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.

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.

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

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.(AU)

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.(AU)

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.

Current aspects in sepsis approach. Turning things around.

The incidence and prevalence of sepsis depend on the definitions and records that we use and we may be underestimating their impact. Up to 60% of the cases come from the community and in 30-60% we obtain microbiological information. Sometimes its presentation is ambiguous and there may be a delay in its detection, especially in the fragile population. Procalcitonin is the most validated biomarker for bacterial sepsis and the one that best discriminates the non-infectious cause. Presepsin and pro-adrenomedullin are useful for early diagnosis, risk stratification and prognosis in septic patients. The combination of biomarkers is even more useful to clarify an infectious cause than any isolated biomarker. Resuscitation with artificial colloids has worse results than crystalloids, especially in patients with renal insufficiency. The combination of saline solution and balanced crystalloids is associated with a better prognosis. Albumin is only recommended in patients who require a large volume of fluids. The modern molecular methods on the direct sample or the identification by MALDI-TOF on positive blood culture have helped to shorten the response times in diagnosis, to optimize the antibiotic treatment and to facilitate stewardship programs. The hemodynamic response in neonates and children is different from that in adults. In neonatal sepsis, persistent pulmonary hypertension leads to an increase in right ventricular afterload and heart failure with hepatomegaly. Hypotension, poor cardiac output with elevated systemic vascular resistance (cold shock) is often a terminal sign in septic shock. Developing ultra-fast Point-of-Care tests (less than 30 minutes), implementing technologies based on omics, big data or massive sequencing or restoring "healthy" microbiomes in critical patients after treatment are the main focuses of research in sepsis. The main benefits of establishing a sepsis code are to decrease the time to achieve diagnosis and treatment, improve organization, unify criteria, promote teamwork to achieve common goals, increase participation, motivation and satisfaction among team members, and reduce costs.

[Invasive fungal infections in children: similarities and differences with adults]. / Infección fúngica invasora en niños: diferencias y homologías con el adulto.

Invasive fungal infections (IFI) are a major cause of morbidity and mortality in immunocompromised adults and children. The purpose of this review was to update the epidemiological, clinical and therapeutic options in children, and to compare them with the adult population. Although there are important differences, the epidemiology, clinical features and risk factors for IFI have many similarities. Patient at risk include neutropenic hematology children, in whom Candida spp. y Aspergillus spp. predominate; primary immunodeficiencies, particularly chronic granulomatous disease with high susceptibility for Aspergillus spp.; and extremely premature infants, in whom C. albicans y C. parapsilosis are more prevalent. Premature babies are prone to dissemination, including the central nervous system. There are peculiarities in radiology and diagnostic biomarkers in children. In pulmonary aspergillosis, clasical signs in CT are usually absent. There is scant information on PCR and beta-D-glucan in children, and more limited on the performance of galactomannan enzyme immunoassay, that does not appear to be much different in neutropenic patients. There is a delay in the development of antifungals, limiting their use in children. Most azoles require therapeutic drug monitoring in children to optimize its safety and effectiveness. Pediatric treatment recommendations are mainly extrapolated from results of clinical trials performed in adults. There is no evidence for the benefit of preemptive therapy in children. It is necessary to foster specific pediatric studies with current and new antifungals to evaluate their pharmacokinetics, safety, and effectiveness at different ages in the pediatric population.

The incidence of AIDS-defining illnesses at a current CD4 count ≥ 200 cells/µL in the post-combination antiretroviral therapy era.

