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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.

Children 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: The optimal management of infants born to HIV-positive mothers who are untreated or have detectable viral load prior to delivery remains controversial. Despite the increasing use of combination antiretroviral therapy (cART) for post-exposure prophylaxis (PEP) of neonates at high risk of HIV infection, there is little safety and pharmacokinetic data to support this approach. The objective of this study was to evaluate the safety and tolerability of cART for PEP in HIV-exposed neonates. Methods: Retrospective study on 148 cART and 145 Zidovudine (ZDV) monotherapy-exposed infants identified from four Canadian centres where cART for PEP has routinely been prescribed in high-risk situations. Physician-reported adverse events and clinical outcomes were extracted by chart review. Haematological and growth parameters at birth, one and six months of age were compared between cART and ZDV-exposed infants using multivariate mixed effects modelling. Results: Non-specific signs and symptoms were reported in 10.2% of cART recipients versus none of the ZDV recipients. Treatment was discontinued prematurely in 9.5% of cART recipients versus 2.1% of ZDV recipients (p = 0.01). In the multivariate model, cART recipients had lower mean haemoglobin (decrease of 2.07 g/L) over the 6-month period compared with ZDV recipients (p = 0.04), but no effect was seen on absolute neutrophil count. cART recipients had lower weight and smaller head circumference at birth and one month of age compared with ZDV-exposed infants; these differences were no longer significant at six months of age. Conclusions: cART administered at treatment doses for PEP in neonates was generally well tolerated, though a higher incidence of non-specific signs and symptoms and early treatment discontinuation occurred among cART recipients. Keywords: Prevention of mother-to-child transmission; HIV; neonatal prophylaxis; safety; combination antiretroviral therapy., Introduction While the overall risk of perinatal HIV transmission in the developed world has decreased to less than 1%, transmission still occurs, most often due to failure to diagnose HIV [...]

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. 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. 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. 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. Rehabilitation 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The antibiotic vancomycin is used to treat Staphylococcus infections that are resistant to penicillin or other antibiotics. The most common side effect of vancomycin is the red man syndrome, which is characterized by the development of a local skin rash and/or hypotension (low blood pressure). The disorder usually resolves after discontinuing the drug. The prevalence of red man syndrome and factors that may predispose to this disorder were assessed. Of 650 children treated with vancomycin, 11 developed the red man syndrome. They were compared with 11 other vancomycin-treated children who did not develop the syndrome. Vancomycin was given for penicillin-resistant Staphylococcus infection or because of penicillin allergy in 73 percent of the children with an adverse reaction and 45 percent of those without a reaction. The average duration of the vancomycin infusion was 46 minutes in patients with the syndrome and 54 minutes in children without it. Slower infusion rates reduced or prevented the syndrome in five patients, indicating the relation of administration of this drug to the development of the side effect. The onset of red man syndrome usually occurred at the end of the infusion, but was also noted as early as 15 minutes after the start of the infusion. The disorder was characterized by a reddish rash on the face, neck, and ears, intense itching, symptoms of hypotension, watery and puffy eyes, a rapid heart rate, respiratory distress, dizziness, agitation, and a mild increase in body temperature. The rash usually disappeared within 20 minutes of stopping the vancomycin infusion. The development of the rash was not related to the blood levels of vancomycin, indicating that the red man syndrome is an idiosyncratic or unusual reaction, rather than a phenomenon that is dependent on the blood concentration of the drug. (Consumer Summary produced by Reliance Medical Information, Inc.)

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. [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]