Past and future of HIV infection. A document based on expert opinion.

HIV infection is now almost 40 years old. In this time, along with the catastrophe and tragedy that it has entailed, it has also represented the capacity of modern society to take on a challenge of this magnitude and to transform an almost uniformly lethal disease into a chronic illness, compatible with a practically normal personal and relationship life. This anniversary seemed an ideal moment to pause and reflect on the future of HIV infection, the challenges that remain to be addressed and the prospects for the immediate future. This reflection has to go beyond merely technical approaches, by specialized professionals, to also address social and ethical aspects. For this reason, the Health Sciences Foundation convened a group of experts in different aspects of this disease to discuss a series of questions that seemed pertinent to all those present. Each question was presented by one of the participants and discussed by the group. The document we offer is the result of this reflection.

Adipokine profiles and lipodystrophy in HIV-infected children during the first 4 years on highly active antiretroviral therapy.

OBJECTIVE: The aim of the study was to evaluate the evolution of plasma adipokines and lipodystrophy in protease inhibitor-naive vertically HIV-infected children on highly active antiretroviral therapy(HAART). PATIENTS AND METHODS: We carried out a multicentre retrospective study of 27 children during 48 months on HAART. Every 3 months, CD4+ T-cells, CD8+ T-cells, viral load (VL), cholesterol, triglycerides, lipoproteins and adipokines were measured. Diagnoses of lipodystrophy were based on clinical examinations. RESULTS: We found hypercholesterolaemia (4200 mg/dL) in 9.5, 30.4, 21.7, 14.3 and 13.3% of the subjects at months 0, 12, 24, 36 and 48, respectively, and hypertriglyceridaemia (4170 mg/dL) in 14.3, 8.3, 13,4.5 and 0% at the same time-points. During follow-up, and especially at the end of the study, we found an increase in plasma resistin levels and significant increases in total plasminogen activator inhibitor type 1, adiponectin, and leptin levels (Po0.05). We also observed slight increases in the leptin/adiponectin ratio, homeostatic model assessment, and C-peptide values during the first months of treatment followed by a moderate decrease or stabilization after 24 months on HAART.At the end of the study, 12 of the 27 children (44.4%) had lipodystrophy, 10 (37%) had lipoatrophy,and 11 (40.7%) had lipohypertrophy; and only three of the 27 children (11.1%) were diagnosed with lipoatrophy and lipohypertrophy with scores 2. CONCLUSIONS: HIV-infected children showed an increase in serum adipokine levels, but this was not associated with the emergence of lipodystrophy during 48 months on HAART.

Brain activity in well-controlled perinatally HIV-infected young adults: a fMRI pilot study. / Actividad cerebral en jóvenes infectados por el virus de la inmunodeficiencia humana por transmisión vertical: estudio piloto de resonancia magnética funcional.

INTRODUCTION AND AIM: Perinatal transmission of human immunodeficiency virus (PHIV) is considered a chronic disease that has highlighted several cognitive deficits. From birth to early adulthood, cognition is known to play a fundamental role. However, although neurocognitive processes associated with PHIV have been extensively described by psychometric testing, data is scarce on neural activity from functional magnetic resonance imaging (fMRI) which provides in vivo physiological information. SUBJECTS AND METHODS: We studied described impaired cognitive processes using fMRI on a group of PHIV adolescents with good immunovirological indications and healthy matched controls. Psychological status and neurocognitive functions were also assessed. RESULTS: There were no significant differences between HIV+ and HIV- groups, either on neurocognitive testing nor in fMRI activity for phonological fluency tasks. Prolonged duration of cART was positively associated with greater brain activity in left inferior frontal gyrus (LIFG) which could indicate functional compensation. CONCLUSIONS: These results suggest that neural activity through fMRI in PHIV adolescents with good daily functioning and good immunovirological control may be similar to their peers.

