Dual latent tuberculosis screening with tuberculin skin tests and QuantiFERON-TB assays before TNF-α inhibitor initiation in children in Spain.

Tumor-necrosis-factor-α inhibitors (anti-TNF-α) are associated with an increased risk of tuberculosis (TB) disease, primarily due to reactivation of latent TB infection (LTBI). We assessed the performance of parallel LTBI screening with tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube assays (QFT-GIT) before anti-TNF-α treatment in children with immune-mediated inflammatory disorders in a low TB-burden setting. We conducted a multicenter cohort study involving 17 pediatric tertiary centers in Spain. LTBI was defined as the presence of a positive TST and/or QFT-GIT result without clinical or radiological signs of TB disease. A total of 270 patients (median age:11.0 years) were included, mainly with rheumatological (55.9%) or inflammatory bowel disease (34.8%). Twelve patients (4.4%) were diagnosed with TB infection at screening (LTBI, n = 11; TB disease, n = 1). Concordance between TST and QFT-GIT results was moderate (TST+/QFT-GIT+, n = 4; TST-/QFT-GIT+, n = 3; TST+/QFT-GIT-, n = 5; kappa coefficient: 0.48, 95% CI: 0.36-0.60). Indeterminate QFT-GIT results occurred in 10 patients (3.7%) and were associated with young age and elevated C-reactive protein concentrations. Eleven of 12 patients with TB infection uneventfully completed standard LTBI or TB treatment. During a median follow-up period of 6.4 years, only 2 patients developed TB disease (incidence density: 130 (95% CI: 20-440) per 100,000 person-years), both probable de novo infections. CONCLUSION: A substantial number of patients were diagnosed with LTBI during screening. The dual strategy identified more cases than either of the tests alone, and test agreement was only moderate. Our data show that in children in a low TB prevalence setting, a dual screening strategy with TST and IGRA before anti-TNF-α treatment is effective. WHAT IS KNOWN: • The optimal screening strategy for latent tuberculosis in children with immune-mediated inflammatory disorders remains uncertain. • Children receiving anti-TNF-α drugs are at increased risk of developing severe tuberculosis disease. WHAT IS NEW: • A dual screening strategy, using TST and an IGRA assay, identified more children with latent tuberculosis than either of the tests alone. • Identification and treatment of latent tuberculosis before initiation of anti-TNF-α therapy averted incident tuberculosis cases.

Early antiretroviral therapy initiation effect on metabolic profile in vertically HIV-1-infected children.

BACKGROUND: Early combined antiretroviral treatment (cART) in perinatally acquired HIV-1 children has been associated with a rapid viral suppression, small HIV-1 reservoir size and reduced mortality and morbidity. Immunometabolism has emerged as an important field in HIV-1 infection offering both relevant knowledge regarding immunopathogenesis and potential targets for therapies against HIV-1. OBJECTIVES: To characterize the proteomic, lipidomic and metabolomic profile of HIV-1-infected children depending on their age at cART initiation. PATIENTS AND METHODS: Plasma samples from perinatally HIV-1-infected children under suppressive cART who initiated an early cART (first 12 weeks after birth, EARLY, n = 10) and late cART (12-50 weeks after birth, LATE, n = 10) were analysed. Comparative plasma proteomics, lipidomics and metabolomics analyses were performed by nanoLC-Orbitrap, UHPLC-qTOF and GC-qTOF, respectively. RESULTS: Seven of the 188 proteins identified exhibited differences comparing EARLY and LATE groups of HIV-1-infected children. Despite no differences in the lipidomic (n = 115) and metabolomic (n = 81) profiles, strong correlations were found between proteins and lipid levels as well as metabolites, including glucidic components and amino acids, with clinical parameters. The ratio among different proteins showed high discriminatory power of EARLY and LATE groups. CONCLUSIONS: Protein signature show a different proinflammatory state associated with a late cART introduction. Its associations with lipid levels and the relationships found between metabolites and clinical parameters may potentially trigger premature non-AIDS events in this HIV-1 population, including atherosclerotic diseases and metabolic disorders. Antiretroviral treatment should be started as soon as possible in perinatally acquired HIV-1-infected children to prevent them from future long-life complications.

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.

