Congenital Cytomegalovirus Testing Outcomes From the ValEAR Trial.

OBJECTIVE: To determine the positivity rate of congenital cytomegalovirus (cCMV) testing among universal, hearing-targeted CMV testing (HT-cCMV) and delayed targeted dried blood spot (DBS) testing newborn screening programs, and to examine the characteristics of successful HT-cCMV testing programs. STUDY DESIGN: Prospective survey of birth hospitals performing early CMV testing. SETTING: Multiple institutions. METHODS: Birth hospitals participating in the National Institutes of Health ValEAR clinical trial were surveyed to determine the rates of cCMV positivity associated with 3 different testing approaches: universal testing, HT-cCMV, and DBS testing. A mixed methods model was created to determine associations between successful HT-cCMV screening and specific screening protocols. RESULTS: Eighty-two birth hospitals were surveyed from February 2019 to December 2021. Seven thousand six hundred seventy infants underwent universal screening, 9017 infants HT-cCMV and 535 infants delayed DBS testing. The rates of cCMV positivity were 0.5%, 1.5%, and 7.3%, respectively. The positivity rate for universal CMV screening was less during the COVID-19 pandemic than that reported prior to the pandemic. There were no statistically significant drops in positivity for any approach during the pandemic. For HT-cCMV testing, unique order sets and rigorous posttesting protocols were associated with successful screening programs. CONCLUSION: Rates of cCMV positivity differed among the 3 approaches. The rates are comparable to cohort studies reported in the literature. Universal CMV prevalence decreased during the pandemic but not significantly. Institutions with specific order set for CMV testing where the primary care physician orders the test and the nurse facilitates the testing process exhibited higher rates of HT-cCMV testing.

Efficacy, Safety, and Tolerability of Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate Fixed-Dose Combination Tablets in Adolescents Living With HIV: Results Through Week 96 from IMPAACT 2014.

BACKGROUND: IMPAACT 2014 study is a phase I/II, multicenter, open-label, nonrandomized study of doravirine (DOR) co-formulated with lamivudine (3TC) and tenofovir disoproxil fumarate (TDF) as fixed-dose combination (DOR FDC) in adolescents with HIV-1. We report the efficacy, safety, and tolerability of DOR FDC through 96 weeks. METHODS: Participants were adolescents aged 12 to <18 years who weighed at least 45 kg and who were either antiretroviral (ARV)-naïve or virologically suppressed without documented resistance mutations to DOR/3TC/TDF. The efficacy endpoint was the proportion of participants with HIV-1 RNA <40 copies/mL assessed at weeks 48 and 96 using the observed failure approach. Safety and tolerability outcomes were incidence of adverse events (AEs) and treatment discontinuations. RESULTS: A total of 45 adolescents, median age 15 (range, 12-17) years, 58% females, were enrolled and 2 (4.4%) participants were ARV naïve. Of the 45 participants, 42 (93.3%) completed the study and 41 (91.1%) completed the study treatment. At week 48, 41/42 (97.6%; 95% confidence interval [CI], 87.4-99.9) and week 96, 37/40 (92.5%; 95% CI, 79.6-98.4) participants had achieved or maintained HIV-1 RNA <40 copies/mL. There were no treatment-related discontinuations due to AEs and no drug-related AEs ≥grade 3 or deaths. CONCLUSIONS: We found once-daily dosing of DOR FDC to be safe and well tolerated for maintaining viral suppression through 96 weeks in adolescents living with HIV-1.

A novel formulation enabled transformation of 3-HIV drugs tenofovir-lamivudine-dolutegravir from short-acting to long-acting all-in-one injectable.

