Abstract Background In recent years, the United States has observed increasing rates of sexually transmitted infections (STIs). Rates are highest amongst the teen and young adult age groups. In addition to the immense healthcare costs associated with STIs, long-term sequelae can be severe on the individual level. The risk of infertility is particularly high for those with repeated or prolonged infection. Upon entering the COVID-19 pandemic, it was unclear if the widespread behavioral changes and disruptions in routine care practices to minimize the further spread of COVID-19 would cause an increase or decrease in the United States’ STI rates. This study sought to determine if there was a change in the incidence of STIs during the first year of the COVID-19 pandemic compared to the year prior in a population at high risk for STIs. Methods A retrospective chart review was performed for 330 patients aged 12 to 41 years (mean 20.2 years, median 20 years, standard deviation 3.75 years) with human immunodeficiency virus (HIV) or on pre-exposure prophylaxis (PrEP) to prevent the acquisition of HIV, who presented for preventative and acute care appointments at a multidisciplinary pediatric and young adult HIV Clinic in the year prior to and during the first year of the COVID-19 pandemic (March 22, 2019-March 21, 2021). Utilizing telehealth, rapid COVID-19 screening, and multimodal patient communication, increased efforts were made in this clinic during the pandemic to maintain appropriate STI screening, testing, treatment, and rescheduling of routine visits when appropriate to minimize COVID-19 exposure and spread. Comparisons were made between the two time periods, which evaluated the incidences of individual and overall STIs diagnosed per person-years, STIs per total tests performed, and time to treatment initiation. Results Between one year prior to and the first year during the COVID-19 pandemic, this clinic experienced no statistically significant rate changes of sexually transmitted infections. A non-significant decreased incidence of chlamydia (22 cases per 100 person-years and 18 cases per 100 person-years, respectively) and unchanged rates of gonorrhea (22 cases per 100 person-years and 22 cases per 100 person-years, respectively) and syphilis (16 cases per 100 person-years and 15 cases per 100 person-years, respectively) were observed. The median times to treatment remained largely unchanged. Conclusion This HIV care clinic experienced a decreased chlamydia infection rate, a trend similar to the CDC United States STI data during this time period. In contrast to the nationally reported increased rates of gonorrhea and syphilis, this clinic experienced unchanged rates. The lack of change in our cohort could reflect that the benefits of a multidisciplinary HIV care model persist despite a pandemic that disrupted routine medical care and behavior practices.

Although mucormycosis is an important cause of morbidity and mortality in children with cancer, our understanding of the typical characteristics of these infections is incomplete. We reviewed all cases of mucormycosis diagnosed at a single pediatric cancer center over 5 decades to identify the clinical features of mucormycosis in pediatric oncology patients and to identify risk factors for mortality. There were 44 cases of mucormycosis diagnosed between 1970-2019. Most patients (89%) had hematological malignancies and a history of prolonged and severe neutropenia (91%). In this series, hyperglycemia and exposure to corticosteroids were common. Pulmonary (36%) and disseminated infections (32%) were most common; rhino-orbital-cerebral infections were relatively infrequent (11%). Rhizopus spp. was the most common etiological agent (40%) followed by Mucor spp. (31%), and Cunninghamella spp. (19%). Overall mortality was 44% and 51% and attributable mortality was 39% and 41% at the end of antifungal therapy and end of follow up, respectively. Attributable mortality fell to 18% in 2010-2019, from 58-60% in previous decades; adjunctive surgery was associated with decreased mortality. Mortality remains unacceptably high despite aggressive antifungal therapy and adjunctive surgery, suggesting novel therapeutic strategies are needed.

The first pediatric AIDS cases were reported in 1982. A decade later, the World Health Organization estimated there were more than 500,000 pediatric AIDS cases resulting from mother-to-child transmission, 90% of which were in sub-Saharan Africa. Although the rate of new infections globally has been cut in half since the peak of the pandemic, human immunodeficiency virus (HIV) remains a public health threat, and rates of new infections continue to increase in some regions. Mother-to-child transmission of HIV has now been virtually eliminated in many parts of the world but remains an issue in resource-limited countries.

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-naïve 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.