Disease disclosure, treatment adherence, and behavioural profile in a cohort of vertically acquired HIV-infected adolescents. NeuroCoRISpeS study.

UNLABELLED: Advances in care and antiretroviral treatment, improved life expectancy and quality of life in children with perinatally-acquired human immunodeficiency virus (HIV) infection. There is increasing interest in the chronic effects of growing up with HIV. The aim of this study was to assess the psychosocial, emotional and behavioural functioning in a cohort of perinatally-acquired HIV-infected adolescents. Data were obtained through semi-structured interviews and the Strengths and Difficulties Questionnaire (SDQ) for emotional and behavioural disorders screening. RESULTS: A total of 95 patients (58% women) were assessed with a median age of 15 years (11-19.1) and a median age at diagnosis of 1.7 years (0-12.2). The median CD4 count, at the inclusion, was 626 cells/mm(3) (132-998), with 34% (10-52%). Viral load was <50 copies/ml in 72% of patients. Eighty-one per cent knew their diagnosis and optimal adherence was achieved in 53%. Passive coping was reported in 58.4% of the adolescents. Only 7.7% of teenagers had a complete and adequate knowledge of their disease and only 18.2% had shared it with their friends. Six unwanted pregnancies occurred (11% of women). Most of them (90%) attended school but 60% had been held back one or more school years. Overall, SDQ scored a risk of behavioural and emotional problems in 24.5%. The report of behaviours associated with hyperactivity was high in 14.9% of the population and borderline in 18.1%. Adolescents with encephalopathy accounted for 44% of those whose total scores fell in either the abnormal and borderline ranges for emotional difficulties (p = .038). CONCLUSION: Perinatally-acquired HIV-infected adolescents showed significant psychosocial and behavioural health risks that should bring attention to prevention and health care programmes. An earlier disclosure to children could favour a better psychological adjustment and a better treatment adherence. Future studies are needed to assess the relationship between vertically acquired HIV-infection and hyperactivity.

[Early diagnosis of human immunodeficiency virus-1 in infants: The prevention of mother-to-child transmission program in Equatorial Guinea]. / Diagnóstico precoz de la infección por el virus de la inmunodeficiencia humana-1 en niños: programa de prevención de la transmisión maternoinfantil en Guinea Ecuatorial.

BACKGROUND: Great efforts have been made in the last few years in order to implement the prevention of mother-to-child transmission (PMTCT) program in Equatorial Guinea (GQ). The aim of this study was to evaluate the rates of mother-to-child HIV transmission based on an HIV early infant diagnosis (EID) program. METHODS: A prospective observational study was performed in the Regional Hospital of Bata and Primary Health Care Centre Maria Rafols, Bata, GQ. Epidemiological, clinical, and microbiological characteristics of HIV-1-infected mothers and their exposed infants were recorded. Dried blood spots (DBS) for HIV-1 EID were collected from November 2012 to December 2013. HIV-1 genome was detected using Siemens VERSANT HIV-1 RNA 1.0 kPCR assay. RESULTS: Sixty nine pairs of women and infants were included. Sixty women (88.2%) had WHO clinical stage 1. Forty seven women (69.2%) were on antiretroviral treatment during pregnancy. Forty five infants (66.1%) received postnatal antiretroviral prophylaxis. Age at first DBS analysis was 2.4 months (IQR 1.2-4.9). One infant died before a HIV-1 diagnosis could be ruled out. Two infants were HIV-1 infected and started HAART before any symptoms were observed. The rate of HIV-1 transmission observed was 2.9% (95%CI 0.2-10.5). CONCLUSIONS: The PMTCT rate was evaluated for the first time in GQ based on EID. EID is the key for early initiation of antiretroviral therapy and to reduce the mortality associated with HIV infection.

Executive summary of the consensus statement of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), Spanish Society of Neurology (SEN), Spanish Society of Immunology (SEI), Spanish Society of Pediatric Infectology (SEIP), Spanish Society of Rheumatology (SER), and Spanish Academy of Dermatology and Venereology (AEDV), on the diagnosis, treatment and prevention of Lyme borreliosis.

