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Background: In North American countries, national guidelines have strongly recommended formula over breastmilk for people with human immunodeficiency virus (HIV) because of concern for HIV transmission. However, data from resource-limited settings suggest the risk is <1% among virally suppressed people. Information regarding breastfeeding experience in high-resource settings is lacking., Methods: A retrospective multisite study was performed for individuals with HIV who breastfed during 2014-2022 in the United States (8 sites) and Canada (3 sites). Descriptive statistics were used for data analysis., Results: Among the 72 cases reported, most had been diagnosed with HIV and were on antiretroviral therapy prior to the index pregnancy and had undetectable viral loads at delivery. Most commonly reported reasons for choosing to breastfeed were health benefits, community expectations, and parent-child bonding. Median duration of breastfeeding was 24 weeks (range, 1 day to 72 weeks). Regimens for infant prophylaxis and protocols for testing of infants and birthing parents varied widely among institutions. No neonatal transmissions occurred among the 94% of infants for whom results were available ≥6 weeks after weaning., Conclusions: This study describes the largest cohort to date of people with HIV who breastfed in North America. Findings demonstrate high variability among institutions in policies, infant prophylaxis, and infant and parental testing practices. The study describes challenges in weighing the potential risks of transmission with personal and community factors. Finally, this study highlights the relatively small numbers of patients with HIV who chose to breastfeed at any 1 location, and the need for further multisite studies to identify best care practices., Competing Interests: Potential conflicts of interest. A. W. reports research funding from NIH and GlaxoSmithKline; consulting fees for advisory board roles with GlaxoSmithKline, Seqirus, and Merck; and payment or honoraria from GlaxoSmithKline (for a podcast) and Merck (meeting presentation). I. B. reports grants or contracts with the Canadian Institutes for Health Research, NIH, Altona, Moderna, and Ferring; consulting fees from Pfizer; and a role with the Society of Obstetricians and Gynecologists of Canada. J. D. reports travel support from the American College of Obstetricians and Gynecologists for the national conference. A. P. reports support from NIAID (grant number K23AI155296) and royalties from UpToDate. K. K. reports meeting honoraria from Takeda Canada. L. A. reports grants or contracts from NIH and the Colorado Department of Public Health and Environment. L. R. reports consulting fees from the University of California, San Francisco Clinicians Consultation Center National Perinatal HIV Hotline. F. K. reports salary support from FRQS and research infrastructure support from the Quebec government (Ministère de la Santé et des Services Sociaux/Service de lutte contre infections transmissibles sexuellement et par le sang). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Rapid identification and isolation of SARS-CoV-2 cases are priorities in school and child care settings to prevent further outbreaks. The objective of this study was to compare the clinical presentation of SARS-CoV-2 infections among preschool (<5 years) versus school-aged (≥5 years) children diagnosed with SARS-CoV-2 infection, and, specifically, the probability of presenting with an isolated symptom, such rhinorrhea or sore throat., Methods: Retrospective study of children (≤18 years of age) diagnosed with SARS-CoV-2 in the outpatient COVID-19 clinic or the Emergency Department at the Centre Hospitalier Universitaire Sainte-Justine (Montreal, Quebec, Canada) February through May 2020., Results: Of 3,789 children tested, 105 (3%) were positive for SARS-CoV-2, and 104 included in the analysis (n=49 age <5 years and n=55 age ≥5 years). While fever was the most common presenting symptom across both age groups, in the absence of fever, the presence of a combination of two or more symptoms identified the majority (92%) of cases. Isolated single symptom presentations were uncommon (<5% of cases). Most importantly, not a single child in either age group presented with isolated rhinorrhea or sore throat., Conclusions: While there are differences in the clinical manifestations of COVID-19 in preschool- versus school-aged children, in both age groups, isolated rhinorrhea was not a manifestation of SARS-CoV-2 infection. These results could help further guide testing criteria and exclusion criteria in child care and school settings., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Canadian Paediatric Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Although sociodemographic factors have been linked with SARS-CoV-2 infection and hospitalizations in adults, there are little data on the association between sociodemographic characteristics and SARS-CoV-2-related hospitalization in children. The objective of this study was to determine the association between area-level material deprivation and incidence of hospitalization with SARS-CoV-2 among children., Methods: We conducted a retrospective cohort study of all children (0 to 17 years of age) with a PCR-confirmed SARS-CoV-2 infection March 1, 2020 through May 31, 2021 at a tertiary-care paediatric hospital, in Montreal, Canada. Data were collected through chart review and included age, sex, and postal code, allowing linkage to dissemination area-level material deprivation, measured with the Pampalon Material Deprivation Index (PMDI) quintiles. We examined the association between PMDI quintiles and hospitalization using Poisson regression., Results: During the study period, 964 children had a positive PCR-confirmed SARS-CoV-2 test and 124 were hospitalized. Children living in the most deprived quintile of PMDI represented 40.7% of hospitalizations. Incidence rate ratio of hospitalization for this group compared to the most privileged quintile was 2.42 (95%CI: 1.33; 4.41)., Conclusion: Children living in the most materially deprived areas had more than twice the rate of hospitalizations for COVID-19 than children living in most privileged areas. Special efforts should be deployed to protect children who live in disadvantaged areas, especially pending vaccination of younger children., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Canadian Paediatric Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Combination antiretroviral therapy (cART) during pregnancy prevents vertical transmission, but many antiretrovirals cross the placenta and several can affect mitochondria. Exposure to maternal human immunodeficiency virus (HIV) and/or cART could have long-term effects on children who are HIV exposed and uninfected (CHEU). Our objective was to compare blood mitochondrial DNA (mtDNA) content in CHEU and children who are HIV unexposed and uninfected (CHUU), at birth and in early life., Methods: Whole-blood mtDNA content at birth and in early life (age 0-3 years) was compared cross-sectionally between CHEU and CHUU. Longitudinal changes in mtDNA content among CHEU was also evaluated., Results: At birth, CHEU status and younger gestational age were associated with higher mtDNA content. These remained independently associated with mtDNA content in multivariable analyses, whether considering all infants, or only those born at term. Longitudinally, CHEU mtDNA levels remained unchanged during the first 6 months of life, and gradually declined thereafter. A separate age- and sex-matched cross-sectional analysis (in 214 CHEU and 214 CHUU) illustrates that the difference in mtDNA between the groups remains detectable throughout the first 3 years of life., Conclusion: The persistently elevated blood mtDNA content observed among CHEU represents a long-term effect, possibly resulting from in utero stresses related to maternal HIV and/or cART. The clinical impact of altered mtDNA levels is unclear., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Studies from multiple countries have suggested impaired immunity in perinatally human immunodeficiency virus (HIV)-exposed uninfected children (HEU), with elevated rates of all-cause hospitalization and infections. We estimated and compared the incidence of all-cause hospitalization and infection-related hospitalization in the first 2 years of life among HEU and HIV-unexposed uninfected children (HUU) in the United States. Among HEU, we evaluated associations of maternal HIV disease-related factors during pregnancy with risk of child hospitalization., Methods: HEU data from subjects enrolled in the Surveillance Monitoring for Antiretroviral Therapy Toxicities Study (SMARTT) cohort who were born during 2006-2017 were analyzed. HUU comparison data were obtained from the Medicaid Analytic Extract database, restricted to states participating in SMARTT. We compared rates of first hospitalization, total hospitalizations, first infection-related hospitalization, total infection-related hospitalizations, and mortality between HEU and HUU using Poisson regression. Among HEU, multivariable Poisson regression models were fitted to evaluate associations of maternal HIV factors with risk of hospitalization., Results: A total of 2404 HEU and 3 605 864 HUU were included in the analysis. HEU children had approximately 2 times greater rates of first hospitalization, total hospitalizations, first infection-related hospitalization, and total infection-related hospitalizations compared with HUUs. There was no significant difference in mortality. Maternal HIV disease factors were not associated with the risk of child infection or hospitalization., Conclusions: Compared with HUU, HEU children in the United States have higher rates of hospitalization and infection-related hospitalization in the first 2 years of life, consistent with studies in other countries. Closer monitoring of HEU infants for infection and further elucidation of immune mechanisms is needed., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: The Early Pediatric Initiation Canada Child Cure Cohort (EPIC4) study is a prospective, multicenter, Canadian cohort study investigating human immunodeficiency virus-1 (HIV-1) reservoirs, chronic inflammation, and immune responses in children with perinatally acquired HIV-1 infection. The focus of this report is HIV-1 reservoirs and correlates in the peripheral blood of children who achieved sustained virologic suppression (SVS) for ≥5 years., Methods: HIV-1 reservoirs were determined by measuring HIV-1 DNA in peripheral blood mononuclear cells and inducible cell-free HIV-1 RNA in CD4+ T-cells by a prostratin analogue stimulation assay. HIV serology was quantified by signal-to-cutoff ratio (S/CO)., Results: Of 228 enrolled participants, 69 achieved SVS for ≥5 years. HIV-1 DNA, inducible cell-free HIV-1 RNA, and S/COs correlated directly with the age of effective combination antiretroviral therapy (cART) initiation (P < .001, P = .036, and P < .001, respectively) and age when SVS was achieved (P = .002, P = .038, and P < .001, respectively) and inversely with the proportion of life spent on effective cART (P < .001, P = .01, and P < .001, respectively) and proportion of life spent