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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., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Little is known about hospitalization in African adolescents with perinatally acquired HIV (PHIV+ adolescents). We described the incidence and causes of hospitalization in participants enrolled in the Cape Town Adolescent Antiretroviral Cohort in South Africa., Methods: Data collected from July 2013 to October 2018 from PHIV+ and HIV- adolescents were analyzed. Participants were assessed every 6 months and data on intercurrent hospitalization were abstracted. Causes of hospitalizations were classified according to ICD-10 codes. Descriptive statistics, time-to-event analysis and Poisson regression were used to describe causes and incidence and to determine incidence rate ratios for factors associated with hospitalization., Results: Five hundred fifteen PHIV+ and 109 HIV- participants had a median follow-up of 4.1 years [interquartile range (IQR): 3.7-4.6]. At enrollment HIV+ participants had a median duration of ART of 7.6 years (IQR: 4.6-9.2), median CD4 count of 713 cells/mm (IQR: 561.0-957.5) and 387 (75%) had a viral load <50 copies/mL. There were 149 hospital admissions over 64 months. Crude incidence rates for hospitalization were 6.6 [95% confidence interval (CI): 5.7-7.8] and 2.2 (95% CI: 1.2-4.3) per 100-person-years (P = <0.01) in HIV + and HIV-, respectively. Ninety of 149 (60%) admissions in HIV+ participants were classified as non-infectious, 36/149 (24%) were infectious and 23/149 (16%) were "other HIV-related" or "unknown." Older age (15-19 years) and maintaining a CD4 >500 cells/cm were associated with decreased risk of hospitalization: adjusted incidence rate ratios of 0.61 (CI: 0.44-0.86, P = <0.01) and 0.68 (CI: 0.49-0.94, P = 0.02), respectively., Conclusions: PHIV+ adolescents had a high incidence of hospitalization despite ART. Strategies addressing infectious and non-infectious morbidity must be strengthened.

We describe the history of mother-to-child-prevention, time to HIV diagnosis and antiretroviral therapy of 55 hospitalized HIV-positive children (median age, 5.7 months). Of 31 (56%) mothers who knew their HIV status prior to pregnancy, 11 (35%) did not attend antenatal clinics; those who did attend had poor viral suppression. Despite rapid recognition and access to treatment, 13% of hospitalized HIV-positive infants died. Strategies to reach the mothers driving vertical transmission are imperative.

Background: Little is known about the course and management of perinatal tuberculosis (TB). We describe the presentation, medical and surgical management of culture-confirmed TB in infants younger than 3 months of age., Methods: We conducted a retrospective study including all infants younger than 3 months of age with culture-confirmed TB admitted to Tygerberg Hospital, Cape Town, South Africa, from March 2003 to June 2015., Results: During the study period, 106 of 2017 (5%) children younger than 13 years of age with culture-confirmed TB were infants younger than 3 months of age. The median age on admission was 67 days (interquartile range, 40-79). Intrathoracic TB was present in 101 (95%) infants; of these, 34 (32%) had extrathoracic TB. Two (2%) infants had extrathoracic TB only, while 3 (3%) infants were asymptomatic and diagnosed as having TB infection only. Forty (38%) infants were HIV-exposed, and 14 (13%) were HIV-infected. The mother was identified as the source case in 53 (50%) infants. Mycobacterium tuberculosis was cultured in a median of 2 (interquartile range, 1-7) specimens per infant; 9 (9%) had drug-resistant TB. Bronchoscopy was done in 37 (35%) infants, and 27 (26%) underwent intrathoracic lymph node decompression. Twelve (11%) infants died during admission, 81(76%) were clinically stable on transfer or discharge from hospital, and outcome was not documented in 13 (12%) infants., Conclusions: TB in young infants often presents with severe intrathoracic disease, including airway compression. Bronchoscopy may aid confirmation of the diagnosis and management; decompression of intrathoracic lymph nodes was common. Mortality in this age group remains high.