The diagnosis of Lyme borreliosis (LB) is based on the epidemiological history, clinical manifestations and microbiological findings in the early disseminated and late phases of the disease. Related to this fact, microbiological diagnostic techniques have recently appeared. Far from facilitating the diagnosis and the clinical-therapeutic management of LB patients, they are generating confusion. Herein, experts and representatives of Spanish Scientific Societies [Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), Spanish Society of Neurology (SEN), Spanish Society of Immunology (SEI), Spanish Society of Pediatric Infectology (SEIP), Spanish Society of Rheumatology (SER), and Spanish Academy of Dermatology and Venereology (AEDV)] exposed the executive summary after reviewing the epidemiology, clinical spectrum, available diagnostic techniques for the diagnosis of Borrelia burgdorferi infection, therapeutic and prevention options of LB. By consensus, recommendations for microbiological diagnosis are offered together with those supporting the therapeutic management and prophylaxis of infection.

Immunogenicity of the Conjugate Meningococcal ACWY-TT Vaccine in Children and Adolescents Living with HIV.

BACKGROUND: Children and adolescents living with HIV (CALHIV) are at high risk of meningococcal infections and may present lower immune responses to vaccines. The objectives of this study were to assess the immunogenicity of the quadrivalent Men ACWY-TT vaccine (Nimenrix®) in CALHIV after a two-dose schedule and to describe possible HIV-related factors that may affect the immunogenic response. METHODS: A multicenter prospective study was designed, including CALHIV followed in five hospitals in Madrid, between 2019 and 2021. Two doses of the Men ACWY-TT vaccine were administered. Serum bactericidal antibody (SBA) assays using rabbit complement (rSBA) against serogroups C, W, and Y were used to determine seroprotection and vaccine response (the proportion achieving a putative protective titer of ≥eight or a ≥four-fold rise in titer from baseline). Serum was collected at baseline, and at 3 and 12 months after vaccination. RESULTS: There were 29 CALHIV included, 76% of whom were perinatally infected. All were receiving TAR and presented a good immunovirological and clinical status overall. At baseline, 45% of CALHIV had seroprotective titers to at least one serogroup, with individual seroprotection rates of 24%, 28%, and 32% against C, W, and Y, respectively. After a two-dose schedule, vaccine response was 83% for each serogroup, eliciting a vaccine response to all serogroups in 69% of them. One year after vaccination, 75% of CALHIV maintained seroprotective titers against the C serogroup, and 96% against W and Y. None of the HIV-related characteristics analyzed could predict vaccine response or antibody duration. CONCLUSIONS: CALHIV who received effective TAR and presented a good immuno-virological situation achieved an appropriate vaccine response after two doses of the Men ACWY-TT vaccine, and antibody-mediated protection against serogroups C, W, and Y was maintained in more than 70% of the patients one year after vaccination.

Adequacy of the 10 mg/kg Daily Dose of Antituberculosis Drug Isoniazid in Infants under 6 Months of Age.

In 2010, the WHO recommended an increase in the daily doses of first-line anti-tuberculosis medicines in children. We aim to characterize the pharmacokinetics of the once-daily isoniazid (INH) dose at 10 mg/kg of body weight in infants <6 months of age. We performed a multicenter pharmacokinetic study in Spain. The N-acetyltransferase 2 gene was analyzed to determine the acetylation status. Samples were analyzed using a validated UPLC-UV assay. A non-compartmental pharmacokinetic analysis was performed. Twenty-three pharmacokinetic profiles were performed in 20 infants (8 females) at a median (IQR) age of 19.0 (12.6-23.3) weeks. The acetylator statuses were homozygous fast (n = 1), heterozygous intermediate (n = 12), and homozygous slow (n = 7). INH median (IQR) Cmax and AUC0-24h values were 4.8 (3.7-6.7) mg/L and 23.5 (13.4-36.7) h*mg/L and the adult targets (>3 mg/L and 11.6-26.3 h*mg/L) were not reached in three and five cases, respectively. The age at assessment or acetylator status had no impact on Cmax values, but a larger INH AUC0-24h (p = 0.025) and trends towards a longer half-life (p = 0.055) and slower clearance (p = 0.070) were observed in homozygous slow acetylators. Treatment was well tolerated; mildly elevated alanine aminotransferase levels were observed in three cases. In our series of young infants receiving isoniazid, no major safety concerns were raised, and the target adult levels were reached in most patients.

