SARS-CoV-2 antibodies in adolescents living with perinatally acquired HIV.

Data on children and adolescents with HIV and coronavirus disease 2019 (COVID-19) co-infection are limited. Clinical and antibody data related to COVID-19 infection in adolescents living with perinatally acquired HIV (ALPHIV) and originally enrolled in the Children with HIV Early Antiretroviral Therapy (CHER) study were collected. We present a descriptive analysis of 53 ALPHIV who were tested for anti-SARS-CoV-2 antibodies. Just over half (53%) of the adolescents tested had positive anti-SARS-CoV-2 antibodies with only one participant describing a prior history of possible symptomatic infection. Contribution: The study contributes to the understanding of SARS-CoV-2 infection and vaccination practices in HIV-positive adolescents.

Cardiometabolic Risk Profiles of Adolescents Living With Perinatally Acquired HIV in South Africa.

BACKGROUND: We assessed the Pathological Determinants of Atherosclerosis in Youth (PDAY) score and other potential cardiovascular disease risk factors in adolescents previously enrolled in the Children with HIV Early antiRetroviral (CHER) and International Maternal Pediatric Adolescent AIDS Clinical Trials Network P1060 clinical trials. METHODS: Coronary artery and abdominal aorta (AA) PDAY scores were calculated for 56 participants over 15 years of age using a weighted combination of dyslipidemia, cigarette smoking, hypertension, obesity, and hyperglycemia. A PDAY score ≥1 is associated with early atherosclerosis. RESULTS: Fifty-six participants were enrolled: 46 (82.1%) on a single-tablet regimen of tenofovir disoproxil fumarate, lamivudine and dolutegravir. Median time on antiretroviral therapy was 15.8 [interquartile range (IQR): 15.8-16.5] years and median time on dolutegravir was 14 (IQR: 10.0-19.0) months. Fasting median high-density lipoprotein cholesterol was 20.1 mg/dL (IQR: 16.0-23.7) and median non-high-density lipoprotein cholesterol was 38.3 mg/dL (IQR: 30.8-44.3). The median systolic blood pressure was 115 mm Hg (IQR: 107-121). Median body mass index was 21.3 kg/m 2 (IQR: 19.5-24.7) and median fasted serum glucose was 82.0 mg/dL (IQR: 75.7-87.3). Only 1 (2%) participant smoked cigarettes, but 5 (9%) smoked hookah pipe and 26 (46.4%) smoked cannabis. Thirty-one (55.4%) participants had coronary artery PDAY scores ≥1 and 33 (58.9%) had AA PDAY scores ≥1. Age was associated with an AA PDAY score ≥1 ( P = 0.02) with a 0.06 increase in AA PDAY score for every month of age (95% confidence interval: 0.01-0.12, P = 0.01). CONCLUSIONS: Adolescents with perinatally acquired HIV appear at risk for cardiovascular disease. Specific tools for monitoring this risk are needed to institute appropriate preventive interventions.

The Determinants of Elevated Pathobiological Determination of Atherosclerosis in Youth Risk Score in Perinatally HIV-Infected Adolescents in South Africa.

