BackgroundLittle is known on outcomes after transition to adult care among adolescents with perinatal HIV infection. Though there is data from other chronic pediatric diseases suggesting increased morbidity and mortality following transfer to adult care, this has not well been studied among the first wave of survivors of perinatal HIV infection. The primary objective of this study was to determine outcomes after transition to adult care among a cohort of HIV-infected adolescents in Québec, Canada. Secondary objectives were to document participant experiences with the transition process, identify barriers to successful transition, and potential changes to improve the transition process.MethodsClinic records were reviewed to identify all perinatally-infected youth who transitioned from the Centre Maternel et Infantile sur le Sida pediatric HIV clinic (Montreal) at age 18 to an adult care provider between 1999 and 2012. Transitioned patients were contacted using last available patient or parental listed phone number on hospital record, internet based telephone directory, or social media. A standardized questionnaire was administered by telephone or in-person interview, and copies of current medical records obtained from treating physicians.ResultsForty-five patients were transferred between 1999 and 2012, among whom 25 consented to the study, eight were lost to follow-up, eight refused participation, and four were deceased. Overall 76 % of patients remained engaged in care, defined by at least one physician visit within 6 months of the interview. Over 50 % reported difficulty with adherence to their current drug regimens. At one-year post-transfer, there was a decrease in the proportion of patients with CD4 count >500 cells/mm3 from 64 to 29 %, and a statistically significant decrease in absolute CD4 count (mean 370 vs 524 cells/mm3, p = 0.04.). The majority (92 %) of participants felt that 18 was too young an age to transfer to adult care, and provided suggestions for improving the transition process.ConclusionsThis group of perinatally-infected youth remained engaged in care after transition, however difficulties with adherence and assuming responsibility for their own care were identified as issues in their post-transition care. The high rate of mortality among them and the changes to their health status post-transition suggest that further work is necessary to document the health outcomes of this group in larger, more diverse cohort settings.

BackgroundReports of increased morbidity and mortality from infectious diseases among HIV Exposed Uninfected (HEU) infants have raised concern about a possible underlying immunodeficiency among them. The objective of this study was to assess the immunological profile of HEU infants born to mothers exhibiting different levels of HIV-1 viremia at the time of delivery.MethodsStudy subjects were enrolled in the Centre maternel et infantile sur le SIDA (CMIS) mother-child cohort between 1997 and 2010 (n =585). Infant CD4+ T cell, CD8+ T cell and CD19+ B cell counts were assessed at 2 and 6 months of age, and compared among HEU infants in groups defined by maternal viral load (VL) at the time of delivery (VL < 50 copies/ml, VL 50–1000 copies/ml, and VL > 1000 copies/ml) in a multivariable analysis.ResultsAt 2 months of age, infants born to mothers with VL > 1000 copies/ml had lower CD4+ T cell counts compared to those born to mothers with VL < 50 copies/ml at the time of delivery (44.3% versus 48.3%, p = 0.007, and 2884 vs. 2432 cells/mm3, p = 0.02). These differences remained significant after adjusting for maternal and infant antiretroviral drug use, gender, race and gestational age, and persisted at 6 months of age. There were no differences in CD8+ T cell count or absolute CD19+ B cell count between groups, though higher CD19+ B cell percentage was seen among infants born to mothers with VL > 1000 copies/ml.ConclusionsThese results suggest that exposure to high levels of HIV-1 viremia in utero, even in the absence of perinatal transmission, may affect the infant’s developing immune system. While further work needs to be done to confirm these findings, they reinforce the need for optimal treatment of HIV infected pregnant women, and careful follow-up of HEU infants.

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Background Limited data is available on raltegravir (RAL) pharmacokinetics during pregnancy and the value of therapeutic drug monitoring (TDM) in pregnancy is unknown. This study aims to describe RAL trough plasma concentrations (Ctrough) during pregnancy and review the impact of RAL TDM on outcomes. Methods Women from the prospective mother-infant HIV cohort of Mother and Children’s Infectious Diseases Center who received RAL during their pregnancy between 2011-2020 were included. TDM reports were reviewed and Ctrough values estimated when possible, using historical RAL half-lives. Results We included 76 pregnant women of which 47 underwent TDM. We observed a significant association between virological response and Ctrough ( p-value .034) with an increase of 0.1 mg/L corresponding to a 2.96 reduction in the risk of having a detectable viral load. The results indicated that in pregnant women a RAL Ctrough threshold of 0.04 mg/L has a higher specificity (75%) as compared to our current Ctrough target value of 0.02 mg/L (25%) and an acceptable sensitivity (77%). No significant differences were observed between Ctrough at each trimester. When comparing pregnancies with and without TDM, no statistically significant differences were observed in the virologic response during pregnancy and at delivery, or with the need for triple antiretroviral prophylaxis in newborns. Conclusions An association between RAL Ctrough and viral load was observed and achieving a RAL Ctrough of 0.04 mg/L or greater is a predictor of virologic response in pregnant women. The impact of TDM in pregnancy, however, could not be demonstrated.

Background One of the most striking observations of the COVID-19 pandemic has been the difference in infection among children vs. adults. Overall, children with SARS-CoV-2 infection generally had milder disease compared to adults, though the cause is not clear. The objective of this study was to compare the humoral response to infection in children vs. adults of a same family. Methods We performed a prospective cohort study at Sainte-Justine University Health Center in Montreal, Canada from July 2020 to March 2021. Children with a positive SARS-CoV-2 PCR were recruited from the COVID-19 clinic (index case), enrollment was offered to all household members. Serum IgG against SARS-CoV-2 native S1/S2 spike proteins was measured using the Diasorin (Liaison XL) assay, 4-6 months following a positive PCR. A mean antibody threshold of 15 Arbitrary unit per ml (AU/ml) was considered seropositive, with 94.4% positive agreement to plaque reduction neutralization tests (PRNT90) at a 1:40 ratio. Antibody titer was compared between children and adults. Results 111 participants (52 adults and 59 children) were recruited from 50 separate families. Characteristic of participants and their clinical symptoms are described in Table 1. Among all participants, 76.3% children were SARS-CoV-2 seropositive vs. 51.9% of adults (p=0.007). Median antibody titer was significantly higher in children vs. adults (82.8 AU, [IQR: 18.4-130], vs 17.0 AU, [IQR: 6.8-77.8], p=0.006); findings were similar among SARS-CoV-2 PCR positive participants only. Overall, 13 participants were PCR positive but seronegative, 7 were PCR negative and seropositive, while 61 were both PCR positive and seropositive. Older participants and those with any comorbidity. Among the PCR positive group, the seropositive participants were younger (median age 31±17 vs 19±17 years, p=0.003) and more likely to have comorbidity (69% vs 29%, p=0.007). Conclusion These results suggest that children have a stronger antibody response to SARS-CoV-2 infection than adults, and that older age and presence of comorbidity are associated with a less robust humoral response. Further work on the differences in response between children and adults may help elucidate mechanisms underlying the severity of disease Disclosures Olivier Drouin, MDCM MsC MPH, Covis Pharma (Research Grant or Support)