclosure during this relatively large, longitudinal study of South African CLHIV, caregivers who had not yet disclosed may have been preparing to do so by discussing their child's health or HIV generally with their child. This highlights the need for clinicians to consistently support caregivers throughout the incremental disclosure process.

We describe tuberculosis (TB) disease among antiretroviral treatment (ART) eligible children living with HIV (CLHIV) in South Africa to highlight TB prevention opportunities.In our secondary analysis among 0- to 12-year-old ART-eligible CLHIV in five Eastern Cape Province health facilities from 2012 to 2015, prevalent TB occurred 90 days before or after enrollment; incident TB occurredgt;90 days after enrollment. Characteristics associated with TB were assessed using logistic and Cox proportional hazards regression with generalized estimating equations.Of 397 enrolled children, 114 (28.7%) had prevalent TB. Higher-income proxy [adjusted odds ratio (aOR) 1.8 [95% confidence interval (CI) 1.3-2.6] for the highest, 1.6 (95% CI 1.6-1.7) for intermediate]; CD4+ cell countlt;350 cells/µl [aOR 1.6 (95% CI 1.1-2.2)]; and malnutrition [aOR 1.6 (95% CI 1.1-2.6)] were associated with prevalent TB. Incident TB was 5.2 per 100 person-years and was associated with delayed ART initiation [hazard ratio (HR) 4.7 (95% CI 2.3-9.4)], malnutrition [HR 1.8 (95% CI 1.1-2.7)] and absence of cotrimoxazole [HR 2.3 (95% CI 1.0-4.9)]. Among 362 children with data, 8.6% received TB preventive treatment.Among these CLHIV, prevalent and incident TB were common. Early ART, cotrimoxazole and addressing malnutrition may prevent TB in these children.We describe tuberculosis (TB) in children living with HIV (CLHIV) eligible for HIV treatment in South Africa to highlight opportunities to prevent TB.We analyzed additional data from our original study of CLHIV who were 0–12 years old and due to start HIV treatment in five health facilities in Eastern Cape Province from 2012 to 2015 and assessed characteristics associated with existing and new TB.Of 397 enrolled children, 114 (28.7%) had existing TB. Children with a higher measure of household income had higher odds of existing TB. CD4+ cell countlt;350 cells/µl and malnutrition were also associated with existing TB. There were 5.2 new cases of TB for every 100 child-years. New TB was 4.7 times more likely for children with delayed HIV treatment start, 1.8 times more likely for children with malnutrition and 2.3 times more likely for children who did not get cotrimoxazole. Among 362 children with data, 8.6% received treatment to prevent TB.Among these CLHIV, existing and new TB were common. Early HIV treatment, cotrimoxazole and addressing malnutrition may prevent TB in these children.

BACKGROUND Early-life metabolic derangements in HIV-exposed uninfected (HEU) infants have been reported. METHODS Pregnant women with HIV and HIV-uninfected pregnant women were enrolled with their newborns in a US cohort from 2011 to 2015. We measured cord insulin, C-peptide, and metabolic cytokines of HEU and HIV-unexposed uninfected (HUU) newborns using ELISA and metabolites, lipid subspecies, and eicosanoids via liquid chromatography/mass spectrometry. Linear regression was employed to assess the association of intrauterine HIV/ART with insulin and C-peptide. Graphical lasso regression was used to identify differences between metabolite/lipid subspecies networks associated with C-peptide. RESULTS Of 118 infants, 56 were HEU, ART exposed. In adjusted analyses, mean cord insulin (β = 0.295, p = 0.03) and C-peptide (β = 0.522, p

Background: There is growing concern about the long-term sequelae [a condition which is the consequence of a previous disease or injury] of perinatally acquired human immunodeficiency virus (HIV). Children living with HIV (CLHIV) present with cardiopulmonary impairments and decreased physical activity which may be due to poor endurance.Objectives: Our study aimed to investigate the sub-maximal endurance of CLHIV compared to a non-infected comparison group.Methods: In this cross-sectional descriptive study 346 CLHIV, between ages five and eleven years, were assessed using the Six Minute Walk Test (6MWT). Blood pressure, heart rate and oxygen saturation were measured pre-test, immediately post-test and five minutes post-test. Clinical and anthropometric data were recorded. Height and weight were assessed using a stadiometer and a digital scale, respectively.Results: 175 CLHIV (52% female) and 171 children without HIV (46% female) participated. All children were Black African. The CLHIV all initiated antiretroviral therapy (ART) at a young age (mean 8.7 months, standard deviation 6.7) and their disease was well controlled (viral load 1000copies/ml). There were no statistically significant differences in submaximal endurance between the two groups (p = 0.831). Age of starting ART and stunted growth were negatively associated (r = -2.8 (p = 0.019) and r = -46.1 (p = 0.027), respectively) with distance walked in the 6MWT by girls living with HIV.Conclusion: CLHIV who initiate ART early with well-controlled disease are able to attain submaximal endurance levels similar to their uninfected peers.Clinical implications: Endurance and physical activity should be monitored in CLHIV. Submaximal endurance levels may improve with age and biological maturation.

