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Background: The COVID-19 outbreak has made funders, researchers and publishers agree to have research publications, as well as other research outputs, such as data, become openly available. In this extraordinary research context of the SARS CoV-2 pandemic, publishers are announcing that their coronavirus-related articles will be made immediately accessible in appropriate open repositories, like PubMed Central (PMC), agreeing upon funders’ and researchers’ instigation. Methods: This work uses Unpaywall, OpenRefine and PubMed to analyse the level of openness of the papers about COVID-19, published during the first quarter of 2020. It also analyses Open Access (OA) articles published about previous coronavirus (SARS CoV-1 and MERS CoV) as a means of comparison. Results: A total of 5,611 COVID-19-related articles were analysed from PubMed. This is a much higher amount for a period of 4 months compared to those found for SARS CoV-1 and MERS during the first year of their first outbreaks (337 and 125 articles, respectively). Regarding the levels of openness, 97.4% of the SARS CoV-2 papers are freely available; similar rates were found for the other coronaviruses. Deeper analysis showed that (i) 68.3% of articles belong to an undefined Bronze category; (ii) 72.1% of all OA papers don’t carry a specific license and in all cases where there is, half of them do not meet Open Access standards; (iii) there is a large proportion that present a copy in a repository, in most cases in PMC, where this trend is also observed. These patterns were found to be repeated in most frequent publishers: Elsevier, Springer and Wiley. Conclusions: Our results suggest that, although scientific production is much higher than during previous epidemics and is open, there is a caveat to this opening, characterized by the absence of fundamental elements and values ​​on which Open Science is based, such as licensing.

Introduction We present a case-control study of non-AIDS-defining cancers (NADCs) in a cohort of HIV-infected patients where we value the incidence, survival and prognostic factors of mortality. Methods All NADCs diagnosis conducted from 2007 to 2011 in 7 hospitals were collected prospectively, with a subsequent follow up until December 2013. A control group of 221 HIV patients without a diagnosis of cancer was randomly selected. Results Two hundred and twenty-one NADCs were diagnosed in an initial cohort of 7067 HIV-infected patients. The most common were: hepatocellular carcinoma 20.5%, lung 18.7%, head and neck 11.9% and anal 10.5%. The incidence rate of NADCs development was 7.84/1000 people-year. In addition to ageing and smoking, time on ART (OR 1.11; 95% CI 1.05–1.17) and PI use (OR 1.72; 95% CI 1.0–2.96) increased the risk of developing a NADC. During follow-up 53.42% died, with a median survival time of 199.5 days. In the analysis of the prognostic factors of mortality the low values of CD4 at tumour diagnosis (OR 0.99; 95% CI 0.99–1.0; p = 0.033), and the previous diagnosis of AIDS (OR 2.06; 95% CI 1.08–3.92) were associated with higher mortality. Conclusions Predictors of NADCs in our cohort were age, smoking, CD4 lymphocytes and time on ART. Mortality is high, with NADC risk factors being low CD4 count and previous diagnosis of AIDS.

Resumen Introduccion Presentamos un estudio caso-control de tumores no definitorios de sida (TNDS) en una cohorte de pacientes infectados por el VIH en la que valoramos las tasas de incidencia, supervivencia y factores pronosticos de mortalidad. Metodos Se recogieron de forma prospectiva en 7 hospitales, los diagnosticos de TNDS realizados de 2007 a 2011, con seguimiento posterior hasta diciembre de 2013. Se seleccionaron de forma aleatoria un grupo control de 221 pacientes VIH sin diagnostico de cancer. Resultados Se diagnosticaron 221 TNDS en una cohorte inicial de 7.067 pacientes VIH. Los mas frecuentes: hepatocarcinoma 20,5%, pulmon 18,7%, cabeza y cuello 11,9% y anal 10,5%. La tasa de incidencia de desarrollo de TNDS fue de 7,84/1.000 pacientes-ano. Ademas de la edad y el tabaco, el tiempo en TAR (OR 1,11; IC 95% 1,05-1,17) y el uso de IP (OR 1,72; IC 95% 1,0-2,96) aumentaron el riesgo de desarrollar un TNDS. Durante el seguimiento fallecieron el 53,42%, con una mediana de supervivencia de 199,5 dias. En el analisis de los factores pronosticos de mortalidad, los valores bajos de CD4 en el momento del diagnostico del tumor (OR 0,99; IC 95% 0,99-1,0; p = 0,033) y el diagnostico previo de sida (OR 2,06; IC 95% 1,08-3,92) se asociaron con una mayor mortalidad. Conclusiones Los predictores de TNDS en nuestra cohorte fueron la edad, el consumo de tabaco, los linfocitos CD4 y el mayor tiempo en TAR. La mortalidad es alta, siendo factores de riesgo los CD4 bajos en el momento del diagnostico del TNDS y el diagnostico previo de sida.

