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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.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.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.Implementation of a test-based strategy is logistically challenging, increases costs, and did not lead to shorter isolation in our institution.

Bictegravir is a potent integrase strand-transfer inhibitor (INSTI) with a high genetic barrier to resistance. Bictegravir, coformulated with emtricitabine and tenofovir alafenamide, is recommended by key European and US HIV treatment guidelines as the preferred single-tablet regimen for adults and adolescents. The aim of this study was to assess the pharmacokinetics, safety, and efficacy of switching to this regimen in virologically suppressed children and adolescents with HIV.In this single-arm, open-label trial, we enrolled virologically suppressed children and adolescents (aged 6 to18 years) with HIV at 22 hospital clinics in South Africa, Thailand, Uganda, and the USA. Eligible participants had a bodyweight of at least 25 kg, were virologically suppressed (HIV-1 RNA50 copies per mL) on a stable ART regimen for at least 6 months before screening, had a CD4 count of at least 200 cells per μL, and an estimated glomerular filtration rate of at least 90 mL/min per 1·73 mBetween Sept 29, 2016 and Feb 16, 2018, we enrolled 102 participants. 100 participants received bictegravir, emtricitabine, and tenofovir alafenamide (cohort 1 [adolescents aged 12 to18 years], n=50; cohort 2 [children aged 6 to12 years], n=50). The mean bictegravir AUCIn adolescents and children with HIV, the bictegravir, emtricitabine, and tenofovir alafenamide single-tablet regimen was well tolerated and maintained virological suppression. Our data support the treatment of HIV in adolescents and children with this single-tablet regimen. At present, the single-tablet regimen is recommended as first-line treatment in the USA for adolescents and as an alternative regimen in children and has the potential to represent an important regimen in the paediatric population.Gilead Sciences.

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.

A sizable portion of youth (ages 13–24) living with HIV in the United States have unsuppressed viral load. The AIDS Interventions (ATN) 152 study [evaluating the Triggered Escalating Real-Time Adherence (TERA) intervention] baseline data were examined to identify correlates of high viremia (>5000 copies/mL) and self-reported adherence, which can help in planning of differentiated services for viremic youth. Depression, HIV-stigma, and cannabis use were common in this sample of 87 youth. Almost half (48%) had high viremia, which associated with enacted stigma, moderate- to high-risk alcohol use, mental health diagnosis, and age ≥21. Self-reported adherence was related to viral load and associated with mental and physical health functioning, depression, social support, self-confident decision-making, total and internalized stigma, adherence motivation, and report of a missed a care visit in the past 6 months. Mental health emerged as a common correlate of viral load and adherence. Clinical Trial Registration number: NCT03292432.

The Adolescent Medicine Trials Network for HIV/AIDS Interventions is evaluating treatment adherence interventions (AI) to improve virologic suppression (VS) among youth with HIV (YWH). Using a microsimulation model, we compared two strategies: standard-of-care (SOC) and a hypothetical 12-month AI that increased cohort-level VS in YWH in care by an absolute ten percentage points and cost $100/month/person. Projected outcomes included primary HIV transmissions, deaths and life-expectancy, lifetime HIV-related costs, and incremental cost-effectiveness ratios (ICERs, $/quality-adjusted life-year [QALY]). Compared to SOC, AI would reduce HIV transmissions by 15% and deaths by 12% at 12 months. AI would improve discounted life expectancy/person by 8 months at an added lifetime cost/person of $5,300, resulting in an ICER of $7,900/QALY. AI would be cost-effective at $2,000/month/person or with efficacies as low as a 1 percentage point increase in VS. YWH-targeted adherence interventions with even modest efficacy could improve life expectancy, prevent onward HIV transmissions, and be cost-effective.La Red de Ensayos Médicos sobre Adolescentes para Realizar Intervenciones sobre el VIH/SIDA está evaluando intervenciones de adherencia (IAs) al tratamiento para mejorar la supresión virológica (SV) entre los jóvenes con VIH (JCV). Usando un modelo de microsimulación, comparamos dos estrategias: cuidado convencional (CC) y una intervención de adherencia hipotética durando 12 meses que aumentaría la SV a nivel de cohorte entre JCV en tratamiento por 10 puntos de porcentuales y que costaría US$ 100/mes/persona. Resultados proyectados incluyeron transmisiones de VIH primarias, muertes y esperanza de vida, costos de por vida asociados con el VIH, y razones incrementales de costo-efectividad (RICEs, $/año de vida ajustado por la calidad [AVAC]). Comparado al CC, la IA reduciría transmisiones de VIH por 15% y muertes por 12% a los 12 meses. La IA mejoraría esperanza de vida descontada/persona por 8 meses a un costo de por vida adicional/persona de US$ 5.300, resultando en una RICE de US$ 7.900/AVAC. La IA sería costo-efectiva a un costo de US$ 2.000/mes/persona o si mejorara SV por al menos un punto porcentual. Intervenciones de adherencia dirigidas a jóvenes con una eficacia incluso modesta podrían mejorar esperanza de vida, prevenir transmisiones de VIH, y ser costo-efectivas.