OBJECTIVE: To develop an injectable dosage form of the daily oral HIV drugs, tenofovir (T), lamivudine (L), and dolutegravir (D), creating a single, complete, all-in-one TLD 3-drug-combination that demonstrates long-acting pharmacokinetics. DESIGN: Using drug-combination-nanoparticle (DcNP) technology to stabilize multiple HIV drugs, the 3-HIV drugs TLD, with disparate physical-chemical properties, are stabilized and assembled with lipid-excipients to form TLD-in-DcNP . TLD-in-DcNP is verified to be stable and suitable for subcutaneous administration. To characterize the plasma time-courses and PBMC concentrations for all 3 drugs, single subcutaneous injections of TLD-in-DcNP were given to nonhuman primates (NHP, M. nemestrina ). RESULTS: Following single-dose TLD-in-DcNP , all drugs exhibited long-acting profiles in NHP plasma with levels that persisted for 4 weeks above predicted viral-effective concentrations for TLD in combination. Times-to-peak were within 24 hr in all NHP for all drugs. Compared to a free-soluble TLD, TLD-in-DcNP provided exposure enhancement and extended duration 7.0-, 2.1-, and 20-fold as AUC boost and 10-, 8.3-, and 5.9-fold as half-life extension. Additionally, DcNP may provide more drug exposure in cells than plasma with PBMC-to-plasma drug ratios exceeding one, suggesting cell-targeted drug-combination delivery. CONCLUSIONS: This study confirms that TLD with disparate properties can be made stable by DcNP to enable TLD concentrations of 4 weeks in NHP. Study results highlighted the potential of TLD-in-DcNP as a convenient all-in-one, complete HIV long-acting product for clinical development.

A Cross-Sectional Survey of Pediatric Infectious Disease Physicians' Approach to Congenital Cytomegalovirus Infection.

Congenital cytomegalovirus (cCMV) continues to be a major public health care issue due to its high prevalence throughout the world. However, there is a paucity of studies evaluating how providers manage this infection. This study surveyed North American Pediatric Infectious Disease (PID) physicians to elicit their approach towards the evaluation and treatment of this condition. Thirty-two PID physicians responded to this survey. Institutional testing and screening for cCMV were infrequently reported. The respondents in general agreed upon most laboratory and diagnostic testing except for neuroimaging. For those tests, there was a disparity in indications for head ultrasound versus brain MRI imaging. Most (68.8%) agreed with the clinical practice of starting valganciclovir in an infant less than 1 month of age with one sign or symptom of disease, and 62.5% would do so for an infant with isolated sensorineural hearing loss. However, only 28.1% would treat cCMV-infected infants older than 1 month of age. In conclusion, few healthcare institutions represented by PID physicians in this cohort had a cCMV screening or testing initiative, yet most respondents would test at a much higher level based on their clinical practice. While there is general consensus in evaluation and treatment of these children, there are disparities in practices regarding neuroimaging and indications for antiviral treatment with respect to age and severity of disease. There is a great need for an evidence based policy statement to standardize cCMV workup and treatment.

The theatre of depression: a role for physical therapy.

INTRODUCTION: The world's population is experiencing an increasing prevalence of depressive disorders. A comprehensive literature review identifies a schism between current medical interventions and the increasing prevalence. Current treatment paradigms warrant analysis. OBJECTIVE: This manuscript theorizes an interdisciplinary team inclusive of physiotherapy as a standard would reverse the increasing prevalence. Physiotherapists' musculoskeletal expertise and biopsychosocial approach play a valuable role in mental health. METHODS: A clinical narrative review of depression, including parallels with chronic pain, is provided as a substantive foundation. The review includes challenges in primary care as the gateway to mental health. Depression's underlying mechanisms, standard interventions, current theories, and future paradigms are explored. RESULTS: A theoretical construct was formulated. This construct identified compromised emotion-regulation and self-efficacy as common dysfunctions that enables and perpetuates depression. Physical activity with cognitive reappraisals positively influences these common dysfunctions and improves general intervention outcomes. The psychologically informed physiotherapist is defined. Physiotherapists can provide functional interventions and cognitive reappraisals that address biopsychosocial needs and build resilience. CONCLUSION: Individualized physical and functional activity that facilitate therapeutic alliance, functional improvements, cognitive reappraisals, emotion-regulation and self-efficacy delivered by a physiotherapist provide sustainable behavioral change and completes the interdisciplinary mental health team.

