Attention and neurodevelopment in young children who are HIV-exposed uninfected.

ABSTRACTChildren HIV-exposed, uninfected (CHEU) are at risk for compromised developmental outcomes. Attention is important for behavioural, cognitive and academic skills, yet has not been thoroughly investigated compared to children HIV-unexposed uninfected (CHUU). Fifty-five CHEU and 51 CHUU children were recruited at 5.5 years of age. Measures of inattention (IA), hyperactivity/impulsivity (HI) and total scores were collected using the parent-reported ADHD-Rating-Scale-IV. Measures of intelligence, visuomotor skills, academics and adaptive functioning were obtained. Analyses of between-group differences were performed as were correlational and multiple regression models, accounting for maternal education, employment and delivery type. Few children met clinical cut-offs for probable ADHD (3.6% CHEU, 2.0% CHUU), and no group differences in measures of IA, HI and combined scores were found. CHEU scored significantly lower than CHUU on intelligence, visuomotor function, academic skills and aspects of adaptive behaviour, though within age expectations. Lower Full-Scale IQ and Processing Speed were associated with higher IA in CHEU and lower adaptive functioning with higher IA in CHUU. Across both groups, children of unemployed mothers had more HI symptoms. CHEU were not at increased risk for attention difficulties at 5.5 years of age. Maternal employment status highlights the contribution of sociodemographic factors in shaping behaviour and neurodevelopment.

Developing a partnership to improve health care delivery to children <18 years with cancer and blood disorders in the English-speaking Caribbean: lessons from the SickKids-Caribbean Initiative (SCI).

In 2013, the SickKids-Caribbean Initiative (SCI) was formalised among The Hospital for Sick Children in Toronto, Canada, the University of the West Indies, and Ministries of Health in six Caribbean countries (Barbados, The Bahamas, Jamaica, St. Lucia, St. Vincent and the Grenadines, and Trinidad and Tobago). The aim was to improve the outcomes and quality of life of children (<18 years) with cancer and blood disorders in the partner countries. Core activities included filling a human resource gap by training paediatric haematologists/oncologists and specialised registered nurses; improving capacity to diagnose and treat diverse haematology/oncology cases; developing and maintaining paediatric oncology databases; creating ongoing advocacy activities with international agencies, decision makers, and civil society; and establishing an integrated administration, management, and funding structure. We describe core program components, successes, and challenges to inform others seeking to improve health service delivery in a multidisciplinary and complex partnership.

Canadian Pediatric & Perinatal HIV/AIDS Research Group consensus recommendations for infant feeding in the HIV context.

Background: Providing comprehensive infant feeding guidance to families affected by HIV is complex and requires a multidisciplinary approach. While exclusive formula feeding remains the preferred recommendation for infants born to women living with HIV (WLWH) in high-income countries, a more nuanced approach that may include the option of breastfeeding under certain circumstances is emerging in many resource-rich countries. Methods: The Canadian Pediatric & Perinatal HIV/AIDS Research Group (CPARG) hosted a Canadian Institute of Health Research-funded meeting in 2016 to develop consensus among multidisciplinary providers around counselling and recommendations for infant feeding. After presentations by adult and paediatric health care providers, basic scientists, and community-based researchers, a subgroup drafted summary evidence-informed recommendations. Along with revisions among CPARG members, a community review was performed by a convenience sample of WLWH who had given birth in the past 5 years from Ontario and Quebec. A legal review was also conducted to ensure understanding of the criminalization potential and concern of HIV transmission and exposure. Results: The Canadian consensus guidelines continue to support formula feeding as the preferred method of infant feeding as it eliminates any residual risk of postnatal vertical transmission. Formula should be made available for all infants born to mothers living with HIV for their first year of life. A comprehensive approach to counselling WLWH is outlined to assist providers to effectively counsel on current evidence to ensure WLWH are fully informed in their decision making. For women meeting criteria to and elect to breastfeed, frequent maternal virologic monitoring and follow-up is required of both mother and infant. Antiretroviral prophylaxis and monitoring are recommended for breastfed infants. The community review highlighted the importance of other supports and counselling needed for implementing effective formula feeding, aside from access to formula. The legal review provided clarifying language around child protection services involvement and the need to provide referral to legal resources or information upon request. Surveillance systems to monitor for cases of breastmilk transmission should be in place to improve gaps in care and develop further knowledge in this area. Conclusion: The Canadian infant feeding consensus guideline is designed to inform and enable better care for WLWH and their babies. Ongoing evaluation of these guidelines as new evidence emerges will be important.