Early-life metabolic derangements in HIV-exposed uninfected (HEU) infants have been reported.Pregnant women with HIV and HIV-uninfected pregnant women were enrolled with their newborns in a US cohort from 2011 to 2015. We measured cord insulin, C-peptide, and metabolic cytokines of HEU and HIV-unexposed uninfected (HUU) newborns using ELISA and metabolites, lipid subspecies, and eicosanoids via liquid chromatography/mass spectrometry. Linear regression was employed to assess the association of intrauterine HIV/ART with insulin and C-peptide. Graphical lasso regression was used to identify differences between metabolite/lipid subspecies networks associated with C-peptide.Of 118 infants, 56 were HEU, ART exposed. In adjusted analyses, mean cord insulin (β = 0.295, p = 0.03) and C-peptide (β = 0.522, p 0.01) were significantly higher in HEU vs. HUU newborns. HEU neonates exhibited primarily positive associations between complex lipids and C-peptide, indicative of fuel storage, and augmented associations between cord eicosanoids and cytokines. HUU neonates exhibited negative associations with lipids and C-peptide indicative of increased fuel utilization.Higher cord insulin and C-peptide in HEU vs. HUU newborns as well as differences in cord metabolites, metabolic-related cytokines, and eicosanoids may reflect a propensity for fuel storage and an inflammatory milieu suggestive of fetal metabolic changes associated with in utero HIV/ART exposure.There is a paucity of studies assessing cord blood and neonatal metabolic health in HIV-exposed uninfected (HEU) newborns, an increasing population worldwide. Compared to HIV-unexposed uninfected (HUU) newborns, HEU newborns exhibit alterations in fuel homeostasis and an inflammatory milieu associated with in utero HIV/antiretroviral therapy (ART) exposure. The long-term implications of these neonatal findings are as yet unknown, but merit continued evaluation as this important and growing population ages into adulthood.

Chronic immune activation associated with human immunodeficiency virus (HIV) infection may have negative consequences on bone acquisition in individuals infected with HIV early in life. Bone mineral density (BMD) and microarchitecture were characterized in 38 HIV-infected men on antiretroviral therapy (18 perinatally-infected, 20 adolescence-infected) and 20 uninfected men age 20 to 25 years by dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HRpQCT). Flow cytometry was utilized to measure CD4+/CD8+ activation (HLADR+CD38+) and senescence (CD28-CD57+) and to quantify circulating osteogenic precursor (COP) cells in peripheral blood mononuclear cells using antibodies to RUNX2 and osteocalcin (OCN). Telomere lengths were measured in sorted COP cells using qPCR. DXA-derived areal BMD Z-scores and HRpQCT-derived volumetric BMD (vBMD) measures were lower in HIV-infected than uninfected men. Proportion of activated and senescent CD4+ and CD8+ T cells were higher in HIV-infected than uninfected men. The percentage of COP cells (mean ± SE) was lower in HIV-infected than uninfected (0.19% ± 0.02% versus 0.43% ± 0.06%; p < 0.0001) men, and also lower in perinatally-infected than adolescence-infected men (0.15% ± 0.02% versus 0.22% ± 0.03%; p < 0.04). A higher proportion of COP cells correlated with higher bone stiffness, a measure of bone strength, whereas a higher proportion of activated CD4+ T cells correlated with lower BMD and stiffness and lower proportion of COP cells. T cell activation with HIV-infection was associated with decreased numbers of osteogenic precursors as well as lower peak bone mass and bone strength. © 2016 American Society for Bone and Mineral Research.

BACKGROUND: Little is known about the prevalence of child mental health (MH) problems in sub-Saharan Africa, where poverty, HIV, and family disruption increase risk. One barrier is the lack of MH assessment tools lay staff can validly and reliably administer in settings with few MH professionals. METHODS: In a South African (SA) peri-urban cohort, we examined psychometric properties of the Strengths and Difficulties Questionnaire (SDQ), a widely used measure of child emotional and behavioral functioning. Data come from a large population-based study (N=1581) of children 4–6 years old. Lay fieldworkers administered the SDQ in isiZulu to caregivers at baseline and two years later. Exploratory factor analysisexamined whether the established SDQ five-factor structure and Total Difficulties score would be replicated. The psychometric model was tailored for ordinal items, and target factor rotation was used. RESULTS: Total Difficulties, Emotional symptoms and Prosocial behavior factors were supported, with partial support for Conduct problems. Peer relationships and Hyperactivity/inattentive subscale items loaded poorly. Subscale Cronbach’s alphas ranged from 0.29 (Peers) to 0.62 (Emotional). Internal consistency of Total Difficulties score was acceptable (0.74); 30% scored in the abnormal range on Total Difficulties, based on UK norms. CONCLUSIONS: SDQ scores in our sample suggest young children in SA are at high risk for MH problems. The SDQ, particularly the Total Difficulties score, may be a useful screening tool in SA. Yet, some subscales did not work in this language and context; if social skills and hyperactivity/inattention arebeing considered, modification or additional measures may be needed.