Pharmacokinetics, Tolerability, and Safety of Doravirine and Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate Fixed-Dose Combination Tablets in Adolescents Living With HIV: Week 24 Results From IMPAACT 2014.

BACKGROUND: We studied the pharmacokinetics (PK) and safety of 100-mg doravirine and doravirine/lamivudine/tenofovir disoproxil fumarate fixed-dose combination (100/300/300 mg DOR FDC) treatment in adolescents with HIV-1. METHODS: Adolescents ages 12 to younger than 18 years were enrolled in 2 sequential cohorts. Cohort 1 evaluated intensive PK and short-term safety of 100-mg single-dose doravirine in adolescents ≥35 kg. Cohort 2 participants either initiated treatment with DOR FDC (antiretroviral (ARV)-naïve) or switched to DOR FDC from a previous ARV regimen (virologically suppressed). The first 10 Cohort 2 participants had intensive PK evaluations, and safety, sparse PK, and HIV RNA were assessed through week 24. RESULTS: Fifty-five adolescents, median age 15.0 years and baseline weight 51.5 kg, were enrolled. Nine participants completed Cohort 1 PK assessments (8 of the 9 participants weighed ≥45 kg) and 45 initiated study drug in Cohort 2. The doravirine geometric mean (GM) AUC 0-∞ was 34.8 µM∙hour, and the GM C 24 was 514 nM after a single dose, with a predicted steady-state GM C 24,ss,pred of 690 nM. Cohort 2 enrolled adolescents weighing ≥45 kg. Plasma concentrations of doravirine, tenofovir, and lamivudine achieved by Cohort 2 participants were similar to those reported in adults. No drug-related serious or grade 3 or 4 adverse events occurred. Forty-two of 45 participants (93.3%; 95% CI: [81.7, 98.6]) achieved or maintained HIV-1 RNA <40 copies/mL. CONCLUSIONS: Doravirine and DOR FDC achieved target PK in adolescents with HIV-1. DOR FDC was well-tolerated and maintained excellent virologic efficacy through 24 weeks, offering a favorable option for adolescents.

HIV Transmission Through Premastication.

Premastication is a potential route of transmission of HIV from caregiver to child. We report the case of a 13-month-old Alaska Native child from rural Alaska who presented with failure to thrive, recurrent pneumonias, severe dental decay, and dysphagia. The mother was HIV-uninfected. Respiratory failure prompted transfer to a children's hospital outside of Alaska where the child received a diagnosis of HIV infection. A grandparent who had been acting as primary caregiver was discovered to be HIV-infected with detectable viral load resulting from intermittent nonadherence to her medication regimen. This grandparent reported feeding the child premasticated food. Sequencing of the hypervariable C2V5 region of the HIV envelope gene in both patients demonstrated less than 0.05% variation, consistent with transmission from grandparent to child. Health care providers should be aware that transmission of HIV can occur via premastication, educate parents and caregivers regarding this risk, and rigorously pursue HIV testing when indicated even in children with HIV-uninfected mothers.

Neonatal Herpes Simplex Virus Infection: Epidemiology and Outcomes in the Modern Era.

BACKGROUND: Over the past several decades, there have been advances in diagnosis and treatment of neonatal herpes simplex virus (HSV) disease. There has been no recent comprehensive evaluation of the impact of these advances on the management and outcomes for neonates with HSV. METHODS: Clinical data for initial presentation, treatment, and outcomes were abstracted from medical records of neonates with HSV treated at Seattle Children's Hospital between 1980 and 2016. RESULTS: One hundred thirty infants with a diagnosis of neonatal HSV were identified. Between 1980 and 2016, high-dose acyclovir treatment for neonatal HSV infection increased from 0% to close to 95%, with subsequent decrease in overall HSV-related mortality from 20.9% to 5.6%. However, even among infants treated with high-dose acyclovir, mortality was 40.9% for infants with disseminated (DIS) disease, and only 55% of infants with central nervous system (CNS) disease were without obvious neurologic abnormalities at 24 months. Over the study period, the time between initial symptoms and diagnosis decreased. Skin recurrences were more common with HSV-2 than HSV-1 (80% vs 55%; P = .02) and in infants with lesions at initial diagnosis (76% vs 47%; P = .02). CONCLUSION: Changes in the standard of care for management of neonatal HSV disease have led to improvements in timeliness of diagnosis and outcome but mortality in infants with DIS disease and neurologic morbidity in infants with CNS disease remain high. Future research should focus on prevention of perinatal infection and subsequent recurrences.