Los Institutos de Investigacion Sanitaria (IIS) son una apuesta estrategica que se configura como el entorno idoneo para desarrollar una investigacion traslacional de excelencia. En las Unidades de Apoyo a la Innovacion (UAI) de estos IIS, se trabaja principalmente en la identificacion y evaluacion del conocimiento susceptible de valorizacion generado en sus Grupos de Investigacion y en todo el entorno de los Hospitales-Organizaciones Sanitarias Integradas (OSIs). Las actividades que desarrolla el IIS Biodonostia estan alineadas con la Estrategia de Investigacion e Innovacion en Salud 2020, asi como con el ambito Biociencias-Salud dentro de la Estrategia RIS3 Euskadi. El Instituto persigue desarrollar estrategias transversales de Especializacion/Diferenciacion (Envejecimiento y Medicina Personalizada) y Orientacion al mercado y a resultados en salud (Innovacion), que movilizan los recursos del propio Instituto y de la OSI Donostialdea para el desarrollo de actividades de I+D+i, con la colaboracion de los Sistemas Empresarial, Cientifico-Tecnologico y de Formacion Profesional. Estas actividades se enfocan al paciente en particular y a la sociedad en general, aprovechando el conocimiento del Sistema aplicado a salud. La colaboracion del Instituto con este Sistema, permite que sea considerado como un agente de promocion economica que puede trasladar el valor al paciente, teniendo impacto en nuestro territorio. De esta forma, se complementan las capacidades de los Sistemas Empresarial, Cientifico-Tecnologico y de Formacion Profesional de Euskadi a favor de la salud, de la mejora del desempeno del propio Sistema Sanitario y de la generacion de riqueza con el fin de conseguir inversion para Proyectos de I+D+i. Concretamente, relacionado con la estrategia transversal de Orientacion al mercado y a resultados en salud (Innovacion), el Instituto apuesta como via de diferenciacion por la innovacion en el ambito quirurgico, con el fin de aumentar su visibilidad como centro de referencia (Biomodelos y Bio-impresion a traves de la creacion de una Unidad Mixta de Impresion 3D, Simulacion y Realidad Virtual, Aumentada y Mixta), con el que los agentes tecnologicos colaboren en el desarrollo de Proyectos de Innovacion que respondan a las necesidades de la poblacion. Los resultados obtenidos, muestran el modelo de Instituto enfocado a la Innovacion: 1- Establecimiento de un procedimiento sistematico disenado para la puesta en marcha de iniciativas innovadoras que faciliten su implementacion: 114 ideas generadas durante 2017, todas ellas en ejecucion. 2- Bottom Up (Convocatoria Intra-Mural de Proyectos de Innovacion de la OSI Donostialdea): Iniciativa que pretende fomentar el diseno y planificacion de nuevos productos/servicios en respuesta a las necesidades del Sistema. Se presentan 35-40 solicitudes/ano de las que 15-20 resultan financiadas con un presupuesto total de aproximadamente 200 mil€. 3- Actividades de Innovacion dirigidas a conseguir que los resultados de I+D+i provenientes de la colaboracion publico-privada lleguen a la sociedad: 49 Contratos de Transferencia firmados en el periodo 2013-2017, siendo los ingresos totales: 1.630.243,45€. La Estrategia disenada ha creado un contexto interno que promueve que todas las personas innoven y emprendan aprovechando el potencial del conocimiento de personas y organizaciones del entorno, gestionando ideas y proyectos para materializarlas en productos, servicios o alternativas al modelo actual.