Background Guidelines for the use of antiretroviral agents in adults and adolescents with HIV recommend that antiretroviral therapy (ART) be started as soon as possible. While rapid initiation of ART in adults with HIV has been well-described, there is relatively little information describing this approach for youth. Methods On April 1, 2018, St. Jude Children's Research Hospital began offering ART to youth with HIV infection at their first clinic visit. We report the results of a quality improvement initiative that compared patients who offered ART at their first visit to a historical cohort of patients who initiated ART at a subsequent visit. Demographic, HIV biomarker, and visit information were abstracted from medical records, described and compared using univariate statistical methods. Results There were 124 ART-naive youth (median age 19 years, 91% male, 94% black) first seen during the indicated time period. A total of 54 patients were in the baseline cohort and 70 patients were in the rapid start cohort. 90% of youth in the rapid start cohort started ART on their first clinic visit. Time from first clinic visit to undetectable viral load was significantly higher in the baseline cohort compared with the rapid start cohort (median 54 vs. 41 days; P = 0.01). Retention in care 12 months following the first clinic visit was comparable and overall high (>80%). Conclusions Starting ART-naive youth with HIV infection on ART at their first clinic visit is feasible, has high acceptance, leads to faster viral load suppression, and is associated with high retention in care.

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.

Objective: To assess the utility of a test-based approach to shorten isolation of healthcare workers with COVID-19 in the setting of the highly transmissible omicron variant Methods: Between December 24th, 2021, to January 5th, 2022 HCWs who tested positive for SARS-CoV-2 were re-tested at least five days since onset of symptoms. Results: 46 sequential fully COVID-19 vaccinated HCWs who had tested positive for SARS-CoV-2 underwent follow up testing. All the isolates were confirmed as omicron variants and only 4 (8.7%) were negative 5 days or more 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.

INTRODUCTION. Evidence-based linkage to care interventions (LTCs) help recently diagnosed HIV+ individuals engage in care in a timely manner yet are heavily impacted by the systems in which they are embedded. METHODS. We developed a prototype agent-based model (ABM) informed by data from an established LTC program targeting youth and young adults aged 13–24 in Memphis, Tennessee. We then tested two interventions to improve LTC in a simulated environment: expanding testing sites versus using current testing site but improving direct referral to LTC staff from organizations providing testing, to understand the impact on timely linkage to care. RESULTS. Improving direct referral to the LTC program decreased days to successful linkage from an average of 30 days to 23 days but expanding testing sites increased average days to 31 days unless those sites also made direct referrals. CONCLUSIONS. We demonstrated how LTC is impacted by the system and interventions for shortening days to linkage to care.

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.

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.

BackgroundSafe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection.MethodsWe conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks. HIV testing and safety evaluations were performed. The primary end point was incident HIV infection.ResultsThe intention-to-treat population included 4566 participants who underwent randomization; 570 (12.5%) identified as transgender women, and the median age was 26 years (interquartile range, 22 to 32). The trial was stopped early for efficacy on review of the results of the first preplanned interim end-point analysis. Among 1698 participants from the United States, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group (incidence, 0.41 per 100 person-years) and 39 in the TDF-FTC group (incidence, 1.22 per 100 person-years) (hazard ratio, 0.34; 95% confidence interval, 0.18 to 0.62). The effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the participants in the cabotegravir group and in 31.3% of those in the TDF-FTC group. In the participants in whom HIV infection was diagnosed after exposure to CAB-LA, INSTI resistance and delays in the detection of HIV infection were noted. No safety concerns were identified.ConclusionsCAB-LA was superior to daily oral TDF-FTC in preventing HIV infection among MSM and transgender women. Strategies are needed to prevent INSTI resistance in cases of CAB-LA PrEP failure. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 083 ClinicalTrials.gov number, NCT02720094.).

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 Trial registration. The St. Jude Tracking of Viral and Host Factors Associated with COVID-19 study; NCT04362995; https://clinicaltrials.gov/ct2/show/NCT04362995.