BACKGROUND: Youth living with perinatally acquired HIV infection (YLPHIV) are at risk of developing atherosclerotic cardiovascular disease. METHODS: We determined the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) coronary arteries (CA) and abdominal aorta (AA) risk scores among YLPHIV who are ≥15 years old in Cape Town Adolescent and Antiretroviral Cohort. PDAY score was calculated using non-high-density lipoprotein, high-density lipoprotein cholesterol, hyperglycemia, hypertension, obesity, and smoking; a score ≥1 was considered elevated. HIV viremia was categorized as sustained (SV) = viral load (VL) >50 copies/mL, transient (TV) = mix of VL >50 and ≤50 copies/mL, or sustained-virologic suppression = VL <50 copies/mL throughout the study. Among YLPHIV, logistic models were fit to assess factors associated with elevated PDAY. RESULTS: Overall, 218 YLPHIV [median age 16.8 (interquartile range: 15.9-17.8) years, male 47%] were included. Among YLPHIV, 8% (n = 17) had SV, and 54% (n = 118) had TV. Median antiretroviral therapy (ART) duration was 12 (interquartile range: 8-14) years. Among YLPHIV, 30.3% and 18.4% had elevated PDAY for CA and AA, respectively.Among YLPHIV, SV [adjusted odds ratio (aOR) = 18.4, P < 0.01] and TV (aOR = 2.10, P = 0.04) compared with virologic suppression and ART duration in years (aOR = 1.12, P = 0.03) were associated with elevated CA. Male sex was associated with both elevated CA and AA (aOR = 2.14, P = 0.02, and aOR = 3.43, P = 0.01, respectively) and association of SV with elevated AA (aOR = 3.24, P = 0.09). CONCLUSIONS: A substantial proportion of YLPHIV have PDAY scores reflecting increased aggregate atherosclerotic risk. Among YLPHIV, viremia, lifetime ART duration, and male sex contribute to this risk, highlighting the importance of HIV control and the need to monitor cardiometabolic health.

Interventional bronchoscopy in pediatric pulmonary tuberculosis.

INTRODUCTION: Lymphobronchial tuberculosis (TB) is common in children with primary TB and enlarged lymph nodes can cause airway compression of the large airways. If not treated correctly, airway compression can result in persistent and permanent parenchymal pathology, as well as irreversible lung destruction. Bronchoscopy was originally used to collect diagnostic samples; however, its role has evolved, and it is now used as an interventional tool in the diagnosis and management of complicated airway disease. Endoscopic treatment guidelines for children with TB are scarce. AREAS COVERED: The role of interventional bronchoscopy in the diagnosis and management of complicated pulmonary TB will be discussed. This review will provide practical insights into how and when to perform interventional procedures in children with complicated TB for both diagnostic and therapeutic purposes. This discussion incorporates current scientific evidence and refers to adult literature, as some of the interventions have only been done in adults but may have a role in children. Limitations and future perspectives will be examined. EXPERT OPINION: Pediatric pulmonary TB lends itself to endoscopic interventions as it is a disease with a good outcome if treated correctly. However, interventions must be limited to safeguard the parenchyma and prevent permanent damage.

Chronic lung disease in children due to SARS-CoV-2 pneumonia: Case series.

The reported prevalence of chronic lung disease (CLD) due to coronavirus 2 (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2)]) pneumonia with the severe acute respiratory syndrome in children is unknown and rarely reported in English literature. In contrast to most other respiratory viruses, children generally have less severe symptoms when infected with SARS-CoV-2. Although only a minority of children with SARS-CoV-2 infection require hospitalization, severe cases have been reported. More severe SARS-CoV-2 respiratory disease in infants has been reported in low- and middle-income countries (LMICs) compared to high-income countries (HICs). We describe our experience of five cases of CLD in children due to SARS-CoV-2 collected between April 2020 and August 2022. We included children who had a history of a positive SARS-CoV-2 polymerase chain reaction (PCR) or antigen test or a positive antibody test in the serum. Three patterns of CLD related to SARS-CoV-2 were identified: (1) CLD in infants postventilation for severe pneumonia (n = 3); (2) small airway disease with bronchiolitis obliterans picture (n = 1) and (3) adolescent with adult-like post-SARS-CoV-2 disease (n = 1). Chest computerized tomography scans showed airspace disease and ground-glass opacities involving both lungs with the development of coarse interstitial markings seen in four patients, reflecting the long-term fibrotic consequences of diffuse alveolar damage that occur in children post-SARS-CoV-2 infection. Children with SARS-CoV-2 infection mostly have mild symptoms with little to no long-term sequelae, but the severe long-term respiratory disease can develop.

Evolving role of chest radiographs for diagnosis of pediatric pulmonary tuberculosis.