Introduction: When integrated care is conceptualized and assessed, health research has to be included in the whole picture. Health research needs to be considered when defining health policies, when building health systems and when setting health professionals’ daily agenda. This is the only way of building a culture of research and of reassuring the impact of public financed research projects in population health outcomes. One of the structures chosen to facilitate the integration of research into health organizations are the Health Research Institutes. The aim of this kind of structure, promoted by Carlos III Health Institute, is to develop high quality basic, epidemiological and clinical research to be easily transferred to health systems, to patients and to society. Biodonostia Health Research Institute (Biodonostia HRS) was the first of its kind at the Basque Country to be recognized. Description of policy context and objective: Besides the development of the existing seven research areas at Biodonostia HRI, in 2013 a strategy for aging research was defined in order to facilitate the emergence of knew knowledge and the collaboration among already settled research groups. Every group was invited to participate and a number of already existing research lines related to aging were identified and new ones were proposed. The development of the new area was based solely on the interest of researchers of targeting aging within their area of expertise, the interest of collaborating with other groups and the decided support from the Institute. Some of the defined research lines were: biology of aging, neurodegeneration, oncogeriatry and frailty (biomarkers and management at primary care). Targeted population: The invitation to be a part of this new strategy was oriented to all the existing groups, but once those were involved, it got wider: the health system (OSI Donostialdea, OSI Bidasoa, Osakidetza general directorate, Health Department of the Basque Country Government), the social system (Diputacion de Gipuzkoa and Matia Institute), Technology Centers (Tecnalia, Cidetec, among others) and the Economy Department of the Basque Country Government. Highlights and Comments on transferability: The main highlights have taken place a different levels: at the macro level, this transversal area has been framed in the Basque Country Smart Specialization Strategy and the European International Partnership of Active and Healthy Ageing (EIP AHA) and at CIBERFES, the national network of research on frailty and aging. At a meso level, the results generated are being considered for the development of Osakidetza’s Strategic Plan, specifically the Program for the care of the elderly. And, finally, at the micro level, the activities developed have helped to involve a high number of health professionals in research related tasks. Conclusions: A Health Research Institute is able to define research strategies and policies that may act as triggers to enhance already existing activity and to make emerge new one, creating a network of collaboration and with capacity to impact health services provision and population health outcomes.

Background: A hypersensitivity reaction (HSR) is associated with abacavir (ABC), a nucleoside reverse transcriptase inhibitor. Genetic association of ABC HSR with the presence of HLA-B*5701 has been demonstrated in PREDICT-1 study, showing a prevalence of 5.6% in HIV-infected population. However the prevalence of this allele in HIV-infected patients in Spain has not been established yet. Method: This is a cross-sectional epidemiological study that included 1,198 patients in 74 centers that serve the HIV-infected population of Spain. HLA-B*5701 was checked both in the hospital lab and one central lab, showing an overall prevalence of this allele of 6%. Results: HLA-B*5701 was most prevalent in Caucasian population (6.5%). Concordance between the local and central lab was very high for positive and negative results (95.7% and 99.3%, respectively). Conclusion: These aspects define this test as a useful tool for the management of HIV-infected patients.

La disciplina de enfermedades infecciosas es reconocida como especialidad clinica en la practica totalidad de los paises de la Union Europea, asi como en los EE. UU., Canada y la mayoria de los paises hispanoamericanos. Aunque los planes de formacion en los distintos paises europeos son heterogeneos, la Seccion de Enfermedades Infecciosas de la Union Europea de Especialidades Medicas (UEMS) trabaja para su armonizacion. El European Board in Infectious Diseases, que data de 1998, recomienda una duracion total del periodo de especializacion de 6 anos, similar al de otras especialidades medicas (2 anos de formacion troncal y 4 de formacion especializada). La actividad asistencial en enfermedades infecciosas en los hospitales de los distintos paises se asemeja, en cuanto a cartera de servicios, a la que existe en los centros espanoles. En este articulo se revisan los programas formativos, la actividad asistencial y la actividad cientifica en la disciplina de enfermedades infecciosas en los distintos paises.