Objective This study aims to assess the product-related, relationship-related, and sex-related factors that act as facilitators and barriers to the acceptability of a vaginal ring (VR) for HIV prevention among adolescent girls. Design Qualitative study. Methods Ninety-six 15 to 17-year-old girls from six urban U.S. sites were enrolled in MTN-023/IPM 030, a 24-week randomized controlled trial assessing the safety and acceptability of a dapivirine VR for HIV prevention. At week 24, 21 girls were randomly selected to participate in in-depth-interviews. Interviews were transcribed verbatim, and data analyzed using a thematic analysis approach. Facilitators and barriers to VR acceptability related to participants' relationships, sexual activity, and characteristics of the VR product were identified. Results Factors related to relationships rarely appeared to act as barriers to VR acceptability; most participants disclosed VR use to sexual partners, and positive reactions from sexual partners, which were common, appeared to facilitate VR acceptability. Emotional and/or physical discomfort surrounding VR use during sex was mentioned occasionally as a barrier to VR acceptability. Product characteristics were most frequently mentioned as barriers to VR acceptability. Many participants reported concerns about the large size of the VR upon first impression. While most found the VR comfortable, some reported pain with VR insertion. Several participants were concerned about VR cleanliness, particularly during menstruation. Conclusion Product considerations, specifically size and use during menstruation, were the most commonly reported barriers to VR acceptability in this study. Adolescent girls may require additional counseling to assuage product concerns regarding a VR for HIV prevention.

Background Children and adolescents with perinatal human immunodeficiency virus (HIV) infection and with low bone mineral density (BMD) may be at higher risk of osteoporosis and fractures in later life than their uninfected peers. Bisphosphonate therapy has been shown to reduce fractures in adults with osteoporosis, but has not been formally studied in youths living with HIV. Methods Fifty-two children and adolescents (aged 11–24 years) perinatally infected with HIV with low lumbar spine (LS) BMD (Z score < −1.5) were randomized to receive once-weekly alendronate or placebo in a double-blind cross-over study designed to assess the safety and efficacy of 48 and 96 weeks of alendronate in the United States and Brazil. All participants received daily calcium carbonate and vitamin D supplementation and were asked to engage in regular weight-bearing exercise. Safety and efficacy are summarized for the initial 48 weeks of the trial. Results Grade 3 or higher abnormal laboratory values, signs, or symptoms developed in 5 of 32 (16%) participants on alendronate and 2 of 18 (11%) on placebo (P > .99). No cases of jaw osteonecrosis, atrial fibrillation, or nonhealing fractures were reported. Mean increases (95% confidence interval) in LS BMD over 48 weeks were significantly larger on alendronate (20% [14%–25%]) than placebo (7% [5%–9%]) (P < .001). Similar improvements were seen for whole body BMD. Conclusions In this small study in children and adolescents perinatally infected with HIV with low LS BMD, 48 weeks of alendronate was well-tolerated, showed no safety concerns, and significantly improved LS and whole body BMD compared to participants on vitamin D/calcium supplementation and exercise alone. Clinical Trials Registration NCT00921557.

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 Keywords: Adolescents, Clinical trials, Men who have sex with men, Vaccine, Human papillomavirus, HIV

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 deaths1-4. Diagnostic tools and serological assays are critical for controlling the outbreak5-7, especially assays designed to quantitate neutralizing antibody levels, considered the best correlate of protection8-11. As vaccines become increasingly available12, it is important to identify reliable methods for measuring neutralizing antibody responses that correlate with authentic virus neutralization but can be performed outside of 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 neutralization9,10,13,14. Here we characterized three enzyme-linked immunosorbent assays (ELISAs) and three pseudotyped VSV virus 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 GFP expressing pseudotyped virus neutralization, and then the ELISAs.

Background The HIV Prevention Trials Network (HPTN) 083 trial demonstrated that long-acting cabotegravir (CAB-LA) was more effective than tenofovir disoproxil fumarate–emtricitabine (TDF/FTC) in preventing human immunodeficiency virus (HIV) in cisgender men and transgender women who have sex with men. We characterized HIV infections that occurred in the blinded phase of HPTN 083. Methods Retrospective testing included HIV testing, viral load testing, quantification of study drugs, and HIV drug resistance testing. Results Fifty-eight infections were evaluated, including 51 incident infections (12 in CAB arm and 39 in TDF/FTC arm). In many cases (5 in CAB arm and 37 in TDF/FTC arm), infection was associated with low or unquantifiable study drug concentrations. In 4 cases, infection occurred with on-time CAB-LA injections and expected plasma CAB concentrations. CAB exposure was associated with prolonged viral suppression and delayed antibody expression. In some cases, delayed HIV diagnosis resulted in CAB provision to participants with undetected infection, delayed antiretroviral therapy, and emergence of drug resistance; most of these infections would have been detected earlier with viral load testing. Conclusions Early detection of HIV infection and prompt antiretroviral therapy initiation could improve clinical outcomes in persons who become infected despite CAB-LA prophylaxis. Further studies are needed to elucidate the correlates of HIV protection in persons receiving CAB-LA.