Background: Earlier diagnosis of HIV-infected infants facilitates earlier access to therapy and improved clinical outcomes. The aim of this study was to describe the management of infants who started antiretroviral therapy (ART) in the first month of life., Methods: A retrospective review was performed on HIV-infected neonates who started ART within the first month of life between January 2013 and March 2015., Results: A total of 997 neonates had 1 HIV polymerase chain reaction test. Of the 997 neonates, 26 (2.6%) tested positive for HIV and 22 initiated therapy in the first month of life. The median age of first HIV polymerase chain reaction test was 7 days. Neonates were started on ART within a median of 7 days of their first HIV test, which equated to a median age of 13.5 [interquartile range (IQR) 7-20] days of life. Median gestational age was 35 weeks (IQR 33-38 weeks), and birth weight was 2170 g (IQR 1773-2480). Nineteen (86.4%) had low birth weight (<2.5 kg) and 16 (72.7%) were premature. Median baseline HIV viral loads were log 4.444 copies/mL (IQR 3.457-5.125), median CD4 counts were 1338 (IQR 803-1928) and CD4% percentages were 36.1% (22.2-45.4). All children initiated zidovudine and lamivudine, 10 with lopinavir/ritonavir and 12 with nevirapine. All children in care are now receiving lopinavir/ritonavir. Of the 22 neonates initiated on treatment, 11 are in care (mean age, 2.1 years), and 2 of these infants had a viral load of <50 copies/ mL when last measured., Conclusions: Early ART initiation in neonates is feasible. Challenges include safe, palatable regimens and continued close follow-up of mothers and infants.

Background: The World Health Organization identified a need for evidence to inform revision of second- and third-line antiretroviral therapy (ART) options in children failing ART. We performed an in-depth scoping review of all available literature on second-line and subsequent ART regimens in children younger than 18 years., Methods: We comprehensively searched, without language or date limitations, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, the World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials.gov., Results: The search retrieved 1982 records. Eighteen studies provided efficacy data: 1 randomized controlled trial, 7 phase II trials, 5 prospective and 5 retrospective cohorts. Five studies evaluated regimens in children failing first-line ART, 4 in children with multidrug resistance and 9 in children with variable treatment experience. Only 10/18 studies reported week 48 or month 12 outcomes. The overall proportion of children with virologic suppression defined by study at week 48 was 61.8%. Although the randomized controlled trial had low risk of bias, outcomes were similar between groups because of highly active optimized background regimens. All phase II and prospective studies were judged to have moderate to high risk of bias. No study compared currently recommended lopinavir-based second-line regimens for nonnucleoside reverse transcriptase inhibitor failures to other non-nonnucleoside reverse transcriptase inhibitor regimens head-to-head., Conclusions: We found no evidence comparing current World Health Organization-recommended second- and third-line ART regimens with regimens including drugs of interest: raltegravir, darunavir, etravirine and atazanavir. Randomized controlled trials or prospective cohort studies with comparator arms, and bridging studies, ideally conducted in resource-limited settings, are required to guide future recommendations.

Background: The burden of childhood tuberculosis (TB) remains significant especially in areas of high HIV prevalence. Clinical diagnosis predominates, despite advances in molecular and microbiological diagnostics. The aim of this study is to identify clinical features associated with culture-confirmed pulmonary TB (PTB) in children., Methods: Children admitted to hospital were enrolled in a study of novel diagnostics for PTB in South Africa. Standardized clinical, radiological and microbiological data were collected. Definite TB was defined by culture of Mycobacterium tuberculosis from a respiratory specimen. Adjusted odds ratios for definite TB were calculated using a multivariate logistic regression model., Results: Adjusted odds ratio (AOR) for definite TB increased with a history of fever for more than 1 week [AOR: 8.54, 95% confidence interval (CI): 2.37-30.74], with a chest radiograph (CXR) suggestive of PTB (AOR: 10.0, 95% CI: 3.22-31.2) and with a positive tuberculin skin test (TST; AOR: 64.4, 95% CI: 14.3-290.5). The likelihood ratio of having definite TB if 2 of these factors (CXR and TST) were present compared with having none of them was 17.7. Cough, household contact with TB, HIV status and wheezing were not significantly associated with definite TB., Conclusions: Prolonged fever, CXR suggestive of TB or a positive TST were predictive of definite TB and should be considered in composite scoring systems for TB diagnosis in high HIV prevalence settings. Other commonly associated symptoms were not associated with definite TB.