Nutritional Supplementation to Increase Influenza Vaccine Response in Children Living With HIV: A Pilot Clinical Trial.

Aims: Vaccine response is poor among children living with HIV. The gut microbiota has been identified as a potential target to improve vaccine immunogenicity, but data are scarce in the context of HIV infection. Methods: Pilot, double-blind, randomized placebo-controlled trial in which 24 HIV-infected children were randomized to receive a mixture of symbiotics, omega-3/6 fatty acids, and amino acids or placebo for 4 weeks, each in combination with ART, and were then immunized against influenza. Vaccine response and safety of the nutritional supplementation were the primary outcomes. Results: Eighteen HIV-infected children completed the follow-up period (mean age 11.5 ± 4.14 years, 61% female). The nutritional supplement was safe but did not enhance the response to the influenza vaccine. A 4-fold rise in antibody titers was obtained in only 37.5% of participants in the intervention arm vs. 40% in the placebo. No immunological or inflammatory predictors of vaccine response were identified. Conclusions: In this exploratory study, a 4-week course of symbiotics did not increase influenza vaccine immunogenicity in HIV-infected children. Larger studies are warranted to address the potential of modulating the microbiome in children living with HIV.

Integrase inhibitors in children and adolescents: clinical use and resistance.

BACKGROUND: Although integrase inhibitor (INI)-based regimens are now the first-line choice for all people living with HIV, experience among children and adolescents is still scarce. We describe the characteristics and outcomes of a paediatric/adolescent cohort on INI-based ART. METHODS: Retrospective analysis of HIV-infected patients below 18 years of age who started an INI-based regimen from 2007 to 2019, enrolled in the Spanish National Adult (CoRIS) and Paediatric (CoRISpe) cohorts. Resistance mutations were identified by the Stanford HIV Drug Resistance Database. RESULTS: Overall, 318 INI-based regimens were implemented in 288 patients [53.8% female; median age at start of 14.3 years (IQR 12.0-16.3)]. Most were born in Spain (69.1%), vertically infected (87.7%) and treatment-experienced (92.7%). The most frequently prescribed INI was dolutegravir (134; 42.1%), followed by raltegravir (110; 34.6%) and elvitegravir (73; 23.0%). The median exposure was 2.0 years (IQR 1.1-3.0). The main reasons to start an INI-based therapy were treatment simplification (54.4%) and virological failure (34.3%). In total, 103 (32.4%) patients interrupted their regimen: 14.5% for simplification and 8.5% due to virological failure. Most subjects who received dolutegravir (85.8%) and elvitegravir (83.6%) did not interrupt their regimen and maintained undetectable viral load. There were only five virological failures with dolutegravir and three with elvitegravir. There were no interruptions related to adverse events. Seven patients with virological failure presented major resistance mutations to INIs; none of them were on dolutegravir. CONCLUSIONS: INI-based regimens were effective and safe for HIV treatment in children and adolescents. Dolutegravir and elvitegravir presented an excellent profile, and most patients achieved and maintained viral suppression.

miRNA Profile Based on ART Delay in Vertically Infected HIV-1 Youths Is Associated With Inflammatory Biomarkers and Activation and Maturation Immune Levels.

Early antiretroviral treatment (ART) in vertically acquired HIV-1-infection is associated with a rapid viral suppression, small HIV-1 reservoir, reduced morbimortality and preserved immune functions. We investigated the miRNA profile from vertically acquired HIV-1-infected young adults based on ART initiation delay and its association with the immune system activation. Using a microRNA panel and multiparametric flow cytometry, miRNome profile obtained from peripheral blood mononuclear cells and its association with adaptive and innate immune components were studied on vertically HIV-1-infected young adults who started ART early (EARLY, 0-53 weeks after birth) and later (LATE, 120-300 weeks). miR-1248 and miR-155-5p, were significantly upregulated in EARLY group compared with LATE group, while miR-501-3p, miR-548d-5p, miR-18a-3p and miR-296-5p were significantly downregulated in EARLY treated group of patients. Strong correlations were obtained between miRNAs levels and soluble biochemical biomarkers and immunological parameters including CD4 T-cell count and maturation by CD69 expression on CD4 T-cells and activation by HLA-DR on CD16high NK cell subsets for miR-1248 and miR-155-5p. In this preliminary study, a distinct miRNA signature discriminates early treated HIV-1-infected young adults. The role of those miRNAs target genes in the modulation of HIV-1 replication and latency may reveal new host signaling pathways that could be manipulated in antiviral strategies. Correlations between miRNAs levels and inflammatory and immunological markers highlight those miRNAs as potential biomarkers for immune inflammation and activation in HIV-1-infected young adults who initiated a late ART.