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.

The objective of this study was to evaluate the feasibility and acceptability of a dynamic, behavioral intervention to optimize medication adherence of adolescents and young adults (AYAs) with HIV newly initiating highly active antiretroviral therapy (HAART) and explore its efficacy on adherence and disease outcomes.The two-arm randomized controlled trial piloted a brief, individualized intervention designed for direct integration into standard clinical care. In total, 32 AYAs with a confirmed HIV diagnosis, reportedly horizontally acquired, and recommended to initiate HAART completed a two-week placebo trial before HAART initiation and were subsequently randomized to standard of care or the individualized intervention. Adherence and disease outcomes were measured over the first six months of HAART.Results supported the primary study aim regarding feasibility (recruitment = 89%, attendance = 81%-100%, intervention exercise completion = 100%) and acceptability (average favorable response = 89%). Data also supported the positive effect of the intervention on select HAART adherence measures and disease outcomes. Adherence (by pharmacy refill) declined in both groups; however, adherence declined more slowly in the intervention group versus standard of care (p.001). In addition, 100% of participants receiving the intervention obtained an undetectable viral load by 3 months and maintained an undetectable viral load at 6 months (vs. 68.8% standard of care).This is one of the first interventions to target adherence for AYAs with HIV newly initiating HAART and designed for delivery in existing clinical care settings. Future research will help confirm efficacy and the potential utility of the intervention in promoting HAART adherence from medication initiation and preventing the decrease in adherence often observed over time.

Background Men who have sex with men (MSM) are at high risk for human papillomavirus (HPV)–related anal cancer. Little is known about the prevalence of low-grade squamous intraepithelial lesions (LSILs) and the anal cancer precursor, high-grade squamous intraepithelial lesions (HSILs), among young MSM with HIV (MSMLWH). HPV vaccination is recommended in this group, but its safety, immunogenicity, and protection against vaccine-type HPV infection and associated LSILs/HSILs have not been studied. Methods Two hundred and sixty MSMLWH aged 18–26 years were screened at 17 US sites for a clinical trial of the quadrivalent (HPV6,11,16,18) HPV (qHPV) vaccine. Those without HSILs were vaccinated at 0, 2, and 6 months. Cytology, high-resolution anoscopy with biopsies of lesions, serology, and HPV testing of the mouth/penis/scrotum/anus/perianus were performed at screening/month 0 and months 7, 12, and 24. Results Among 260 MSMLWH screened, the most common reason for exclusion was detection of HSILs in 88/260 (34%). 144 MSMLWH were enrolled. 47% of enrollees were previously exposed to HPV16. No incident qHPV type–associated anal LSILs/HSILs were detected among men naive to that type, compared with 11.1, 2.2, 4.5, and 2.8 cases/100 person-years for HPV6,11,16,18–associated LSILs/HSILs, respectively, among those previously exposed to that type. qHPV was immunogenic and safe with no vaccine-associated serious adverse events. Conclusions 18–26-year-old MSMLWH naive to qHPV vaccine types were protected against incident qHPV type–associated LSILs/HSILs. Given their high prevalence of HSILs, there is an urgent need to vaccinate young MSMLWH before exposure to vaccine HPV types, before initiating sexual activity, and to perform catch-up vaccination., A high proportion of 18-26 year-old men-who-have-sex-with-men-living-with-HIV screened for a quadrivalent HPV (qHPV) vaccine trial had anal low-grade/high-grade squamous intraepithelial lesions (LSIL/HSIL). Vaccinees naive to qHPV types were protected against incident qHPV type-associated-LSIL/HSIL. Vaccination before sexual initiation is critically important.

BACKGROUND Single-center reports of central line-associated bloodstream infection (CLABSI) and the subcategory of mucosal barrier injury laboratory-confirmed bloodstream infection (MBI-LCBI) in pediatric hematology oncology transplant (PHO) patients have focused on the inpatient setting. Characterization of MBI-LCBI across PHO centers and management settings (inpatient and ambulatory) is urgently needed to inform surveillance and prevention strategies. METHODS Prospectively collected data from August 1, 2013, to December 31, 2015, on CLABSI (including MBI-LCBI) from a US PHO multicenter quality improvement network database was analyzed. CDC National Healthcare Safety Network definitions were applied for inpatient events and adapted for ambulatory events. RESULTS Thirty-five PHO centers reported 401 ambulatory and 416 inpatient MBI-LCBI events. Ambulatory and inpatient MBI-LCBI rates were 0.085 and 1.01 per 1000 line days, respectively. Fifty-three percent of inpatient CLABSIs were MBI-LCBIs versus 32% in the ambulatory setting (P