The purpose of this study was to evaluate the pharmacokinetics of ritonavir-boosted fosamprenavir during pregnancy and postpartum. Amprenavir (the active moiety of fosamprenavir) and ritonavir intensive pharmacokinetic evaluations were performed at steady state during the second and third trimesters of pregnancy and postpartum. Plasma concentrations of amprenavir and ritonavir were measured using high-performance liquid chromatography. The target amprenavir area under the concentration-versus-time curve (AUC) was higher than the 10th percentile (27.

BACKGROUND:HIV-infected, postpartum women on antiretroviral therapy (ART) have high rates of viremia. We examined predictors of postpartum viremia in the PROMISE study. METHODS:Women with pre-ART CD4 T-cell counts ≥400 cells/mm who started ART during pregnancy were randomized postpartum to continue ART (CTART) or discontinue ART (DCART). Viral load and self-reported adherence were collected every 12 weeks, up to 144 weeks. Women in DCART reinitiated therapy when clinically indicated. Viremia was defined as 2 consecutive viral loads >1000 copies/mL after 24 weeks on ART. Adherence was dichotomized as missing versus not missing ART doses in the past 4 weeks. Predictors of viremia were examined using Cox proportional hazards regression with adherence as a time-varying covariate. RESULTS:Among 802 women in the CTART arm, median age at entry was 27 years and median CD4 T-cell count 696 cells/mm. Of 175 women in CTART with viremia (22%), 141 had resistance data, and 12% had resistance to their current regimen. There was an estimated 0.12 probability of viremia by week 48 and 0.25 by week 144. Predictors of viremia included missed ART doses within the past 4 weeks, younger age, shorter duration of pre-entry ART, and being from the South American/Caribbean region. Of 137 women in DCART who reinitiated therapy, probability of viremia was similar to CTART (0.24 by week 96; 0.27 by week 144). CONCLUSIONS:Rates of postpartum viremia are high and viremia is more likely in younger postpartum women who start ART later in pregnancy. Interventions should target these higher-risk women.

Youth perinatally HIV infected (PHIV) or HIV exposed, but uninfected (PHEU), are aging into adolescence and adulthood with multiple complex risk factors for mental health (MH) problems and poor MH treatment utilization. Our aims were to estimate prevalence of MH diagnoses, clinically significant symptoms, and MH treatment utilization among youth with PHIV and among PHEU youth, 10-22 years old. We also aimed to identify correlates of diagnoses and treatment utilization. Analyses of data from standardized interviews, behavioral assessments, and chart review of 551 youth revealed that 36% had a previous or current MH diagnosis, with no significant HIV status group differences. Prevalence of clinically significant symptoms was 15% for both groups, of whom a third had no diagnosis, and half were not receiving treatment. Among youth with a current MH diagnosis, those with PHIV had greater utilization of services than PHEU youth (67% vs. 51%; p=0.04). Factors associated with MH diagnoses and/or treatment utilization included caregiver characteristics, age and sex of child, HIV status, and stressful life events. Prevalence of MH diagnoses was higher than in the general population, but lower than in similar perinatally HIV-exposed cohorts, with some unmet service needs, particularly in PHEU youth. Family characteristics warrant careful consideration in early diagnosis and treatment of MH problems among youth affected by HIV.