Targeting the Gut Microbiota of Vertically HIV-Infected Children to Decrease Inflammation and Immunoactivation: A Pilot Clinical Trial.

Aims: Children with HIV exhibit chronic inflammation and immune dysfunction despite antiretroviral therapy (ART). Strategies targeting persistent inflammation are needed to improve health in people living with HIV. The gut microbiota likely interacts with the immune system, but the clinical implications of modulating the dysbiosis by nutritional supplementation are unclear. Methods: Pilot, double-blind, randomized placebo-controlled trial in which 24 HIV-infected on ART were randomized to supplementation with a daily mixture of symbiotics, omega-3/6 fatty acids and amino acids, or placebo four weeks, in combination with ART. We analyzed inflammatory markers and T-cell activation changes and their correlations with shifts in fecal microbiota. Results: Twenty-four HIV-infected children were recruited and randomized to receive a symbiotic nutritional supplement or placebo. Mean age was 12 ± 3.9 years, 62.5% were female. All were on ART and had HIV RNA < 50/mL. We did not detect changes in inflammatory (IL-6, IL-7, IP-10), microbial translocation (sCD14), mucosal integrity markers (IFABP, zonulin) or the kynurenine to tryptophan ratio, or changes in markers of the adaptive immune response in relation to the intervention. However, we found correlations between several key bacteria and the assessed inflammatory and immunological parameters, supporting a role of the microbiota in immune modulation in children with HIV. Conclusions: In this exploratory study, a four-week nutritional supplementation had no significant effects in terms of decreasing inflammation, microbial translocation, or T-cell activation in HIV-infected children. However, the correlations found support the interaction between gut microbiota and the immune system.

Effects of perinatal HIV-infection on the cortical thickness and subcortical gray matter volumes in young adulthood.

ABSTRACT: Brain atrophy has been observed in perinatally HIV-infected patients (PHIV) despite initiation on combined antiretroviral treatment (cART), but neuroimaging studies are limited. We aimed to evaluate cortical thickness (CT) and subcortical gray matter (GM) volumes of PHIV youths with stable immunovirological situation and with a normal daily performance.A prospective cross-sectional study was conducted. A total of 25 PHIV patients on cART and 25 HIV-negative (HIV-) controls matched by age, sex, level of education, and socioeconomic status underwent a magnetic resonance imaging scan. CAT12 toolbox was used to extract CT values from T1w images using parcellations from Desikan-Killiany atlas (DK40). To measure regional brain volumes, native segmented images were parceled in regions of interest according to the Neuromorphometrics Atlas. Neuropsychological assessment and psychopathological symptoms were documented.Fifty participants were included (60% females, median age 20 years [interquartile range, IQR 19-23], 64% Whites). No differences regarding neuropsychological tests or psychopathological symptoms were found between groups (all P > .05). All participants presented an average performance in the Fluid Intelligence (FI) test (PHIV mean: -0.12, HIV- mean: 0.24), When comparing CT, PHIV-infected patients showed thinner cortices compared with their peers in fusiform gyrus (P = .000, P = .009), lateral-orbitofrontal gyrus (P = .006, P = .0024), and right parsobitalis gyrus (P = .047). Regarding subcortical GM volumes, PHIV patients showed lower right amygdala (P = .014) and left putamen (P = .016) volumes when compared with HIV- controls. Within the PHIV group, higher CD4 count was associated with higher volumes in right putamen (B = 0.00000038, P = .045). Moreover, increased age at cART initiation and lower nadir CD4 count was associated with larger volumes in left accumbens (B = 0.0000046, P = .033; B = -0.00000008, P = .045, respectively).PHIV patients showed thinner cortices of areas in temporal, orbito-frontal and occipital lobes and lower volumes of subcortical GM volumes when compared with the HIV- control group, suggesting cortical and subcortical brain alterations in otherwise neuroasymptomatic patients. Nevertheless, larger and longitudinal studies are required to determine the impact of HIV on brain structure in PHIV patients and to further identify risk and protective factors that could be implicated.

Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure.

OBJECTIVES: We analysed the prevalence of M184V/I and/or K65R/E/N mutations archived in proviral DNA (pDNA) in youths with perinatal HIV, virological control and who previously carried these resistance mutations in historic plasma samples. METHODS: We included vertically HIV-infected youths/young adults aged ≥10 years in the Madrid Cohort of HIV-1 Infected Children and Adolescents, exposed to lamivudine and/or emtricitabine, with M184V/I and/or K65R/E/N in historic plasma samples, on antiretroviral therapy (ART), virologically suppressed (HIV-1 RNA <50 copies/mL), and with available PBMCs in the Spanish HIV BioBank. Genomic DNA was extracted from PBMCs and HIV-1 RT gene was amplified and sequenced for resistance testing by Stanford HIV Resistance tool. RESULTS: Among the 225 patients under follow-up in the study cohort, 13 (5.8%) met selection criteria, and RT sequences were recovered in 12 (92.3%) of them. All but one were Spaniards, carrying subtype B, with a median age at PBMCs sampling of 21.3 years (IQR: 15.6-23.1) with 4 years (IQR 2.1-6.5) of suppressed viral load (VL). Nine (75%) youths did not present M184V/I in pDNA after at least 1 year of viral suppression. In December 2019, the remaining three subjects carrying M184V/I in pDNA maintained suppressed viraemia, and two still used emtricitabine in ART. CONCLUSIONS: The prevalence of resistance mutations to lamivudine and emtricitabine in pDNA in a cohort of youths perinatally infected with HIV who remain with undetectable VL, previously lamivudine and/or emtricitabine experienced, was infrequent. Our results indicate that ART including lamivudine or emtricitabine may also be safe and successful in youths with perinatal HIV with previous experience of and resistances to these drugs detected in plasma.

Congenital Cutaneous Candidiasis With Systemic Dissemination in a Preterm Infant.

Congenital cutaneous candidiasis is an infrequent invasive fungal infection that usually appears in the first days of life. Extremely low birth weight infants are the most frequently affected. Classic presentation includes diffuse extensive erythematous rash with papules, plaques, pustules and vesicles, which later undergoes desquamation. Systemic dissemination is common in extremely low birth weight infants. Blood, urine and cerebrospinal fluid evaluation should be included in the initial assessment. Early and prolonged treatment has been associated with decreased mortality. We report the case of congenital cutaneous candidiasis in a preterm infant. Early skin lesion recognition allowed establishing adequate treatment in the first hours of life.

Clinical, Immunological, and Virological Outcomes Among Youths With Perinatal HIV After Transition to Adult Units in Spain From 1997 to 2016.

BACKGROUND: Children living with HIV are reaching adulthood and transitioning to adult clinics. This study aimed to describe clinical and immunovirological status after transition in patients with perinatal HIV. METHODS: Patients participating in the Spanish multicenter pediatric HIV cohort (CoRISpe) transferred to adult care (FARO cohort) from 1997 to 2016 were included. Clinical and immunovirological data were collected from 12 years old to the last follow-up moment after transition (up to December 2017). We used mixed-effect models to analyze changes in CD4 counts or viral suppression and multivariate analysis for risk factors for virological failure (VF) and immune status after transition. Transition years were classified into 5-year periods. RESULTS: Three hundred thirty-two youths were included. The median age at transition was 18 years (interquartile range: 16.3-18.9) and 58.1% women. The median follow-up time after transition was 6.6 years (interquartile range: 4.6-9.8), and 11 patients (3.3%) died. The immunovirological status at transition improved over the last periods. Globally, VF decreased from 27.7% at transition to 14.4% at 3 years post-transition (P < 0.001), but no changes were observed in the last 2 transition periods. There were no significant differences in CD4 over the transition period. Risk factors for VF after transition were female sex, being born abroad and VF at transition, and for lower CD4 after transition were Romani heritage, younger age at transition, lower CD4 nadir, and CD4 at transition. CONCLUSIONS: After transition, virological suppression improved in the early transition periods, and immunological status remained stable. Nevertheless, some patients had higher risk of worse outcomes. Identifying these patients may aid during transition.