Historique: La transmission de conseils détaillés sur l'alimentation du nourrisson aux familles touchée par le VIH est complexe et exige une approche multidisciplinaire. Il est recommandé de recourir exclusivement aux préparations commerciales chez les nourrissons de mères vivant avec le VIH (MVIH) dans les pays à revenu élevé, mais une approche plus nuancée, qui peut inclure l'allaitement dans certaines situations, émerge dans de nombreux pays riches en ressources. Méthodologie: Le Groupe canadien de recherche pédiatrique et périnatale sur le VIH/sida (CPARG) a tenu un congrès financé par Les Instituts de recherche en santé du Canada en 2016 pour parvenir à un consensus de la part des professionnels multidisciplinaires sur le counseling et les recommandations à l'égard de l'alimentation du nourrisson. Après les présentations de professionnels de la santé pédiatrique, de chercheurs fondamentaux et de chercheurs communautaires, un sous-groupe a rédigé une synthèse des recommandations reposant sur des données probantes. En plus des révisions proposées par les membres de la CPARG, un échantillon de commodité de MVIH qui avaient accouché dans les cinq années précédentes en Ontario et au Québec a procédé à un examen communautaire. Une révision juridique a également permis de bien comprendre le potentiel de criminalisation et les inquiétudes quant à la transmission du VIH et à l'exposition à ce virus. Résultats: Les lignes directrices consensuelles canadiennes continuent de préconiser l'utilisation des préparations commerciales pour l'alimentation des nourrissons, car elles éliminent tout risque résiduel de transmission verticale après la naissance. Ces préparations doivent être mises à la disposition de tous les nourrissons nés de MVIH jusqu'à l'âge d'un an. Une approche détaillée du counseling auprès des MVIH est présentée pour aider les professionnels à leur donner des conseils efficaces sur les données probantes à jour, afin qu'elles puissent prendre une décision pleinement éclairée. Chez les femmes qui respectent les critères et qui choisissent d'allaiter, la surveillance virologique fréquente de la mère et un suivi de la mère et du nourrisson s'imposent. La prophylaxie antirétrovirale et la surveillance des nourrissons allaités sont recommandées. La révision communautaire a fait ressortir l'importance d'autres mesures de soutien et de counseling pour mettre en place une alimentation efficace à l'aide des préparations commerciales, en plus de l'accès à ces préparations. L'analyse juridique a permis de préciser les énoncés entourant la participation des services de protection de l'enfance et la nécessité de diriger les familles vers des ressources ou de l'information juridiques, sur demande. Des systèmes de surveillance visant à répertorier les cas de transmission par le lait maternel devraient être en place pour corriger les lacunes en matière de soins et accroître les connaissances dans ce domaine. Conclusion: Les lignes directrices consensuelles canadiennes sur l'alimentation des nourrissons sont conçues pour éclairer les soins aux MVIH et à leurs nourrissons et pour les améliorer. Il sera important d'assurer l'évaluation continue de ces lignes directrices à mesure que de nouvelles données probantes seront découvertes.

Video directly observed therapy to improve adherence of human immunodeficiency virus infected adolescents to combination antiretroviral therapy: a proof-of-concept study.

