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ObjectivesSeveral single-tablet regimens (STRs) are now available and are recommended for first-line antiretroviral therapy (ART); however, STR use for youth with HIV (YHIV) has not been systematically studied. We examined the characteristics associated with initiation of STRs versus multi-tablet regimens (MTRs) and the virological outcomes for youth with nonperinatally acquired HIV (nPHIV).MethodsA retrospective cohort study of nPHIV youth aged 13-24 years initiating ART between 2006 and 2014 at 18 US HIV clinical sites in the HIV Research Network was performed. The outcomes measured were initiation of STRs versus MTRs, virological suppression (VS) at 12 months, and time to VS. Demographic and clinical factors associated with initiation of STR versus MTR ART and VS ( 500 cells/μL (AOR 1.76; 95% CI 1.0-3.10). STR use was not associated with a shorter time to VS compared with MTR use [hazard ratio (HR) 1.07; 95% CI 0.90-1.28].ConclusionsUse of STR was associated with a greater likelihood of sustained VS 12 months after ART initiation in YHIV.

BACKGROUND: The extent to which drug-resistant human immunodeficiency virus type 1 (HIV-1) acquired through mother-to-child transmission (MTCT) or failed chemoprophylaxis populates viral reservoirs and limits responses to antiretroviral treatment in infants is unknown. METHODS: We evaluated the presence, type, and persistence of drug-resistant HIV-1 in pretreatment plasma and resting CD4(+) T cells from US infants enrolled in a multicenter, open-label, phase 1/2 treatment trial of lopinavir/ritonavir (Pediatric AIDS Clinical Trials Group Protocol 1030) in young infants. RESULTS: Twenty-two consecutively enrolled infants initiating highly active antiretroviral therapy at a median age of 9.7 weeks and treated for up to 96 weeks were studied. Drug-resistant HIV-1 was present in 5 (23.8%) of 21 infants analyzed; 4 (80.0%) had nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1, only 1 of whom had a history of receiving nevirapine chemoprophylaxis. All 4 infants had NNRTI-resistant variants other than the K103N mutation. The fifth infant had the M184V mutation. Drug-resistant virus was archived in the resting CD4(+) T cell latent reservoir in all 5 infants. CONCLUSIONS: The high rate, types, and early archiving of drug-resistant HIV-1 suggests that resistance testing be considered for infants, especially when an NNRTI-based regimen is planned. Furthermore, drug-resistance outcomes in infants should be an important secondary end point in MTCT trials. Copyright © 2007 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

During the past century the excitement of discovering antibiotics as a treatment of infectious diseases has given way to a sense of complacency and acceptance that when faced with antimicrobial resistance there will always be new and better antimicrobial agents to use. Now, with clear indications of a decline in pharmaceutical company interest in anti-infective research, at the same time when multi-drug resistant micro-organisms continue to be reported, it is very important to review the prudent use of the available agents to fight these micro-organisms. Injudicious use of antibiotics is a global problem with some countries more affected than others. There is no dearth of interest in this subject with scores of scholarly articles written about it. While over the counter access to antibiotics is mentioned as an important contributor towards injudicious antibiotic use in developing nations, as shown in a number of studies, there are many provider, practice and patient characteristics which drive antibiotic overuse in developed nations such as the United States. Recognizing that a thorough review of this subject goes far and beyond the page limitations of a review article we provide a summary of some of the salient aspects of this global problem with a focus towards readers practicing in developing nations. [ABSTRACT FROM AUTHOR]

Background: Case investigations and contact tracing are essential disease control measures used by health departments. Early in the pandemic, they were seen as a key strategy to stop COVID-19 spread. The CDC urged rapid action to scale up and train a large workforce and collaborate across public and private agencies to halt COVID-19 transmission., Methods: We developed a program for case investigation and contact tracing that followed CDC and local health guidelines, compliant with the Occupational Safety and Health Administration (OSHA) regulations and tailored to the needs and resources of our institution. Program staff were trained and assessed for competency before joining the program., Results: From March 2020 to May 2021, we performed 838 COVID-19 case investigations, which led to 136 contacts. Most employees reported a known SARS-CoV-2 exposure from the community ( n  = 435) or household ( n  = 343). Only seven (5.1%) employees were determined as more likely than not to have SARS-CoV-2 infection related to workplace exposure, and when so, lapses in following the masking recommendations were identified. Between June 2021-February 2022, our program adjusted to the demand of the different waves, particularly omicron, by significantly reducing the amount of data collected. No transmission from employees to patients or caregivers was observed during this period., Conclusion: Prompt implementation of case investigation and contact tracing is possible, and it effectively reduces workplace exposures. This approach can be adapted to suit the specific needs and requirements of various healthcare settings, particularly those serving the most vulnerable patient populations., Competing Interests: RH has served on advisory boards for Abbott Diagnostics and T2 Diagnostics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hijano, Dennis, Hoffman, Tang, Hayden, St. Jude COVID-19 Case Investigation and Contact Tracing Team, Gaur and Hakim.)