Introduccion La comarca del Bajo Deba comunico la incidencia mas elevada de la comunidad autonoma vasca en el Proyecto Multicentrico de Investigacion en Tuberculosis (PMIT) realizado en Espana en 1996-1997. Analizamos las caracteristicas clinicas y epidemiologicas de la poblacion tuberculosa diagnosticada en nuestra comarca en el periodo en estudio. Metodos Estudio ambispectivo observacional. Resultados Se han diagnosticado 584 pacientes; 509 casos han sido de localizacion respiratoria, y 75 casos, extrarrespiratorios. La tasa media de incidencia por ano ha sido 64,5 casos por 100.000 habitantes (91,6 en 1995-1998; 34,9 en 2003-2006). La tasa media de casos baciliferos ha sido 20,7 por 100.000 y ano (33,8 en 1995-1998; 12,9 en 2003-2006). El grupo etario mas afectado en el cuatrienio 1995-1998 fue el de 15-24 anos (tasa de incidencia media de 199,4 casos por 100.000 y por ano); en 2003-2006 lo ha sido el de mayores de 75 anos (121,1 casos por 100.000 y por ano). Se hallaban coinfectados por el VIH 53 pacientes (9%) (porcentaje medio anual del 11,6% en 1995-1998; el 7% en 2003-2006). Se ha obtenido un cultivo de Lowenstein positivo en 431 pacientes (73,8%). La resistencia a isoniacida ha sido del 1,4% de entre 287 cepas analizadas y no se ha detectado multirresistencia. Nueve pacientes eran inmigrantes (1,5%). El cumplimiento del tratamiento en el Bajo Deba en el periodo 1995-2006 ha sido satisfactorio en 505 pacientes (86,4%), mientras en la provincia de Guipuzcoa lo era en 1.956 de 2.525 pacientes diagnosticados y tratados en el mismo lapso de tiempo (77,5%) (p Conclusiones La comarca del Bajo Deba presenta una alta incidencia de tuberculosis en el periodo estudiado. La evolucion epidemiologica ha sido positiva con disminucion de la incidencia de tuberculosis, de la contagiosidad, de la coinfeccion por el virus de la inmunodeficiencia humana (VIH), y con desplazamiento de las mayores tasas de enfermedad desde los grupos jovenes a la tercera edad. La resistencia a tuberculostaticos y la inmigracion no han tenido un papel determinante en la epidemiologia. El porcentaje de casos confirmados microbiologicamente ha sido alto y el cumplimiento del tratamiento, satisfactorio.

Opportunistic infections continue to be a cause of morbidity and mortality in HIV-infected patients. They often arise because of severe immunosuppression resulting from poor adherence to antiretroviral therapy, failure of antiretroviral therapy, or unawareness of HIV infection by patients whose first clinical manifestation of AIDS is an opportunistic infection. The present article is an executive summary of the document that updates the previous recommendations on the prevention and treatment of opportunistic infections in HIV-infected patients, namely, infections by parasites, fungi, viruses, mycobacteria, and bacteria, as well as imported infections. The article also addresses immune reconstitution inflammatory syndrome. This document is intended for all professionals who work in clinical practice in the field of HIV infection. (C) 2016 Elsevier Espana, S.L.U. and Sociedad Espanola de Enfermedades Infecciosas y Microbiologia Clinica. All rights reserved.

OBJECTIVE: This consensus document is an update of antiretroviral therapy (ART) recommendations for adult patients infected with the human immunodeficiency virus (HIV). METHODS: To formulate these recommendations, a panel composed of members of the Grupo de Estudio de Sida (GESIDA; AIDS Study Group) and the Plan Nacional sobre el Sida (PNS; Spanish AIDS Plan) reviewed the advances in current understanding of the pathophysiology of HIV, the safety and efficacy findings from clinical trials, and the results from cohort and pharmacokinetic studies published in biomedical journals or presented at scientific meetings over the last years. Three levels of evidence were defined according to the source of the data: randomized studies (level A), cohort or case-control studies (level B), and expert opinion (level C). The decision to recommend, consider or not recommend ART was established in each of these situations. RESULTS: ART consisting of at least three drugs is currently the initial treatment of choice for chronic HIV infection. These regimens should include 2 NRTI + 1 NNRTI or 2 NRTI + 1 PI. Initiation of ART is recommended in patients with symptomatic HIV infection. In asymptomatic patients, initiation of ART is recommended on the basis of CD4+ lymphocyte counts per L and plasma viral load, as follows: 1) Therapy should be started in patients with CD4+ counts of 350 cells/µL. The initial objective of ART is to achieve an undetectable viral load. Adherence to therapy plays an essential role in maintaining the antiviral response. Because of the development of cross resistance, therapeutic options are limited when ART fails. Genotype studies are useful in these cases. Toxicity is a limiting factor in the use of ART, although the benefits outweigh the risks. In addition, the criteria for the use of ART are discussed in situations of acute infection, pregnancy, and post-exposure prophylaxis, and in the management of co-infection of HIV with HCV or HBV. CONCLUSIONS: CD4+ lymphocyte count is the most important reference factor for initiating ART in asymptomatic patients. The large number of available drugs, the increased sensitivity of tests to monitor viral load, and the possibility to determine viral resistance is leading to a more individualized approach to therapy.