IMPORTANCE Since 1994, the US Department of Health and Human Services has published treatment guidelines for pregnant women living with HIV. Understanding how well prescribing patterns correspond with treatment guidelines could inform health policy and influence future clinical practice. OBJECTIVES To compare antiretroviral prescribing practices over time among pregnant women living with HIV with Department of Health and Human Services treatment guidelines and identify factors associated with receiving recommended regimens. DESIGN, SETTING, AND PARTICIPANTS A prospective cohort study of 1582 pregnant women living with HIV were enrolled in the Pediatric HIV/AIDS Cohort Study Surveillance Monitoring of ART (antiretroviral therapy) Toxicities study between January 1, 2008, and June 30, 2017. The study was conducted at 18 academic research hospitals in the United States. EXPOSURES Antiretroviral medications (ARVs) prescribed during pregnancy. MAIN OUTCOMES AND MEASURES Proportion of regimens prescribed to pregnant women living with HIV qualifying as preferred or alternative according to Department of Health and Human Services guidelines, stratified by timing of initiation. RESULTS Of 1867 pregnancies (among 1582 pregnant women living with HIV with a mean [SD] age of 28.6 [6.1] years at conception), 1264 (67.7%) occurred among women self-identified as black, 480 (25.7%) self-identified as white, and 123 (6.6%) self-identified as other or unreported race/ethnicity. Antiretroviral medications were initiated prior to conception for 790 women (42.3%), resumed during pregnancy for 625 women (33.5%), and initiated during pregnancy for 452 women (24.2%). Only 925 pregnancies (49.5%) were associated with prescribed ARVs designated as preferred or alternative, while 492 (26.4%) involved ARVs with insufficient evidence for use during pregnancy and 136 (7.3%) involved ARVs that were not recommended during pregnancy. A higher proportion of treatment-naive pregnant women initiating ARVs were prescribed preferred or alternative ARVs compared with those resuming ARVs or those treated with ARVs before conception (316 of 452 [69.9%] vs 325 of 625 [52.0%] vs 284 of 790 [35.9%]; P < .001). A total of 91 of 452 women (20.1%) initiating ARVs during pregnancy were prescribed ARVs with insufficient evidence for use during pregnancy or not recommended during pregnancy. Among women resuming ARVs, those with a viral load greater than 1000 copies/mL early in pregnancy had higher odds of being prescribed guideline-recommended ARVs (adjusted odds ratio, 2.03 [95% CI, 1.33-3.10]) compared with those with a viral load of 400 copies/mL or less. CONCLUSIONS AND RELEVANCE This study suggests that US ARV prescribing practices for pregnant women living with HIV do not align well with national guidelines. This finding is particularly concerning when treatment is initiated during pregnancy. Further research is needed to understand disparities between prescribing practices and evidence-based guideline recommendations.

Background: Disordered bone mineral metabolism and low vitamin D concentrations are associated with cardiovascular abnormalities; few studies have evaluated this relationship in HIV-infected youth. Setting: The Adolescent Master Protocol is a Pediatric HIV/AIDS Cohort Study network study conducted across 14 US sites. Methods: Among perinatally HIV-infected (PHIV) and perinatally HIV-exposed but uninfected (PHEU) youth enrolled in the Adolescent Master Protocol, we evaluated associations of vitamin D [measured as 25-hydroxy-vitamin D (25-OHD)], parathyroid hormone (PTH), calcium, phosphate, and fibroblast growth factor-23 (FGF-23) concentrations with echocardiographic measures of left ventricular (LV) structure, function, and concentrations of NT-proBNP, a biomarker of cardiac damage. Results: Among 485 participants (305 PHIV and 180 PHEU) with echocardiograms and bone mineralization measures, low 25-OHD (<20 ng/mL) was common among all participants (48% PHIV and 44% PHEU), but elevated PTH (>65 pg/mL) was identified more often among PHIV participants than PHEU participants (9% vs 3%, P = 0.02). After adjusting for HIV status and demographic covariates, both low 25-OHD and elevated PTH were associated with lower mean LV mass z-scores, whereas elevated PTH was associated with higher mean fractional shortening z-scores. Participants with low 25-OHD also had slightly higher mean LV endsystolic wall stress z-scores, but differences were more pronounced in PHEU participants than in PHIV participants. FGF-23 was inversely related to end-diastolic septal thickness, both overall and among PHIV participants. Conclusions: In this cohort of PHIV and PHEU youth, we observed associations of 25-OHD, PTH, and FGF-23 with both structural and functional cardiac parameters, supporting links between bone mineral metabolism and cardiac status.