BACKGROUND: Few studies consider the incidence of individual AIDS-defining illnesses (ADIs) at higher CD4 counts, relevant on a population level for monitoring and resource allocation. METHODS: Individuals from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) aged ≥14 years with ≥1 CD4 count of ≥200 µL between 1998 and 2010 were included. Incidence rates (per 1000 person-years of follow-up [PYFU]) were calculated for each ADI within different CD4 strata; Poisson regression, using generalized estimating equations and robust standard errors, was used to model rates of ADIs with current CD4 ≥500/µL. RESULTS: A total of 12 135 ADIs occurred at a CD4 count of ≥200 cells/µL among 207 539 persons with 1 154 803 PYFU. Incidence rates declined from 20.5 per 1000 PYFU (95% confidence interval [CI], 20.0-21.1 per 1000 PYFU) with current CD4 200-349 cells/µL to 4.1 per 1000 PYFU (95% CI, 3.6-4.6 per 1000 PYFU) with current CD4 ≥ 1000 cells/µL. Persons with a current CD4 of 500-749 cells/µL had a significantly higher rate of ADIs (adjusted incidence rate ratio [aIRR], 1.20; 95% CI, 1.10-1.32), whereas those with a current CD4 of ≥1000 cells/µL had a similar rate (aIRR, 0.92; 95% CI, .79-1.07), compared to a current CD4 of 750-999 cells/µL. Results were consistent in persons with high or low viral load. Findings were stronger for malignant ADIs (aIRR, 1.52; 95% CI, 1.25-1.86) than for nonmalignant ADIs (aIRR, 1.12; 95% CI, 1.01-1.25), comparing persons with a current CD4 of 500-749 cells/µL to 750-999 cells/µL. DISCUSSION: The incidence of ADIs was higher in individuals with a current CD4 count of 500-749 cells/µL compared to those with a CD4 count of 750-999 cells/µL, but did not decrease further at higher CD4 counts. Results were similar in patients virologically suppressed on combination antiretroviral therapy, suggesting that immune reconstitution is not complete until the CD4 increases to >750 cells/µL.

Análisis ecológico y perfil materno de la transmisión vertical del virus de la inmunodeficiencia humana en la Comunidad de Madrid desde 1980 hasta 2008 / An ecological analysis and the maternal profile of vertical HIV transmission in the Community of Madrid from 1980 until 2008

La pandemia del sida sigue siendo uno de los principales problemas que afectan al desarrollo y la seguridad en todo el mundo. En España, y más específicamente en la Comunidad de Madrid (CM), los primeros afectados fueron hombres homosexual eso bisexuales, seguidos de adictos a drogas por vía parenteral (ADVP) y la vía heterosexual; esta última afectaba principalmente a las mujeres, y la transmisión vertical (TV). La TV es la prioritaria en los niños (95,3%). A 31 de diciembre de 2008, la cohorte de niños infectados por TV de la CM estaba constituida por 261 pacientes, de los que 48 se habían quedado huérfanos de madre; estos niños vivieron el deterioro de la madre a causa de la enfermedad, con las graves repercusiones en la calidad de vida que este hecho implica, y afectando de manera significativa a su desarrollo. Además, se observó un cambio en la vía de transmisión de las madres a partir de 2002 (la principal vía era la heterosexual frente a ADVP), debido al aumento de la población inmigrante y a una modificación en el paradigma socioambiental, ya que estas madres no pertenecían a grupos con prácticas de riesgo, aunque sí mantuvieron contactos de riesgo. En cuanto a la TV, existe una asociación significativa entre el descenso de infecciones por el virus de la inmunodeficiencia humana (VIH) tipo 1 y los tratamientos antirretrovirales recibidos como profilaxis en el embarazo y el parto. Sin embargo, no puede decirse que la TV esté erradicada, por lo que sigue siendo un problema de salud pública relevante (AU)

The AIDS pandemic continues to be one of the main problems affecting development and safety throughout the world, in Spain and more specifically in the Community of Madrid(CM). The first to be affected were homosexual/bisexual men, followed by intravenous drug users and infection through heterosexual transmission, a route which affected women, and vertical transmission (VT). VT dominates in children (95.3%). At 31 December 2008, the cohort of children infected via VT in the CM was made up of 261 children. Of those children, 48 had lost their mothers after witnessing their deterioration due to the disease, which had serious repercussions on the children’s quality of life and substantially affected their development. Moreover, a change was seen in the route of transmission in mothers as of 2002, with the main route being heterosexual contact versus intravenous drug use. That change was brought about by the increase in the immigrant population and by a change in the socio-environmental paradigm since these mothers did not belong to groups with risk practices, but their sexual practices did involve contact that put them at risk. With regard to VT, there is a significant association between the decrease in HIV-1 infections and the taking of antiretroviral treatments like prophylaxis during pregnancy and birth. Nevertheless, VT has not yet been eradicated, which means it continues to be a relevant public health problem (AU)