Objetivo Efectuar una puesta al dia de las recomendaciones sobre el tratamiento antirretroviral (TAR) para los adultos infectados por el virus de la inmunodeficiencia humana (VIH). Metodos Estas recomendaciones se han consensuado por un comite del Grupo de Estudio de Sida (GESIDA) y del Plan Nacional sobre el Sida (PNS). Para ello se han revisado los avances en la fisiopatologia del VIH, los resultados de eficacia y seguridad de ensayos clinicos, estudios de cohortes y de farmacocinetica, publicados en revistas biomedicas o presentados en congresos en los ultimos anos. Se han definido tres niveles de evidencia segun la procedencia de los datos: estudios aleatorizados (nivel A), de cohortes o de caso-control (nivel B), u opinion de expertos (nivel C). En cada una de las situaciones se ha establecido recomendar, considerar o no recomendar el TAR. Resultados En el momento actual, el TAR con combinaciones de al menos tres farmacos constituye el tratamiento de inicio de eleccion de la infeccion cronica por el VIH. Estas pautas deben incluir dos inhibidores de la transcriptasa inversa analogos de nucleosidos (ITIAN) mas un no nucleosido (ITINN) o dos ITIAN mas un inhibidor de la proteasa (IP). En los pacientes con una infeccion por VIH sintomatica se recomienda iniciar TAR. En los pacientes asintomaticos el inicio de TAR se basara en la cifra de linfocitos CD4+/μl y en la carga viral plasmatica (CVP): a) en pacientes con linfocitos CD4+ 350 cel./μl se puede diferir el inicio del TAR. El objetivo del TAR inicial es lograr una CVP indetectable. La adherencia al TAR tiene un papel fundamental en la duracion de la respuesta antiviral. Las opciones terapeuticas en los fracasos del TAR son limitadas por la aparicion de resistencias cruzadas. Los estudios genotipicos en estos casos son de utilidad. La toxicidad es un factor limitante del TAR, aunque los beneficios superan los posibles perjuicios. Tambien se discuten los criterios de TAR de la infeccion aguda, embarazo y profilaxis postexposicion, y el manejo de la coinfeccion por el VIH y los virus de la hepatitis C y B (VHC y VHB). Conclusiones La cifra de linfocitos CD4+ es el factor de referencia mas importante para iniciar el TAR en pacientes asintomaticos. Por otra parte, el numero considerable de farmacos disponibles, los metodos de monitorizacion mas sensibles (CVP), y la posibilidad de determinar las resistencias hacen que las estrategias terapeuticas sean mucho mas individualizadas.

Objective To assess the clinical characteristics and the factors that influenced the prognosis of patients with HIV and infection caused by Rhodococcus equi . Design Observational, multicenter study in 29 Spanish general hospitals. Setting These hospitals comprised a total of 20,250 beds for acute patients and served a population of 9,716,880 inhabitants. Patients All patients with HIV and diagnosed R equi infection until September 1998. Results During the study period, 19,374 cases of AIDS were diagnosed. Sixty-seven patients were included (55 male patients; mean ± SD age, 31.7 ± 5.8 years). At the time of diagnosis of R equi infection, the mean CD4+ lymphocyte count was 35/μL (range, 1 to 183/μL) and the stage of HIV infection was A3 in 10.4% of patients, B3 in 31.3%, C3 in 56.7%, and unknown in 1.5%. R equi was most commonly isolated in sputum (52.2%), blood cultures (50.7%), and samples from bronchoscopy (31.3%). Chest radiographic findings were abnormal in 65 patients (97%). Infiltrates were observed in all of them, with cavitations in 45 patients. The most active antibiotics against the strains isolated were vancomycin, amikacin, rifampicin, imipenem, ciprofloxacin, and erythromycin. After a mean follow-up of 10.7 ± 12.8 months, 23 patients (34.3%) died due to causes related to R equi infection and 6 other patients showed evidence of progression of the infection. The absence of highly active antiretroviral therapy (HAART) was independently associated with mortality related to R equi infection (relative risk, 53.4; 95% confidence interval, 1.7 to 1,699). Survival of patients treated with HAART was much higher than that of patients who did not receive this therapy. Conclusions Infection by R equi is an infrequent, opportunistic complication of HIV infection and occurs during advanced stages of immunodepression. In these patients, it leads to a severe illness that usually causes a bacteremic, cavitary pneumonia, although HAART can improve the prognosis.