Institutionally chartered Data and Safety Monitoring Boards: structured approaches to assuring participant safety in clinical research.

Data and Safety Monitoring Boards (DSMBs) derived from the need to monitor large federally funded multi-center clinical trials and evolved to include commercial and other large and complex trials. Eventually, academic health centers also created institutionally focused trial monitoring mechanisms. The basic general principles that define traditional DSMBs extend to the institutional level. The primary responsibilities are assuring safety of the participants, preserving the integrity of the trial, and ensuring the reliability of the results. Institutionally chartered DSMBs meet these responsibilities but usually have fewer members, have a structure specific to the needs of the trial, are more focused and/or have different scope reviewing smaller, single site, higher risk, and investigator-initiated studies and are flexible to accommodate institution-specific requirements and approaches. Their purpose is to meet the responsibilities of oversight for safety and data integrity, ensure proper study design, rigor and conduct, as well as provide statistical support appropriate to the setting of the research. Academic health centers should recognize the importance and existence of institution level safety and data monitoring and provide support as much as possible. Investigators should have sufficient resources available to assemble DSMBs. The Clinical and Translational Science Awards Collaborative DSMB Workgroup provides an online manual to assist investigators.

Atypical Severe Shock-like Reactions in Adolescents After Trimethoprim-Sulfamethoxazole Therapy.

Severe drug hypersensitivity reactions to antibiotics are rare but trimethoprim-sulfamethoxazole (TMP-SMX) is uniquely associated with numerous and varied manifestations including a reaction resembling septic shock, first observed in human immunodeficiency virus (HIV)/AIDS patients. Over the past 25 years about 20 cases have been reported and an association with the virus and related immune system dysregulation was assumed. However, recent reports in adults have recognized similar shock-like reactions in non-HIV infected individuals. Here we review severe TMP-SMX hypersensitivity reactions and within the context of these known reactions, describe three non-HIV infected adolescent patients with shock-like reactions to TMP-SMX observed in one institution over 1.5 years.

Feasibility of connecting regional research programs to national multisite trials emanating from the CTSA Trial Innovation Network.

A collaborative research model was developed and tested to enable regional healthcare systems to join multisite clinical trials emanating from the Clinical and Translational Science Award (CTSA) Trial Innovation Network (TIN) by the Institute of Translational Health Sciences at the University of Washington and the Northwest Participant and Clinical Interactions (NW PCI) Network. The NW PCI is a collaborative group of regional research programs located at medical centers, healthcare systems, and universities across Washington, Wyoming, Alaska, Montana, and Idaho. This article describes the purpose, development, barriers, and initial experience with feasibility assessment for TIN-supported studies in the NW PCI. The tools and processes of the NW PCI Network were adapted to enable network sites to assess studies for clinical relevance and feasibility. Seven of seventeen TIN-supported studies were reviewed for consideration; three of which resulted in successful completion of study documentation for site selection by NW PCI sites. The NW PCI/TIN model can be adapted by other CTSAs to increase involvement of regional research programs in national multisite clinical research studies. Barriers to expanding TIN-supported trials to regional networks include short timelines for study document submissions, insufficient site reimbursement rates, and non-feasible study designs.

Laboratory Diagnosis of Sexually Transmitted Infections in Cases of Suspected Child Sexual Abuse.

