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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We studied a cohort of children initiated on treatment doses of combination antiretroviral therapy within 72 hours of birth. In children who achieved sustained virologic suppression, measures of HIV-1 reservoir size in peripheral blood were very low.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/106 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/106 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. [ABSTRACT FROM AUTHOR]