Background Perinatal HIV transmission has substantially decreased with combination antiretroviral regimens, but complications in children who are HIV-exposed but uninfected, such as microcephaly, warrant ongoing surveillance. We aimed to evaluate whether individual in utero antiretroviral exposures were associated with increased risk of microcephaly based on long-term follow-up of infants and children who are HIV-exposed but uninfected. Methods We evaluated children aged younger than 18 years who were HIV-exposed but uninfected with at least one head circumference measurement while enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study at 22 clinical sites in the USA, including Puerto Rico. This prospective cohort study was done by the Pediatric HIV/AIDS Cohort Study network. Microcephaly was defined as having a head circumference Z score <-2 according to the 2000 US Centers for Disease Control and Prevention growth charts for children 6-36 months old and according to Nellhaus standards (head circumference <2nd percentile) after 36 months (SMARTT criteria); an alternate definition for microcephaly was based on applying Nellhaus standards across all ages (Nellhaus criteria). Modified Poisson regression models were fit to obtain relative risks (RRs) for associations between in utero antiretroviral exposure and microcephaly status, adjusted for potential confounders. Neurodevelopmental functioning was compared in children who are HIV-exposed but uninfected with or without microcephaly. Findings Between March 21, 2007, and Aug 1, 2017, 3055 participants enrolled in SMARTT had at least one head circumference measurement. The cumulative incidence of microcephaly over a median of 5.1 years of follow-up (IQR 3.0-7.2) was 159 (5.2%, 95% CI 4.4-6.1) by Nellhaus criteria and 70 (2.3%, 1.8-2.9) by SMARTT criteria. In adjusted models, in utero exposure to efavirenz (4.7% exposed) was associated with increased risk of microcephaly by both Nellhaus standards (adjusted RR 2.02, 95% CI 1.16-3.51) and SMARTT criteria (2.56, 1.22-5.37). These associations were more pronounced in children exposed to combination regimens of efavirenz that included zidovudine plus lamivudine than those including tenofovir plus emtricitabine. Protective associations were observed for darunavir exposure (adjusted RR 0.50, 95% CI 0.24-1.00). Children who are HIV-exposed but uninfected with microcephaly had lower mean scores on neurodevelopmental assessments at age 1 and 5 years and a higher prevalence of neurodevelopmental impairment than those without microcephaly. Interpretation These findings support consideration of alternatives to efavirenz as part of first-line antiretroviral therapy for pregnant women. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

Background: Metabolic perturbations in HIV-exposed uninfected (HEU) obese youth may differ from those in the general obese pediatric population. Methods: Metabolic parameters of obese (body mass index Z-score >95th percentile) HEU youth in the Pediatric HIV/AIDS Cohort Study (PHACS) Surveillance Monitoring of ART Toxicities (SMARTT) study were compared with a matched sample of obese youth from the US National Health and Nutrition Examination Survey (NHANES). We evaluated systolic and diastolic hypertension (blood pressure ≥90th percentile for age, sex, and height), total cholesterol >200 mg/dL, high-density lipoprotein cholesterol <35 mg/dL, low-density lipoprotein cholesterol >130 mg/dL, triglycerides (TGs) >150 mg/dL, and Homeostatic Model Assessment–Insulin Resistance >4.0. Modified Poisson regression models were fit to quantify the prevalence ratio (PR) of each outcome comparing the 2 cohorts, adjusting for confounders. Results: The blood pressure outcome analytic subgroup included 1096 participants (n = 304 HEU), the total cholesterol and high-density lipoprotein cholesterol subgroup 1301 participants (n = 385 HEU), and the low-density lipoprotein cholesterol, TG, and Homeostatic Model Assessment–Insulin Resistance subgroup 271 (n = 83 HEU). After adjustment, obese HEU youth had a higher prevalence of systolic and diastolic hypertension [PR = 3.34, 95% confidence interval (CI): 2.48 to 4.50; PR = 2.04, 95% CI: 1.18 to 3.52, respectively], but lower prevalence of insulin resistance (PR = 0.67, 95% CI: 0.54 to 0.85) and hypercholesterolemia (PR = 0.67, 95% CI: 0.44 to 1.01) compared with obese NHANES youth. Conclusions: In the United States, obese HEU youth seem to have an increased risk of hypertension, but lower risk of insulin resistance and hypercholesterolemia, compared with a general obese pediatric population. Monitoring for cardiovascular morbidity in adulthood may be warranted in HEU children.