Laboratory diagnosis of microbial agents associated with sexually transmitted infections plays an important role in both the care of victims of child sexual abuse (CSA) and the investigation of suspected CSA incidents, with law enforcement implications. Rapid and sensitive test results prompt immediate actions to treat and protect the victimized children. The development and maturation of automated nucleic acid amplification tests (NAATs) has greatly improved the assay sensitivity and specificity, with only a 1- to 2-h turnaround time. Unfortunately, the performance characteristics of NAATs have been determined largely with a few limited specimen types and evaluated in adults only. This minireview attempts to cover the scope of infectious agents potentially implicated in CSA, specimen collection, laboratory test modalities, and laboratory report constraints, further complicated by infrequently collected specimen types from prepubertal children <13 years of age.

Via media: Role and responsibilities of the independent safety officer.

Every research study that includes volunteer participants requires safety assurances in proportion to the risks of the study. Investigator-initiated clinical research can present unique regulatory challenges particularly for studies with a risk profile that warrants more oversight than minimal risk but less than for large, commercial, or high-risk research. The use of an independent safety officer (ISO) offers a middle way of right-sizing oversight to match the risk. ISOs are clinicians or researchers with relevant expertise who are independent of the investigator and the research study. Their relationship to the study is defined by a formal charter which is aligned with the protocol and Data and Safety Monitoring Plan to address the oversight process, responsibilities of the ISO, and clearly describe the variables to be monitored. The ISO responsibilities include reviewing safety data, adverse events, recruitment, demographics, study progress, data quality, protocol changes, and any new scientific information that pertains to the trial. Finally, the ISO reports in their review on any significant findings may propose modifications to the study or a need to stop the trial.

Hepatic, Renal, Hematologic, and Inflammatory Markers in HIV-Infected Children on Long-term Suppressive Antiretroviral Therapy.

BACKGROUND: Data on long-term toxicity of antiretroviral therapy (ART) in HIV-infected children are sparse. PENPACT-1 was an open-label trial in which HIV-infected children were assigned randomly to receive protease inhibitor (PI)- or nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based ART. METHODS: We examined changes in clinical, immunologic, and inflammatory markers from baseline to year 4 in the subset of children in the PENPACT-1 study who experienced viral suppression between week 24 and year 4 of ART. Liver enzyme, creatinine, and cholesterol levels and hematologic parameters were assessed during the trial. Cystatin C, high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), d-dimer, and soluble CD14 (sCD14) were assayed from cryopreserved specimens. RESULTS: Ninety-nine children (52 on PI-based and 47 on NNRTI-based ART) met inclusion criteria. The median age at initiation of ART was 6.5 years (interquartile range [IQR], 3.7-13.4 years), and 22% were aged <3 years at ART initiation; 56% of the PI-treated children received lopinavir/ritonavir, and 70% of NNRTI-treated children received efavirenz initially. We found no evidence of significant clinical toxicity in either group; growth, liver, kidney, and hematologic parameters either remained unchanged or improved between baseline and year 4. Total cholesterol levels increased modestly, but no difference between the groups was found. IL-6 and hs-CRP levels decreased more after 4 years in the NNRTI-based ART group. The median change in IL-6 level was -0.35 pg/ml in the PI-based ART group and -1.0 in the NNRTI-based ART group (P = .05), and the median change in hs-CRP level was 0.25 µg/ml in the PI-based ART group and -0.95 µg/ml in the NNRTI-based ART group (P = .005). CONCLUSION: These results support the safety of prolonged ART use in HIV-infected children and suggest that suppressive NNRTI-based regimens can be associated with lower levels of systemic inflammation.

Decline in CD4 T lymphocytes with monotherapy bridging strategy for non-adherent adolescents living with HIV infection: Results of the IMPAACT P1094 randomized trial.