Virological outcome among HIV infected patients transferred from pediatric care to adult units in Madrid, Spain (1997-2017).

The aim of this transversal study was to describe the virological and immunological features of HIV-infected youths transferred from pediatric to adult care units since 1997 vs. the non-transferred patients from the Madrid Cohort of HIV-infected children and adolescents in Spain. We included 106 non-transferred and 184 transferred patients under clinical follow-up in 17 public hospitals in Madrid by the end of December 2017. Virological and immunological outcomes were compared in transferred vs. non-transferred patients. ART drug resistance mutations and HIV-variants were analyzed in all subjects with available resistance pol genotypes and/or genotypic resistance profiles. Among the study cohort, 133 (72.3%) of 184 transferred and 75 (70.7%) of 106 non-transferred patients had available resistance genotypes. Most (88.9%) of transferred had ART experience at sampling. A third (33.3%) had had a triple-class experience. Acquired drug resistance (ADR) prevalence was significantly higher in pretreated transferred than non-transferred patients (71.8% vs. 44%; p = 0.0009), mainly to NRTI (72.8% vs. 31.1%; p < 0.0001) and PI (29.1% vs. 12%; p = 0.0262). HIV-1 non-B variants were less frequent in transferred vs. non-transferred (6.9% vs. 32%; p < 0.0001). In conclusion, the frequent resistant genotypes found in transferred youths justifies the reinforcement of HIV resistance monitoring after the transition to avoid future therapeutic failures.

Effect of a Nutritional Intervention on the Intestinal Microbiota of Vertically HIV-Infected Children: The Pediabiota Study.

AIMS: The gut microbiota exerts a critical influence in the immune system. The gut microbiota of human virus immunodeficiency (HIV)-infected children remains barely explored. We aimed to characterize the fecal microbiota in vertically HIV-infected children and to explore the effects of its modulation with a symbiotic nutritional intervention. METHODS: a pilot, double blind, randomized placebo-controlled study including HIV-infected children who were randomized to receive a nutritional supplementation including prebiotics and probiotics or placebo for four weeks. HIV-uninfected siblings were recruited as controls. The V3-V4 region of the 16S rRNA gene was sequenced in fecal samples. RESULTS: 22 HIV-infected children on antiretroviral therapy (ART) and with viral load (VL) <50/mL completed the follow-up period. Mean age was 11.4 ± 3.4 years, eight (32%) were male. Their microbiota showed reduced alpha diversity compared to controls and distinct beta diversity at the genus level (Adonis p = 0.042). Patients showed decreased abundance of commensals Faecalibacterium and an increase in Prevotella, Akkermansia and Escherichia. The nutritional intervention shaped the microbiota towards the control group, without a clear directionality. CONCLUSIONS: Vertical HIV infection is characterized by changes in gut microbiota structure, distinct at the compositional level from the findings reported in adults. A short nutritional intervention attenuated bacterial dysbiosis, without clear changes at the community level. SUMMARY: In a group of 24 vertically HIV-infected children, in comparison to 11 uninfected controls, intestinal dysbiosis was observed despite effective ART. Although not fully effective to restore the microbiota, a short intervention with pre/probiotics attenuated bacterial dysbiosis.

Variable immunodeficiency study: Evaluation of two European cohorts within a variety of clinical phenotypes.