Objectives To estimate birth prevalence of congenital cytomegalovirus (cCMV) in HIV-exposed uninfected children born in the current era of combination antiretroviral therapy and describe cCMV-related neurodevelopmental and hearing outcomes. Study design The Surveillance Monitoring for ART Toxicities cohort study follows HIV-exposed uninfected children at 22 sites in the US and Puerto Rico. Birth cCMV prevalence was estimated in a subset of participants who had blood pellets collected within three weeks of birth and underwent >= 1 of 6 assessments evaluating cognitive and language development including an audiologic examination between 1 and 5 years of age. Detection of CMV DNA by polymerase chain reaction testing of peripheral blood mononuclear cells was used to diagnose cCMV. Proportions of suboptimal assessment scores were compared by cCMV status using Fisher exact test. Results Mothers of 895 eligible HIV-exposed uninfected children delivered between 2007 and 2015. Most (90%) were on combination antiretroviral therapy, 88% had an HIV viral load of <= 400 copies/mL, and 93% had CD4 cell counts of >= 200 cells/mu L. Eight infants were diagnosed with cCMV, yielding an estimated prevalence of 0.89% (95% CI, 0.39H-1.75%). After adjusting for a sensitivity of 70%-75% for the testing method, projected prevalence was 1.2%-1.3%. No differences were observed in cognitive, language and hearing assessments by cCMV status. Conclusions Although birth cCMV prevalence in HIV-exposed uninfected children born to women with well-controlled HIV is trending down compared with earlier combination antiretroviral therapy-era estimates, it is above the 0.4% reported for the general US population. HIV-exposed uninfected children remain at increased risk for cCMV.

BACKGROUNDPersons who are infected with human immunodeficiency virus (HIV) are at high risk of human papillomavirus (HPV)-associated cancers. The objectives are to compare antibody titers to HPV 6, 11, 16, and 18 and rate of abnormal cytology between perinatally HIV-infected (PHIV) and perinatally HIV-exposed, uninfected (PHEU) youth.METHODSThis is a prospective observational cohort study of HPV4 vaccinated youth performed as part of the multicenter Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol. Seroconversion and geometric mean titer (GMT) against HPV types 6, 11, 16, and 18 were calculated. Vaccine effectiveness included rates of abnormal cervical cytology and genital warts.RESULTSSeroconversion to HPV 6, 11, 16, and 18 occurred in 83%, 84%, 90%, and 62% of 310 vaccinated PHIV youth compared to 94%, 96%, 99%, and 87% of 148 vaccinated PHEU youth, respectively (P < .05 for all comparisons). GMTs were lower in the PHIV vs PHEU within each category of HPV4 doses received. Higher GMTs were associated with younger age, lower HIV type 1 RNA viral load, and higher CD4% at first HPV4 vaccination, as well as shorter duration between last vaccine dose and antibody specimen. Abnormal cytology occurred in 33 of 56 PHIV and 1 of 7 PHEU sexually active vaccinated females, yielding incidence rates per 100 person-years of 15.0 (10.9 to 20.6) and 2.9 (0.4 to 22.3), respectively.CONCLUSIONAntibody titers to HPV4 were lower for all serotypes in PHIV compared to PHEU youth. Protection against abnormal cytology was also diminished in sexually active PHIV females.

While children's exposure to environmental lead in the United States has decreased, areas of elevated levels remain. Because lead exposure is a risk factor for developmental delays, it should be considered when studying neurodevelopmental effects of in utero antiretroviral medication (ARV) exposure in the growing population of perinatally HIV-exposed, uninfected (PHEU) children. We compared blood lead levels (BPb) in PHEU children enrolled in the Surveillance Monitoring of ART Toxicities (SMARTT) Study to U.S. children, assessed associations with neurodevelopment, and explored whether associations between in utero ARV and neurodevelopment are modified by BPb. Prevalence of elevated BPb (5g/dl) at ages 1-2 years was calculated by year and race/ethnicity and compared to that for children in the National Health and Nutrition Examination Survey (NHANES 2002-2010). Associations between elevated BPb and neurodevelopment at 1 and 3 years were assessed. Associations between ARVs (tenofovir disoproxil fumarate [TDF]; atazanavir) and neurodevelopment were evaluated within BPb level (5g/dl vs. <5g/dl). Mean BPb in SMARTT decreased from 5.9 to 2.7g/dl between 1998 and 2014; prevalence of elevated BPb decreased from 50% to 4%. Both were consistently higher than in NHANES. Elevated BPb was associated with cognitive delay at age 3 (adjusted odds ratio: 1.64; 95% confidence interval: 0.95-2.90). At age 1, TDF was associated with delay only among those with elevated BPb. PHEU children more often had elevated BPb than the general U.S. pediatric population. Exposure to environmental lead is one of several factors that may place these children at higher risk for neurodevelopmental delay.