Objectives. We assessed pediatric influenza vaccination in relation to community influenza activity. Methods. We examined seasonal influenza vaccination in 34 012 children aged 6 months through 18 years from 5 academically affiliated clinics in northern Manhattan, New York (an urban low-income community) during the 2004–2008 seasons using hospital and city immunization registries. We calculated the cumulative number of administered influenza vaccine doses and proportion of children with any (≥ 1 dose) or full (1–2 doses per age recommendations) vaccination at the onset and peak of community polymerase chain reaction–confirmed influenza activity according to state surveillance reports and by March 31 each season. Results. Influenza vaccine administration began before October 1, peaked before influenza activity onset, and declined gradually over each season. Coverage at influenza activity onset, peak, and by March 31 increased over the 5 seasons. However, most children lacked full vaccination at these time points, particularly adolescents, minorities, and those requiring 2 doses. Conclusions. Despite early initiation of influenza vaccination, few children were fully vaccinated when influenza began circulating. Interventions should address factors negatively affecting timely influenza vaccination, especially in high-risk populations.

Few studies have assessed metabolic and body composition alterations in perinatally HIV-infected African children on antiretroviral therapy (ART). We compared metabolic profiles and regional fat of children on ritonavir-boosted lopinavir (lopinavir/ritonavir), lamivudine and stavudine to those switched to nevirapine, lamivudine and stavudine.This study evaluated metabolic and body composition outcomes in 156 HIV-infected children completing a randomised trial that assessed the continued use of lopinavir/ritonavir-based ART or switch to nevirapine-based ART in Johannesburg, South Africa (2005-2010). Fasting total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides total and regional body fat (BF) were measured. A clinical assessment for lipodystrophy (LD) was conducted.156 children (mean age 5.1±0.8 years, mean duration of treatment 4.2±0.7 years, mean time since randomisation 3.4±0.7 years) were enrolled. 85 were randomised to the lopinavir/ritonavir group and 71 to the nevirapine group. The lopinavir/ritonavir group had lower mean HDL (1.3±0.4 vs 1.5±0.4 mmol/l, p0.001) and higher mean TC (4.4±1.0 vs 4.1±0.8 mmol/l, p=0.097), LDL (2.6±0.9 vs 2.3±0.7 mmol/l, p=0.018) and triglycerides (1.1±0.4 vs 0.8±0.3 mmol/l, p0.001). The lopinavir/ritonavir group had more total BF by mean skinfold sum (43±11.1 vs 39±10.1 mm, p=0.031) and BF% by bioelectrical impedance analysis (17.0±7.0 vs 14.1±8.0%, p=0.022). Thirteen (8.4%) met criteria for LD.Unfavourable alterations in lipid profile and triglycerides, and differences in fat are detectable in young HIV-infected South African children receiving lopinavir/ritonavir-based regimens versus those switched to nevirapine-based regimens. Interventions to mitigate these alterations are warranted to reduce long-term cardiovascular disease risk.

Chronic immune activation associated with human immunodeficiency virus (HIV) infection may have negative consequences on bone acquisition in individuals infected with HIV early in life. Bone mineral density (BMD) and microarchitecture were characterized in 38 HIV-infected men on antiretroviral therapy (18 perinatally-infected, 20 adolescence-infected) and 20 uninfected men age 20 to 25 years by dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HRpQCT). Flow cytometry was utilized to measure CD4+/CD8+ activation (HLADR+CD38+) and senescence (CD28-CD57+) and to quantify circulating osteogenic precursor (COP) cells in peripheral blood mononuclear cells using antibodies to RUNX2 and osteocalcin (OCN). Telomere lengths were measured in sorted COP cells using qPCR. DXA-derived areal BMD Z-scores and HRpQCT-derived volumetric BMD (vBMD) measures were lower in HIV-infected than uninfected men. Proportion of activated and senescent CD4+ and CD8+ T cells were higher in HIV-infected than uninfected men. The percentage of COP cells (mean ± SE) was lower in HIV-infected than uninfected (0.19% ± 0.02% versus 0.43% ± 0.06%; p 0.0001) men, and also lower in perinatally-infected than adolescence-infected men (0.15% ± 0.02% versus 0.22% ± 0.03%; p 0.04). A higher proportion of COP cells correlated with higher bone stiffness, a measure of bone strength, whereas a higher proportion of activated CD4+ T cells correlated with lower BMD and stiffness and lower proportion of COP cells. T cell activation with HIV-infection was associated with decreased numbers of osteogenic precursors as well as lower peak bone mass and bone strength. © 2016 American Society for Bone and Mineral Research.