Introduction: Youth living with HIV in the US have low rates of viral suppression, in part because of challenges with antiretroviral therapy adherence., Methods: Daily dosing in the Adolescent Medicine Trials Network for HIV/AIDS Interventions 152 study, a randomized controlled trial of a 12-week adherence intervention (triggered escalating real-time adherence intervention) for viremic youth, compared with standard of care (SOC), was measured by electronic dose monitoring (EDM) throughout 48 weeks of follow-up. EDM data collected over the first 24 weeks were used to characterize patterns of antiretroviral therapy adherence with group-based trajectory models., Results: Four trajectory groups were identified among the 85 participants included in the analysis during the intervention phase of the study: (Worst) no interaction with EDM, (Declining) initially moderate EDM-based adherence followed by steep declines, (Good) initially high EDM-based adherence with modest declines, and (Best) consistently high EDM-based adherence. Being in the SOC arm, not being in school, higher evasiveness and panic decision-making scores, and lower adherence motivation were associated with higher odds of being in a worse trajectory group ( P < 0.05). A general decline in dosing was observed in the 12 weeks postintervention, when all participants were managed using SOC., Conclusions: Use of group-based trajectory models allowed a more nuanced understanding of EDM-based adherence over time compared with collapsed summary measures. In addition to the study intervention, other factors influencing EDM-based adherence included being in school, decision-making styles, and adherence-related motivation. This information can be used to design better intervention services for youth living with HIV., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Although numerous studies have evaluated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using cycle threshold (Ct) values as a surrogate of viral ribonucleic acid (RNA) load, few studies have used standardized, quantitative methods. We validated a quantitative SARS-CoV-2 digital polymerase chain reaction assay normalized to World Health Organization International Units and correlated viral RNA load with symptoms and disease severity., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: The objective of this study is to assess the utility of a nucleic acid amplification test-based approach to shorten isolation of healthcare workers (HCWs) with COVID-19 in the setting of the highly transmissible omicron variant., Methods: Between December 24, 2021, and January 5, 2022, HCWs who tested positive for SARS-CoV-2 were retested with PCR at least 5 days since onset of symptoms., Results: Forty-six sequential fully COVID-19 vaccinated HCWs who had tested positive for SARS-CoV-2 underwent follow-up testing. All the samples were confirmed as omicron variants and only four (8.7%) were negative in the follow-up test performed at a median of 6 (range 5-12) since onset of symptoms., Conclusions: Implementation of a test-based strategy is logistically challenging, increases costs, and did not lead to shorter isolation in our institution., (© 2022 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: COVID-19 has caused over 305 million infections and nearly 5.5 million deaths globally. With complete eradication unlikely, organizations will need to evaluate their risk and the benefits of mitigation strategies, including the effects of regular asymptomatic testing. We developed a web application and R package that provides estimates and visualizations to aid the assessment of organizational infection risk and testing benefits to facilitate decision-making, which combines internal and community information with malleable assumptions., Results: Our web application, covidscreen, presents estimated values of risk metrics in an intuitive graphical format. It shows the current expected number of active, primarily community-acquired infections among employees in an organization. It calculates and explains the absolute and relative risk reduction of an intervention, relative to the baseline scenario, and shows the value of testing vaccinated and unvaccinated employees. In addition, the web interface allows users to profile risk over a chosen range of input values. The performance and output are illustrated using simulations and a real-world example from the employee testing program of a pediatric oncology specialty hospital., Conclusions: As the COVID-19 pandemic continues to evolve, covidscreen can assist organizations in making informed decisions about whether to incorporate covid test based screening as part of their on-campus risk-mitigation strategy. The web application, R package, and source code are freely available online (see "Availability of data and materials")., (© 2022. The Author(s).)

To understand reinfection rates and correlates of protection for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we established eight different longitudinal cohorts in 2020 under the umbrella of the PARIS (Protection Associated with Rapid Immunity to SARS-CoV-2)/SPARTA (SARS SeroPrevalence And Respiratory Tract Assessment) studies. Here, we describe the PARIS/SPARTA cohorts, the harmonized assays and analysis that are performed across the cohorts, as well as case definitions for SARS-CoV-2 infection and reinfection that have been established by the team of PARIS/SPARTA investigators. IMPORTANCE Determining reinfection rates and correlates of protection against SARS-CoV-2 infection induced by both natural infection and vaccination is of high significance for the prevention and control of coronavirus disease 2019 (COVID-19). Furthermore, understanding reinfections or infection after vaccination and the role immune escape plays in these scenarios will inform the need for updates of the current SARS-CoV-2 vaccines and help update guidelines suitable for the postpandemic world.