BACKGROUND:Fetal bone effects of maternal tenofovir use have not been well studied. We sought to compare whole-body bone mineral content (BMC) of newborns exposed vs not exposed to tenofovir in utero.METHODS:We enrolled participants from April 2011 to June 2013 at 14 US clinical sites. Singleton infants of women with human immunodeficiency virus (HIV) infection who took tenofovir in late pregnancy (tenofovir-exposed) or no tenofovir during pregnancy (tenofovir-unexposed) were enrolled during late pregnancy or within 72 hours of birth. Infants born before 36 weeks gestation or with confirmed HIV infection were excluded. Whole-body BMC was measured in the first month of life and compared with that of the tenofovir-exposed and tenofovir-unexposed newborns, unadjusted and adjusted for covariates.RESULTS:Seventy-four tenofovir-exposed and 69 tenofovir-unexposed infants had evaluable BMC measurements. Tenofovir-exposed mothers were more likely to be married (31% vs 22%; P = .04) and to use boosted protease inhibitors (84% vs 62%; P = .004). Tenofovir-exposed newborns did not differ from unexposed newborns on mean gestational age (38.2 vs 38.1 weeks) or mean length (-0.41 vs -0.18) or weight (-0.71 vs -0.48) Z-scores. The mean (standard deviation) BMC of tenofovir-exposed infants was 12% lower than for unexposed infants (56.0 [11.8] vs 63.8 [16.6] g; P = .002). The adjusted mean bone mineral content was 5.3 g lower (95% confidence interval, -9.5, -1.2; P = .013) in the tenofovir-exposed infants.CONCLUSIONS:Maternal tenofovir use is associated with significantly lower neonatal BMC. The duration and clinical significance of this finding should be evaluated in longitudinal studies.CLINICAL TRIALS REGISTRATION:ClinicalTrials.gov NCT01310023.

BACKGROUND Invasive mold infections (IMIs) are a leading cause of mortality in immunocompromised children, yet there has never been an international epidemiologic investigation of pediatric IMIs. METHODS This international, prospective cohort study was performed to characterize the epidemiology, antifungal therapy, and outcomes of pediatric IMIs. Children (≤18 years) with proven or probable IMIs were enrolled between August 2007 and May 2011 at 22 sites. Risk factors, underlying diagnoses, and treatments were recorded. Outcomes were assessed at 12 weeks after diagnosis using European Organization for Research and Treatment of Cancer/Mycoses Study Group response criteria. RESULTS One hundred thirty-one pediatric patients with IMIs were enrolled; the most common IMI was invasive aspergillosis ([IA] 75%). Children with IA and those with other types of IMIs had similar underlying risk factors, except that children with IMIs caused by non-Aspergillus species were more likely to have received mold-active antifungal agents preceding diagnosis. The most commonly used antifungal classes after diagnosis were triazoles (82%) and polyenes (63%). Combination therapy was used in 53% of patients. Use of combination therapy was associated with an increased risk of adverse events (risk ratio, 1.98; 95% confidence interval, 1.06-3.68; P = .031), although there was no detectable difference in outcome. CONCLUSIONS Although risk factors for IMIs are similar across specific subtypes, preceding antifungal therapy may be an important modifier. Combination antifungal therapy requires further study to determine its true risks and benefits.

BACKGROUND:Invasive fungal infections are a major cause of morbidity and mortality among solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients, but few data have been reported on the epidemiology of endemic fungal infections in these populations.METHODS:Fifteen institutions belonging to the Transplant-Associated Infection Surveillance Network prospectively enrolled SOT and HCT recipients with histoplasmosis, blastomycosis, or coccidioidomycosis occurring between March 2001 and March 2006.RESULTS:A total of 70 patients (64 SOT recipients and 6 HCT recipients) had infection with an endemic mycosis, including 52 with histoplasmosis, 9 with blastomycosis, and 9 with coccidioidomycosis. The 12-month cumulative incidence rate among SOT recipients for histoplasmosis was 0.102%. Occurrence of infection was bimodal; 28 (40%) infections occurred in the first 6 months post transplantation, and 24 (34%) occurred between 2 and 11 years post transplantation. Three patients were documented to have acquired infection from the donor organ. Seven SOT recipients with histoplasmosis and 3 with coccidioidomycosis died (16%); no HCT recipient died.CONCLUSIONS:This 5-year multicenter prospective surveillance study found that endemic mycoses occur uncommonly in SOT and HCT recipients, and that the period at risk extends for years after transplantation.