Análisis socioeconómico y demográfico de la prevalencia en niños infectados por el virus de la inmunodeficiencia humana por transmisión vertical en la Comunidad de Madrid / A socio-economic and demographic analysis of the prevalence of paediatric HIV due to vertical transmission in the Community of Madrid

España sigue siendo uno de los países con tasas más altas deincidencia del virus de la inmunodeficiencia humana (VIH)/sidaen Europa occidental. La Comunidad de Madrid es la zona másafectada por la infección, con un total de 17.667 casos de sidahasta diciembre de 2008, lo que representa el 23,9% de loscasos registrados en toda España. En dicha comunidad se identificaroncomo áreas básicas de transmisión los distritos delsur y del norte-este, especialmente Usera, Puente de Vallecas,San Blas y Hortaleza, con una mayor prevalencia en el númerode casos de transmisión vertical. También se observó un cambiorespecto al flujo migratorio en los diferentes distritos de laciudad, coincidiendo los distritos con mayor censo de inmigrantescon un registro superior de las tasas de prevalencia de lainfección por el VIH por transmisión vertical. La prevalencia decasos de VIH por transmisión vertical se correlacionó significativamentecon el porcentaje de los inmigrantes (p= –0,544; p=0,011), personas sin estudios (p= 0,487; p= 0,025), mujeres desempleadas(p= 0,477; p= 0,029) y población con una renta percápita baja (p= –0,508; p= 0,019). Por otra parte, cabe pensarque estas zonas sur y norte-este, a su vez, pueden ser franjasimportantes para la propagación de otras enfermedades infecciosas,por lo que la presente memoria podría contribuir aldesarrollo de estrategias efectivas para la educación sobre elVIH, en cuanto a la prevención de situaciones de riesgo(AU)

Spain continues to be one of the countries with the highest HIV/AIDS incidence rates in Western Europe. The Community of Madrid is the area most affected by the infection, with a total of 17,667 cases of AIDS until December 2008, accounting for 23.9% of the cases recorded on a nation level. The south and north-eastern districts of the aforementioned Community, and especially Usera, Puente de Vallecas, San Blas and Hortaleza, were identified as basic transmission areas with a higher prevalence of cases of vertical transmission. A change was also observed with regard to the migration flow in the different districts of the city, with the districts with the highest numbers of immigrants coinciding with those with the highest recorded prevalence rates of cases of vertically transmitted HIV. The prevalence of cases of vertically transmitted HIV was significantly correlated with the percentage of migrants (p= –0.544; p=0.011), people without degrees (p= 0.487; p= 0.025), un employed women (p= 0.477; p= 0.029) and populations with a low per capitain come (p= –0.508; p= 0.019). Moreover, this leads to the thought that these south and north-eastern districts may also be important areas for the spread of other infectious diseases and, therefore, this report may contribute to the development of effective strategies for HIV education as regards the prevention of risk situations (AU)

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.

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.

[Prevalence of resistance to antiretroviral drugs in Spain]. / Prevalencia de resistencia a fármacos antirretrovirales en España.

INTRODUCTION: The development of resistance to antiretroviral therapy (ART) reduces the effectiveness of these drugs in HIV-infected children. METHODS: We performed a cross-sectional study in 86 vertically HIV-infected children, divided into four groups according to prior treatment: group 1: nucleoside reverse transcriptase inhibitor (NRTI), group 2: NRTI and non-nucleoside reverse transcriptase inhibitor (NNRTI), group 3: NRTI and protease inhibitor (PI), group 4: NRTI, NNRTI and PI. RESULTS: In group 1 (11 children), the median treatment duration was 35 months (26 to 108). Nucleoside-associated mutations (NAMs) were found in 10 of these patients and the Q151M multiresistance mutation was found in two. The three children in group 2 were treated for 9, 32 and 42 months with NRTI and NNRTI. One child showed three NAMs and another showed Q151M. Two children had the K103N mutation. Group 3 (36 children) received treatment with NRTI and PI for 48.0 +/- 27.6 and 23.0 +/- 14.6 months, respectively. NAMs were observed in 94 % of the patients in this group, and one child showed the Q151M mutation. In group 4 (36 children) total treatment duration was 70.0 +/- 36.1 months (13.0 +/- 12.1 months with NNRTI, and 39.0 +/- 14.3 months with PI). NAMs were observed in all patients in this group, and Q151M was found in three children. K103N and Y181C were detected in 24 (67%) and 10 (28%) of the children respectively, while 32 (90%) showed primary mutations to PI. CONCLUSIONS: A high prevalence of resistance mutations to NRTI and early appearance of resistance to NNRTI were observed in treated children.