[New diagnosis of HIV infection in children]. / Nuevos diagnósticos de infección VIH en niños.

INTRODUCTION: The number of children of immigrant origin in the last few years has increased the cohort of HIV-infected children in the Community of Madrid. The objectives of the study were to evaluate the epidemiological and clinical characteristics of the new diagnosed children and describe the different subtypes of HIV-1. PATIENTS AND METHODS: The new diagnosed children were analysed from the year 1997, divided into 3 periods: P1 (1997-2000), P2 (2001-2004), P3 (2005-2009). The regions and countries of origin, the clinical, immune and viral characteristics, as well as the response to treatment were analysed. The subtypes of HIV-1 were evaluated by phylogenetic analysis of protease genes and reverse transcriptase. RESULTS: We identified 141 new diagnoses of HIV infection, the percentage of immigrant origin in P1 was (22.5%), P2 (50%) and P3 (68%). The origin had changed from Latin America in P1 to sub-Saharan Africa in P3. There were no differences between Spanish and immigrant children in the age at diagnosis, the CDC clinical stage A/B/C, viral load, percentage of CD4 at diagnosis and actual. Better viral response was more likely in immigrants after the first regimen of HAART (Highly active antiretroviral treatment) independently of the treatment received. A total of 66 subtypes were obtained, 24% were subtypes non-B (56% recombinants forms). All subtypes of Spanish children (43) and Latin American (5) were subtypes B, and all the children from sub-Saharan Africa (14) were subtypes non-B. CONCLUSION: There were no differences between immigrants and Spanish children infected by HIV, except the different subtypes of HIV-1.

Experience with using second life for medical education in a family and community medicine education unit.

BACKGROUND: The application of new technologies to the education of health professionals is both a challenge and a necessity. Virtual worlds are increasingly being explored as a support for education. AIM: The aim of this work is to study the suitability of Second Life (SL) as an educational tool for primary healthcare professionals. DESIGN: Qualitative study of accredited clinical sessions in SL included in a continuing professional development (CPD) programme for primary healthcare professionals. LOCATION: Zaragoza I Zone Family and Community Medicine Education Unit (EU) and 9 health centres operated by the Aragonese Health Service, Aragon, Spain. METHOD: The EU held two training workshops in SL for 16 healthcare professionals from 9 health centres by means of two workshops, and requested them to facilitate clinical sessions in SL. Attendance was open to all personnel from the EU and the 9 health centres. After a trail period of clinical sessions held at 5 health centres between May and November 2010, the CPD-accredited clinical sessions were held at 9 health centres between February and April 2011. PARTICIPANTS: 76 healthcare professionals attended the CPD-accredited clinical sessions in SL. MAIN MEASUREMENTS: Questionnaire on completion of the clinical sessions. RESULTS: Response rate: 42-100%. Questionnaire completed by each health centre on completion of the CPD-accredited clinical sessions: Access to SL: 2 centres were unable to gain access. Sound problems: 0% (0/9). Image problems: 0% (0/9). Voice/text chat: used in 100% (10/9); 0 incidents. Questionnaire completed by participants in the CPD-accredited clinical sessions: Preference for SL as a tool: 100% (76/76). Strengths of this method: 74% (56/76) considered it eliminated the need to travel; 68% (52/76) believed it made more effective use of educational resources; and 47% (36/76) considered it improved accessibility. Weaknesses: 91% (69/76) experienced technical problems, while; 9% (7/76) thought it was impersonal and with little interaction. 65.79% (50/76) believed it was better than other distance learning methods and 38.16% (29/76) believed it was better than face-to-face learning. CONCLUSIONS: SL is a tool that allows educational activities to be designed that involve a number of health centres in different geographical locations, consequently eliminating the need to travel and making more effective use of educational resources.

Partial substitution of frozen-fresh food by an experimental diet in Litopenaeus vannamei (Boone, 1931) (Decapoda: Dendrobranchiata: Penaeidae) broodstock.