TITLE: Actividad cerebral en jóvenes infectados por el virus de la inmunodeficiencia humana por transmisión vertical: estudio piloto de resonancia magnética funcional.Introducción y objetivos. La infección por el virus de la inmunodeficiencia humana de transmisión vertical (VIH-TV) constituye una enfermedad crónica que puede asociar múltiples alteraciones cognitivas que pueden influenciar el desarrollo de estos pacientes desde la infancia a la vida adulta. Sin embargo, aunque las alteraciones neurocognitivas vinculadas al VIH-TV están ampliamente descritas y valoradas mediante pruebas psicométricas, no existen apenas estudios de actividad neuronal medida a través de la resonancia magnética funcional (RMf). Sujetos y métodos. Analizar la utilidad de la RMf a través de la realización de tareas motoras y de fluidez verbal en un grupo de adolescentes y jóvenes con VIH-TV con buen control inmunovirológico y compararlo con un grupo control negativo de características similares. Se evaluaron también alteraciones psicológicas y funciones neurocognitivas. Resultados. No se encontraron diferencias significativas entre el grupo VIH+ y el grupo control para las tareas ejecutadas durante la RMf ni en la evaluación neurocognitiva. Un mayor tiempo de terapia combinada antirretroviral se asoció de forma directa con una mayor actividad en el giro frontal inferior izquierdo, lo cual podría indicar una posible compensación funcional. Conclusiones. Estos resultados sugieren que la actividad neuronal medida a través de la RMf en adolescentes con VIH-TV y buen control inmunovirológico es similar a la de sus pares.

Opportunistic infections and organ-specific diseases in HIV-1-infected children: a cohort study (1990-2006).

OBJECTIVES: Highly active antiretroviral therapy (HAART) has dramatically changed the natural history of HIV infection in children, but there are few studies in the literature about the incidence of clinical manifestations after HAART in this population, compared with adults. The aim of this study was to describe the influence of the widespread use of HAART on the development of opportunistic infections and organ-specific diseases in HIV-infected children. METHODS: An observational study of a cohort of 366 vertically HIV-infected children followed from 1990 to 2006 was carried out. According to the main antiretroviral protocol used, three calendar periods (CPs) were defined and compared: CP1 (1990-1996: no patients on HAART), CP2 (1997-1999: <60% on HAART) and CP3 (2000-2006: >60% on HAART). RESULTS: Children experienced a progressive increase in CD4 T cell count (P<0.05) and a decrease in HIV viral load from 1996 onwards (P<0.05). Similarly, rates of death, AIDS, opportunistic infections (bacteraemia, candidosis, cryptosporidiosis and bacterial pneumonia) and organ-specific diseases (wasting syndrome, thrombocytopenia, cardiomyopathy, lymphoid interstitial pneumonia and HIV-associated encephalopathy) were lower in CP2 and CP3 than in CP1. CONCLUSIONS: This study provides evidence of improved clinical outcomes in HIV-infected children over time and shows that mortality, AIDS, opportunistic infections and organ-specific diseases declined as HAART was progressively instituted in this population.

Significant differences between verbal and non-verbal intellectual scales on a perinatally HIV-infected cohort: from pediatrics to young adults.

Delayed neurodevelopment is a common outcome in perinatally HIV-infected children. Our aim was to assess the intellectual profile of our cohort, considering both the infection and socio-environmental related variables. A cross-sectional cohort study was undertaken at seven major hospitals in Spain belonging to the CoRISpeS cohort (n = 97). Patients were followed up according to a standard protocol. Intellectual measures, psychosocial profile and HIV infection-related data have been analysed. The average patient age was 15 years. The median CD4 cell percentage was 35% (1,59). Viral load was undetectable in 80% of the patients and 27% were on AIDS category; 38% of whom had encephalopathy. The average composite score of both crystallized intelligence (CI) and intelligence quotient (IQ) for the cohort was lower than that of the general population (p < 0.001). Results revealed a significant difference of 38% between crystallized and fluid intelligence. There was a clear association between IQ and age of diagnosis (p = 0.022); CI and CDC classification (p = 0.035), CD4 count (p = 0.011) and CD4 nadir (p = 0.001). Higher parental education was associated with better performance across all intelligence scales (p < 0.002). A regression model showed that CI was influenced by the academic level of caregivers (p = 0.002), age at start of cART (p = 0.050) and primary language (p = 0.058). Findings revealed significant differences in verbal and non-verbal intellectual scales resulting in a misleading IQ Composite score. Crystallized intelligence demonstrated the highest level of impairment despite adequate treatment and good immunovirological status, while fluid intelligence results were average. Caregiver level of education was the strongest factor across all intelligence measures.

Clinical practice update of antifungal prophylaxis in immunocompromised children.