Adherence to antiretroviral therapy (ART) is a major challenge for many youth living with HIV (YLWH). In this prospective proof-of-concept study, we assessed the feasibility and acceptability of conducting a study of video directly observed therapy (VDOT) as a method of improving medication adherence in YLWH who had a history of poor adherence to ART. The study had four phases; phase I - VDOT daily (4 months) using Facetime®; phase II - daily texting (2 months); phase III - weekly texting (3 months); phase IV - no intervention (3 months). Participants were seen in clinic on a monthly basis for assessment and laboratory evaluation. Five of eight eligible participants were enrolled. All achieved virologic suppression one month after enrollment. Three of five completed the study protocol and maintained virologic suppression through the 12-month period of study. Participant responses to the end-of-study questionnaire indicated satisfaction with the intervention and thought VDOT was helpful to them. Healthcare providers thought that the intervention was effective for some youth but was at times burdensome. This proof-of-concept study demonstrated that VDOT may be effective at improving medication adherence in previously poorly adherent YLWH and that larger studies of VDOT for such patients are both feasible and warranted.

Chitinase-3-like Protein 1 Is Associated with Poor Virologic Control and Immune Activation in Children Living with HIV.

Perinatally infected children living with HIV (CLWH) face lifelong infection and associated inflammatory injury. Chitinase-like 3 protein-1 (CHI3L1) is expressed by activated neutrophils and may be a clinically informative marker of systemic inflammation in CLWH. We conducted a multi-centre, cross-sectional study of CLWH, enrolled in the Early Pediatric Initiation Canadian Child Cure Cohort Study (EPIC4). Plasma levels of CHI3L1, pro-inflammatory cytokines, and markers of microbial translocation were measured by enzyme-linked immunosorbent assays. Longitudinal clinical characteristics (viral load, neutrophil count, CD4+ and CD8+ T-lymphocyte counts, and antiretroviral (ARV) regimen) were abstracted from patient medical records. One-hundred-and-five (105) CLWH (median age 13 years, 62% female) were included in the study. Seventy-seven (81%) had viral suppression on combination antiviral therapy (cART). The median CHI3L1 level was 25 µg/L (IQR 19-39). CHI3L1 was directly correlated with neutrophil count (ρ = 0.22, p = 0.023) and inversely correlated with CD4/CD8 lymphocyte ratio (ρ = -0.35, p = 0.00040). Children with detectable viral load had higher levels of CHI3L1 (40 µg/L (interquartile range, IQR 33-44) versus 24 µg/L (IQR 19-35), p = 0.0047). CHI3L1 levels were also correlated with markers of microbial translocation soluble CD14 (ρ = 0.26, p = 0.010) and lipopolysaccharide-binding protein (ρ = 0.23, p = 0.023). We did not detect differences in CHI3L1 between different cART regimens. High levels of neutrophil activation marker CHI3L1 are associated with poor virologic control, immune dysregulation, and microbial translocation in CLWH on cART.

Is Routine Therapeutic Drug Monitoring of Anti-Retroviral Agents Warranted in Children Living with HIV?

OBJECTIVE: The utility of routine therapeutic drug monitoring (TDM) in children living with HIV has not been extensively studied. The purpose of this study was to assess this strategy. METHODS: This was a single-center, prospective observational study of routine TDM for protease inhibitors (PIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and integrase strand transfer inhibitors (INSTIs) in children living with HIV who were receiving antiretroviral therapy (ART) between February and December 2014. Outcome measures included the proportion of serum antiretroviral (ARV) medication concentrations in the therapeutic range (target values extrapolated from adult data) and the effect of serum concentrations on virologic control, medication adherence, and toxicity. RESULTS: Forty-eight children with a median age of 13 years (interquartile range, 3-18) were included. Median viral load (VL) and CD4% were <40 copies/mL (range, <40-124) and 37.4% (range, 8.4-47.9), respectively. Adherence was considered excellent in 95.8% of patients. Of the 50 serum trough concentrations (PI n = 19 [38%]; NNRTI n = 27 [54%]; INSTI n = 4 [8%]), 66% (n = 33) were in the therapeutic range, 12% (n = 6) were subtherapeutic, and 22% (n = 11) were supratherapeutic. There was no statistically significant correlation between serum ARV concentrations and patient demographics, VL, CD4%, or adherence. No clinically significant adverse events were noted. One dose adjustment was made for a subtherapeutic serum raltegravir concentration, likely attributable to interaction with ritonavir. CONCLUSIONS: This study does not support routine TDM in healthy children living with HIV who are well controlled on antiretroviral medication regimens. A more targeted strategy, such as when adherence is questioned or when there are suspected drug interactions, may be more appropriate.