The aim of this study was to determine the effect of completely or partially replacing fresh foods from the broodstock diet with an experimental diet. During a 40-day period, three dietary treatments were tested on Litopeaneus vannamei broodstock. As part of the first dietary treatment, denoted as "FF", broodstock shrimp were fed only fresh frozen food (squid, polychaete, mussel and Artemia biomass). The second treatment denoted as "ED" was 100% an artificial experimental diet. The third treatment, denoted as MD, comprised both the experimental diet and the fresh-frozen food (only squid and mussel were used). In terms of fertile spawns, females with ≥ 1 spawn, females with ≥ 2 spawn, and fecundity, the MD treatment did not differ significantly from the FF treatment. Fecundity was lowest among females receiving the ED treatment. MD treatment demonstrated equivalent fertility in females, and sperm rate in males to that of the FF treatment. The highest normal sperm rate was found in the ED and MD treatments. As a result, a combination of fresh food and the experimental diet resulted in a more balanced reproduction performance.

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.

Pediatric Chagas disease in the non-endemic area of Madrid: A fifteen-year review (2004-2018).

BACKGROUND: Chagas disease (CD) has become an emerging global health problem in association with the immigration of individuals from endemic areas (in LatinAmerica) to other countries.Spain is the country in Europe with the highest number of CD cases. Concerning pediatric CD, treatment is not only better tolerated by younger children but also has greater cure possibilities. The aim of this study was to describe clinical and epidemiological aspects of CD in a pediatric population diagnosed of 10 hospitals in the Community of Madrid during the 2004-2018 period, as well as the safety and efficacy of CD treatment on this population. METHODOLOGY/PRINCIPAL FINDINGS: A multicenter, retrospective, descriptive study was conducted. The studied population included all identified children under the age of 18 with a diagnosis of CD. Diagnosis was performed with a positive parasitological test (with subsequent confirmation) or confirmed persistence of positive serology beyond 9 months, for children younger than one year-old, and with two different positive serological tests, for children older than one. Fifty-one children were included (59% male; 50.9% born in Spain). All mothers were from Latin America. The median age at diagnosis was 0.7 months for those under one year of age, and 11.08 years for those older than one year-old. Only one case presented a symptomatic course (hydrops faetalis, haemodynamic instability at birth, ascites, anaemia). For 94% treatment was completed. Considering patients who received benznidazole (47), AE were recorded in 48,9%. Among the 32 patients older than one year-old treated with benznidazole, 18 (56.25%) had adverse events whereas in the 15 under one year, 5(33,3%) did. Eigtheen (78.2%) of the patients with benznidazole AE were older than one year-old(median age 11.4 years). Of the patients treated with nifurtimox (9), AE were reported in 3 cases (33,3%). Cure was confirmed in 80% of the children under one year-old vs 4.3% in those older (p<0.001). Loss to follow- up occurred in 35.3% of patients. CONCLUSIONS/SIGNIFICANCES: Screening programs of CD since birth allow early diagnosis and treatment, with a significantly higher cure rate in children treated before one year of age, with lower incidence of adverse events. The high proportion of patients lost to follow-up in this vulnerable population is of concern.

Innate and adaptive abnormalities in youth with vertically acquired HIV through a multicentre cohort in Spain.

INTRODUCTION: Immune abnormalities have been described among youth with vertically acquired HIV (YWVH) despite antiretroviral treatment (ART). The CD4/CD8 ratio could be a useful prognostic marker. We assess immune activation and senescence in a cohort of YWVH in comparison to youth without vertically acquired HIV. METHODS: YWVH under suppressive ART were included and compared to a group of HIV-negative donors (HD) matched by age and sex, from September 2019 to September 2020. Subset distribution and expression of activation, maturation, senescence and exhaustion markers on T and NK cells were studied on peripheral blood mononuclear cells by multiparametric flow cytometry. RESULTS: Thirty-two YWVH (median age: 24.4 years (interquartile range: 22.5 to 28.3 years)) were included. Among YWVH, CD4- and CD8-T cells showed high levels of activation (HLA-DR/CD38), IL-7 receptor expression (CD127) and exhaustion (TIM-3). Regarding NK cells, YWVH showed increased levels of activation and exhaustion markers compared to HD. Strong inverted correlations were observed between T-cell activation (HLA-DR/CD38), senescence (CD57) and exhaustion (TIGIT, PD-1) levels with the CD4/CD8 ratio among YWVH. HLA-DR, CD69, NKG2D and NKG2A expression levels on NK cells also correlated with the CD4/CD8 ratio. Age at ART initiation was directly associated with higher frequency of CD16high NK-cell subsets, exhaustion T-cell levels (CD57, TIM3) and NK cells activation levels. CONCLUSIONS: Immunological changes associated with vertically acquired HIV, characterized by increased activation and exhaustion levels in innate and adaptive immune components, are only partially restored by ART. The CD4/CD8 ratio can be a useful marker of disease progression for routine clinical practice.