Chest radiographs (CXR) have played an important and evolving role in diagnosis, classification and management of pediatric pulmonary tuberculosis (TB). During the pre-chemotherapy era, CXR aided in determining infectiousness, mainly to guide isolation practices, by detecting calcified and non-calcified lymphadenopathy. The availability of TB chemotherapy from the mid-1900s increased the urgency to find accurate diagnostic tools for what had become a treatable disease. Chest radiographs provided the mainstay of diagnosis in children, despite high inter-reader variability limiting its accuracy. The development of cross-sectional imaging modalities, such as computed tomography, provided more accurate intra-thoracic lymph node assessment, but these modalities have major availability, cost and radiation exposure disadvantages. As a consequence, CXR remains the most widely used modality for childhood  pulmonary TB diagnosis, given its relatively low cost and accessibility. Publication of the revised 2022 World Health Organization Consolidated TB guidelines added practical value to CXR interpretation in children, by allowing the selection of children for shorter TB treatment using radiological signs of severity of disease, that have high reliability. This article provides a review of the historical journey and evolving role of CXR in pediatric pulmonary TB.

The hard part we often forget: providing care to children and adolescents with advanced HIV disease.

INTRODUCTION: Many children and adolescents living with HIV still present with severe immunosuppression with morbidity and mortality remaining high in those starting antiretroviral therapy (ART) when hospitalized. DISCUSSION: The major causes of morbidity and mortality in children living with HIV are pneumonia, tuberculosis, bloodstream infections, diarrhoeal disease and severe acute malnutrition. In contrast to adults, cryptococcal meningitis is rare in children under 5 years of age but increases in adolescence. In 2021, the World Health Organizations (WHO) consolidated guidelines for managing HIV disease and rapid ART included recommendations for children and adolescents. In addition, a WHO technical brief released in 2020 highlighted the various interventions that are specifically related to children and adolescents with advanced HIV disease (AHD). We discuss the common clinical presentations of children and adolescents with AHD with a focus on diagnosis, prevention and treatment, highlight some of the challenges in the implementation of the existing package of care, and emphasize the importance of additional research to address the needs of children and adolescents with AHD. CONCLUSIONS: There are limited data informing these recommendations and an urgent need for further research on how to implement optimal strategies to ensure tailored approaches to prevent and treat AHD in children and adolescents. Holistic care that goes beyond a simple choice of ART regimen should be provided to all children and adolescents with AHD.

Decreased Hepatic Steatosis in South African Adolescents With Perinatal HIV Switching to Dolutegravir-containing Regimens.

BACKGROUND: Although dolutegravir (DTG) has a favorable metabolic profile, it has been linked to excess weight gain. We evaluated changes in hepatic steatosis in adolescents with perinatally acquired HIV switching to DTG-containing antiretroviral therapy (ART). METHODS: Virologically suppressed adolescents switched to dolutegravir for a minimum of 4 months or on unchanged ART (84% protease inhibitor) were assessed prospectively with anthropometry, transient elastography with controlled attenuation parameter (CAP) and fasting metabolic profiles. ART regimens were determined independently of the study. RESULTS: In total 68 adolescents [baseline median age 13.5 years [interquartile range (IQR): 12.5-14.4 years]; 42 (62%) female] were recruited. However, 38 remained on the same regimen and were followed for a median of 98 weeks (IQR: 48-108 weeks), and 30 switched to DTG and were followed for a median of 52 weeks (IQR: 49-101). There was no baseline difference in CAP between groups. There was no significant change in body mass index z-score in either group, but the median CAP in the DTG group decreased by -40dB/m (IQR: -51 to -31 dB/m) after a median of 44 weeks (IQR: 28-50 weeks) on DTG, compared to +1dB/m (IQR: -29 to +14 dB/m) in adolescents not switched ( P < 0 .01). Cholesterol and triglycerides were lower in those switched. Whereas hepatic steatosis prevalence decreased from 17% to 3% in adolescents who switched to dolutegravir, its prevalence doubled from 8% to 16% in those not switched ( P = 0.1). CONCLUSIONS: In this exploratory study, adolescents switched to DTG-containing regimens had reduced hepatic steatosis, cholesterol and triglycerides with no excess weight gain compared to those on unchanged ART.

