A Bayesian Model to Predict COVID-19 Severity in Children.

BACKGROUND: We aimed to identify risk factors causing critical disease in hospitalized children with COVID-19 and to build a predictive model to anticipate the probability of need for critical care. METHODS: We conducted a multicenter, prospective study of children with SARS-CoV-2 infection in 52 Spanish hospitals. The primary outcome was the need for critical care. We used a multivariable Bayesian model to estimate the probability of needing critical care. RESULTS: The study enrolled 350 children from March 12, 2020, to July 1, 2020: 292 (83.4%) and 214 (73.7%) were considered to have relevant COVID-19, of whom 24.2% required critical care. Four major clinical syndromes of decreasing severity were identified: multi-inflammatory syndrome (MIS-C) (17.3%), bronchopulmonary (51.4%), gastrointestinal (11.6%), and mild syndrome (19.6%). Main risk factors were high C-reactive protein and creatinine concentration, lymphopenia, low platelets, anemia, tachycardia, age, neutrophilia, leukocytosis, and low oxygen saturation. These risk factors increased the risk of critical disease depending on the syndrome: the more severe the syndrome, the more risk the factors conferred. Based on our findings, we developed an online risk prediction tool (https://rserver.h12o.es/pediatria/EPICOAPP/, username: user, password: 0000). CONCLUSIONS: Risk factors for severe COVID-19 include inflammation, cytopenia, age, comorbidities, and organ dysfunction. The more severe the syndrome, the more the risk factor increases the risk of critical illness. Risk of severe disease can be predicted with a Bayesian model.

High prevalence of X4/DM-tropic variants in children and adolescents infected with HIV-1 by vertical transmission.

BACKGROUND: We studied HIV coreceptor tropism in vertically HIV-infected children and adolescents with the objective of predicting the proportion of children and adolescents that could be treated with CCR5 (R5) antagonists. METHODS: One hundred eighteen multidrug-resistant pediatric patients (36 children and 82 adolescents) were enrolled in a cross-sectional study. Viral tropism was assessed using the new phenotypic HIV-1 tropism coreceptor assay information and Trofile. RESULTS: Of 118 antiretroviral-experienced HIV-infected children and adolescents, 49 (57.0%) had dual-tropic and 20 (23.3%) had X4-tropic viruses by tropism coreceptor assay information testing. Only 17 (19.7%) showed R5-tropic variants. HIV-1 coreceptor usage was not detectable in 32 of 118 (27%) patients. Among 24 children and 62 adolescents with tropism coreceptor assay information results, 17 (70.8%) children and 51 (82.2%) adolescents showed viruses with dual-tropic or X4-tropic variants. Additionally, Trofile (ES) was performed in 42 of 118 patients with HIV-1 RNA > 1000 copies/mL. No patient showed X4-tropic variants; dual-tropic viruses were observed in 12 (28.6%) patients. In 6 (14.3%) patients, HIV tropism could not be determined. X4-tropic variants were more common in children (P = 0.031). CD4 T cell percentage was significantly lower in children (P = 0.011) and adolescents (P = 0.027) with R5-tropic viruses than in those with X4-tropic viruses. CONCLUSIONS: The presence of X4-tropic variants in more than 80% of our cohort of antiretroviral-experienced children and adolescents with vertical HIV-1 infection indicates a very limited role for CCR5 antagonists as part of salvage regimens for highly treatment-experienced vertically HIV-1-infected patients with extensive antiretroviral drug resistance and limited treatment options.

Causes of death in pediatric patients vertically infected by the human immunodeficiency virus type 1 in Madrid, Spain, from 1982 to mid-2009.

BACKGROUND: Effective therapies have increased life expectancy of human immunodeficiency virus (HIV)-infected pediatric patients. We investigated the underlying causes of death, mortality, and acquired immune deficiency syndrome (AIDS) rates in HIV-infected pediatric patients in Madrid, Spain. METHODS: We studied a multicenter cohort of 478 HIV-infected pediatric patients in Madrid. Mortality and AIDS incidence rates, causes of death, CD4 T-cell, and HIV RNA were analyzed during calendar periods (CPs): pre-HAART (highly active antiretroviral therapy) (CP1: 1982-1996) and post-HAART era (CP2: 1997-2009). RESULTS: During 5690 person-years of follow-up 157 (32.8%) deaths occurred. Median age at death increased (CP1: 3.2 years [1.0-6.3] vs. CP2: 7.7 years [3.1-11.4]; P < 0.01). Mortality and AIDS rates decreased 10.6-fold (95% confidence intervals [CI]: 6.9-16.7) and 6.9-fold (95% CI: 5.0-9.6), respectively, between CPs. Nevertheless, mortality was 10.4-fold (95% CI: 5.8-18.8; P < 0.001) higher than in age-similar general population in late-CP2. In all, 169 causes of death were reported. Multiple causes were reported in 16 of 151 (10.6%) patients. In 81.1% (137/169), the causes were AIDS-defining, 11.8% (20/169) HIV-related, and 7.1% (12/169) non-HIV-related. Infections were the leading causes (60.8%, 101/166); from 1999 to 2007 the risk of death from infections was 115.9 times (95% CI: 42.0-265.8; P < 0.001) higher than in the age-similar general population. Comorbidity was reported in 66.9% (101/151) of patients. Median HIV-1 RNA at death decreased (CP1: 5.9 [5.0-6.3]; CP2: 5.3 [4.2-5.8]; P < 0.01). CONCLUSIONS: Despite decline in mortality and AIDS rates, it is important to monitor all causes of death as prolonged survival might allow underlying comorbidity to become more clinically relevant.