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

Background: Bictegravir a potent integrase strand transfer inhibitor (INSTI) with a high barrier to resistance, coformulated with emtricitabine and tenofovir alafenamide, is a guidelines-recommended and preferred single-tablet regimen for adults and adolescents. The aim of this study was to evaluate the pharmacokinetics, safety, and efficacy of switching to this regimen in virologically suppressed children and adolescents living with HIV. Methods: In this prospective, multi-country, 48-week, Phase 2/3, single-arm, open-label trial (ClinicalTrials.gov, number NCT02881320), virologically suppressed children and adolescents (6 to

SARS-CoV-2 infection causes diverse outcomes ranging from asymptomatic infection to respiratory distress and death. A major unresolved question is whether prior immunity to endemic, human common cold coronaviruses (hCCCoV) impacts susceptibility to SARS-CoV-2 infection or immunity following infection and vaccination. Therefore, we analyzed samples from the same individuals before and after SARS-CoV-2 infection or vaccination. We found hCCCoV antibody levels increase after SARS-CoV-2 exposure, demonstrating cross-reactivity. However, a case-control study indicates baseline hCCCoV antibody levels are not associated with protection against SARS-CoV-2 infection. Rather, higher magnitudes of pre-existing betacoronavirus antibodies correlate with more SARS-CoV-2 antibodies following infection, an indicator of greater disease severity. Additionally, immunization with hCCCoV spike proteins before SARS-CoV-2 immunization impedes generation of SARS-CoV-2 neutralizing antibodies in mice. Together, these data suggest pre-existing hCCCoV antibodies hinder SARS-CoV-2 antibody-based immunity following infection and provide insight on how pre-existing coronavirus immunity impacts SARS-CoV-2 infection, which is critical considering emerging variants., Graphical Abstract, A major unresolved question is whether prior immunity to endemic, human common cold coronaviruses (hCCCoV) impacts susceptibility to SARS-CoV-2 infection. Lin et al. analyze hCCCoV antibodies in the same individuals before and after SARS-CoV-2 infection, finding pre-existing betacoronavirus antibodies may hinder SARS-CoV-2 effective immunity following infection.

Background Infection is the most important cause of treatment-related morbidity and mortality in pediatric patients treated for acute lymphoblastic leukemia (ALL). Although routine in adults with leukemia, antibacterial prophylaxis is controversial in pediatrics because of insufficient evidence for its efficacy or antibiotic choice and concerns about promoting antibiotic resistance and Clostridium difficile infection. Methods This was a single-center, observational cohort study of patients with newly diagnosed ALL, comparing prospectively collected infection-related outcomes in patients who received no prophylaxis, levofloxacin prophylaxis, or other prophylaxis during induction therapy on the total XVI study. A propensity score-weighted logistic regression model was used to adjust for confounders. Results Of 344 included patients, 173 received no prophylaxis, 69 received levofloxacin prophylaxis, and 102 received other prophylaxis regimens. Patients receiving prophylaxis had longer duration of neutropenia. Prophylaxis reduced the odds of febrile neutropenia, likely bacterial infection, and bloodstream infection by ≥70%. Levofloxacin prophylaxis alone reduced these infections, but it also reduced cephalosporin, aminoglycoside, and vancomycin exposure and reduced the odds of C. difficile infection by >95%. No increase in breakthrough infections with antibiotic-resistant organisms was seen, but this cannot be excluded. Conclusions This is the largest study to date of antibacterial prophylaxis during induction therapy for pediatric ALL and the first to include a broad-spectrum fluoroquinolone. Prophylaxis prevented febrile neutropenia and systemic infection. Levofloxacin prophylaxis also minimized the use of treatment antibiotics and drastically reduced C. difficile infection. Although long-term antibiotic-resistance monitoring is needed, these data support using targeted prophylaxis with levofloxacin in children undergoing induction chemotherapy for ALL. Clinical trials registration NCT00549848.