INTRODUCTION: Management of persistently non-adherent youth living with HIV (YLHIV) with virologic failure (VF) on combination antiretroviral therapy (cART) remains challenging. One strategy has been using 3TC/ FTC monotherapy (3TC/FTC), which in the presence of the M184V resistance mutation, does not suppress viral replication nor select for additional drug resistance mutations, and reduces viral fitness with limited side effects. P1094 compared the immunologic outcome of continuing failing cART vs. switching to 3TC/FTC as a "bridging strategy" to subsequent suppressive cART for non-adherent YLHIV with pre-existing M184V resistance. MATERIALS & METHODS: Participants with documented nonadherence, M184V mutation, CD4+ T cell count ≥100 cells/mm3 and VF (HIV-1 plasma RNA ≥400 copies/mL (2.6 log10 HIV-1 RNA) were enrolled and randomized to continue failing cART vs. switch to 3TC/FTC. The primary endpoint (time to ≥30% CD4+ T cell decline or development of CDC class C events) at 28-weeks were assessed by Kaplan-Meier (K-M) curves in an intent-to-treat analysis. RESULTS: Thirty-three perinatally acquired YLHIV participants (16 continuing cART and 17 3TC/FTC) enrolled in the study. The median age, entry CD4+ T cell count, and viral load were 15 years (Inter-quartile range (IQR) 14-20), 472 cells/mm3 (IQR 384-651), and 4.0 log10HIV-1 RNA copies/ml (IQR 3.2-4.5), respectively. Five participants, all in the 3TC/FTC arm, reached the primary endpoint for absolute CD4+ T cell decline (p = 0.02, exact log-rank test comparing monotherapy to cART). The Kaplan-Meier estimate of probability of primary endpoint on 3TC/FTC at 28 weeks was 0.41 (standard error 0.14). There were no CDC class C events or deaths and no statistically significant difference in frequencies of adverse events between the arms. CONCLUSIONS: Non-adherent participants randomized to 3TC/FTC were more likely than those maintained on failing cART to experience a confirmed decline in CD4+ count of ≥30%. Although this study suffers from limitations of small sample size and premature discontinuation, the randomized comparison to continuing failing cART indicates that 3TC/FTC provides inferior protection from immunologic deterioration for non-adherent youth with M184V resistance. Better alternatives to 3TC/FTC such as ART with higher barriers to resistance and novel adherence and treatment strategies for nonadherent youth are urgently needed. TRIAL REGISTRATION: Clinical Trials.gov NCT01338025.

The interaction between equipoise and logistics in clinical trials: A case study.

INTRODUCTION: Equipoise is usually discussed as an ethical issue in clinical trials. However, it also has practical implications. BACKGROUND: Clinical equipoise is usually construed to mean uncertainty or disagreement among the expert clinician community. However, an individual physician's sense of equipoise may vary by location, based on the local standard of care or availability of specific treatment options, and these differences can affect providers' willingness to enroll participants into clinical trials. There are also logistical barriers to enrollment in international trials due to prolonged timelines for approvals by government agencies and ethical review boards. CASE STUDY: A multinational clinical trial of bridging strategies for treatment of non-adherent HIV-infected youth, experienced differing perceptions of equipoise due to disparities in availability of treatment options by country. Unfortunately, the countries with most demand for the trial were those where the approval process was most delayed, and the study was closed early due to slow accrual. DISCUSSION: When planning multicenter clinical trials, it is important to take into account heterogeneity among research sites and try to anticipate differences in equipoise and logistical factors between sites, in order to plan to address these issues at the design stage.

Safety and Efficacy of Atorvastatin in Human Immunodeficiency Virus-infected Children, Adolescents and Young Adults With Hyperlipidemia.