Complicated intrathoracic tuberculosis: Role of therapeutic interventional bronchoscopy.

In recent years bronchoscopy equipment has been improved with smaller instruments and larger size working channels. This has ensured that bronchoscopy offers both therapeutic and interventional options. As the experience of paediatric interventional pulmonologists continues to grow, more interventions are being performed. There is a scarcity of published evidence in the field of interventional bronchoscopy in paediatrics. This is even more relevant for complicated pulmonary tuberculosis (PTB). Therapeutic interventional bronchoscopy procedures can be used in the management of complicated tuberculosis, including for endoscopic enucleations, closure of fistulas, dilatations of bronchial stenosis and severe haemoptysis. Endoscopic therapeutic procedures in children with complicated TB may prevent thoracotomy. If done carefully these interventional procedures have a low complication rate.

Intrathoracic tuberculosis: Role of interventional bronchoscopy in diagnosis.

Tuberculosis (TB) is the leading cause of death from a single infectious agent globally. Mortality is related to the delay in diagnosis and starting treatment. According to new guidelines it is very important to classify pulmonary tuberculosis (PTB) as severe or not severe disease due to the difference in treatment duration. Bronchoscopy is the gold standard for assessing the degree of airway compression and obstruction in paediatric PTB. Paediatric bronchoscopy has evolved from a primarily diagnostic procedure to include interventional bronchoscopy for diagnostic purposes. Endobronchial ultrasound (EBUS) has increased the potential of sampling mediastinal lymph nodes both for histological diagnosis and microbiological confirmation.

Hospitalization among infants who initiate antiretroviral therapy before 3 months of age.

INTRODUCTION: Studies examining hospitalization among infants with HIV in resource-limited settings, in the context of early infant diagnosis and early antiretroviral therapy (ART) initiation, are limited. METHODS: We used routinely collected data on infants who initiated ART aged <3 months (Western Cape province, South Africa; 2013-2017) to describe hospitalization from birth until 12 months post-ART initiation. Record reviews were additionally performed at three tertiary-level facilities. We used mixed-effects Poisson regression to examine factors associated with hospitalization. RESULTS: Among 840 infants, 579 (69%) were hospitalized; 36% had >1 hospitalization. Median age at ART initiation decreased from 57 days (interquartile range [IQR] 22-74; 2013-2015) to 19 days (IQR 5-54; 2016-2017). Early neonatal hospitalization (age <7 days) occurred in 271 infants (32%) and represented 24% of hospitalizations (272/1131). Overall, 443 infants (53%) were hospitalized at age ≥7 days, including 13% with hospitalizations pre-ART initiation, 15% pre and post-ART initiation and 25% post-ART initiation. Excluding early neonatal hospitalizations, initiating ART at older age vs. age <1 week was associated with higher hospitalization rates: adjusted incidence rate ratios (95% confidence interval) were 1.86 (1.31-2.64); 2.31 (1.62-3.29) and 2.47 (1.76-3.46) if ART initiation age was 1-4 weeks; 5-8 weeks and 9-12 weeks respectively. Among infants whose hospital records were reviewed, reasons for early neonatal hospitalizations mostly related to prematurity or low birthweight (n = 46/60; 77%) whereas hospitalizations at age ≥7 days were mostly due to infections (n = 206/243; 85%). CONCLUSIONS: Earlier ART initiation is associated with lower hospitalization rates. High hospitalization rates, despite initiation age <3 months, is concerning.

Advancing the prevention and treatment of HIV in children: priorities for research and development.

