Off-label Use of Long-Acting Injectable Antiretroviral Therapy: A Single Center Retrospective Review of Youth Living With HIV With Detectable HIV RNA Starting Injectable Therapy.

Nineteen youth living with HIV (YLWH) opted for injectable cabotegravir and rilpivirine without oral lead in and without achieving an undetectable HIV viral load (VL) for the 3 months prior to initiation. All achieved undetectable status within 3 months (3 injections) and maintained an undetectable status through 6-12 months of therapy.

Increased mortality in infants with abnormal T-cell receptor excision circles.

BACKGROUND: T-Cell Receptor Excision Circles based newborn screening (TREC-NBS) allows for early detection of T-cell lymphopenia in infants with primary immunodeficiency disorders (PIDD). The utility of abnormal TREC-NBS in infants without PIDD is not well studied. We sought to evaluate the association of abnormal TREC-NBS with mortality. METHODS: 365,207 TREC-NBS from October 2011 to December 2014 were reviewed. 467 newborns had abnormal screens and did not meet the criteria for a PIDD diagnosis. Cases were matched to controls (1:3) based on gestational age, birth weight, neonatal intensive care unit status (NICU), and race. Data were obtained through NBS, birth and death certificates records from the Michigan Department of Health and Human Services (MDHHS) databases. RESULTS: Infants with abnormal TREC-NBS had higher mortality even when PIDD was ruled-out. Transient abnormal TREC-NBS was not associated with higher mortality, but unresolved or late abnormal TREC-NBS was associated with higher mortality. Infants with late abnormal TREC-NBS had severe prematurity, lower birth weight, lower Apgar scores, and higher percentage of congenital anomalies. CONCLUSION: Infants with abnormal TREC-NBS may be at a higher risk of morbidity and mortality and should be carefully followed, especially if discharged home before a repeat screen can be completed. IMPACT: This study explores the risk factors and mortality for newborns with secondary T-cell lymphopenia captured on T-Cell Receptor Excision Circles based newborn screening (TREC-NBS). Abnormal TREC-NBS allows for prompt life-saving interventions for primary immunological conditions such as Severe Combined Immunodeficiency (SCID), but can also be associated with non-immunologic conditions. Unresolved and late abnormal TREC-NBS is associated with higher mortality even without primary immunodeficiency, likely detected in infants with more severe prematurity, lower birth weight, and congenital anomalies. TREC-NBS positive infants with secondary T-cell lymphopenia require special attention and close monitoring.

Treasure (Hunt for) Your Health! Addressing Pediatric Social Determinants of Health Through Child-Friendly Community Engagement Events.

Social determinants of health (SDoH), including factors such as education level, housing, poverty, racism, and food insecurity and their impact on health outcomes have been well documented. The "Wayne Pediatrics Health and Nutrition Expo" held at Detroit's Eastern Market was an activity-based health and nutrition event addressing pediatric SDoH. Partnering with community organizations, the event had 10 stations addressing SDoH: access to a primary-care pediatrician; HIV-care and prevention; childhood literacy; clothing & winter coats; mental health and childhood development; nutrition; staying active; vaccination; and food insecurity. The free, public event featured a child-themed treasure hunt and map, music, giveaways, and live demonstrations, all in a family-friendly park atmosphere. While SDoH are considered "non-medical" factors that contribute to health and may be difficult to completely address for any individual child, our practice addressed several key SDoH at a single-day, hands-on, child-friendly community event based on the local needs of children.

Information, Motivation, Behavioral Skills Model in Youth Newly Starting Antiretroviral Treatment.

An understanding of adherence among youth newly starting antiretroviral therapy (ART) is critical but understudied. The information-motivation-behavioral skills (IMB) model is often used to understand health behaviors, but has rarely been studied in youth with HIV. In a multi-site sample of 153 youth newly starting ART, structural equation modeling was utilized to test this model. The model was generally supported with information and behavioral skills directly related to the decision to adhere, while motivation was indirectly related through behavioral skills. Results suggest that interventions focusing on improving IMB constructs for medication adherence are important for preventing non-adherence in youth newly starting ART.

RESUMEN: El entendimiento de la adherencia en jóvenes que recién comienzan ART es fundamental, pero se ha estudiado poco. El modelo de información-motivación-habilidades conductuales (IMB, por sus siglas en inglés) se usa a menudo para comprender los comportamientos de salud, pero rara vez se ha estudiado en jóvenes que viven con el VIH. En una muestra de múltiples sitios de 153 jóvenes que recién comenzaban ART, se utilizó el análisis de ecuaciones estructurales para probar este modelo. En general, el modelo fue apoyado con información y habilidades conductuales directamente relacionadas con la decisión de adherirse, mientras que la motivación se relacionó indirectamente a través de las habilidades conductuales. Los resultados sugieren que las intervenciones que se enfocan en mejorar los aspectos del modelo IMB para la adherencia al medicamento son importantes para prevenir la falta de adherencia en los jóvenes que recién comienzan ART.