with SVS (P < .001, P = .079, and P < .001, respectively). Inducible cell-free HIV-1 RNA correlated with HIV-1 DNA, most particularly in children with SVS, without virologic blips, that was achieved with the first cART regimen initiated prior to 6 months of age (rho = 0.74; P = .037) or later (rho = 0.87; P < .001). S/COs correlated with HIV-1 DNA (P = .003), but less so with inducible cell-free HIV-1 RNA (P = .09)., Conclusions: The prostratin analogue stimulation assay, with its lower blood volume requirement, could be a valuable method for evaluating inducible HIV-1 reservoirs in children. Standard commercial HIV serology may be a practical initial indirect measure of reservoir size in the peripheral blood of children with perinatally acquired HIV-1 infection., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Maternal combination antiretroviral therapy (cART) during pregnancy could impact the health of human immunodeficiency virus (HIV)-exposed, HIV-uninfected (HEU) children, because some antiretrovirals cross the placenta and can inhibit telomerase. Our objective was to compare leukocyte telomere length (LTL) in HEU children and HIV-unexposed, HIV-uninfected (HUU) children at birth and in early life and to investigate any relationship with cART exposure., Methods: HEU and HUU children's blood LTL was compared cross-sectionally at birth, and during the first three years of life. Longitudinal HEU LTL dynamics was evaluated over that same period., Results: At birth, the LTL in HEU children (n = 114) was not shorter than that in HUU children (n = 86), but female infants had longer LTL than male infants. Maternal cART (duration or type) showed no association with shorter infant LTL. Among 214 HEU children age- and sex-matched at a 1:1 ratio to HUU children, LTL declined similarly in both groups. In a longitudinal analysis, LTL attrition in HEU children was rapid from birth to 1 year of age and gradual thereafter. Zidovudine prophylaxis did not significantly alter LTL., Conclusions: Our results indicate that from birth to 3 years of age, the LTL in HEU children is not negatively affected by exposure to maternal HIV infection and cART, at least not to the regimens used within this Canadian cohort, a reassuring finding., (© The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Congenital cytomegalovirus infection (cCMV) is the most common congenital infection, occurring in approximately 0.5% of live births. Most infected newborns are asymptomatic, but up to 20% develop sensorineural hearing loss or other permanent neurologic sequelae. The presentation of newborns with symptomatic cCMV is highly variable, and the infection is usually not diagnosed in the absence of a screening program. Newborn cCMV screening programs are estimated to be beneficial and cost-effective, and are increasingly being implemented. Diagnosis requires direct detection of virus in a sample obtained before 3 weeks of life, and is best performed by polymerase chain reaction (PCR) of saliva or urine, either of which is more sensitive than dried blood spot. Antiviral treatment of selected newborns with cCMV-related disease appears to improve hearing and neurocognitive outcomes. All infected infants should be evaluated promptly to determine appropriate therapy, and receive close audiologic and developmental follow-up.

Background: A human immunodeficiency virus type 1 (HIV-1)-infected infant started on combination antiretroviral therapy (cART) at 30 hours of life was recently reported to have no detectable plasma viremia after discontinuing cART. The current study investigated the impact of early cART initiation on measures of HIV-1 reservoir size in HIV-1-infected children with sustained virologic suppression., Methods: Children born to HIV-1-infected mothers and started on cART within 72 hours of birth at 3 Canadian centers were assessed. HIV serology, HIV-1-specific cell-mediated immune responses, plasma viremia, cell-associated HIV-1 DNA and RNA, presence of replication-competent HIV-1, and HLA genotype were determined for HIV-1-infected children with sustained virologic suppression., Results: Of 136 cART-treated children, 12 were vertically infected (8.8%). In the 4 who achieved sustained virologic suppression, HIV serology, HIV-1-specific cell-mediated immune responses (Gag, Nef), and ultrasensitive viral load were negative. HIV-1 DNA was not detected in enriched CD4(+) T cells of the 4 children (<2.6 copies/10(6) CD4(+) T cells), whereas HIV-1 RNA was detected (19.5-130 copies/1.5 µg RNA). No virion-associated HIV-1 RNA was detected following mitogenic stimulation of peripheral blood CD4(+) T cells (5.4-8.0 million CD4(+) T cells) in these 4 children, but replication competent virus was detected by quantitative co-culture involving a higher number of cells in 1 of 2 children tested (0.1 infectious units/10(6) CD4(+) T cells)., Conclusions: In perinatally HIV-1-infected newborns, initiation of cART within 72 hours of birth may significantly reduce the size of the HIV-1 reservoirs. Cessation of cART may be necessary to determine whether functional HIV cure can be achieved in such children., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Combined antiretroviral therapy allows children with human immunodeficiency virus (HIV) to reach adulthood. We studied 45 adolescents at the time of transfer to adult care. Despite universal healthcare access, over two-thirds of the adolescents were failing treatment, which was manifested by detectable HIV-1 viral load, CD4 counts <200 cells/ mm(3), and/or triple-class drug resistance., (© The Author 2012. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)