BACKGROUND Limited information exists regarding the use of posaconazole for treating systemic fungal infections in children, adolescents, and young adults with cancer. At St. Jude Children's Research Hospital, the recommended posaconazole dose in patients weighing less than 34 kg is 18–24 mg/kg daily, given in 4 divided doses. For patients aged 13 years or older or those weighing 34 kg or more, the recommended dose is 800 mg daily, given orally in 4 divided doses. OBJECTIVE To determine whether the current posaconazole dosing guidelines achieve target posaconazole plasma concentrations of 0.7 μg/mL or greater. METHODS This retrospective clinical study examined data from patients who received treatment-dose posaconazole and had at least 1 posaconazole plasma concentration measurement. RESULTS Data from 33 patients who received posaconazole for the treatment of fungal infections were analyzed. The median age of patients was 11.5 years (range 0.5–23.2). Twenty-one of 33 patients (63.6%) had posaconazole concentrations of 0.7 μg/mL or greater (median 1.4; range 0.7–2.98) at the first measurement. The median posaconazole dosage referenced to total body weight in these patients was 20 mg/kg/day. Patients with concentrations less than 0.7 μg/mL (median 0.4; range 0.025–0.69) received lower posaconazole dosages when referenced to body weight (median 12.9 mg/kg/day; p = 0.02). Of the 12 patients with concentrations less than 0.7 μg/mL, 7 (58.3%) were aged 13 years or older. CONCLUSIONS The current dosing approach for posaconazole yielded therapeutic plasma concentrations more frequently in patients younger than 13 years than in those 13 years or older. This difference may be related to the practice of capping adolescent and young adult doses at the suggested maximum adult daily dose. Therefore, we recommend weight-based dosing in all pediatric, adolescent, and young adult patients with cancer, with routine therapeutic drug monitoring to ensure adequate concentrations.

BACKGROUND:Invasive mould infections are a significant cause of morbidity and mortality in pediatric cancer patients, particularly in those undergoing aggressive myeloablative chemotherapy. Voriconazole has been described as an appropriate and effective prophylactic agent in adults with cancer.METHODS:We compared the etiology, predisposing factors and outcomes of invasive mould infection in patients treated for acute myeloid leukemia before and after implementation of voriconazole prophylaxis in a pediatric cancer center.RESULTS:We observed no difference in the number of invasive mould infection between groups. However, isolated organisms were markedly different, with a shift from aspergillosis to phaeohyphomycosis after the implementation of voriconazole prophylaxis. Survival at 90 days was improved in patients receiving voriconazole prophylaxis (P = 0.05). We did not identify a significant increase in the incidence of zygomycosis associated with routine use of voriconazole prophylaxis.CONCLUSIONS:Voriconazole prophylaxis was associated with improved survival in pediatric patients with acute myeloid leukemia, although other factors may be involved. Voriconazole prophylaxis was associated with a marked change in the pattern of mould infections, with a significant reduction in aspergillosis.

Invasive mould infections are a significant cause of morbidity and mortality in pediatric cancer patients, particularly in those undergoing aggressive myeloablative chemotherapy. Voriconazole has been described as an appropriate and effective prophylactic agent in adults with cancer.We compared the etiology, predisposing factors and outcomes of invasive mould infection in patients treated for acute myeloid leukemia before and after implementation of voriconazole prophylaxis in a pediatric cancer center.We observed no difference in the number of invasive mould infection between groups. However, isolated organisms were markedly different, with a shift from aspergillosis to phaeohyphomycosis after the implementation of voriconazole prophylaxis. Survival at 90 days was improved in patients receiving voriconazole prophylaxis (P = 0.05). We did not identify a significant increase in the incidence of zygomycosis associated with routine use of voriconazole prophylaxis.Voriconazole prophylaxis was associated with improved survival in pediatric patients with acute myeloid leukemia, although other factors may be involved. Voriconazole prophylaxis was associated with a marked change in the pattern of mould infections, with a significant reduction in aspergillosis.