Review of Treatment for Adenosine Deaminase Deficiency (ADA) Severe Combined Immunodeficiency (SCID).

Adenosine deaminase deficiency (ADA) is a purine salvage pathway deficiency that results in buildup of toxic metabolites causing death in rapidly dividing cells, especially lymphocytes. The most complete form of ADA leads to severe combined immune deficiency (SCID). Treatment with enzyme replacement therapy (ERT) was developed in the 1970s and became the treatment for ADA SCID by the 1980s. It remains an option for some infants with SCID, and a stopgap measure for others awaiting curative therapy. For some infants with ADA SCID who have matching family donors hematopoietic stem cell transplant (HSCT) is an option for cure. Gene therapy for ADA SCID, approved in some countries and in trials in others, is becoming possible for more infants with this disorder. This review covers the history of ADA SCID, the treatment options to date and particularly the history of the development of gene therapy for ADA SCID and the current state of the risks and benefits of the gene therapy option.

Newborn tandem mass spectroscopy screening for adenosine deaminase deficiency.

BACKGROUND: Newborn screening (NBS) by means of T cell receptor excision circles (TREC) is now universal in the United States, Puerto Rico, and the Navajo Nation as a strategy to identify severe combined immunodeficiency (SCID) in newborns. Owing to the characteristics of adenosine deaminase (ADA) deficiency, a small but important number of cases can be missed by this screening. OBJECTIVE: To evaluate the results of the first year statewide NBS for ADA by means of dried blood spot NBS. METHODS: On October 7, 2019, the state of Michigan began screening newborn dried blood spots for ADA deficiency by means of the Neobase-2 tandem mass spectroscopy (TMS) kit. We report 1 known case of ADA deficiency in the 18 months before screening. We then reviewed the results of the first 2 years of TMS ADA screening in Michigan. RESULTS: There was 1 patient with ADA deficiency known to our centers in the 18 months before initiation of TMS ADA screening; this patient died of complications of their disease. In the first 2 years of TMS ADA NBS, 206,321 infants were screened, and 2 patients had positive ADA screen results. Both patients had ADA deficiency confirmed through biochemical and genetic testing. One patient identified also had a positive TREC screen and was confirmed to have ADA-SCID. CONCLUSION: In our first 2 years, TMS NBS for ADA deficiency identified 2 patients with ADA deficiency at negligible cost, including 1 patient who would not have been identified by TREC NBS. This report provides initial evidence of the value of specific NBS for ADA deficiency.

Randomized Controlled Trial of a Remote Coaching mHealth Adherence Intervention in Youth Living with HIV.

Youth living with HIV (YLWH) in the US have low rates of viral suppression (VS). In a prospective randomized clinical trial (ATN152) that enrolled 89 YLWH on antiretroviral therapy (ART) with detectable viral load, we evaluated a 12 week triggered escalating real-time adherence (TERA) intervention with remote coaching, electronic dose monitoring (EDM), and outreach for missed/delayed doses compared to standard of care (SOC). Median [Q1, Q3] percent days with EDM opening was higher in TERA (72% (47%, 89%)) versus SOC (41% (21%, 59%); p < 0.001) and incidence of numbers of 7 day gaps between openings were lower (TERA to SOC ratio: 0.40; 95% CI 0.30, 0.53; p < 0.001). There were no differences in VS at week 12 (TERA 35%; 95% CI 21%, 51% versus SOC 36%; 95% CI 22%, 51%; p > 0.99) or later time-points. The intervention improved adherence but not VS in heavily ART-experienced YLWH. Remote coaching more closely tailored to the unique dosing patterns and duration of need for youth struggling to reach VS warrants further investigation.

Inborn Errors of Immunity Associated With Type 2 Inflammation in the USIDNET Registry.

Background: Monogenic conditions that disrupt proper development and/or function of the immune system are termed inborn errors of immunity (IEIs), also known as primary immunodeficiencies. Patients with IEIs often suffer from other manifestations in addition to infection, and allergic inflammation is an increasingly recognized feature of these conditions. Methods: We performed a retrospective analysis of IEIs presenting with allergic inflammation as reported in the USIDNET registry. Our inclusion criteria comprised of patients with a reported monogenic cause for IEI where reported lab eosinophil and/or IgE values were available for the patient prior to them receiving potentially curative therapy. Patients were excluded if we were unable to determine the defective gene underlying their IEI. Patients were classified as having eosinophilia or elevated IgE when their record included at least 1 eosinophil count or IgE value that was greater than the age stratified upper limit of normal. We compared the proportion of patients with eosinophilia or elevated IgE with the proportion of samples in a reference population that fall above the upper limit of normal (2.5%). Results: The query submitted to the USIDNET registry identified 1409 patients meeting inclusion criteria with a monogenic cause for their IEI diagnosis, of which 975 had eosinophil counts and 645 had IgE levels obtained prior to transplantation or gene therapy that were available for analysis. Overall, 18.8% (183/975) of the patients evaluated from the USIDNET registry had eosinophilia and 20.9% (135/645) had an elevated IgE. IEIs caused by defects in 32 genes were found to be significantly associated with eosinophilia and/or an elevated IgE level, spanning 7 of the 10 IEI categories according to the International Union of Immunological Societies classification. Conclusion: Type 2 inflammation manifesting as eosinophilia or elevated IgE is found in a broad range of IEIs in the USIDNET registry. Our findings suggest that allergic immune dysregulation may be more widespread in IEIs than previously reported.