Background: SJ733, a newly developed inhibitor of P. falciparum ATP4, has a favorable safety profile and rapid antiparasitic effect but insufficient duration to deliver a single-dose cure of malaria. We investigated the safety, tolerability, and pharmacokinetics of a multidose SJ733 regimen and a single-dose pharmacoboost approach using cobicistat to inhibit CYP3A4, thereby increasing exposure., Methods: Two multidose unboosted cohorts (n = 9) (SJ733, 300 mg and 600 mg daily for 3 days) followed by three single-dose boosted cohorts combining SJ733 (n = 18) (75-, 300-, or 600-mg single dose) with cobicistat (150-mg single dose) as a pharmacokinetic booster were evaluated in healthy volunteers (ClinicalTrials.gov: NCT02661373)., Findings: All participants tolerated SJ733 well, with no serious adverse events (AEs), dose-limiting toxicity, or clinically significant electrocardiogram or laboratory test findings. All reported AEs were Grade 1, clinically insignificant, and considered unlikely or unrelated to SJ733. Compared to unboosted cohorts, the SJ733/cobicistat-boosted cohorts showed a median increase in area under the curve and maximum concentration of 3·9 × and 2·6 ×, respectively, and a median decrease in the ratio of the major CYP3A-produced metabolite SJ506 to parent drug of 4·6 × . Incorporating these data in a model of parasite dynamics indicated that a 3-day regimen of SJ733/cobicistat (600 mg/150 mg daily) relative to a single 600-mg dose ± cobicistat would increase parasite clearance from 10 6 to 10 12 parasites/µL., Interpretation: The multidose and pharmacoboosted approaches to delivering SJ733 were well-tolerated and significantly increased drug exposure and prediction of cure. This study supports the further development of SJ733 and demonstrates an innovative pharmacoboost approach for an antimalarial., Funding: Global Health Innovative Technology Fund, Medicines for Malaria Venture, National Institutes of Health, and American Lebanese Syrian Associated Charities., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

COVID-19 remains a challenge worldwide, and testing of asymptomatic individuals remains critical to pandemic control measures. Starting March 2020, a total of 7497 hospital employees were tested at least weekly for SARS CoV-2; the cumulative incidence of asymptomatic infections was 5.64%. Consistently over a 14-month period half of COVID-19 infections (414 of 820, total) were detected through the asymptomatic screening program, a third of whom never developed any symptoms during follow-up. Prompt detection and isolation of these cases substantially reduced the risk of potential workplace and outside of workplace transmission. COVID-19 vaccinations of the workforce were initiated in December 2020. Twenty-one individuals tested positive after being fully vaccinated (3.9 per 1000 vaccinated). Most (61.9%) remained asymptomatic and in majority (75%) the virus could not be sequenced due to low template RNA levels in swab samples. Further routine testing of vaccinated asymptomatic employees was stopped and will be redeployed if needed; routine testing for those not vaccinated continues. Asymptomatic SARS-CoV-2 testing, as a part of enhanced screening, monitors local dynamics of the COVID-19 pandemic and can provide valuable data to assess the ongoing impact of COVID-19 vaccination and SARS-CoV-2 variants, inform risk mitigation, and guide adaptive, operational planning including titration of screening strategies over time, based on infection risk modifiers such as vaccination., Competing Interests: PGT is on the Scientific Advisory Board for Cytoagents Inc. RTH has served on advisory boards for Roche Molecular and Quidel Corporation. All other authors have no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and has since caused a global pandemic resulting in millions of cases and deaths. Diagnostic tools and serological assays are critical for controlling the outbreak, especially assays designed to quantitate neutralizing antibody levels, considered the best correlate of protection. As vaccines become increasingly available, it is important to identify reliable methods for measuring neutralizing antibody responses that correlate with authentic virus neutralization but can be performed outside biosafety level 3 (BSL3) laboratories. While many neutralizing assays using pseudotyped virus have been developed, there have been few studies comparing the different assays to each other as surrogates for authentic virus neutralization. Here, we characterized three enzyme-linked immunosorbent assays (ELISAs) and three pseudotyped vesicular stomatitis virus (VSV) neutralization assays and assessed their concordance with authentic virus neutralization. The most accurate assays for predicting authentic virus neutralization were luciferase- and secreted embryonic alkaline phosphatase (SEAP)-expressing pseudotyped virus neutralizations, followed by green fluorescent protein (GFP)-expressing pseudotyped virus neutralization, and then the ELISAs. IMPORTANCE The ongoing COVID-19 pandemic is caused by infection with severe acute respiratory syndrome virus 2 (SARS-CoV-2). Prior infection or vaccination can be detected by the presence of antibodies in the blood. Antibodies in the blood are also considered to be protective against future infections from the same virus. The "gold standard" assay for detecting protective antibodies against SARS-CoV-2 is neutralization of authentic SARS-CoV-2 virus. However, this assay can only be performed under highly restrictive biocontainment conditions. We therefore characterized six antibody-detecting assays for their correlation with authentic virus neutralization. The significance of our research is in outlining the advantages and disadvantages of the different assays and identifying the optimal surrogate assay for authentic virus neutralization. This will allow for more accurate assessments of protective immunity against SARS-CoV-2 following infection and vaccination.