Objetivo Efectuar una puesta al dia de las recomendaciones sobre el tratamiento antirretroviral (TAR) para los adultos infectados por el virus de la inmunodeficiencia humana (VIH). Metodos Estas recomendaciones se han consensuado por un comite del Grupo de Estudio de Sida (GESIDA) y del Plan Nacional sobre el Sida (PNS). Para ello, se han revisado los avances en la fisiopatologia del VIH, los resultados de eficacia y seguridad de ensayos clinicos, estudios de cohortes y de farmacocinetica, publicados en revistas biomedicas o presentados en congresos en los ultimos anos. Se han definido tres niveles de evidencia segun la procedencia de los datos: estudios aleatorizados (nivel A), de cohortes o de caso-control (nivel B) u opinion de expertos (nivel C). En cada una de las situaciones se ha establecido recomendar, considerar o no recomendar el TAR. Resultados En el momento actual, el TAR con combinaciones de al menos 3 farmacos constituye el tratamiento de eleccion de la infeccion cronica por el VIH. En los pacientes con una infeccion por VIH sintomatica se recomienda iniciar el TAR. En los pacientes asintomaticos el inicio de TAR se basara en la cifra de linfocitos CD4+/μl y en la carga viral plasmatica (CVP): a) en pacientes con linfocitos CD4+ 350 cel./μl se puede diferir el inicio del TAR. El objetivo del TAR es lograr una CVP indetectable. La adherencia al TAR tiene un papel en la durabilidad de la respuesta antiviral. Las opciones terapeuticas en los fracasos del TAR son limitadas por la aparicion de resistencias cruzadas. Los estudios genotipicos en estos casos son de utilidad. La toxicidad es un factor limitante del TAR. Tambien se discuten los criterios de TAR de la infeccion aguda, embarazo y profilaxis postexposicion, y el manejo de la coinfeccion por el VIH y los virus de las hepatitis B y C (VHC y VHB). Conclusiones En la actualidad existe una actitud mas conservadora para iniciar el TAR que en recomendaciones previas. La cifra de linfocitos CD4+ es el factor de referencia mas importante para iniciar el TAR en pacientes asintomaticos. Por otra parte, el numero considerable de farmacos disponibles, los metodos de monitorizacion mas sensibles (CVP) y la posibilidad de determinar las resistencias hacen que las estrategias terapeuticas sean mucho mas individualizadas.

Eight HIV-2-infected Caucasian men living in the same geographical area in Gipuzkoa (northern Spain) have been identified in the last 5 years. HIV-2 infection in this area is uncommon, and no other cases of HIV-2 infection have been found after extensive testing for HIV-1/2 antibodies. Epidemiological data suggested a possible link among the identified subjects, with homosexual contact being the most likely way of transmission. A genetic analysis of four of the subjects, from whom specimens were available, was conducted. Phylogenetic and signature pattern studies of the reverse transcriptase (RT) and env genes supported a single source of infection. Interindividual nucleotide variability ranged from 2.4 to 4.8% in the RT region and from 5.2 to 6.1% in the env gene, whereas the mean divergence between patient and control strains was 9.8 and 18.3%, respectively. The nucleotide and amino acid signature patterns were closely related in viruses from the four examined individuals. This is the first report of a cluster of HIV-2 infections with genetic sequence data support. The singularity of this cluster should alert clinicians on the possibility of HIV-2 outside endemic areas.

Fundamentos. La neutropenia persistente es frecuente en pacientes infectados por el virus de la inmunodeficiencia humana (VIH) con inmunodepresion grave. El factor estimulante de colonias de granulocitos (G-CSF) induce la proliferacion y diferenciacion de los precursores de los granulocitos. Nuestro objetivo ha sido valorar la respuesta a la terapia con G-CSF en pacientes con infeccion avanzada por VIH y neutropenia prolongada. Metodos. Revision retrospectiva entre el 1-12-92 y el 30-1-98 de los episodios con un recuento de neutrofilos menor de 1.000 x 106/litro, durante al menos 7 dias y que en algun momento han evolucionado a cifras menores de 500 x 106/litro. Resultados. Se estudian 36 episodios. En 9 de ellos se realizo tratamiento con G-CSF con una mediana de duracion de 9 (3-76) semanas. El numero de episodios de neutropenia que precisaron ingresar por fiebre relacionada con la misma fue significativamente menor entre los que recibieron G-CSF frente a los que no lo hicieron (22,2% frente al 66,7%). CONCLUSION. En este estudio, el menor riesgo de ingreso por fiebre y neutropenia se asocia significativamente con la administracion de G-CSF en pacientes con recuentos de neutrofilos menores de 500 x 106/litro, con una buena tolerancia al tratamiento.