Chronic Granulomatous Disease With Inflammatory Bowel Disease: Clinical Presentation, Treatment, and Outcomes From the USIDNET Registry.

BACKGROUND: Chronic granulomatous disease (CGD) is an inborn error of immunity caused by defects in the phagocytic nicotinamide adenine dinucleotide phosphate oxidase complex, leading to increased susceptibility to infection and inflammatory autoimmune diseases. Up to 50% of patients have gastrointestinal (GI) involvement and meet diagnostic criteria for inflammatory bowel disease (CGD-IBD). OBJECTIVE: We analyzed patients with CGD from the US Immunodeficiency Network (USIDNET) registry to determine whether IBD changes the presentation, treatment, and outcomes of patients with CGD. METHODS: A retrospective evaluation of CGD cases from the USIDNET registry was completed. CGD-IBD was defined as the presence of any major physician-reported inflammatory, noninfectious GI disease manifestation. Demographic information, conditions, infections, antimicrobial therapies, immunomodulator use, and hematopoietic stem cell transplantation data were analyzed. RESULTS: Of 194 patients with a diagnosis of CGD, 96 met criteria for IBD and 98 were categorized in the non-IBD group. Patients with CGD-IBD had an increased rate of infection compared with the non-IBD group (0.66 vs 0.36 infections/patient/year). Enteric organism infections were more common in patients with IBD. Immunomodulators were used at a significantly higher percentage in patients with IBD compared with patients without IBD (80% vs 56%, P < .001). Of the entire CGD cohort, 17 patients died (8.8%), with no significant difference between patients with IBD and patients without IBD (P = 1.00). CONCLUSION: Infectious events, enteric organism infections, and use of immunomodulatory drugs were higher in patients with IBD than patients without IBD; however, mortality was not increased. Patients with CGD and concurrent IBD are at increased risk for disease complications, supporting the importance of early recognition, diagnosis, and treatment.

Tailored Motivational Interviewing (TMI): A Pilot Implementation-Effectiveness Trial to Promote MI Competence in Adolescent HIV Clinics.

This brief report describes results of piloted Tailored Motivational Interviewing (TMI). Tailoring focused on site-specific training needs, target patient behaviors, and implementation facilitators and barriers that staff anticipated. Participating staff (N = 31) at two adolescent HIV clinics completed a pre-training qualitative interview (N = 27), and MI competency assessments based on three pre- and six post-training standard patient role-plays (N = 27). Results included pre- to post-training MI competence improvement (t (153) = - 4.13, p ≤ 0.001) and change in competency category distribution (X2 = (2, N = 155) = 15.72, p ≤ 0.001), providing initial support for the implementation of TMI in adolescent HIV clinic settings.

Humoral Immune Deficiencies of Childhood.

The most common primary immune deficiencies are those of the humoral immune system, and most of these present in childhood. The severity of these disorders ranges from transient deficiencies to deficiencies that are associated with a complete loss of ability to make adequate or functional antibodies, and have infectious as well as noninfectious complications. This article reviews, in a case-based discussion, the most common of the humoral immune deficiencies; their presentations, diagnoses, treatments; and, when known, the genetic defects.

Innate Immunity.

The innate immune response system forms an important line of defense by deploying a limited number of receptors specific for conserved microbial components. This deployment generates a rapid inflammatory response, while activating the adaptive immune system. Improvements in our understanding of the innate immune system have allowed us to explore various therapeutic strategies via modulation of the immune response.

Newborn Screening for Severe Combined Immunodeficiency.

The T-cell receptor excision circle (TREC) assay is an effective screening tool for severe combined immunodeficiency (SCID). The TREC assay was designed to detect typical SCID and leaky SCID, but any condition causing low naïve T-cell counts will also be detected. Newborn screening for SCID using the TREC assay has proven itself to be highly sensitive and cost-efficient. This review covers the history of SCID newborn screening, elaborates on the SCID subtypes and TREC assay limitations, and discusses diagnostic and management considerations for infants with a positive screen.