Neurodevelopment of HIV-exposed uninfected children compared with HIV-unexposed uninfected children during early childhood.

HIV-exposed uninfected (HEU) children during the preschool and early school ages may be at-risk for neurodevelopmental challenges due to in utero and perinatal exposure to HIV and/or antiretroviral (ARV) medications. HEU children and HIV-unexposed uninfected (HUU) children from the community were recruited and tested at 3 to 4 and 5 to 6 years of age. Demographic information, HIV/ARV exposure and measures of intelligence, visuomotor skills, and adaptive functioning were obtained. Nonparametric tests assessed group differences and multiple regression analyses adjusted for demographic variables. Additional multiple regression analyses were performed within the HEU group to investigate associations between neurodevelopmental measures and variables of HIV/ARV exposure. At 3 to 4 years, 211 HEU children and 31 HUU children were assessed, and 144 HEU children and 58 HUU children were assessed at 5 to 6 years of age. At 3 to 4 years of age, HEU children scored significantly lower on measures of Full-Scale IQ, Performance IQ, visual motor integration, and adaptive functioning. At 5 to 6 years of age, HEU children scored significantly lower on all neurodevelopmental measures. At both ages, children who were female and those with mothers who were employed achieved higher scores on measures intellectual ability and/or adaptive functioning. Within the HEU group, no consistent associations were found between neurodevelopmental measures and HIV/ARV specific variables. HEU children demonstrated significantly lower scores on neurodevelopmental measures than HUU children during early childhood. Gaps in verbal intellectual abilities were identified with age, highlighting the importance of monitoring neurodevelopment in this population over time. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Early academic achievement of HIV-exposed uninfected children compared to HIV-unexposed uninfected children at 5 years of age.

HIV-exposed uninfected (HEU) children may be at-risk for poorer academic achievement compared to HIV-unexposed uninfected (HUU) children due to in utero and perinatal exposure to HIV and/or anti-retroviral (ARV) medication. Understanding the risk factors for academic underachievement is important for implementing timely intervention and academic supports. HEU (N = 110, mean (SD) age 5.59 (0.22) years) and HUU (N = 43, mean (SD) age 5.73 (0.64) years) children completed assessments of general intelligence (WPPSI-III) and academic achievement (WRAT-4). Parent interviews and medical record reviews were used to obtain sociodemographic and maternal health data. HUU children scored significantly higher than HEU children on single word reading (p = 0.006), math calculation skills (p = 0.003), Verbal IQ, Performance IQ, Full Scale IQ, and Processing Speed (all WPPSI-III measures p < 0.001). Verbal IQ at 3-4 years predicted academic achievement at 5-6 years of age, yet sociodemographic and medical factors did not. These findings demonstrate that HEU children obtained significantly lower scores of intellectual, reading, and math abilities during early childhood. Addressing these early gaps before HEU children enter primary school will be critical for optimizing their learning and academic potential.

The relationship between stigma and a rehabilitation framework [international classification of functioning, disability and health (ICF)]: three case studies of women living with HIV in Lusaka, Zambia.

PURPOSE: To explore how the International Classification of Functioning, Disability and Health, a rehabilitation framework, can provide a holistic understanding of stigma experiences of three women living with human immunodeficiency virus in Lusaka, Zambia. METHODS: A secondary analysis of three cases by drawing on interview transcripts collected as part of a larger longitudinal study with eighteen women living with the virus. The interview tool used the rehabilitation framework to ask questions about the impact of the virus on the body, daily activities, social participation and the future. Vignettes were produced for each of the eighteen women including information on stigma and the rehabilitation framework. Three case studies were developed from women who provided comprehensive accounts of stigma and the International Classification of Functioning, Disability and Health. RESULTS: Stigma experiences aligned well with three dimensions of the International Classification of Functioning, Disability and Health: participation restrictions, environmental and personal factors. These domains were used to understand stigma in three forms (i.e. enacted, self and structural stigma) as experienced by these women. CONCLUSIONS: More research is needed to ascertain how stigma and rehabilitation are related in other environments and populations and to explore how to mitigate stigma within the rehabilitation context.IMPLICATIONS FOR REHABILITATIONRehabilitation professionals deal with aspects of stigma and discrimination in their clinical work and this analysis offers a way to consider HIV-related stigma within rehabilitation in an organized and theoretically-informed way.The insights from this study are important for the field of HIV and for advancing understanding of the complexities of stigma in the context of rehabilitation more broadly.This analysis offers guidance to rehabilitation providers about the nuanced and multi-faceted ways that stigma can occur in the context of rehabilitation, including within their own clinical practice.