Summary Background No once-daily single-tablet regimen is available for HIV-infected children under 12 years. The single-tablet, fixed-dose combination of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide is a once-daily, integrase strand transfer inhibitor-based regimen approved in the USA and European Union for individuals aged 12 years or older. In this study, we aimed to assess the pharmacokinetics, safety, and efficacy of this regimen in virologically suppressed, HIV-infected children. Methods In this single-arm, open-label trial, we enrolled virologically suppressed, HIV-infected children from five hospital clinics in Uganda, the USA, and Thailand. Eligible participants were aged 6–11 years, weighed 25 kg or more, had virological suppression ( tau ) for elvitegravir and the AUC from time zero to the last quantifiable concentration (AUC last ) of tenofovir alafenamide, treatment-emergent serious adverse events, and all treatment-emergent adverse events. Results from baseline to week 24 are reported, unless specified otherwise. Primary and safety analyses included all enrolled participants who received one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT01854775. Findings Between July 27 and Sept 28, 2015, we screened 26 children, of whom 23 were enrolled and initiated treatment. Median age was 10 years (IQR 8–11), median weight was 30·5 kg (IQR 27·5–33·0), and all participants had virological suppression. The mean AUC tau of elvitegravir was 33 814 ng × h/mL (coefficient of variation 58%), and the mean AUC last of tenofovir alafenamide was 333 ng × h/mL (45%). Exposures to elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide were higher, but modestly so, than those previously reported in adults. All 23 participants tolerated the regimen well; there were no serious adverse events or adverse event-related discontinuations. All participants maintained virological suppression (HIV-1 RNA Interpretation The fixed-dose combination of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide was efficacious and well tolerated in virologically suppressed, HIV-infected children. Although plasma exposure of all components was higher than has been reported in adults, there were no safety concerns and the overall bone and renal safety profile was favourable. These data support the use of this regimen in children at least 25 kg in weight. Funding Gilead Sciences.

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.

Summary Background (+)-SJ000557733 (SJ733) is a novel, orally bioavailable inhibitor of Plasmodium falciparum ATP4. In this first-in-human and induced blood-stage malaria phase 1a/b trial, we investigated the safety, tolerability, pharmacokinetics, and antimalarial activity of SJ733 in humans. Methods The phase 1a was a single-centre, dose-escalation, first-in-human study of SJ733 allowing modifications to dose increments and dose-cohort size on the basis of safety and pharmacokinetic results. The phase 1a took place at St Jude Children's Research Hospital and at the University of Tennessee Clinical Research Center (Memphis, TN, USA). Enrolment in more than one non-consecutive dose cohort was allowed with at least 14 days required between doses. Participants were fasted in seven dose cohorts and fed in one 600 mg dose cohort. Single ascending doses of SJ733 (75, 150, 300, 600, 900, or 1200 mg) were administered to participants, who were followed up for 14 days after SJ733 dosing. Phase 1a primary endpoints were safety, tolerability, and pharmacokinetics of SJ733, and identification of an SJ733 dose to test in the induced blood-stage malaria model. The phase 1b was a single-centre, open-label, volunteer infection study using the induced blood-stage malaria model in which fasted participants were intravenously infected with blood-stage P falciparum and subsequently treated with a single dose of SJ733. Phase 1b took place at Q-Pharm (Herston, QLD, Australia) and was initiated only after phase 1a showed that exposure exceeding the threshold minimum exposure could be safely achieved in humans. Participants were inoculated on day 0 with P falciparum-infected human erythrocytes (around 2800 parasites in the 150 mg dose cohort and around 2300 parasites in the 600 mg dose cohort), and parasitaemia was monitored before malaria inoculation, after inoculation, immediately before SJ733 dosing, and then post-dose. Participants were treated with SJ733 within 24 h of reaching 5000 parasites per mL or at a clinical score higher than 6. Phase 1b primary endpoints were calculation of a parasite reduction ratio (PRR48) and parasite clearance half-life, and safety and tolerability of SJ733 (incidence, severity, and drug-relatedness of adverse events). In both phases of the trial, SJ733 hydrochloride salt was formulated as a powder blend in capsules containing 75 mg or 300 mg for oral administration. Healthy men and women (of non-childbearing potential) aged 18–55 years were eligible for both studies. Both studies are registered with ClinicalTrials.gov ( NCT02661373 for the phase 1a and NCT02867059 for the phase 1b). Findings In the phase 1a, 23 healthy participants were enrolled and received one to three non-consecutive doses of SJ733 between March 14 and Dec 7, 2016. SJ733 was safe and well tolerated at all doses and in fasted and fed conditions. 119 adverse events were recorded: 54 (45%) were unrelated, 63 (53%) unlikely to be related, and two (2%) possibly related to SJ733. In the phase 1b, 17 malaria-naive, healthy participants were enrolled. Seven participants in the 150 mg dose cohort were inoculated and dosed with SJ733. Eight participants in the 600 mg dose cohort were inoculated, but two participants could not be dosed with SJ733. Two additional participants were subsequently inoculated and dosed with SJ733. SJ733 exposure increased proportional to the dose through to the 600 mg dose, then was saturable at higher doses. Fasted participants receiving 600 mg exceeded the target area under the concentration curve extrapolated to infinity (AUC0–∞) of 13 000 μg × h/L (median AUC0–∞ 24 283 [IQR 16 135–31 311] μg × h/L, median terminal half-life 17·4 h [IQR 16·1–24·0], and median timepoint at which peak plasma concentration is reached 1·0 h [0·6–1·3]), and this dose was tested in the phase 1b. All 15 participants dosed with SJ733 had at least one adverse event. Of the 172 adverse events recorded, 128 (74%) were mild. The only adverse event attributed to SJ733 was mild bilateral foot paraesthesia that lasted 3·75 h and resolved spontaneously. The most common adverse events were related to malaria. Based on parasite clearance half-life, the derived log10 PRR48 and corresponding parasite clearance half-lives were 2·2 (95% CI 2·0–2·5) and 6·47 h (95% CI 5·88–7·18) for 150 mg, and 4·1 (3·7–4·4) and 3·56 h (3·29–3·88) for 600 mg. Interpretation The favourable pharmacokinetic, tolerability, and safety profile of SJ733, and rapid antiparasitic effect support its development as a fast-acting component of combination antimalarial therapy. Funding Global Health Innovative Technology Fund, Medicines for Malaria Venture, and the American Lebanese Syrian Associated Charities.