The efficacy of coronavirus disease 2019 (COVID-19) vaccines administered after COVID-19-specific monoclonal antibody is unknown, and "antibody interference" might hinder immune responses leading to vaccine failure. In an institutional review board-approved prospective study, we found that an individual who received mRNA COVID-19 vaccination <40 days after COVID-19-specific monoclonal antibody therapy for symptomatic COVID-19 had similar postvaccine antibody responses to SARS-CoV-2 receptor binding domain (RBD) for 4 important SARS-CoV-2 variants (B.1, B.1.1.7, B.1.351, and P.1) as other participants who were also vaccinated following COVID-19. Vaccination against COVID-19 shortly after COVID-19-specific monoclonal antibody can boost and expand antibody protection, questioning the need to delay vaccination in this setting., Trial Registration: The St. Jude Tracking of Viral and Host Factors Associated with COVID-19 study; NCT04362995; https://clinicaltrials.gov/ct2/show/NCT04362995., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Malaria volunteer infection studies (VISs) accelerate new drug and vaccine development. In the induced blood-stage malaria (IBSM) model, volunteers are inoculated with erythrocytes infected with Plasmodium falciparum . Observations of elevated liver enzymes in the IBSM model with new chemical entities (NCEs) promoted an analysis of available data. Data were reviewed from eight IBSM studies of seven different NCEs, plus two studies with the registered antimalarial piperaquine conducted between June 2013 and January 2017 at QIMR Berghofer, Brisbane, Australia. Alanine aminotransferase (ALT) was elevated (> 2.5 times the upper limit of normal [×ULN]) in 20/114 (17.5%) participants. Of these, 8.9% (10/114) had moderate increases (> 2.5-5 × ULN), noted in seven studies of six different NCEs ± piperaquine or piperaquine alone, and 8.9% (10/114) had severe elevations (> 5 × ULN), occurring in six studies of six different NCEs ± piperaquine. Aspartate aminotransferase (AST) was elevated (> 2.5 × ULN) in 11.4% (13/114) of participants, across six of the 10 studies. Bilirubin was > 2 × ULN in one participant. Published data from other VIS models, using sporozoite inoculation by systemic administration or mosquito feeding, also showed moderate/severe liver enzyme elevations. In conclusion, liver enzyme elevations in IBSM studies are most likely multifactorial and could be caused by the model conditions, that is, malaria infection/parasite density and/or effective parasite clearance, or by participant-specific risk factors, acetaminophen administration, or direct hepatotoxicity of the test drug. We make recommendations that may mitigate the risk of liver enzyme elevations in future VISs and propose measures to assist their interpretation, should they occur.

Background: Young women aged 15-24 years are disproportionately affected by the HIV epidemic. Two phase III trials of a vaginal ring containing 25-mg dapivirine demonstrated HIV-1 risk reduction in adult women older than 21 years but not in those aged 18-21 years. Lack of protection was correlated with low adherence., Methods: In this phase-IIa, randomized, double-blind, placebo-controlled, US, multicenter trial of the dapivirine ring in sexually active females, aged 15-17 years, participants were randomized 3:1 to a dapivirine or placebo ring to be inserted monthly for 6 months (NCT02028338). Primary safety end points included grade 2 product related adverse events and any grade 3 and higher adverse events. Adherence to ring use was assessed by plasma dapivirine concentrations, residual levels in used rings, and self-report. A plasma dapivirine concentration of >95 pg/mL was used to define short-term adherence; a residual ring level of <23.5 mg was used to define long-term adherence. Acceptability was assessed through computer-assisted self-interviews., Results: Ninety-six participants were enrolled across 6 US sites. The median age was 16.0 years. There were no differences in safety outcomes between treatment arms. Adherence to the dapivirine ring was demonstrated by both plasma measurements (87%) and residual drug levels in rings (95%). Forty-two percent (95% confidence interval: 32 to 52) of participants reported that they never removed the ring. Participants noted no discomfort due to the ring at 87% of visits and "liking" the ring at 93% of visits., Conclusion: The dapivirine vaginal ring, a promising topical microbicide, was well tolerated and acceptable in young US adolescents.