Treatment Experience and Repeat Pregnancy Impact the Effectiveness of Non-Nucleoside Reverse Transcription Inhibitor-Highly Active Antiretroviral Therapy for the Prevention of Mother to Child Transmission of Human Immunodeficiency Virus.

Non-nucleoside reverse transcription inhibitor (NNRTI)-containing antiretroviral therapy (ART) for the prevention of mother to child transmission (PMTCT) of human immunodeficiency virus (HIV) has led to dramatic reductions in perinatal HIV infection in resource-constrained settings. Nonetheless, PMTCT programs are complicated by repeat pregnancies, in which long-term or repeat exposures to PMTCT regimens over time may lead to the acquisition of HIV drug resistance mutations, and consequent treatment failure. In this study, we retrospectively assessed the effectiveness of the NNRTI-based PMTCT protocol from 2008 to 2010 in The Bahamas National HIV/AIDS Program. We show that women who had been in repeat pregnancies and those who were already prescribed ART at conception were at increased risk of virologic failure, relative to treatment-inexperienced women and primigravida, respectively (AOR 3.1, 95% CI: 1.3-7.1, p = .008 and AOR 5.0, 95% CI: 1.8-14.1, p = .002). In addition, women undergoing treatment at conception were more likely to possess HIVDR mutations relative to treatment-naive women (AOR 447.1, 95% CI: 17.9-11,173.5, p = .001). Therefore, individual treatment history is a key metric determining the effectiveness of current and future PMTCT interventions. The implications of this to PMTCT programmatic success in light of the most recent WHO guidelines are discussed.

Knowledge and awareness of Human Papillomavirus (HPV) and HPV vaccines among Caribbean youth: the case of the Bahamas.

There is a high burden of cervical cancer in the Caribbean region, particularly in the Bahamas, yet there are few studies of Human Papillomavirus (HPV) and HPV vaccine in the region. The objective of this study was to assess the knowledge and awareness of HPV and the HPV vaccine among school-aged youth (15-18 years) living in the Bahamas.Cross-sectional data were obtained from the "Getting to Zero" HIV study in the Bahamas conducted in 2014/2015 (n = 1553). The questionnaire elicited information on knowledge of HPV and HPV vaccines, using previously validated scales. Data analysis included Chi-square tests and Mann Whitney U test.In this sample of school-aged youth, only 10.7% (146/1364) had ever heard of HPV. With respect to those who were sexually active (n = 685), only 10.7% had ever heard of HPV. For those who had heard of HPV, knowledge of HPV and HPV vaccines was assessed on an HPV Knowledge and HPV Vaccine Knowledge scale, respectively. There was no statistically significant difference in mean HPV knowledge score between males and females, or HPV vaccine knowledge scores, between males and females.There was a general lack of awareness of HPV and HPV vaccines among school-aged youth in the Bahamas. This is an important gap in the HPV vaccine strategy and cancer prevention, as this is the age at which most people acquire HPV. It emphasizes the importance of developing a careful implementation plan, with an evaluation of knowledge and attitudes, in order to have an effective HPV vaccine uptake.

Clinical Correlates of Human Immunodeficiency Virus-1 (HIV-1) DNA and Inducible HIV-1 RNA Reservoirs in Peripheral Blood in Children With Perinatally Acquired HIV-1 Infection With Sustained Virologic Suppression for at Least 5 Years.

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.

Challenges to achieving and maintaining viral suppression among children living with HIV.