Due to the rise in the number and types of immunosuppressed patients, invasive fungal infections (IFI) are an increasing and major cause of morbidity and mortality in immunocompromised adults and children. There is a broad group of pediatric patients at risk for IFI in whom primary and/or secondary antifungal prophylaxis (AFP) should be considered despite scant evidence. Pediatric groups at risk for IFI includes extremely premature infants in some settings, while in high-risk children with cancer receiving chemotherapy or undergoing haematopoietic stem cell transplantation (HCT), AFP against yeast and moulds is usually recommended. For solid organ transplanted, children, prophylaxis depends on the type of transplant and associated risk factors. In children with primary or acquired immunodeficiency such as HIV or long-term immunosuppressive treatment, AFP depends on the type of immunodeficiency and the degree of immunosuppression. Chronic granulomatous disease is associated with a particular high-risk of IFI and anti-mould prophylaxis is always indicated. In contrast, AFP is not generally recommended in children with long stay in intensive care units. The choice of AFP is limited by the approval of antifungal agents in different age groups and by their pharmacokinetics characteristics. This document aims to review current available information on AFP in children and to provide a comprehensive proposal for each type of patient.

How Thinking About the Donor Influences Post-traumatic Growth in Liver Transplant Recipients.

OBJECTIVE: The aim of this work was to find out whether thinking frequently about the donor influences post-traumatic growth of liver transplant recipients. METHODS: The sample of 240 patients selected was made up of 185 men and 55 women with an overall mean age of 60.21 (SD 9.3) years. All of them had received liver transplants from cadaver donors. Transplant recipients were asked whether they thought frequently about the donor (yes or no) and filled out the Post-traumatic Growth Inventory. The t test for unpaired samples was applied to analyze how thinking frequently about the donor or not influenced post-traumatic growth. We also calculated the effect sizes by means of Cohen d or Cohen w depending on the nature of the variables analyzed (quantitative or qualitative). RESULTS: The liver transplant recipients who thought frequently about the donor, compared with those who did not, had higher total scores on post-traumatic growth (P = .000; d = 0.57; medium effect size). Furthermore, considering the effect sizes, the differences between the subgroups were more relevant on the following subscales: new possibilities (P = .000; d = 0.53; medium effect size), appreciation of life (P = .000; d = 0.60; medium effect size), and spiritual change (P = .000; d = 0.54; medium effect size). CONCLUSIONS: Patients who think frequently about the donor have more post-traumatic growth than those who do not.

Family Caregivers of Liver Transplant Recipients: Coping Strategies Associated With Different Levels of Post-traumatic Growth.

OBJECTIVE: Analyze the influence of 2 variables (post-traumatic growth and time since liver transplantation) on coping strategies used by the transplant recipient's family members. METHODS: In all, 218 family members who were their main caregivers of liver transplant recipients were selected. They were evaluated using the Posttraumatic Growth Inventory and the Brief COPE. A 3 × 3 factorial analysis of variance was used to analyze the influence that post-traumatic growth level (low, medium, and high) and time since transplantation (≤3.5 years, >3.5 to ≤9 years, and >9 years) exerted on caregiver coping strategies. RESULTS: No interactive effects between the two factors in the study were found. The only significant main effect was the influence of the post-traumatic growth factor on the following variables: instrumental support (P = .007), emotional support (P = .005), self-distraction (P = .006), positive reframing (P = .000), acceptance (P = .013), and religion (P = <.001). According to the most relevant effect sizes, low post-traumatic growth compared with medium growth was associated with less use of self-distraction (P = .006, d = -0.52, medium effect size), positive reframing (P = .001, d = -0.62, medium effect size), and religion (P = .000, d = -0.66, medium effect size), and in comparison with high growth, it was associated with less use of positive reframing (P = .002, d = -0.56, medium effect size) and religion (P = .000, d = 0.87, large effect size). CONCLUSION: Regardless of the time elapsed since the stressful life event (liver transplantation), family members with low post-traumatic growth usually use fewer coping strategies involving a positive, transcendent vision to deal with transplantation.

[Use of extra-hospital emergency systems in the treatment of acute stroke in the region of Murcia. Possible repercussions on the urgent care of stroke patients]. / Utilización del sistema de emergencias extrahospitalario en el tratamiento del ictus agudo en la región de Murcia. Posible repercusión en la asistencia sanitaria urgente del ictus.