Background Pediatric hematology/oncology (PHO) patients receiving therapy or undergoing hematopoietic stem cell transplantation (HSCT) often require a central line and are at risk for bloodstream infections (BSI). There are limited data describing outcomes of BSI in PHO and HSCT patients. Methods This is a multicenter (n = 17) retrospective analysis of outcomes of patients who developed a BSI. Centers involved participated in a quality improvement collaborative referred to as the Childhood Cancer and Blood Disorder Network within the Children's Hospital Association. The main outcome measures were all-cause mortality at 3, 10, and 30 days after positive culture date; transfer to the intensive care unit (ICU) within 48 hours of positive culture; and central line removal within seven days of the positive blood culture. Results Nine hundred fifty-seven BSI were included in the analysis. Three hundred fifty-four BSI (37%) were associated with at least one adverse outcome. All-cause mortality was 1% (n = 9), 3% (n = 26), and 6% (n = 57) at 3, 10, and 30 days after BSI, respectively. In the 165 BSI (17%) associated with admission to the ICU, the median ICU stay was four days (IQR 2-10). Twenty-one percent of all infections (n = 203) were associated with central line removal within seven days of positive blood culture. Conclusions BSI in PHO and HSCT patients are associated with adverse outcomes. These data will assist in defining the impact of BSI in this population and demonstrate the need for quality improvement and research efforts to decrease them.

This study aims to describe an association between the Pfizer-BioNTech (BNT162b2) vaccine and decreased risk of symptomatic and asymptomatic infections with SARS-CoV-2 in hospital employees.

Several 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).A 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 ( 400 HIV-1 RNA copies/mL) at 12 months after initiation were assessed using multivariable logistic regression. Cox proportional hazards regression was used to assess VS within the first year.Of 987 youth, 67% initiated STRs. Of the 589 who had viral load data at 1 year, 84% of those on STRs versus 67% of those on MTRs achieved VS (P 0.01). VS was associated with STR use [adjusted odds ratio (AOR) 1.61; 95% confidence interval (CI) 1.01-2.58], white (AOR 2.41; 95% CI 1.13-5.13) or Hispanic (AOR 2.38; 95% CI 1.32-4.27) race/ethnicity, and baseline CD4 count 351-500 cells/μL (AOR 1.94; 95% CI 1.18-3.19) and 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].Use of STR was associated with a greater likelihood of sustained VS 12 months after ART initiation in YHIV.

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.

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.