INTRODUCTION: Given the wide heterogeneity of common variable immunodeficiency (CVID), several groups have proposed clinical and immunological classifications to better define follow-up and prognostic algorithms. The present study aims to validate recent clinical and laboratory algorithms, based on different combinations of CVID biomarkers, to provide more personalized treatment and follow-up strategies. METHODS: We analysed clinical and immunological features of 80 patients with suspected or diagnosed CVID, in two reference centres of Portugal and Spain. Clinical manifestations were categorized into clinical phenotyping proposed by Chapel et al. [1] that included cytopenia; polyclonal lymphocytic infiltration; unexplained enteropathy; and no disease-related complications. RESULTS: 76% of patients in our cohort entered one of the four categories of clinical phenotyping, without overlap (cytopenia; polyclonal lymphocytic infiltration; unexplained enteropathy; and no disease-related complications). The most prominent phenotype was "cytopenia" (40%) followed by "polyclonal lymphocytic infiltration" (19%). The remaining 24% patients of our cohort had overlap of 2 clinical phenotypes (cytopenia and unexplained enteropathy mainly). A delay of CVID diagnosis in more than 6 years presented 3.7-fold higher risk of developing lymphoproliferation and/or malignancy (p < 0.05), and was associated with increased CD8+CD45RO + T-lymphocytes (p < 0.05). An association between decreased switched-memory B cells with lymphoproliferation and malignancy was observed (p < 0.03 and p < 0.05, respectively). CD4 + T-lymphocytopenia correlated with autoimmune phenotype, with 30% prevalence (p < 0.05). HLA-DR7 expression was related to CVID onset in early life in our patients (13 vs 25 years), and DQ2.5 or DQ2.2 with unexplained enteropathy (p < 0.05). CONCLUSIONS: The phenotypic and genetic study is crucial for an adequate clinical orientation of CVID patients. In these two independent cohorts of patients, classification based in clinical and laboratory algorithms, provides more personalized treatment and follow-up strategies.

Neurocognitive and quality of life study in perinatally HIV-infected young people and their peers. NeuroCoRISpeS study.

BACKGROUND: Assessing the role of HIV and non-HIV related factors is essential for a better understanding of the neurocognitive outcomes in perinatally HIV-infected (PHIV+) young people. The aim of our study was to assess cognition and quality of life (QoL) of a PHIV+ cohort of young people and to compare it with a control group. METHODS: Thirty PHIV+ and 30 HIV(-) healthy young adults matched by age, sex and socioeconomic status completed a protocol that included neurocognitive tests, a psychosocial semi-structured interview and a QoL questionnaire (PedsQL). Neurocognitive domain-specific and domain-general (NPZ-5) Z-scores were calculated. CDC AIDS-defining category C or not C (PHIV+/C, PHIV+/noC) was considered to evaluate differences within the PHIV+ group. Univariate and multivariate analysis were performed. RESULTS: Sixty patients were included; 67% were female; median age (IQR) 19 years (18-21). Regarding PHIV+ young people, 27% showed CDC C category (none encephalopathy), 93% were on ART and 77% had undetectable viral load. No differences regarding occupation were found, although the HIV(-) group repeated less grades (p=0.028) and had a higher education level (p=0.021). No differences were found between PHIV+/noC and HIV(-) participants. However, the PHIV+/C group showed poorer performance than PHIV+/noC (NPZ-5, p=0.037) and HIV(-) subjects (crystallised intelligence, p=0.025; intelligence quotient, p=0.016). Higher nadir CD4+ T-cell count was related to better Z-score in memory (p=0.007) and NPZ-5 (p=0.025). Earlier and longer exposure to ART resulted in better performance in memory (p=0.004) and executive functions (p=0.015), respectively. CONCLUSIONS: No significant differences were found in the neurocognitive profile nor QoL between PHIV+/noC and HIV(-) adolescents; however, PHIV+/C participants obtained lower scores. The use of longer and earlier ART seems to have a beneficial effect.

Analysis of the impact of diagnostic virology tests on the use of antibiotics in paediatric inpatients with community-acquired pneumonia. / Análisis del impacto de los test de diagnóstico virológico en el consumo de antibióticos en pacientes pediátricos ingresados por neumonía adquirida en la comunidad.

