RESUMEN
BACKGROUND: In high-resource settings, the survival of children with immunocompromise (IC) has increased and immunosuppressive therapies are increasingly being used. This study aimed to determine the clinical characteristics, performance of diagnostic tools, and outcome of IC children with tuberculosis (TB) in Europe. METHODS: Multicenter, matched case-control study within the Pediatric Tuberculosis Network European Trials Group, capturing TB cases <18 years diagnosed 2000-2020. RESULTS: A total of 417 TB cases were included, comprising 139 children who are IC (human immunodeficiency virus, inborn errors of immunity, drug-induced immunosuppression, and other immunocompromising conditions) and 278 non-IC children as controls. Nonrespiratory TB was more frequent among cases than controls (32.4% vs 21.2%; P = .013). Patients with IC had an increased likelihood of presenting with severe disease (57.6% vs 38.5%; P < .001; odds ratio [95% confidence interval], 2.073 [1.37-3.13]). Children with IC had higher rates of false-negative tuberculin skin test (31.9% vs 6.0%; P < .001) and QuantiFERON-TB Gold assay (30.0% vs 7.3%; P < .001) results at diagnosis. Overall, the microbiological confirmation rate was similar in IC and non-IC cases (58.3% vs 49.3%; P = .083). Although the mortality in children with IC was <1%, the rate of long-term sequelae was significantly higher than in non-IC cases (14.8% vs 6.1%; P = .004). CONCLUSIONS: Children with IC and TB in Europe have increased rates of nonrespiratory TB, severe disease, and long-term sequelae. Immune-based TB tests have poor sensitivity in those children. Future research should focus on developing improved immunological TB tests that perform better in patients with IC, and determining the reasons for the increased risk of long-term sequelae, with the aim to design preventive management strategies.
Asunto(s)
Huésped Inmunocomprometido , Tuberculosis , Humanos , Estudios de Casos y Controles , Niño , Masculino , Femenino , Adolescente , Europa (Continente)/epidemiología , Tuberculosis/epidemiología , Tuberculosis/diagnóstico , Preescolar , Lactante , Prueba de Tuberculina , Antituberculosos/uso terapéuticoRESUMEN
HIV-1 elite controllers (EC) maintain undetectable viral loads (VL) in the absence of antiretroviral treatment. However, these subjects have heterogeneous clinical outcomes, including a proportion that loses HIV-1 control over time. In this work, we compared, in a longitudinal design, transient EC, analyzed before and after the loss of virological control, with persistent EC. The aim was to identify factors leading to the loss of natural virological control of HIV-1 infection with a longitudinal retrospective study design. Gag-specific T-cell responses were assessed by in vitro intracellular polycytokine production quantified by flow cytometry. Viral diversity determinations and sequence dating were performed in proviral DNA by PCR amplification at limiting dilution of env and gag genes. The expression profile of 70 serum cytokines and chemokines was assessed by multiplex immunoassays. We identified transient EC as subjects with low Gag-specific T-cell polyfunctionality, high viral diversity, and high proinflammatory cytokine levels before the loss of control. Gag-specific T-cell polyfunctionality was inversely associated with viral diversity in transient controllers before the loss of control (r = -0.8; P = 0.02). RANTES was a potential biomarker of transient control. This study identified virological and immunological factors, including inflammatory biomarkers associated with two different phenotypes within EC. These results may allow a more accurate definition of EC, which could help in better clinical management of these individuals and in the development of future curative approaches.IMPORTANCE There is a rare group of HIV-infected patients who have the extraordinary capacity to maintain undetectable viral load levels in the absence of antiretroviral treatment, the so-called HIV-1 elite controllers (EC). However, there is a proportion within these subjects that eventually loses this capability. In this work, we found differences in virological and immune factors, including soluble inflammatory biomarkers, between subjects with persistent control of viral replication and EC that will lose virological control. The identification of these factors could be a key point for a right medical care of those EC who are going to lose natural control of viral replication and for the design of future immunotherapeutic strategies using as a model the natural persistent control of HIV infection.
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Linfocitos T CD4-Positivos/inmunología , Infecciones por VIH/inmunología , VIH-1/inmunología , Inflamación/inmunología , Leucocitos Mononucleares/inmunología , Replicación Viral , Adulto , Linfocitos T CD4-Positivos/virología , Citocinas/metabolismo , Femenino , Infecciones por VIH/virología , Humanos , Inflamación/virología , Leucocitos Mononucleares/virología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Carga ViralRESUMEN
BACKGROUND: Despite metabolic disorders in HIV-infected children being widely described, there is still a lack of agreed criteria for diagnoses and management. Numerous studies are coming from other settings and results are heterogeneous when assessing several analytical and clinical parameters. OBJECTIVES: To describe the prevalence of metabolic disorders and associated risk factors in the Spanish National cohort of HIV-infected pediatric patients (CoRISpe). METHODS: This was a cross-sectional study following all vertically HIV-infected children and adolescents in three referral centers included in the CoRISpe. Metabolic data (fasting lipids, glucose and insulin levels and thyroid hormone levels) were collected. Fat distribution was clinically assessed by expert clinicians. RESULTS: We included 157 patients [median age 13 years, interquartile range (IQR) 10-16]. Median duration of antiretroviral therapy was 10.2 years (IQR 5.0-13.0). Almost 20% of patients had insulin resistance and this was associated with hepatitis C co-infection, current use of stavudine (d4T) and hypertriglyceridemia. Hypercholesterolemia and hypertriglyceridemia were found in 23.9% and 24.8% of patients and were associated with current use of protease inhibitors (p = 0.042 and p = 0.022, respectively). Abnormal fat distribution was observed in 63 patients (40.5%): lipoatrophy in 32 (20.4%), lipohypertrophy in eight (5.1%) and a mixed pattern in 23 patients (14.6%), and it was significantly associated with previous exposure to stavudine (p < 0.001). CONCLUSIONS: Metabolic disorders are a significant problem in our HIV-infected pediatric population. We need to encourage the development of global strategies and the creation of consensus guidelines that can decrease the cardiovascular risk in this population.
Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Infecciones por VIH/epidemiología , Infecciones por VIH/transmisión , Transmisión Vertical de Enfermedad Infecciosa/estadística & datos numéricos , Enfermedades Metabólicas/epidemiología , Adolescente , Adulto , Niño , Estudios Transversales , Dislipidemias/epidemiología , Femenino , Humanos , Resistencia a la Insulina , Masculino , Análisis Multivariante , Factores de RiesgoRESUMEN
Regular screening methods may miss the diagnosis of occult hepatitis B infection and seronegative hepatitis C virus infection in immunocompromised patients. A cross-sectional study within a Spanish cohort of HIV-infected children yielded 6 of 254 (2.4%) possible occult hepatitis B infection cases and 2 of 254 (0.8%) seronegative hepatitis C virus-infected patients. Implementation of occult hepatitis screening in the routine care of these children may be warranted.