Importance Bacteremia causes considerable morbidity among children with acute leukemia and those undergoing hematopoietic stem cell transplantation (HSCT). There are limited data on the effect of antibiotic prophylaxis in children. Objective To determine the efficacy and risks of levofloxacin prophylaxis in children receiving intensive chemotherapy for acute leukemia or undergoing HSCT. Design, setting, and participants In this multicenter, open-label, randomized trial, patients (6 months-21 years) receiving intensive chemotherapy were enrolled (September 2011-April 2016) in 2 separate groups-acute leukemia, consisting of acute myeloid leukemia or relapsed acute lymphoblastic leukemia, and HSCT recipients-at 76 centers in the United States and Canada, with follow-up completed September 2017. Interventions Patients with acute leukemia were randomized to receive levofloxacin prophylaxis for 2 consecutive cycles of chemotherapy (n = 100) or no prophylaxis (n = 100). Those undergoing HSCT were randomized to receive levofloxacin prophylaxis during 1 HSCT procedure (n = 210) or no prophylaxis (n = 214). Main outcomes and measures The primary outcome was the occurrence of bacteremia during 2 chemotherapy cycles (acute leukemia) or 1 transplant procedure (HSCT). Secondary outcomes included fever and neutropenia, severe infection, invasive fungal disease, Clostridium difficile-associated diarrhea, and musculoskeletal toxic effects. Results A total of 624 patients, 200 with acute leukemia (median [interquartile range {IQR}] age, 11 years [6-15 years]; 46% female) and 424 undergoing HSCT (median [IQR] age, 7 years [3-14]; 38% female), were enrolled. Among 195 patients with acute leukemia, the likelihood of bacteremia was significantly lower in the levofloxacin prophylaxis group than in the control group (21.9% vs 43.4%; risk difference, 21.6%; 95% CI, 8.8%-34.4%, P = .001), whereas among 418 patients undergoing HSCT, the risk of bacteremia was not significantly lower in the levofloxacin prophylaxis group (11.0% vs 17.3%; risk difference, 6.3%; 95% CI, 0.3%-13.0%; P = .06). Fever and neutropenia were less common in the levofloxacin group (71.2% vs 82.1%; risk difference, 10.8%; 95% CI, 4.2%-17.5%; P = .002). There were no significant differences in severe infection (3.6% vs 5.9%; risk difference, 2.3%; 95% CI, -1.1% to 5.6%; P = .20), invasive fungal disease (2.9% vs 2.0%; risk difference, -1.0%; 95% CI, -3.4% to 1.5%, P = .41), C difficile-associated diarrhea (2.3% vs 5.2%; risk difference, 2.9%; 95% CI, -0.1% to 5.9%; P = .07), or musculoskeletal toxic effects at 2 months (11.4% vs 16.3%; risk difference, 4.8%; 95% CI, -1.6% to 11.2%; P = .15) or at 12 months (10.1% vs 14.4%; risk difference, 4.3%; 95% CI, -3.4% to 12.0%; P = .28) between the levofloxacin and control groups. Conclusions and relevance Among children with acute leukemia receiving intensive chemotherapy, receipt of levofloxacin prophylaxis compared with no prophylaxis resulted in a significant reduction in bacteremia. However, there was no significant reduction in bacteremia for levofloxacin prophylaxis among children undergoing HSCT.

Background: Youth living with HIV (YLWH) are confronted with many self-care challenges that can be experienced as overwhelming in the context of normal developmental processes that characterize adolescence and young adulthood. A sizable minority of YLWH have unsuppressed viral loads in the United States attributable to antiretroviral therapy (ART) nonadherence. Interventions to promote sustained viral suppression in YLWH are needed. Objective: The aim of this study is to evaluate the efficacy of the Triggered Escalating Real-Time Adherence (TERA) intervention in comparison with standard of care (SOC) in YLWH (aged 13-24 years) failing ART on (1) primary outcome measures—HIV viral suppression (VLS), defined as both

Volume 86, no. 2, e00574-17, 2018, [https://doi.org/10.1128/IAI.00574-17][1]. Supplemental material: Tables S1 to S7 were inadvertently not posted upon publication. Revised supplemental material is posted at . [1]: /lookup/doi/10.1128

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.

Bacillus cereus remains an important cause of infections, particularly in immunocompromised hosts. While typically associated with enteric infections, disease manifestations can be quite diverse and include skin infections, bacteremia, pneumonia, and meningitis. Whether there are any genetic correlates of bacterial strains with particular clinical manifestations remains unknown. To address this gap in understanding, we undertook whole-genome analysis of B. cereus strains isolated from patients with a range of disease manifestations, including noninvasive colonizing disease, superficial skin infections, and invasive bacteremia. Interestingly, strains involved in skin infection tended to form a distinct genetic cluster compared to isolates associated with invasive disease. Other disease manifestations, despite not being exclusively clustered, nonetheless had unique genetic features. The unique features associated with the specific types of infections ranged from traditional virulence determinants to metabolic pathways and gene regulators. These data represent the largest genetic analysis to date of pathogenic B. cereus isolates with associated clinical parameters.

Emerging research in adults with HIV suggests negative body image may be found at a higher rate in this group. To date, few studies have examined body image in adolescents living with HIV. This exploratory study aimed to characterize body image perceptions among youth living with HIV. Adolescents (n = 143; age range 16-24 years; 69 % male) completed an Audio Computer Assisted Self-Interview Questionnaire that assessed body image, psychosocial, medical and sociodemographic information. Medical history and physical functioning information were abstracted from medical records. Results showed normative global body image on the Multidimensional Body Self-Relations Questionnaire-Appearance Scales. Some subscale elevations were observed; including decreased interest in self-care and appearance, as well as concerns with individual body areas. Overall, youth reported preference for own body shape on the Figure Rating Scale; however, 41 % of youth classified as "overweight" per CDC body mass index reported contentment with current body size. Further, 47 % of youth classified as "normal" weight desired to have larger body size. Youth identified as men who have sex with men most often reported desiring larger body size. Implications for clinical care are discussed.