Most current guidelines state that antiretroviral therapy should be considered for HIV-infected patients with plasma HIV RNA5000-10000 copies/ml and CD4 cells500 x 10(6) cells/l. However, there is increasing concern about whether this is the optimal point to begin treatment or whether it is better to delay the initiation to more advanced stages.To study the immunological and virological benefits of starting antiretroviral therapy at these early stages.A total of 161 HIV-infected asymptomatic patients with CD4 cell count500 x 10(6) cells/l and viral load10000 copies/ml were randomly assigned to one of five treatment groups: no treatment, twice daily zidovudine and thrice daily zalcitabine (ZDV-ddC), twice daily zidovudine and didanosine (ZDV-ddI), twice daily stavudine and didanosine (D4T-ddI), or a twice daily three-drug regimen with stavudine and lamivudine and ritonavir. The endpoints were progression to350 x 10(6) cells/l CD4 cells, to500 x 10(6) cells/l with either two Centers for Disease Control class B symptoms or an increase of viral load0.5 log10 copies/ml above baseline, or to AIDS or death. In various substudies, the lymphoid tissue and cerebrospinal fluid viral load, development of genotypic resistance, proliferative responses to mitogens and cytomegalovirus, and HIV-1 specific antigens and other immunophenotypic markers were also analysed.Progression rates to study endpoints within 1 year were greater in the control group (31%) than in all groups receiving antiretroviral therapy pooled together (5%; estimated hazard ratio 7.41; 95% confidence interval 5.72-74.55; P0.001). The peak mean viral load decrease was greater in the three-drug group when compared with any of the three groups with a two-drug regimen (2.32, 1.65, 1.72 and 1.84, respectively; Por = 0.001). At 1 year, viral load remained below 20 copies/ml in 30 out of 33 patients in the three-drug group (91%) and in only eight out of 94 patients (9%) in two-drug groups (P = 0.001). The peak mean increase in CD4 cells was also greater in the three-drug group than in the double treatment arms (259 versus 85, 144 and 145 x 10(6) cells/l, respectively; P = 0.001). By comparison, 36% of patients in the three-drug group regimen had to change the therapy as a result of adverse events. Substudies were performed in 60 patients recruited at two sites. Tonsillar tissue HIV RNA was measured in seven patients (two in the two-drug groups and five in the three-drug group) in whom plasma HIV RNA was20 copies/ml at 1 year. It was 15151 and 133333 copies/mg tissue in the two patients from the two-drug group,40 copies/mg tissue in four patients in the three-drug group, and 485 copies/mg in one patient in the three-drug group. At 1 year there was a mean increase of 4.21+/-2.94% in CD8+CD38+ cells in the control group and a decrease of 9.48+/-3.36% in the two-drug groups (P = 0.01), and 19.87+/-3.64 in the three-drug group (P = 0.001 and P = 0.05, for comparisons with control group and two-drug groups, respectively). Although proliferative responses to cytomegalovirus antigens were significantly greater in those receiving antiretroviral therapy, response to HIV-1 p24 antigen was not detected in any patient in either treatment group.This study supports the recommendation to start antiretroviral therapy with a three-drug combination during very early stages of HIV-1 disease, at least if viral load is above a cut-off point (10000 copies/ml in our study). The risk of progression was sevenfold higher in non-treated patients at 8 months of follow-up. Some immune system parameters improved toward normal values after 1 year of antiretroviral therapy, but the proliferative response of CD4 T lymphocytes against the p24 HIV-1 antigen was not recovered. Therapeutic approaches with more potent, better-tolerated and more convenient regimens will increasingly favour early intervention with antiretroviral t

Despite the huge advance that antiretroviral therapy represents for the prognosis of infection by the human immunodeficiency virus (HIV), opportunistic infections (OIs) continue to be a cause of morbidity and mortality in HIV-infected patients. OIs often arise because of severe immunosuppression resulting from poor adherence to antiretroviral therapy, failure of antiretroviral therapy, or unawareness of HIV infection by patients whose first clinical manifestation of AIDS is an OI. The present article updates our previous guidelines on the prevention and treatment of various OIs in HIV-infected patients, namely, infections by parasites, fungi, viruses, mycobacteria, and bacteria, as well as imported infections. The article also addresses immune reconstitution inflammatory syndrome.