The aims of this study were to: 1) determine prevalence of anogenital and oral HPV, 2) determine concordance between HPV at anal, perianal, scrotal/penile, and oral sites; and 3) describe factors associated with anogenital HPV types targeted by the 9-valent vaccine. Data were collected from 2012 to 2015 among men who have sex with men 18-26 years of age enrolled in a vaccine trial (N = 145). Penile/scrotal, perianal, anal, and oral samples were tested for 61 HPV types. Logistic regression was used to identify factors associated with types in the 9-valent vaccine. Participants' mean age was 23.0 years, 55.2% were African-American, and 26.2% were Hispanic; 93% had anal, 40% penile, and 6% oral HPV. Among those with anogenital infection, 18% had HPV16. Concordance was low between anogenital and oral sites. Factors independently associated with a 9-valent vaccine-type HPV were: race (African-American vs. White, OR=2.67, 95% CI=1.11-6.42), current smoking (yes vs. no, OR=2.37, 95% CI=1.03-5.48), and number of recent receptive anal sex partners (2+ vs. 0, OR=3.47, 95% CI=1.16-10.4). Most MSM were not infected with HPV16 or HPV18, suggesting that they may still benefit from HPV vaccination, but anogenital HPV was very common, highlighting the importance of vaccinating men before sexual initiation. CLINICAL TRIAL NUMBER: NCT01209325., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The United States Centers for Disease Control and Prevention estimates that approximately 60,000 US youth are living with HIV. US youth living with HIV (YLWH) have poorer outcomes compared with adults, including lower rates of diagnosis, engagement, retention, and virologic suppression. With Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) support, new trials of youth-centered interventions to improve retention in care and medication adherence among YLWH are underway., Objective: This study aimed to use a computer simulation model, the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)-Adolescent Model, to evaluate selected ongoing and forthcoming ATN interventions to improve viral load suppression among YLWH and to define the benchmarks for uptake, effectiveness, durability of effect, and cost that will make these interventions clinically beneficial and cost-effective., Methods: This protocol, ATN 161, establishes the ATN Modeling Core. The Modeling Core leverages extensive data-already collected by successfully completed National Institutes of Health-supported studies-to develop novel approaches for modeling critical components of HIV disease and care in YLWH. As new data emerge from ongoing ATN trials during the award period about the effectiveness of novel interventions, the CEPAC-Adolescent simulation model will serve as a flexible tool to project their long-term clinical impact and cost-effectiveness. The Modeling Core will derive model input parameters and create a model structure that reflects key aspects of HIV acquisition, progression, and treatment in YLWH. The ATN Modeling Core Steering Committee, with guidance from ATN leadership and scientific experts, will select and prioritize specific model-based analyses as well as provide feedback on derivation of model input parameters and model assumptions. Project-specific teams will help frame research questions for model-based analyses as well as provide feedback regarding project-specific inputs, results, sensitivity analyses, and policy conclusions., Results: This project was funded as of September 2017., Conclusions: The ATN Modeling Core will provide critical information to guide the scale-up of ATN interventions and the translation of ATN data into policy recommendations for YLWH in the United States., (©Anne M Neilan, Kunjal Patel, Allison L Agwu, Ingrid V Bassett, K Rivet Amico, Catherine M Crespi, Aditya H Gaur, Keith J Horvath, Kimberly A Powers, H Jonathon Rendina, Lisa B Hightow-Weidman, Xiaoming Li, Sylvie Naar, Sharon Nachman, Jeffrey T Parsons, Kit N Simpson, Bonita F Stanton, Kenneth A Freedberg, Audrey C Bangs, Michael G Hudgens, Andrea L Ciaranello. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 16.04.2019.)

Objectives: This study's primary objective was to characterize attitudes to long-acting antiretrovirals (LAARV), among youth aged 13-24 years living with perinatally acquired HIV and nonperinatally acquired HIV. Secondary objectives included: assessing whether those with detectable HIV RNA PCR viral load had higher enthusiasm for LAARV compared to those with suppressed viral load, and examining characteristics associated with LAARV enthusiasm., Methods: A cross-sectional survey of 303 youth living with HIV (YHIV) followed at 4 pediatric/adolescent HIV clinics in the United States was performed to determine interest in LAARV, using a modified survey instrument previously used in adults. Interest in LAARV across groups was compared. Poisson regression with robust variance was used to determine the impact of various characteristics on interest in LAARV., Findings: Overall, 88% of YHIV reported probable or definite willingness to use LAARV. The enthusiasm level was similar between youth with perinatally acquired HIV and nonperinatally acquired HIV (P = 0.93). Youth with HIV viral load >1000 copies per milliliter had significantly higher interest than youth with suppressed viral load [prevalence ratio 1.12 (95% confidence interval: 1.03 to 1.20); P = 0.005]. Female youth participants who had had past experience with implantable contraceptive methods had a significantly higher interest in LAARV (100% vs. 85.5%; P = 0.002). Proportion of respondents endorsing definite willingness to use was significantly higher with decreased injection frequency compared with increased injection frequency., Interpretation: YHIV at 4 urban US pediatric/adolescent HIV clinics had high levels of enthusiasm for LAARV. LAARV should be given high priority as a potentially viable treatment option to improve clinical outcomes in YHIV.