INTRODUCTION: Viruses are one of the most common causes of community-acquired pneumonia (CAP) in children. Early identification of respiratory viruses could result in a decrease in the use of antibiotics. METHODS: Observational, retrospective study from January 2014 to June 2018, that included paediatric patients admitted with a diagnosis of CAP in a tertiary hospital, in which antigenic tests and/or viral PCR on a respiratory sample was performed. RESULTS: A total of 105 CAP episodes were included, with identification of a respiratory virus in 93 (88.6%) cases. Patients with respiratory syncytial virus (RSV) detection had a lower onset of empirical antibiotic therapy (35.1% vs. 55.9%, P-value=.042). In addition, cases with RSV or influenza identification required shorter duration of antibiotic therapy (receiving 45.6% ≥2 days vs. 68.8% of those not identified, P=.017). CONCLUSION: The use of respiratory virus diagnostic techniques in our setting can optimise antibiotic use in children admitted with CAP.

Longitudinal evolution of vertically HIV/HCV-co-infected vs HCV-mono-infected children.

HIV co-infection has been suggested to play a deleterious role on the pathogenesis of liver fibrosis among vertically HCV-infected children. The aim of this study was to describe the longitudinal evolution of vertically acquired HIV/HCV co-infection in youths, in comparison with HCV infection alone. This was a retrospective, multicentre study including vertically HIV/HCV-co-infected patients and age- and sex-matched vertically HCV-mono-infected patients. Progression to advanced liver fibrosis, defined as F3 or more by elastography or METAVIR biopsy staging, and response to treatment were compared by means of univariate and multivariate regression analyses and Cox regression models. Sixty-seven co-infected patients were compared with 67 matched HCV-mono-infected patients. No progression to advanced liver disease was observed during the first decade. At a median age of 20.0 [19.0, 22.0] years, 26.7% co-infected vs 20% mono-infected had progressed to advanced fibrosis (P = .617). Peg-IFN/RBV for HCV treatment was given to 37.9% vs 86.6% (P-value < .001). At treatment initiation, co-infected patients were older (16.9 ± 4.1 vs 11.7 ± 4.5 years, P < .001), and 47.1% vs 7.1% showed advanced fibrosis (P < .003), with no differences in hard-to-treat genotype distribution. Sustained viral response was comparable between groups (43.5% vs 44.0%, P = .122). In vertically HIV/HCV-co-infected patients, the progression to liver fibrosis was rare during childhood. At the end of adolescence, over 25% of patients displayed advanced liver disease. Response to Peg-IFN/RBV was poor and comparable in both groups, supporting the need for fast access to early treatment with direct-acting antivirals against HCV for vertically co-infected patients.

Growth Patterns in Children With Congenital Cytomegalovirus Infection.

BACKGROUND: Congenital cytomegalovirus infection (CMVc) affects 0.7%-6% of recent births. Among its clinical manifestations are low weight and length at birth. OBJECTIVE: Describe the growth patterns of children with CMVc in their early years. METHODS: Observational, multicenter study of patients with CMVc. Anthropometric data were collected during the first 2 years of life and compared with World Health Organization standards. RESULTS: Anthropometric characteristics of 383 children with CMVc were studied, of which 198 (51%) were symptomatic at birth. At birth, 9% were small for gestational age (SGA) in terms of their weight and length and 17% had microcephaly. At 24 ± 3 months, 10% had a weight and length ≤2 SD, and 13% a head circumference ≤2 SD. Of those who were SGA at birth, at 24 ± 3 months >20% remained at ≤2 SD of their weight and length. Conversely, 75% of children with low weight or length at 24 ± 3 had not been SGA at birth. 20% of infants with microcephaly at birth remained with microcephaly, and 10% of those without microcephaly developed it at 24 ± 3 months. The average growth rate in length and weight was normal. Patients who were symptomatic at birth, premature and with motor and neurocognitive impairment had a significantly higher risk of low weight and length at 24 ± 3 months. CONCLUSION: Around 10% of children with CMVc are at ≤2 SD in weight, length and head circumference at 24 ± 3 months. The lack of adequate growth is associated with symptoms at birth, prematurity and motor and neurocognitive impairment. Growth impairment could be incorporated into the symptomatic spectrum of CMVc.

[Position statement of the Spanish Association of Paediatrics-Spanish Society of Paediatric Infectious Diseases (AEP-SEIP) on the treatment of multidrug-resistant bacterial infections]. / Documento de posicionamiento de la Asociación Española de Pediatría-Sociedad Española de Infectología Pediátrica (AEP-SEIP) sobre el tratamiento de las infecciones por bacterias multirresistentes.