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.

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.

Perinatal HCV Transmission Rate in HIV/HCV Coinfected women with access to ART in Madrid, Spain.

BACKGROUND: Maternal HIV coinfection is a key factor for mother-to-child transmission (MTCT) of HCV. However, data about HCV MTCT in HIV/HCV-coinfected pregnant women on combined antiretroviral treatment (ART) are scarce. This study assessed the HCV MTCT rate in the Madrid Cohort of HIV-infected women. METHODS: Retrospective study within the Madrid Cohort of HIV-infected pregnant women (2000-2012). Epidemiological, clinical and treatment related variables were analysed for the mother and infant pairs. HCV MTCT rate was determined. RESULTS: Three hundred thirty-nine HIV/HCV-coinfected women and their exposed infants were recorded. A total of 227 (67%) paired mother-children had available data of HCV follow-up and were included for the analysis. Sixteen children (rate 7.0%, 95%CI 3.7-10.4%) were HCV infected by 18 months of age, none of them coinfected with HIV. HIV/HCV-coinfected pregnant women were mostly of Spanish origin with a background of previous injection drug use. HCV-genotype 1 was predominant. The characteristics of mothers that transmitted HCV were similar to those that did not transmit HCV with respect to sociodemographic and clinical features. A high rate (50%) of preterm deliveries was observed. Infants infected with HCV were similar at birth in weight, length and head circumference than those uninfected. CONCLUSION: MTCT rates of HCV among HIV/HCV-coinfected women on ART within the Madrid cohort were lower than previously described. However, rates are still significant and strategies to eliminate any HCV transmission from mother to child are needed.

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.

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 on weight and height with the use of HAART in HIV-infected children.

BACKGROUND: There are few data on long-term effects of highly active antiretroviral therapy (HAART) on weight and height in HIV-infected children. OBJECTIVES: Our objective was to assess the effect of HAART on the weight and height of HIV-infected children over time in the Madrid cohort, and analyze possible factors associated with the effect. PATIENTS AND METHODS: This was a retrospective study of HIV-infected children starting HAART in 1997 or later. Serial measurements of weight, height and body mass index (BMI) were performed and converted to z-scores using the Spanish revised reference data. Changes from baseline in weight, height and BMI at 12, 24, 36, 48 and 60 months were determined. Associations of z-scores at the last visit with immunologic (CD4% above 25%) and virologic responses (more than 50% of samples below 400 copies/mL), CDC (Centers for Disease Control) clinical category, and the presence and type of lipodystrophy (lipoatrophy or lipohypertrophy) were evaluated. RESULTS: Twelve hundred and twelve children, 97% of them vertically-infected, received HAART starting in 1997 for a median of 71 months (4-102 months). Median age at initiation of HAART was 6 years (1 month-18 years). Thirty-nine percentage were antiretroviral naive and 61% had received NRTI therapy previously. Thirty-two percentage and 53% had CDC class C and immunologic class 3, respectively. At the final evaluation, 24% of children remained on their first combination therapy, 39% on the second and 37% had received at least 3 different HAART regimens. Fifty-one percentage were classified as virologic responders. Thirty-nine percentage of children in this study were diagnosed with lipodystrophy. At baseline, median z-score for weight, height and BMI were -0.45, -0.60 and -0.33, respectively. HAART was associated with significant increases in z-scores of weight and height but not BMI at the different time-points analyzed. Virologic nonresponders had significantly lower z-scores for weight and height but not for BMI. CDC class C was associated with lower z-scores for height. No differences in final measurements were observed for baseline CD4, immunologic response or lipoatrophy. Children with lipohypertophy had a significantly higher BMI at the last visit. CONCLUSIONS: HIV-infected children experienced a continued catch-up in weight and height 5 years after starting HAART. Virologic control is related to sustained growth.