Children and adolescents with acute myeloid leukemia (AML) are at risk of life-threatening bacterial infections, especially with viridans group streptococci. Primary antibacterial prophylaxis with vancomycin-based regimens reduces this risk but might increase the risks of renal or liver toxicity or Clostridium difficile infection (CDI). A retrospective review of data for patients treated for newly diagnosed AML at St. Jude Children's Research Hospital between 2002 and 2008 was conducted. Nephrotoxicity was classified according to pediatric risk, injury, failure, loss, and end-stage renal disease (pRIFLE) criteria and hepatotoxicity according to Common Terminology Criteria for Adverse Events (CTCAE) criteria. The risks of nephrotoxicity, hepatotoxicity, and CDI were compared between patients receiving vancomycin-based prophylaxis, no intravenous prophylaxis, or other prophylaxis. Generalized linear mixed models were used to address potential confounding. A total of 392 chemotherapy courses (108 with no intravenous prophylaxis, 218 with vancomycin-based prophylaxis, and 66 with other prophylaxis) for 111 patients were included. Development of pRIFLE risk, injury, and failure occurred in 190, 44, and 2 courses, respectively. Increases of at least one, two, and three grades for hepatotoxicity occurred in 189, 52, and 19 courses, respectively. After adjustment for confounders, vancomycin-based prophylaxis was not associated with nephrotoxicity or hepatotoxicity and reduced the risk of CDI, compared to no intravenous prophylaxis (0.9% versus 6.5%; P = 0.007) or other prophylactic regimens (0.9% versus 3.0%; P = 0.23). Despite concerns about vancomycin toxicity, vancomycin-based prophylaxis in pediatric patients with AML did not increase the risk of nephrotoxicity or hepatotoxicity and reduced the risk of CDI. Caution is advised to avoid contributing to antibiotic resistance., (Copyright © 2018 American Society for Microbiology.)

Highly active antiretroviral therapy (HAART) nonadherence is related to negative health outcomes and is well-documented in adolescents and young adults (AYAs) with behaviorally acquired HIV. Few studies describe methods to improve adherence in this population. This retrospective study describes placebo pill trial use (ie, pills with inert substance prescribed to practice taking HAART) in AYAs initiating HAART and its relation to disease outcomes. Sixty-two AYAs initiated HAART during the review period. Disease outcomes during the first year of standard clinical care were abstracted from medical records. In all, 72.6% of participants received ≥1 pill trial and 27.4% received ≥2 trials. Placebo trial use was not independently related to adherence post-HAART initiation. "Prescription" of a second trial was related to less optimal disease status over the first 6 months of treatment. Placebo trials have the potential to inform clinical care, aid in identifying AYAs at risk for nonadherence, and may provide a novel intervention strategy before/after HAART initiation.

Aim: Identify the functional status of the uridine-diphosphate glucuronyl transferase 1A1 (UGT1A1) -3279T>G (*60) variant., Materials & Methods: Retrospective review of clinically obtained serum bilirubin concentrations in pediatric patients to evaluate the association of the UGT1A1 -3279T>G (*60) variant with bilirubin concentrations and assessed linkage disequilibrium of the UGT1A1 -3279T>G (*60) and A(TA)7TAA (*28) variants., Results: Total bilirubin concentration did not differ between patients who had a UGT1A1*1/*1 diplotype and patients homozygous for the UGT1A1 -3279T>G (*60/*60) variant. Total bilirubin concentration was lower in patients homozygous for the UGT1A1 -3279T>G (*60/*60) variant than in patients homozygous for the UGT1A1 A(TA)7TAA (*28/*28) variant (p < 0.01). The -3279T>G (*60) and A(TA)7TAA (*28) variants were in strong incomplete linkage disequilibrium in both black and white patients., Conclusion: The presence of the UGT1A1 -3279T>G (*60) variant is not associated with increased bilirubin concentrations.

Background: The HIV care continuum (diagnosis, linkage to care, retention in care, receipt of antiretroviral therapy (ART), viral suppression) has been used to identify opportunities for improving the delivery of HIV care. Continuum steps are typically calculated in a conditional manner, with the number of persons completing the prior step serving as the base population for the next step. This approach may underestimate the prevalence of viral suppression by excluding patients who are suppressed but do not meet standard definitions of retention in care. Understanding how retention in care and viral suppression interact and change over time may improve our ability to intervene on these steps in the continuum., Methods: We followed 17,140 patients at 11 U.S. HIV clinics between 2010-2012. For each calendar year, patients were classified into one of five categories: (1) retained/suppressed, (2) retained/not-suppressed, (3) not-retained/suppressed, (4) not-retained/not-suppressed, and (5) lost to follow-up (for calendar years 2011 and 2012 only). Retained individuals were those completing ≥ 2 HIV medical visits separated by ≥ 90 days in the year. Persons not retained completed ≥ 1 HIV medical visit during the year, but did not meet the retention definition. Persons lost to follow-up had no HIV medical visits in the year. HIV viral suppression was defined as HIV-1 RNA ≤ 200 copies/mL at the last measure in the year. Multinomial logistic regression was used to determine the probability of patients' transitioning between retention/suppression categories from 2010 to 2011 and 2010 to 2012, adjusting for age, sex, race/ethnicity, HIV risk factor, insurance status, CD4 count, and use of ART., Results: Overall, 65.8% of patients were retained/suppressed, 17.4% retained/not-suppressed, 10.0% not-retained/suppressed, and 6.8% not-retained/not-suppressed in 2010. 59.5% of patients maintained the same status in 2011 (kappa=0.458) and 53.3% maintained the same status in 2012 (kappa=0.437)., Conclusions: Not counting patients not-retained/suppressed as virally suppressed, as is commonly done in the HIV care continuum, underestimated the proportion suppressed by 13%. Applying the care continuum in a longitudinal manner will enhance its utility.