Long-term efficacy and safety of fosamprenavir in human immunodeficiency virus-infected pediatric patients.

Fosamprenavir (FPV) efficacy in human immunodeficiency virus (HIV)-infected pediatric patients is still being evaluated in ongoing clinical trials. The long-term efficacy and safety of FPV boosted with ritonavir (FPV/r) was evaluated in 20 antiretroviral-naive and antiretroviral-experienced HIV-vertically infected pediatric patients. Analyses of CD4(+) T-cells, HIV-ribonucleic acid (RNA), and clinical status were performed during a median of 180 weeks. Initially, median HIV-RNA was 4.6 log(10) in naive and 4.4 log(10) in pretreated patients. Median CD4(+) T-cell was 17% and 31%, respectively. After FPV/r treatment, 18 of 20 patients achieved undetectable HIV-RNA and 4 of 20 experienced adverse events. To date, FPV/r treatment has shown sustained antiviral response and immunologic improvement in our 20 patients.

Immunological recovery and metabolic disorders in severe immunodeficiency HIV type 1-infected children on highly active antiretroviral therapy.

Little is known about immunologic reconstitution in children on highly active antiretroviral treatment (HAART) during very long-term periods. A retrospective study was carried out to assess the effectiveness and development of metabolic disorders after very long-term periods on HAART in HIV-infected children with severe immunodeficiency. We included 55 children who were stratified into three groups according to %CD4(+) pre-HAART and rate of immunologic recovery: (1) S1-Rec: CD4(+) < or =5% at baseline and slow immunologic recovery; (2) S2-Rec: CD4(+) 5-15% at baseline and slow immunologic recovery; (3) R-Rec: CD4(+) < or =15% at baseline and rapid immunologic recovery (reference group). An adequate immune recovery after 8 years on HAART was achieved by only 25% of children. S1-Rec never achieved a mean of CD4(+) > or =25% after 8 years on HAART. All children had a significant increase in plasma cholesterol levels during the first 2 years. Afterward, cholesterol levels reached a plateau and remained stable until year 8 of follow-up. Higher rates of lipodystrophy were found in the R-Rec group [14 (100%)] than in the S1-Rec group [9/19 (47.4%)] or the S2-Rec group [13/20 (65%)] at the end of the study (p = 0.006). Overall, having a low nadir of CD4(+) hindered immune reconstitution; however, children with rapid immunologic recovery showed a higher prevalence of the lipodystrophy syndrome.

Long-term response to highly active antiretroviral therapy with lopinavir/ritonavir in pre-treated vertically HIV-infected children.

BACKGROUND: Immune recovery after prolonged highly active antiretroviral therapy (HAART) with lopinavir/ritonavir has been reported in adults but not in children. Our study aimed at evaluating the long-term use of lopinavir/ritonavir among children in a clinical setting. METHODS: We carried out a retrospective study on 69 protease inhibitor (PI)-experienced vertically HIV-infected children on HAART containing lopinavir/ritonavir. We analysed the changes in percentage CD4+ cell count (%CD4+) and viral load (VL) and identified prognostic factors to achieve CD4+ >25% and undetectable VL (uVL) ( 100,000 copies/mL. We found that %CD4+ at baseline had a strong positive association with achieving CD4+ >25% at 6, 12, 18, 24, 36 and 48 months of follow-up. We also found that length of PI use had a negative association with reaching CD4+ >25% at 24 and 48 months and achieving uVL at 12 and 24 months. VL at baseline had a negative association with achieving uVL at 18 and 24 months. CONCLUSIONS: Our study demonstrates ongoing immune recovery among children on HAART with lopinavir/ritonavir after 4 years of follow-up. Lopinavir/ritonavir, when given as part of a salvage regimen, is safe and well tolerated in HIV-infected children.

Long-term response to highly active antiretroviral therapy in human immunodeficiency virus and hepatitis C virus coinfected children: 6 years of follow-up.

We carried out a retrospective study to analyze the long-term response to highly active antiretroviral therapy of 19 vertically human immunodeficiency virus type 1/hepatitis C virus (HCV-1/HIV) coinfected children. The clinical, immunologic, viral, and biochemical variables were assayed at 0, 1, 2, 3, 4, 5, and 6 years of follow-up. Our data suggest that CD4 T-cell recovery and viral load control during long-term highly active antiretroviral therapy among HIV-1/HCV children were similar to those described in HIV-1 monoinfected children, but hepatic function was significantly altered in HIV-1/HCV children.

Impact of highly active antiretroviral therapy on CD4+ T cells and viral load of children with AIDS: a population-based study.

In this study, we sought to characterize the changes over time at the population level on CD4(+) T cells and plasma viral load (VL) levels of HIV-1-infected children with or without AIDS. We carried out a retrospective study in 114 HIV-infected children during the calendar period that a highly active antiretroviral therapy (HAART) protocol was used. The HAART protocol consisted of three drugs: nucleoside analogue HIV-1 reverse transcriptase inhibitors, and/or HIV protease inhibitors, and/or nonnucleoside analogue HIV-1 reverse transcriptase inhibitors. The mean of CD4(+) T cells percentage and log(10) VL per calendar year were stratified by AIDS diagnostic. As new HAART strategies become available, an increase of CD4(+) T cells and a decrease of VL were observed over time, in children with and without AIDS. In 2001, children with AIDS reached values of CD4(+) T cells and VL similar to children without AIDS. In conclusion, our study shows that the generalized use of HAART has permitted improvement in immunological and virological status of HIV-infected children without AIDS, and more importantly in children with AIDS.