OBJECTIVES: The objective of this study was to determine the time to, and durability of, viral suppression, among Canadian children living with HIV after initiation of combination antiretroviral therapy (cART). DESIGN: Prospective, multicenter Canadian cohort study (Early Pediatric Initiation Canada Child Cure Cohort), using both prospective and retrospectively collected data. METHODS: Kaplan-Meir survival estimates with Cox regression were used to determine the time to and risk factors for viral suppression, defined as two consecutive undetectable viral loads (<50 copies/ml) at least 30 days apart after initiation of cART. RESULTS: A total of 228 children were enrolled between December 2014 and December 2018. The time to viral suppression was significantly shorter among children initiating cART after 5 ≤ 5 vs. years or less of age [adjusted hazard ratio (aHR) 1.57, 95% confidence interval (CI) 1.13-2.20], among those born after 2010 vs. prior (aHR 1.71, 95% CI 1.04-2.79), and among those without child protection services involvement (aHR 1.44, 95% CI 1.03-2.01). Overall, 27% of children had a viral rebound within 3 years of achieving viral suppression; the risk of viral rebound was significantly lower among children initiating cART after 5 vs. 5 years or less of age [adjusted odds ratio (aOR): 0.32, 95% CI 0.13-0.81], those whose families had not received social assistance (aOR 0.16, 95% CI 0.06-0.46), and females vs. males (aOR 0.51, 95% CI 0.26-0.99). CONCLUSION: Only 73% of the children in the Early Pediatric Initiation Canada Child Cure Cohort had maintained viral suppression 3 years after it was first achieved. Age at cART initiation, and socioeconomic factors were predictors of both time to viral suppression and risk of viral rebound in this cohort.

"Getting to Zero New HIV Infections in the Caribbean": Knowledge and Attitudes Toward Male Circumcision Among Adolescent Males in The Bahamas.

Male circumcision (MC) plays a significant role in reducing new HIV infections, particularly in high prevalence countries. This cross-sectional study assesses the prevalence of MC and attitudes toward MC among youth aged 15-18 years in The Bahamas, a medium HIV prevalence country. The survey included 797 young men who completed a questionnaire on MC. Data analyses included chi-squared tests. The self-reported prevalence of MC among youth was 16.7% (121/759). Most of the circumcised youth were circumcised as infants, 84% (107/121) were pleased with their circumcision, and 71% would recommend it to others. For uncircumcised youth, 35% (189/533) would consider voluntary male circumcision (VMC) and 26% would recommend MC to others. In all scenarios, circumcised youth were more likely to be positive about MC. Among uncircumcised young men, being older (17-18 years compared to 15-16 years) was the only variable statistically associated with considering MC or recommending MC. After being presented with information on the benefits of MC for HIV prevention, the number of men who were positive about MC increased. Most of the young men in this cohort would consider VMC for reducing HIV incidence. Also, many stated that, if they had a male child, they would have him circumcised. The attitudes of these youth emphasize the need to provide information on HIV in addition to general health benefits of MC if there were to be a sustainable MC program within this population.

Brief Report: Higher Levels of Angiopoietin-1 Are Associated With Early and Sustained Viral Suppression in Children Living With Vertically Acquired HIV.

BACKGROUND: Systemic inflammation, platelet dysfunction, and endothelial activation persist in people living with HIV despite sustained virologic suppression (SVS) with combined antiretroviral therapy (cART) and may lead to complications such as atherosclerosis and cardiovascular disease. Angiopoietin-1 (Ang-1) is a key regulator of angiogenesis and endothelial activation and has been studied as an objective biomarker in disease states such as atherosclerosis, sepsis, and severe malaria. SETTING: Eight pediatric HIV care centers across Canada. METHODS: Cross-sectional study of 61 children living with vertically acquired HIV on cART with undetectable RNA viral load. Plasma levels of Ang-1 were measured by ELISA and analyzed in relation to clinical characteristics abstracted from medical records. RESULTS: Ang-1 levels were directly correlated with clinical indices of virologic control: cumulative proportion of life on effective cART (ρ = +0.35, P = 0.0078) and cumulative proportion of life with SVS (ρ = +0.36, P = 0.0049). Furthermore, higher Ang-1 levels were associated with younger age at SVS (ρ = -0.56, P < 0.0001). These associations remained statistically significant in multivariable linear regression models adjusting for potential confounders (P < 0.05 for all associations). CONCLUSIONS: Early effective cART and SVS were associated with higher Ang-1 levels in children living with vertically acquired HIV-1.