Prevalencia de resistencia a fármacos antirretrovirales en España / Prevalence of resistance to antiretroviral drugs in Spain

Introducción La aparición de resistencias a los antirretrovirales (ARV) compromete la eficacia del tratamiento antirretroviral (TAR) en los niños infectados por el virus de la inmunodeficiencia humana (VIH). Métodos Se realizó un estudio transversal en 86 niños divididos en 4 grupos según su historia de TAR previo: 1. inhibidores de la retrotranscriptasa análogos de nucleósido (NRTI); 2. NRTI e inhibidores de la retrotranscriptasa no análogos de nucleósido (NNRTI); 3. NRTI e inhibidores de la proteasa (IP); 4. NRTI, NNRTI e IP. Resultados En el grupo 1 (11 niños) la mediana de TAR fue de 35 meses (26-108). En 10 pacientes se detectaron mutaciones asociadas a los análogos de timidina (NAM) y en 2 pacientes se halló el complejo de multirresistencia Q151M. Los 3 niños del grupo 2, recibieron 9, 32 y 42 meses respectivamente de TAR con NNRTI. En un paciente de este grupo se aislaron 3 NAM y en otro el complejo Q151M. 2 pacientes tenían la mutación K103N. En el grupo 3 (36 niños) la media de duración de tratamiento con NRTI e IP era de 48,0 ± 27,6 y 23,0 ± 14,6 meses, respectivamente. El 94 % de los pacientes de este grupo, tenían NAM y un paciente tenía el complejo Q151M. En el grupo 4 (36 niños) el tiempo previo de TAR era de 70,0 ± 36,1 meses (NNRTI: 13,0 ± 12,1 meses; IP: 39,0 ± 14,3 meses). Todos los pacientes tenían NAM y 3 pacientes tenían el complejo Q151M. Las mutaciones K103N y Y181C se hallaron en 24 (67 %) y 10 (28 %) de los pacientes, respectivamente. Un total de 32 pacientes (90 %) tenían alguna mutación primaria a IP. Conclusiones La aparición de resistencias a los ARV es frecuente en niños, siendo de rápida aparición con los NNRTI

Introduction The development of resistance to antiretroviral therapy (ART) reduces the effectiveness of these drugs in HIV-infected children. Methods We performed a cross-sectional study in 86 vertically HIV-infected children, divided into four groups according to prior treatment: group 1: nucleoside reverse transcriptase inhibitor (NRTI), group 2: NRTI and non-nucleoside reverse transcriptase inhibitor (NNRTI), group 3: NRTI and protease inhibitor (PI), group 4: NRTI, NNRTI and PI. Results In group 1 (11 children), the median treatment duration was 35 months (26 to 108). Nucleoside-associated mutations (NAMs) were found in 10 of these patients and the Q151M multiresistance mutation was found in two. The three children in group 2 were treated for 9, 32 and 42 months with NRTI and NNRTI. One child showed three NAMs and another showed Q151M. Two children had the K103N mutation. Group 3 (36 children) received treatment with NRTI and PI for 48.0 ± 27.6 and 23.0 ± 14.6 months, respectively. NAMs were observed in 94 % of the patients in this group, and one child showed the Q151M mutation. In group 4 (36 children) total treatment duration was 70.0 ± 36.1 months (13.0 ± 12.1 months with NNRTI, and 39.0 ± 14.3 months with PI). NAMs were observed in all patients in this group, and Q151M was found in three children. K103N and Y181C were detected in 24 (67 %) and 10 (28 %) of the children respectively, while 32 (90 %) showed primary mutations to PI. Conclusions A high prevalence of resistance mutations to NRTI and early appearance of resistance to NNRTI were observed in treated children

Recommendations from SPNS/GEAM/SENBA/SENPE/AEDN/SEDCA/GESIDA on nutrition in the HIV-infected patient.

