Search

ImportanceMost research to understand postacute sequelae of SARS-CoV-2 infection (PASC), or long COVID, has focused on adults, with less known about this complex condition in children. Research is needed to characterize pediatric PASC to enable studies of underlying mechanisms that will guide future treatment.ObjectiveTo identify the most common prolonged symptoms experienced by children (aged 6 to 17 years) after SARS-CoV-2 infection, how these symptoms differ by age (school-age [6-11 years] vs adolescents [12-17 years]), how they cluster into distinct phenotypes, and what symptoms in combination could be used as an empirically derived index to assist researchers to study the likely presence of PASC.Design, setting, and participantsMulticenter longitudinal observational cohort study with participants recruited from more than 60 US health care and community settings between March 2022 and December 2023, including school-age children and adolescents with and without SARS-CoV-2 infection history.ExposureSARS-CoV-2 infection.Main outcomes and measuresPASC and 89 prolonged symptoms across 9 symptom domains.ResultsA total of 898 school-age children (751 with previous SARS-CoV-2 infection [referred to as infected] and 147 without [referred to as uninfected]; mean age, 8.6 years; 49% female; 11% were Black or African American, 34% were Hispanic, Latino, or Spanish, and 60% were White) and 4469 adolescents (3109 infected and 1360 uninfected; mean age, 14.8 years; 48% female; 13% were Black or African American, 21% were Hispanic, Latino, or Spanish, and 73% were White) were included. Median time between first infection and symptom survey was 506 days for school-age children and 556 days for adolescents. In models adjusted for sex and race and ethnicity, 14 symptoms in both school-age children and adolescents were more common in those with SARS-CoV-2 infection history compared with those without infection history, with 4 additional symptoms in school-age children only and 3 in adolescents only. These symptoms affected almost every organ system. Combinations of symptoms most associated with infection history were identified to form a PASC research index for each age group; these indices correlated with poorer overall health and quality of life. The index emphasizes neurocognitive, pain, and gastrointestinal symptoms in school-age children but change or loss in smell or taste, pain, and fatigue/malaise-related symptoms in adolescents. Clustering analyses identified 4 PASC symptom phenotypes in school-age children and 3 in adolescents.Conclusions and relevanceThis study developed research indices for characterizing PASC in children and adolescents. Symptom patterns were similar but distinguishable between the 2 groups, highlighting the importance of characterizing PASC separately for these age ranges.

P1093 is a multicenter, open-label, phase I/II study of pharmacokinetics, safety, and tolerability of dolutegravir plus an optimized background regimen in pediatric participants aged 4 weeks to

BackgroundP1093 is an ongoing phase I/II multicenter open-label study of dolutegravir plus an optimized background regimen in age-defined pediatric cohorts; here we report the long-term safety and virologic efficacy outcomes for the oldest cohort.MethodsThe study enrolled human immunodeficiency virus type 1 (HIV-1)-infected treatment-experienced adolescents aged 12 to

ObjectiveThe aim of this study was to estimate the long-term metabolic effects of initiating a lopinavir/ritonavir (LPV/r)-based regimen as a first-line therapy for HIV-infected children less than 3 years of age in resource-limited settings.DesignA prospective cohort study after conclusion of the P1060 randomized clinical trials (ClinicalTrials.gov Identifier: NCT00307151), with an overall follow-up of 7 years.MethodsLongitudinal total cholesterol and triglyceride measures were compared between 222 and 227 children randomized to initiate LPV/r and nevirapine (NVP)-based regimens, respectively. Adipokines (adiponectin and leptin) and biomarkers of inflammation [C-reactive protein and interleukin (IL)-6], microbial translocation (lipopolysaccharide) and immune activation (sCD14), measured in 117 participants at a median of 45 weeks of follow-up, were also compared by a randomized arm.ResultsMean total cholesterol and the percentage of participants with borderline or high total cholesterol was higher in the LPV/r arm from years 3 to 7 of follow-up than in the NVP arm (adjusted relative differences ranging from 10.9 to 23.4 mg/dl and adjusted relative risks ranging from a 60% increased risk to a more than four-fold increased risk for cholesterol ≥170 mg/dl at 7 years of follow-up). Initiation of a LPV/r-based regimen was not associated with high triglycerides over follow-up or large differences in markers of metabolic syndrome, inflammation, microbial translocation or immune activation.ConclusionGiven the virologic superiority of LPV/r-based regimens in young children and open questions regarding the roll-out of dolutegravir in resource-limited settings, children are currently being maintained on LPV/r-based regimens. Our results suggest continual assessment of total cholesterol among young children initiating a LPV/r-based regimen to monitor cardiometabolic health.