Human parainfluenza virus type 1 (hPIV-1) is the most common cause of laryngotracheobronchitis (croup), resulting in tens of thousands of hospitalizations each year in the United States alone. No licensed vaccine is yet available. We have developed murine PIV-1 (Sendai virus [SeV]) as a live Jennerian vaccine for hPIV-1. Here, we describe vaccine testing in healthy 3- to 6-year-old hPIV-1-seropositive children in a dose escalation study. One dose of the vaccine (5 × 10(5), 5 × 10(6), or 5 × 10(7) 50% egg infectious doses) was delivered by the intranasal route to each study participant. The vaccine was well tolerated by all the study participants. There was no sign of vaccine virus replication in the airway in any participant. Most children exhibited an increase in antibody binding and neutralizing responses toward hPIV-1 within 4 weeks from the time of vaccination. In several children, antibody responses remained above incoming levels for at least 6 months after vaccination. Data suggest that SeV may provide a benefit to 3- to 6-year-old children, even when vaccine recipients have preexisting cross-reactive antibodies due to previous exposures to hPIV-1. Results encourage the testing of SeV administration in young seronegative children to protect against the serious respiratory tract diseases caused by hPIV-1 infections., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Objective: To evaluate the application of the National Healthcare Safety Network (NHSN) central line-associated bloodstream infection (CLABSI) definition in pediatric intensive care units (PICUs) and pediatric hematology/oncology units (PHOUs) participating in a multicenter quality improvement collaborative to reduce CLABSIs; to identify sources of variability in the application of the definition., Design: Online survey using 18 standardized case scenarios. Each described a positive blood culture in a patient and required a yes- or-no answer to the question "Is this a CLABSI?" NHSN staff responses were the reference standard., Setting: Sixty-five US PICUs and PHOUs., Participants: Staff who routinely adjudicate CLABSIs using NHSN definitions., Results: Sixty responses were received from 58 (89%) of 65 institutions; 78% of respondents were infection preventionists, infection control officers, or infectious disease physicians. Responses matched those of NHSN staff for 78% of questions. The mean (SE) percentage of concurring answers did not differ for scenarios evaluating application of 1 of the 3 criteria ("known pathogen," 78% [1.7%]; "skin contaminant, >1 year of age," 76% [SE, 2.5%]; "skin contaminant, ≤1 year of age," 81% [3.8%]; [Formula: see text]). The mean percentage of concurring answers was lower for scenarios requiring respondents to determine whether a CLABSI was present or incubating on admission (64% [4.6%]; [Formula: see text]) or to distinguish between primary and secondary bacteremia (65% [2.5%]; [Formula: see text])., Conclusions: The accuracy of application of the CLABSI definition was suboptimal. Efforts to reduce variability in identifying CLABSIs that are present or incubating on admission and in distinguishing primary from secondary bloodstream infection are needed.

Across 36 US pediatric oncology centers, 576 central line-associated bloodstream infections (CLABSIs) were reported over a 21-month period. Most infections occurred in those with leukemia and/or profound neutropenia. The contribution of viridans streptococci infections was striking. Study findings depict the contemporary epidemiology of CLABSIs in hospitalized pediatric cancer patients.

Background: Three cases of pediatric HIV transmission attributed to the feeding practice of premasticating food for children have been reported. The degree of risk that premastication poses for pediatric HIV transmission and the prevalence of this behavior among HIV-infected caregivers is unknown., Methods: During December 2009 to February 2010, we conducted a case-control investigation of late-diagnosed HIV infection in children at 6 HIV clinics using in-person and telephone interviews. A cross-sectional investigation of premastication was conducted in concert with this case-control investigation., Results: We compared 11 case-patients to 35 HIV-exposed controls of similar age. Sixteen (35%) of 46 children were fed premasticated food, 10 (22%) by an HIV-infected caregiver. Twenty-seven percent of case-patients received premasticated food from an HIV-infected caregiver compared with 20% of controls (odds ratio = 1.5; 95% confidence interval = 0.3 to 7.1). In the cross-sectional investigation, 48 (31%) of 154 primary caregivers of children aged ≥6 months reported the children received premasticated food from themselves or someone else. The prevalence of premastication decreased with increasing caregiver age and had been used to feed children aged 1-36 months., Conclusions: Premastication, a potential route of HIV transmission to children, was a common practice of caregivers. Public health officials and health care providers should educate the public about the potential risk of disease transmission via premastication.