AIM: To examine the use of extra-hospital emergency systems in the urgent care of stroke patients in our region and their influence on the time required to reach hospital, the time needed to perform an urgent computerised axial tomography (CAT) scan and the delay in receiving attention from the specialist. PATIENTS AND METHODS: Samples were collected from 232 stroke patients out of the total number admitted to our hospitals. Data about the stroke were collected prospectively, and included the arrival time, the time required to perform the CAT scan and the time the specialist devoted to attending the patient. Data were also gathered about the different extra-hospital transport and emergency systems. A statistical analysis was performed to determine the effect of using the extra-hospital emergency procedures on the different variables. RESULTS: A total of 53.6% of patients arrived within the first three hours. 38.7% went straight to hospital, 25% visited extra-hospital Emergency Services first, and 18.5% made a prior visit to Primary Care. 51.5% found their own way to the hospital and 46.7% arrived by ambulance. Mean time taken to perform an urgent CAT scan: 190.4 minutes; mean time required for specialist attention: 25.65 hours. The only statistically significant relation was the use of extra-hospital emergency systems and health care transport according to the type of stroke: both were more likely to be used in cases of haemorrhagic stroke. CONCLUSIONS: In hospitals in the Murcia region, the use of the extra-hospital emergency system and the means of transport utilised do not affect the time stroke patients take to reach hospital or the time needed to perform an urgent CAT scan or the delay in receiving attention from a specialist; the aetiology of the stroke does, however, influence the use of such services.

The neurofibroma of the oesophagus. Case report.

A case of oesophageal neurofibroma is reported; its low incidence among the benign tumours of the oesophagus is pointed out. The clinical, radiologic and histologic features of this very rare tumour are described.

Urine arsenic concentrations in healthy adults as indicators of environmental contamination: relation with some pathologies.

Arsenic concentrations were determined in 126 urine samples by hydride generation atomic absorption spectrometry. Samples were mineralized with nitric acid in a thermostated mineralization block. This technique was compared with a method that involves mineralization in a microwave digestion bomb. A mean recovery percentage of 100.80 +/- 5.57% was obtained. The relative standard deviation ranged from 1.7 to 10.52%. It was found that subject sex and age did not affect urine As levels (P > 0.05). The mean urine As levels in patients with hepatic injury (4.24 +/- 1.98 micrograms/l), diabetes (3.44 +/- 2.36 micrograms/l) and myocardial infarction (3.64 +/- 1.85 micrograms/l) were not statistically different (P > 0.05) to that found in the control group (healthy subjects) (3.68 +/- 2.27 micrograms/l). This result could be related to the fact that the regulation of As in the human organism is independent of these diseases. Measured As concentrations in the eight basic health zones of the study area were not statistically different (P > 0.01). This fact demonstrates the existence of a similarly low environmental As distribution in coastal and mountainous zones.

[Emotional facial paresis as a symptom of a spontaneous carotid dissection]. / Paresia facial emocional como síntoma de una disección espontánea de carótida: a propósito de un caso.

Emotional facial paresis consists of the absence of facial movements during emotional stimulus, as laughing, with a normal voluntary facial mobility. The anatomic ways responsible for the emotional facial mobility have been already studied. We present a case of emotional facial paresis caused by a striatum-capsular infarct secondary to a spontaneous dissection of the internal carotid artery.

[Herpes zoster ophthalmicus with contralateral hemiplegia]. / Herpes zoster oftálmico con hemiplejia contralateral.

A 57-year-old patient nonimmunosuppressed who had zoster ophthalmicus associated to contralateral hemiplegia is presented. We noticed on the CT scan an infarction of left caudate nucleus, as well as in the angiography signs of vasculitis. We comment on the clinical and diagnosis features and suggest possible benefit effects of the treatment with acyclovir.

Short communication: evaluation of the effect of enfuvirtide in 11 HIV-1 vertically infected pediatric patients outside clinical trials.

The effect of enfuvirtide (ENF) in 11 HIV-1 heavily antiretroviral-experienced children and adolescents enrolled in the HIV-1 Paediatric Spanish cohort was further investigated. Patients who received ENF with novel drugs (etravirine, darunavir, and/or tipranavir) reached and maintained undetectable plasma HIV-1 RNA levels and showed immunological recovery within the first 3 months of therapy that was maintained during the follow-up. Viremia was not fully suppressed in patients who did not combine ENF with novel drugs but interestingly, immunological benefit was observed in half of these patients. Therefore, ENF showed a greater and more stable efficacy when administrated with novel drugs.

Unusual case presentations associated with the CD45 C77G polymorphism.

CD45, the leucocyte common antigen, is a haematopoietic cell specific tyrosine phosphatase. Human polymorphic CD45 variants are associated with autoimmune and infectious diseases and alter the phenotype and function of lymphocytes, establishing CD45 as an important regulator of immune function. Here we report four patients with diverse diseases with unusual clinical features. All four have the C77G polymorphism of CD45 exon 4, which alters the splicing and CD45RA/CD45R0 phenotype of lymphocytes. We suggest that C77G may be a contributing factor in these unusual cases.