Nearly all cervical cancers are caused by persistent high-risk human papillomavirus (hrHPV) infection. There are 14 recognized hrHPV genotypes (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68), and hrHPV genotypes 16 and 18 comprise approximately 66% of all cases worldwide. An additional 15% of cervical cancers are caused by hrHPV genotypes 31, 33, 45, 52, and 58. Screening patients for hrHPV as a mechanism for implementation of early treatment is a proven strategy for decreasing the incidence of HPV-related neoplasia, cervical cancer in particular. Here, we present population data from an HPV screening initiative in Kosovo designed to better understand the prevalence of the country's HPV burden and local incidence of cervical cancer by hrHPV genotype. Nearly 2000 women were screened for hrHPV using a real-time polymerase chain reaction (real-time PCR) assay followed by melt curve analysis to establish the prevalence of hrHPV in Kosovo. Additionally, DNA was extracted from 200 formalin-fixed, paraffin embedded cervical tumors and tested for hrHPV using the same method. Cervical screening samples revealed a high prevalence of hrHPV genotypes 16 and 51, while cervical cancer specimens predominantly harbored genotypes 16, 18, and 45. This is the first comprehensive screening study for evaluating the prevalence of hrHPV genotypes in Kosovo on screening cervical brush samples and cervical neoplasms. Given the geographic distribution of hrHPV genotypes and the WHO's global initiative to eliminate cervical cancer, this study can support and direct vaccination efforts to cover highly prevalent hrHPV genotypes in Kosovo's at-risk population. [ABSTRACT FROM AUTHOR]

The role of the thymus in HIV-1 pathogenesis remains unclear. We developed an assay to quantify the number of recent thymic emigrants in blood based on the detection of a major excisional DNA byproduct (termed alpha1 circle) of T cell receptor rearrangement. By studying 532 normal individuals, we found that alpha1 circle numbers in blood remain high for the first 10-15 yr of life, a sharp drop is seen in the late teen years, and a gradual decline occurs thereafter. Compared with age-matched uninfected control individuals, alpha1 circle numbers in HIV-1-infected adults were significantly reduced; however, there were many individuals with normal alpha1 circle numbers. In 74 individuals receiving highly active antiretroviral therapy, we found no appreciable effect on alpha1 circle numbers in those whose baseline values were already within the normal range, but significant increases were observed in those with a preexisting impairment. The increases in alpha1 circle numbers were, however, numerically insufficient to account for the rise in levels of naive T lymphocytes. Overall, it is difficult to invoke thymic regenerative failure as a generalized mechanism for CD4 lymphocyte depletion in HIV-1 infection, as alpha1 circle numbers are normal in a substantial subset of HIV-1-infected individuals.

Introduction: The number of HIV-infected children and adolescents requiring second-line antiretroviral treatment (ART) is increasing in low- and middle-income countries (LMIC). However, the effectiveness of paediatric second-line ART and potential risk factors for virologic failure are poorly characterized. We performed an aggregate analysis of second-line ART outcomes for children and assessed the need for paediatric third-line ART. Methods: We performed a multicentre analysis by systematically reviewing the literature to identify cohorts of children and adolescents receiving second-line ART in LMIC, contacting the corresponding study groups and including patient-level data on virologic and clinical outcomes. Kaplan--Meier survival estimates and Cox proportional hazard models were used to describe cumulative rates and predictors of virologic failure. Virologic failure was defined as two consecutive viral load measurements >1000 copies/ml after at least six months of second-line treatment. Results: We included 12 cohorts representing 928 children on second-line protease inhibitor (PI)-based ART in 14 countries in Asia and sub-Saharan Africa. After 24 months, 16.4% (95% confidence interval (CI): 13.9-19.4) of children experienced virologic failure. Adolescents (10-18 years) had failure rates of 14.5 (95% CI 11.9-17.6) per 100 person-years compared to 4.5 (95% CI 3.4-5.8) for younger children (3-9 years). Risk factors for virologic failure were adolescence (adjusted hazard ratio [aHR] 3.93, p < 0.001) and short duration of first-line ART before treatment switch (aHR 0.64 and 0.53, p = 0.008, for 24-48 months and >48 months, respectively, compared to Conclusions: In LMIC, paediatric PI-based second-line ART was associated with relatively low virologic failure rates. However, adolescents showed exceptionally poor virologic outcomes in LMIC, and optimizing their HIV care requires urgent attention. In addition, 16% of children and adolescents failed PI-based treatment and will require integrase inhibitors to construct salvage regimens. These drugs are currently not available in LMIC. Keywords: antiretroviral treatment; children; adolescents; virologic failure; HIV-1; second-line treatment, Introduction Worldwide, the number of HIV-infected children receiving antiretroviral treatment (ART) has more than doubled since 2010 to an estimated 823,000 in 2014 [1]. In low- and middle-income countries (LMIC), [...]