Objectives: Increasing numbers of youth are becoming HIV-infected and need highly active antiretroviral therapy (HAART). We hypothesized that behaviorally HIV-infected youth (BIY) ages 18 to 24 years are less likely than adults (25 years or older) to receive HAART and, once initiated, more likely to discontinue their first HAART regimen., Methods: Longitudinal analysis of treatment-naïve patients (age 18 years or older) meeting criteria for HAART and followed at HIV Research Network sites (2002-2008). Time from meeting criteria to HAART initiation and duration on first regimen were assessed using Cox proportional hazards regression., Results: A total of 3127 (268 youth, 2859 adult) treatment-naïve, HIV-infected patients met criteria. BIY were more likely to be black (66.8% vs 51.1%; P < 0.01) and less likely to identify injection drug use HIV risk (1.1% vs 8.8%; P < 0.01) than adults 25 years of age or older. Nearly 69% of BIY started HAART versus 79% of adults (P < 0.001). Adults 25 to 29 years of age (adjusted hazards ratio [AHR], 1.39; 95% confidence interval [CI], 1.12-1.73) and 50 years of age or older (AHR, 1.24; 95% CI, 1.00-1.54), but not 30 to 49 years (AHR, 1.19; 95% CI, 0.99-1.44) were more likely to initiate HAART than BIY. Attending four or more HIV provider visits within 1 year of meeting criteria was associated with HAART initiation (AHR, 1.91; 1.70-2.14). CD4 200 to 350 versus less than 200 cells/mm (AHR, 0.57; 95% CI, 0.52-0.63), and injection drug use (AHR, 0.80; 95% CI, 0.69-0.92) were associated with a lower likelihood of HAART initiation. There were no age-related differences in duration of the first regimen., Conclusion: BIY are less likely to start HAART when meeting treatment criteria. Addressing factors associated with this disparity is critical to improving care for youth.

The incidence of and risk factors for community-acquired pneumonia (CAP) are described from 2000 to 2005 in a multicenter US cohort of HIV-infected children. In 736 patients, 87 episodes of CAP (33.2 events/1000 person-years) had a mean CD4% of 23% (controls: 30%) and mean CD4 cell count of 668 cells/μl (controls: 870 cells/μl). CAP incidence decreased 44% from 2000-2001 to 2002-2005. On multivariate analysis, viral load at least 100 000 copies/ml (odds ratio 3.98; confidence interval 1.05-15.13) was associated with CAP. Herd immunity through pneumococcal immunization may have diluted the effect of individual immunization in this cohort.

Current methods for diagnosis of catheter-related infection (CRI) are cumbersome and may require removal of the central venous catheter (CVC). A prospective study was conducted to validate the difference in time to detection (DTD) of cultures of blood samples obtained simultaneously from a peripheral vein (PV) and from the CVC for differentiation of CRI and non-CRI. During a 15-month period, 9 episodes were categorized as CRI and 24 as non-CRI. The median DTD for patients with CRI was significantly higher than that for patients with non-CRI (457 vs. -4 min; P<.001). The optimum cutoff point for diagnosis of CRI was a DTD of > or =120 min (sensitivity, 88.9%; specificity, 100%). With pretest probability of CRI ranging from 28% to 54%, the positive predictive value of a DTD of > or =120 min for the diagnosis of CRI was 100%; the negative predictive value was 89%-96%. On the basis of findings from this study, which is the largest, to date, to involve pediatric patients with tunneled CVCs and the first to use paired quantitative blood cultures as a "criterion standard," DTD was found to be a simple, reliable tool for diagnosis of CRI in hospitals that use continuously read blood culture systems.

Two cases of Bacillus cereus meningitis in immunocompromised children at our hospital within a 2-month period prompted us to review B. cereus--related invasive disease. We identified 12 patients with B. cereus isolated in blood cultures from September 1988 through August 2000 at our institution. Three of these patients also had B. cereus isolated from CSF specimens; 1 additional patient had possible CNS involvement (33%, group A), whereas 8 patients had no evidence of CNS involvement (67%, group B). Patients in group A were more likely to have neutropenia at the onset of sepsis and were more likely to have an unfavorable outcome. They were also more likely to have received intrathecal chemotherapy in the week before the onset of their illness. Two patients from group A died. One survived with severe sequelae. The fourth patient had mild sequelae at follow-up. No sequelae or deaths occurred among patients in group B. In patients with unfavorable outcomes, the interval from the time of recognition of illness to irreversible damage or death was short, which demonstrates a need for increased awareness, early diagnosis, and more-effective therapy, particularly that which addresses B. cereus toxins.