OBJECTIVE: to make recommendations on the approach to nutritional problems (malnutrition, cachexia, micronutrient deficiency, obesity, lipodystrophy) affecting HIV-infected patients. METHODS: these recommendations have been agreed upon by a group of expertes in the nutrition and care of HIV-infected patients, on behalf of the different groups involved in drafting them. Therefore, the latest advances in pathophysiology, epidemiology, and clinical care presented in studies published in medical journals or at scientific meetings were evaluated. RESULTS: there is no single method of evaluating nutrition, and diferent techniques--CT, MRI, and DXA--must be combined. The energy requirements of symptomatic patients increase by 20-30%. There is no evidence to support the increase in protein or fat intake. Micronutrient supplementation in only necessary in special circumstances (vitamin A in children and pregnant woman). Aerobic and resistance excercise is beneficial both for cardiovascular health and for improving lean mass and muscular strength. It is important to follow the rules of food safety at every stage in the chain. Therapeutic intervention in anorexia and cachexia must be tailored, by combining nutritional and pharmacological support (appetite stimulants, anabolic steroids, and, in some cases, testosterone). Artificial nutrition (oral supplementation, enteral or parenteral nutrition) is safe and efficacious, and improves nutritional status and response to therapy. In children, nutritional recommendations must be made early, and are a necessary component of therapy. CONCLUSION: appropriate nutritional evaluation and relevant therapeutic action are an essential part of the care of HIV-infected patients.

Dynamics of progression markers in a non-study population of human immunodeficiency virus-1 vertically infected infants with different antiretroviral treatments.

UNLABELLED: Treatment with highly active antiretroviral therapy (HAART) has been shown to modify viral replication dynamics and lead to a significant recovery of CD4+ T-cells. A retrospective multicentre observational study was performed in a non-study population of 151 HIV-1-infected children, categorized into four groups according to therapy: untreated (NT), on monotherapy (MT) with a nucleoside inhibitor, on combination therapy (CT) with two nucleoside inhibitors, and on HAART, protease inhibitor containing regimens, to assess the "real-life" effectiveness of these different therapies on plasma viral load (VL) and CD4+ T-cells. VL was quantified using a standard molecular assay. CD4+ and CD8+ T-cells subsets were determined by flow cytometry. The HAART group showed the highest relative proportion (RP) of increases in 5, 10, 15 and 20% of CD4+ T-cells over baseline, and the earliest fall-off of VL (0.5, 1, 1.5 and 2 log10 copies ml-1). The RP of the fall-off of 0.5, 1, 1.5 and 2 log10 VL below baseline was 3-fold higher in HAART group than in the MT and CT groups. However, no differences were found among the groups of treated children in reaching undetectable VL. CONCLUSION: A better evolution of VL and CD4+ T-cells was evident in children on HAART, indicating a positive effect on the immune system and clinical status, inhibiting HIV-1 replication and enabling the recovery of CD4+ T-cell counts.

Impact of antiretroviral protocols on dynamics of AIDS progression markers.

AIMS: To assess the "real life" effectiveness of different antiretroviral therapies (ART). METHODS: A retrospective multicentre observational study in 150 HIV-1 vertically infected children on the progression to AIDS (study A), and in 61 HIV-1 infected children on the evolution of the most relevant markers of progression (study B). All children were categorised into four groups: untreated (NT); on monotherapy (MT); on combination therapy (dual-ART); and on potent ART (HAART). RESULTS: No child in the HAART group progressed to AIDS, whereas 14 children in the NT and seven in the MT groups progressed to AIDS, respectively, the differences being statistically significant. There was a mean increase of 8 units of %CD4+ per year; this was greater in the HAART group than in the other groups. The mean decrease in viral load was 0.65 log(10) copies/ml per year; this was greater in the HAART group than in the NT and MT groups. The HAART group had the lowest probability of returning to baseline %CD4+ and viral load. CONCLUSION: Potent ART had the greatest protective effect against progression to AIDS in this observational study.