Safe and effective paediatric formulations of the most promising antiretroviral drugs are crucial to advance the treatment and prevention of HIV in neonates, infants, children, and adolescents. The WHO Paediatric Drug Optimization for HIV (PADO-HIV) group brings together stakeholders and experts every 2-3 years to identify priority products and define research gaps in the development of new HIV drugs and formulations for children in low-income and middle-income countries. PADO-HIV 5 met from Sept 27 to Oct 15, 2021. The group evaluated HIV agents from known and novel drug classes, oral and parenteral long-acting formulations, and developments in broadly neutralising antibodies, and included focused sessions on neonates and new delivery technologies. A list of medium-term and long-term priorities was generated, and research questions were defined. This forward-looking analysis is intended to provide guidance to funders, drug developers, and researchers, and to accelerate access for children to the best HIV drugs and formulations.

Third-Line Antiretroviral Therapy: What Do We Do When the Appropriate Formulations Are Not Available?

Children on antiretroviral therapy have limited options, particularly if they are failing therapy and live in resource-poor settings. We describe three cases where children accessed third-line antiretroviral therapy off-label, or used them extemporaneously with successful outcomes. We then review the evidence for performing this measure. There is an urgent need for appropriate formulations to treat young children who require a third-line or salvage regimen.

Immunization for Children Living With HIV: A Scoping Review.

BACKGROUND: Immunosuppression secondary to human immunodeficiency virus (HIV) increases the risk of vaccine-preventable diseases in children living with HIV (CLHIV). Although vaccines are cost-effective interventions, their efficacy, immunogenicity, safety, and persistence of post-vaccination immunity in CLHIV receiving antiretroviral therapy (ART) is unclear. We aimed at identifying existing scientific evidence on immunization of CLHIV generated in the last 10 years to identify the need for a systematic review. METHODS: Studies were identified using a broad search strategy applied in multiple databases. Included studies involved CLHIV aged 0-10 years and presented outcomes on safety, efficacy, effectiveness, immunogenicity, and use of booster vaccines. RESULTS: Nineteen publications were identified. There was variable immunogenicity to and efficacy of vaccines by HIV and ART status. All vaccines were safe. CONCLUSION: The heterogeneity of available studies makes it complex to do a systematic review and meta-analysis. A more uniform approach to sampling and follow-up in future studies would make comparison and interpretation of results more robust.

Childhood Cancers Misdiagnosed as Tuberculosis in a High Tuberculosis Burden Setting.

BACKGROUND: Tuberculosis (TB) and childhood cancers have overlapping presentations and malignancies may be misdiagnosed as TB in high TB-burden settings. METHODS: This retrospective study investigated the diagnosis of TB in children with cancer registered in the Tygerberg Hospital Childhood Tumor Registry from 2008 to 2018. We studied children on anti-tuberculosis treatment (ATT) at cancer diagnosis or diagnosed with TB within 1 month of cancer diagnosis. We describe the circumstances and extent of this misdiagnosis, quantify the delay in therapy and document the outcomes of these children. RESULTS: Twenty-seven of 539 (5%) children in the registry started ATT before cancer diagnosis. Both pulmonary and extrapulmonary TB complicated the cancer diagnosis. Of the 27 patients on ATT at cancer diagnosis, 22 (81%) had contact with a TB case and in 6 of 12 children (50%) a tuberculin skin test was positive. At cancer diagnosis, 16/27 (59%) children had chest radiograph changes interpreted as TB with 11/27 (41%) regarded as suggestive of TB on expert review. The median diagnostic delay between TB and cancer diagnoses was 25 days (interquartile range 3.5-58). Of 539 children with cancer, 204 (38%) died of cancer, including 18/30 (60%) children on ATT at cancer diagnosis or diagnosed with TB within 1 month of cancer diagnosis (odds ratio 2.6; 95% confidence interval: 1.2-5.4; P = 0.012). CONCLUSIONS: The clinical and radiologic overlap of TB and cancer causes diagnostic confusion in a significant number of children with cancer and may contribute to increased mortality.