A progressive increase in the incidence of infections caused by multidrug-resistant microorganisms is being reported. Among these resistant microorganisms, the main threats are extended-spectrum ß-lactamase-, AmpC-, and carbapenemase-producing Gram-negative bacilli, methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. To address this important problem, it is essential to establish pediatric Antimicrobial Stewardship programs, perform active epidemiological surveillance and develop an adequate infection control policy. The therapeutic approach of these infections is often complex, frequently requiring antibiotics with less experience in children. In this position document made by the Spanish Association of Pediatrics and the Spanish Society of Pediatric Infectious Diseases, the epidemiology and treatment of these infections are reviewed according to the best available evidence.

Sociodemographic changes and trends in the rates of new perinatal HIV diagnoses and transmission in Spain from 1997 to 2015.

BACKGROUND: There are not enough nationwide studies on perinatal HIV transmission in connection with a combination of antiretroviral treatments in Spain. Our objectives were to study sociodemographic changes and trends in the rates of HIV diagnoses and perinatal transmission in Spain from 1997 to 2015. METHODS: A retrospective study using data from Spanish Paediatric HIV Network (CoRISpe) and Spanish Minimum Basic Data Set (MDBS) was performed. HIV- diagnosed children between 1997 and 2015 were selected. Sociodemographic, clinical and immunovirological data of HIV-infected children and their mothers were studied in four calendar periods (P1: 1997-2000; P2: 2001-2005; P3: 2006-2010; P4: 2011-2015). Rates of perinatal HIV diagnoses and transmission from 1997 to 2015 were calculated. RESULTS: A total of 532 HIV-infected children were included in this study. Of these children, 406 were Spanish (76.3%) and 126 immigrants (23.7%). A decrease in the number of HIV diagnoses, 203 (38.2%) children in the first (P1), 149 (28%) in the second (P2), 130 (24.4%) in the third (P3) and 50 (9.4%) in the fourth (P4) calendar periods was studied. The same decrease in the Spanish HIV-infected children (P1, 174 (46.6%), P2, 115 (30.8%), P3, 65 (17.4%) and P4, 19 (5.1%)) was monitored. However, an increase in the number of HIV diagnoses by sexual contact (P1: 0%; P2: 1.3%; P3: 4.6%; P4: 16%) was observed. The rates of new perinatal HIV diagnoses and perinatal transmission in Spanish children decreased from 0.167 to 0.005 per 100,000 inhabitants and 11.4% to 0.4% between 1997 and 2015, respectively. CONCLUSIONS: A decline of perinatal HIV diagnoses and transmission was observed. However, an increase of teen-agers HIV diagnoses with sexual infection was studied. Public awareness campaigns directed to teen-agers are advisable to prevent HIV infection by sexual contact.

Prognostic factors of a lower CD4/CD8 ratio in long term viral suppression HIV infected children.

BACKGROUND: Combination antiretroviral therapy (cART) is associated with marked immune reconstitution. Although a long term viral suppression is achievable, not all children however, attain complete immunological recovery due to persistent immune activation. We use CD4/CD8 ratio like a marker of immune reconstitution. METHODS: Perinatal HIV-infected children who underwent a first-line cART, achieved viral suppression in the first year and maintained it for more than 5 years, with no viral rebound were included. Logistic models were applied to estimate the prognostic factors, clinical characteristics at cART start, of a lower CD4/CD8 ratio at the last visit. RESULTS: 146 HIV-infected children were included: 77% Caucasian, 45% male and 28% CDC C. Median age at cART initiation was 2.3 years (IQR: 0.5-6.2). 42 (30%) children received mono-dual therapy previously to cART. Time of undetectable viral load was 9.5 years (IQR: 7.8, 12.5). 33% of the children not achieved CD4/CD8 ratio >1. Univariate analysis showed an association between CD4/CD8 <1 with lower CD4 nadir and baseline CD4; older age at diagnosis and at cART initiation; and a previous exposure to mono-dual therapy. Multivariate analysis also revealed relationship between CD4/CD8 <1 and lower CD4 nadir (OR: 1.002, CI 95% 1.000-1.004) as well as previous exposure to mono-dual therapy (OR: 0.16, CI 95% 0.003-0.720). CONCLUSIONS: CD4/CD8 >1 was not achieved in 33% of the children. Lower CD4 nadir and previous exposure to suboptimal therapy, before initiating cART, are factors showing independently association with a worse immune recovery (CD4/CD8 < 1).