BACKGROUND: Human immunodeficiency virus (HIV)-infected children receiving antiretroviral therapy (ART) have increased prevalence of hyperlipidemia and risk factors for cardiovascular disease. No studies have investigated the efficacy and safety of statins in this population. METHODS: HIV-infected youth 10 to <24 years of age on stable ART with low-density lipoprotein cholesterol (LDL-C) ≥130 mg/dL for ≥6 months initiated atorvastatin 10 mg once daily. Atorvastatin was increased to 20 mg if LDL-C efficacy criteria (LDL-C < 110 mg/dL or decreased ≥30% from baseline) were not met at week 4. Primary outcomes were safety and efficacy. RESULTS: Twenty-eight youth initiated atorvastatin; 7 were 10-15 years and 21 were 15-24 years. Mean baseline LDL-C was 161 mg/dL (standard deviation 19 mg/dL). Efficacy criteria were met at week 4 by 17 of 27 (63%) participants. Atorvastatin was increased to 20 mg in 10 participants. Mean LDL-C decreased from baseline by 30% (90% confidence interval: 26%, 35%) at week 4, 28% (90% confidence interval: 23%, 33%) at week 24 and 26% (90% confidence interval: 20%, 33%) at week 48. LDL-C was less than 110 mg/dL in 44% at week 4, 42% at week 12 and 46% at weeks 24 and 48. Total cholesterol, non high-density lipoprotein (non-HDL)-C and apolipoprotein B decreased significantly, but IL-6 and high-sensitivity C-reactive protein did not. Two participants in the younger age group discontinued study for toxicities possibly related to atorvastatin. CONCLUSIONS: Atorvastatin lowered total cholesterol, LDL-C, non HDL-C and apolipoprotein B in HIV-infected youth with ART-associated hyperlipidemia. Atorvastatin could be considered for HIV-infected children with hyperlipidemia, but safety monitoring is important particularly in younger children.

Health Outcomes of International HIV-infected Adoptees in the US.

BACKGROUND: International adoption of HIV-infected children is becoming increasingly common. Their health has not yet been described. METHODS: HIV-infected international adoptees or refugees in foster care aged 0-20 years followed at Seattle Children's Hospital or Children's Hospital Colorado between January 1, 2004 and May 31, 2013 were included. Parameters were collected through retrospective chart review of baseline (first 6 months at study site) and annual follow-up visits. RESULTS: Africa (90%) was the primary region of origin for the 79 children who met inclusion criteria. Median follow-up was 3 years (range: 0-7). At baseline, acute malnutrition was uncommon (8%); however, stunting occurred in 32%. Most stunting resolved during the study period. The most common medical issues at baseline were dermatologic (Tinea and Molluscum contagiosum) and gastrointestinal (parasites and diarrhea). Almost half (48%) had either mental health issues or behavioral problems. Educational delays (50%) were also common. Upon adoption, only 1% was severely (CD4% < 15%) immunosuppressed. Fifty-nine (75%) were on antiretroviral therapy (ART); 45 of these (76%) had suppressed viral load (VL). Of 14 children on ART with detectable VL, 11 (79%) demonstrated non-nucleoside reverse transcriptase inhibitor resistance and 1 (7%) protease inhibitor resistance. CONCLUSIONS: In this cohort of HIV-infected international adoptees, severe immunosuppression was uncommon. Most medical issues were mild. Stunting was common at baseline but largely resolved. Mental health issues, behavioral problems, and educational delays were common. Most children were on ART at adoption and most of these showed suppressed VL. Non-nucleoside reverse transcriptase inhibitor mutations were present in most viremic children.

Research START: A Multimethod Study of Barriers and Accelerators of Recruiting Research Participants.

Under-recruitment into clinical trials is a common and costly problem that undermines medical research. To better understand barriers to recruitment into clinical trials in our region, we conducted a multimethod descriptive study. We initially surveyed investigators who had conducted or were currently conducting studies that utilized an adult or pediatric clinical research center (n = 92). We then conducted focus groups and key informant interviews with investigators, coordinators, and other stakeholders in clinical and translational research (n = 32 individuals). Only 41% of respondents reported that they had or were successfully meeting recruitment goals and 24% of the closed studies actually met their targeted recruitment goals. Varied reasons were identified for poor recruitment but there was not a single investigator or study "phenotype" that predicted enrollment outcome. Investigators commonly recruited from their own practice or clinic, and 29% used a manual electronic medical record search. The majority of investigators would utilize a service that provides recruitment advice, including feasibility assessment and consultation, easier access to the electronic health record and assistance with institutional review board and other regulatory requirements. Our findings suggest potential benefits providing assistance across a range of services that can be individualized to the varied needs of clinical and translational investigators.