The study aims to evaluate the efficacy of different antiretroviral therapies in children who were given single-dose nevirapine. Results indicate that in the case of such children with nevirapine exposure, antiretroviral treatment consisting of zidovudine and lamivudine plus ritonavir-boosted lopinavir resulted in better outcomes.

The effects of protease inhibitor (PI) on lipid measures in a large cohort of perinatally HIV- infected children followed from birth is examined. Results reveal that children on PI- containing regimens have a higher risk of both hypercholesterolemia (HC) and hypertriglyceridemia (HT).

Research has been conducted on non-breast-fed infants exposed to HIV. The use of quantitative HIV RNA testing has been used for the diagnosis in these infants, and the results demonstrate that this testing can be used for the HIV-exposed infants but there is a chance of a false-positive test results.

The authors have evaluated zidovudine use guideline implementation in HIV-infected women and their newborns. Results demonstrate that zidovudine use by pregnant HIV-infected women and their infants has increased since the publication of 1994 guidelines in the United States.

CD4+ lymphocyte counts and HIV RNA blood levels appear to be fairly accurate predictors of AIDS progression in children infected with HIV. Researchers followed the prognosis of 566 HIV-infected infants and children and measured blood levels of CD4+ lymphocytes and HIV RNA every 24 weeks. The risk of disease progression increased as the blood levels of HIV RNA increased. The two-year disease progression rate was less than 5% in children with CD4+ lymphocyte counts greater than 200-500 and with viral RNA counts less than 10,000 copies per milliliter of blood., Context.--Pediatric human immunodeficiency virus (HIV) infection has unique viral pathogenetic features that preclude routine extrapolation from adult studies and require specific analysis. Objectives.--To evaluate the prognostic value of 2 key laboratory markers--plasma RNA and [CD4.sup.+] lymphocyte count--for HIV disease progression in infants and children and to establish targeted values for optimal outcome. Design.--Data from a cohort of 566 infants and children who participated in a randomized, placebo-controlled trial of nucleoside reverse transcriptase inhibitors (ACTG 152) were analyzed. The trial was conducted between 1991 and 1995 and enrolled a heterogenous cohort of antiretroviral therapy--naive children (age, 3 months to 18 years); patients had a median follow-up of 32 months. Main Outcome Measures.--The trial clinical end points consisted of time to first HIV disease progression (growth failure, decline in neurologic or neurodevelopmental function, opportunistic infections) or death. Results.--Baseline plasma RNA levels were high (age group medians, 5 x [10.sup.4] to [is greater than] [10.sup.6] copies/mL), and both baseline RNA and [CD4.sup.+] lymphocyte count were independently predictive of subsequent clinical course. Risk reduction for disease progression between 49% and 64% was observed for each [log.sup.10] reduction in baseline RNA and was linear without suggestion of a threshold or age effect. Disease progression predictive power was enhanced by the combined use of plasma RNA and [CD4.sup.+] cell count. Marker values of less than 10 000 copies/mL for plasma RNA and greater than 500 x [10.sup.6]/L ([is less than] 6.5 years of age) or greater than 200 x [10.sup.6]/L ([is greater than] 6.5 years) for [CD4.sup.+] cell count were associated with a 2-year disease progression rate of less than 5%. Conclusions.--Two key laboratory markers--plasma RNA and [CD4.sup.+] lymphocyte count--are independent predictors of clinical course among HIV-infected infants and children. The linear, age-independent relationship between [log.sup.10] plasma RNA and relative risk of disease progression strongly supports therapeutic efforts to achieve plasma virus levels as low as possible. JAMA. 1998;279:756-761