Impact of HIV on the health-related quality of life in youth with perinatally acquired HIV.

BACKGROUND: Studies investigating health-related quality of life (HRQoL) in youth with perinatally acquired HIV (PHIV+) are scarce. This study aimed to compare HRQoL of PHIV+ to sociodemographic-matched youth not living with HIV (HIV-), Spanish general youth population, and to explore associations between sociodemographic variables, drug consumption, and HRQoL. METHODS: PHIV+ youth were randomly selected from CoRISpe database (Cohort of the Spanish Pediatric HIV Network). HRQoL was evaluated by SF-12v2. RESULTS: Thirty-nine PHIV+ youth (mean age: 23.36 years, SD = 3.83) and thirty-nine HIV- youth (mean age: 22.97 years, SD = 3.80) participated in this study. PHIV+ obtained lower scores in SF-12 physical health subscale (PCS) than HIV- (P = 0.001) and Spanish general youth population (P = 0.006). PHIV+ had lower scores on the mental health subscale (MCS) than the Spanish general youth population (P < 0.001). PHIV+ who were at school obtained better scores than those were not at school. PHIV+ youth who had used cocaine and cannabis had lower scores in MCS (P = 0.002). CONCLUSIONS: There is a need for HRQoL management in the associated medical follow-up.

Measurement of Typhim Vi IgG as a Diagnostic Tool to Determine Anti-polysaccharide Antibody Production Deficiency in Children.

Background: The assessment of specific polysaccharide antibody production plays a pivotal role in the diagnosis of humoral primary immunodeficiencies (PID). The response to 23-valent pneumococcal vaccine (PPV) remains the gold standard for the diagnosis of polysaccharide antibodies. However, in Spain, the interpretation of pure polysaccharide 23-valent immunization is hampered by the high endemicity of pneumococcal disease and the generalization of the 13-valent adjuvant pneumococcal vaccination. Specific Typhim Vi vaccination (TV) immunoglobulin G IgG response to immunization is useful in adult PID, but there is no data regarding children. Objectives: To evaluate the clinical utility of TV IgG production as a diagnostic tool to determine anti-polysaccharide antibody production deficiency in children, when the response to PPV is unclear and isolated determination of serotypes is unfeasible. Methods: We conducted a single-institution prospective observational study on 61 children with recurrent infections. Baseline specific antibodies against PPV and TV were evaluated. In 28 children (46%), the response to the production of antibodies confirmed a clinical suspicion of humoral PID, and they were therefore immunized with 23-valent pneumococcal vaccine and Typhim Vi. Both specific antibody responses were measured by ELISA (The Binding Site Group Ltd, Birmingham, UK) using previously published cut-offs. Results: Seventy percent of the 61 children displayed baseline PPV IgG > 27 mg/L, whereas only 8% showed TV IgG > 28 U/mL (p < 0.0001). Twenty-one of 28 children (75%) achieved a 3-fold increase in post-vaccination TV IgG levels, whereas only 3% achieved a 4-fold increase in PPV IgG post vaccination, mainly due to high baseline PPV IgG titers. When we classified children according to their response to TV as responders or non-responders and compared this with the well-known clinical warning signs of the Jeffrey Modell Foundation. The proportions of children with history of pneumonia and the need for intravenous antibiotics were significantly higher in TV IgG non-responders than in TV IgG responders (p = 0.02 and p = 0.01, respectively). Conclusion: Response to TV can be considered an ancillary diagnostic tool to determine polysaccharide antibodies in children, particularly when isolated determination of pneumococcal serotypes is not feasible. TV provides a useful asset for clinicians in the era of conjugate PPV vaccination, with clinical relevance. Further research is warranted for validation.