Quality Metrics for Antimicrobial Stewardship Programs.

BACKGROUND: Antimicrobial stewardship programs (ASPs) are targeted to optimize antimicrobial use. However, pediatric metrics used to measure outcomes of ASPs are not well established. Our aim for this project was to identify, refine, and develop consensus on standard metrics for pediatric ASPs. METHODS: By using a modified Delphi process, 2 surveys were sent to experts and stakeholders to establish consensus on the utility of metrics. These were subdivided into 4 ASP domains: (1) antimicrobial consumption, (2) microbiologic outcomes, (3) clinical outcomes, and (4) process measures. Respondents were asked to rank the scientific merit, impact, feasibility, and accountability of each metric. Metrics with ≥75% agreement for scientific merit were included and metrics with ≤25% agreement were discarded. Consensus was finalized with a face-to-face meeting and final survey. RESULTS: Thirty-eight participants from 15 pediatric hospitals across Canada completed all 3 rounds of the Delphi survey. In the domain of antimicrobial consumption, the 2 selected metrics were (1) days of therapy per 1000 patient-days and (2) total antimicrobial days. The clinical and process outcomes chosen were (1) 30-day readmission rate and (2) adherence to ASP recommendations, respectively. A microbiologic outcome was felt to be important and feasible, but consensus could not be obtained on a measure. Several barriers to implementation of the metrics were identified, including information technology limitations at various centers. CONCLUSIONS: We obtained consensus on 4 metrics to evaluate pediatric antimicrobial stewardship activities in Canada. Adoption of these metrics by pediatric ASPs will facilitate measurement of outcomes nationally and internationally.

The conceptualization of stigma within a rehabilitation framework using HIV as an example.

Stigma theory is concerned with inclusion and opportunities that influence well-being. Rehabilitation is also concerned with social inclusion and well-being. This is a central concern in one of the leading rehabilitation theories, the World Health Organization's International Classification of Functioning, Disability and Health. Despite these shared concerns, the relationship between the fields of stigma and rehabilitation has not been well theorized to date. Using human immunodeficiency virus (HIV) as an example, this article presents an analysis of three ways that stigma may be conceptualized within the context of the International Classification of Functioning, Disability and Health. Three broad spheres of stigma are described: enacted, self, and structural stigma. These three forms of stigma are then aligned in unique ways with three particular constructs of the International Classification of Functioning, Disability and Health: participation restrictions, environmental, and personal contextual factors. This conceptualization illustrates how rehabilitation professionals and other practitioners, policy makers and researchers can better understand the dynamic and nuanced forms of stigma and how they relate to rehabilitation. Implications for rehabilitation This article enables rehabilitation professionals to better understand stigma as it relates to rehabilitation and human immunodeficiency virus. Rehabilitation professionals have the important job of allies and advocates for persons experiencing restrictions in these domains as a result of stigma.

Canadian Pediatric Antimicrobial Stewardship Programs: Current Resources and Implementation Characteristics.

Antimicrobial stewardship programs (ASPs) became an accreditation requirement for Canadian hospitals in 2013. Pediatric programs are in various stages of program development and implementation, with 93% of surveyed Canadian academic pediatric hospitals having established ASPs. The programs varied in their team composition, implementation of stewardship strategies, and measured metrics. Infect Control Hosp Epidemiol 2018;39:350-354.

Optimizing Blood Collection and Processing for Quantiferon-TB Gold in-Tube Testing Gives Low Rates of Indeterminate Results: Clinical Implications.

The rate of low-mitogen indeterminate interferon-gamma release assay results at a hospital with expert pediatric phlebotomy and rapid incubation of specimens was 0.96%. All low-mitogen indeterminate results were found to be associated with an immunocompromised or anergic state. We describe a child where an unexpected indeterminate interferon-gamma release assay test pointed to an underlying anergic condition and was of diagnostic significance.