Background. It is unknown whether a Toxoplasma gondii-specific T cell response is restored after successful combined antiretroviral therapy (cART) in patients with AIDS and current or previous toxoplasmic encephalitis (TE). Methods. We performed a multicenter cross-sectional study with 17 healthy T. gondii-positive human immunodeficiency virus (HIV)-1-uninfected individuals and 90 patients coinfected with HIV-1 and T. gondii distributed in 5 groups according to their CD4(+) T cell counts and T. gondii infection (with or without current or previous TE). We investigated the lymphocyte proliferative response (LPR) and interferon (IFN)-gamma production in response to T. gondii soluble antigen extract (SATg) and as CD4(+) and CD8(+) T cell subsets. Results. SATg-specific LPR and IFN-gamma production were not observed in many of the most immunosuppressed patients (CD4(+) T cell count, 200 cells/mu L) who presented with TE and had already stopped secondary TE prophylaxis. Similar results were found in immunocompetent asymptomatic patients who did not receive TE prophylaxis. The predictors of SATg-specific T cell responses and IFN-gamma production were a cART-mediated increase in CD4(+) T cell count and LPR to phytohemagglutinin and viral suppression and a decrease in the activated (CD38(+)) CD8(+) T cell count, respectively. Conclusions. cART restores T. gondii-specific CD4 T cell responses in most patients with AIDS who had previous TE. Our data support the safety of withdrawing TE prophylaxis when the CD4 1 T cell count returns to levels >200 cells/mu L.

Twenty-nine intravenous drug abusers (ivda), with asymptomatic HIV infection at entry, were sequentially studied at 4- to 6-month intervals for variable follow-up periods (mean, 19.6 months). Two of them progressed to AIDS and another one fell into the IV-C2 stage of the CDC classification at the end of the study. CD8 + lymphoid subsets (CD57 + , CD38 + , and HLA-DR + ) were sequentially analyzed in peripheral blood samples along the follow-up. Both absolute number and percentage of cells within these subsets were found significantly increased over those observed in normal controls. Minor changes were appreciated throughout the follow-up CD8 + CD38 + and CD8 + DR + cells increased slightly ( P + CD57 + subset did not change significantly. In order to determine whether abnormalities in these subsets are associated with immune dysfunction, we looked for correlation between the quantification of CD8 + subpopulations and other parameters of cellular immunity. Percentage of CD8 + CD38 + or CD8 + DR + cells inversely correlates with absolute number of CD4 + cells ( P + subset also correlates with the proliferative response to mitogens in lymphoid cultures. Thus, the enumeration of these populations of CD8 + cells may provide some additional information about the immune status of HIV-infected ivda.

Late diagnosis of HIV-1 infection is quite frequent in Western countries. Very few randomized clinical trials to determine the best antiretroviral treatment in patients with advanced HIV-1 infection have been performed. To compare immune reconstitution in two groups of very immunosuppressed (less than 100 CD4(+) cells/microl), antiretroviral-naive HIV-1-infected adults, 65 patients were randomly assigned in a 1:1 ratio to receive zidovudine + lamivudine + efavirenz (group A, 34 patients) or zidovudine + lamivudine + ritonavir-boosted indinavir (group B, 31 patients). The median (interquartile range) CD4(+) cell increase after 12 and 36 months was +199 (101, 258) and +299 (170, 464) cells/microl in the efavirenz arm and +136 (57, 235) and +228 (119, 465) cells/microl in the ritonavir-boosted indinavir arm (p0.05 for all time points). The proportion (95% confidence interval) of patients achieving HIV-1 RNA levels under 50 copies/ml was significantly greater in the efavirenz arm at 3 years by the intention-to-treat analysis [59% (41%, 75%) vs. 23% (10%, 41%)], whereas no differences were found in the on-treatment analysis. Immune activation (CD8(+)CD38(+) and CD8(+)CD38DR(+) T cells) was significantly lower for the efavirenz arm from month 6 to month 24. Adverse events were more frequent in the ritonavir-boosted indinavir arm. Almost all cases of disease progression and death were observed in the first year of treatment, with no significant differences between the two arms (p = 0.79 by the log-rank test). At 1 and 3 years, the immune reconstitution induced by an efavirenz-based regimen in very immunosuppressed patients was at least as potent as that induced by a ritonavir-boosted protease inhibitor-based antiretroviral regimen.

Infectious Diseases is a recognised clinical specialty in almost all European countries, in the United States of America, Canada and most countries in Central and South America. Even though the training programs are heterogeneous in the different European countries, the Infectious Diseases section of the UEMS (European Union of Medical Specialties) is working to harmonise them. In 1998, the European Board of Infectious Diseases recommended a 6-year training period, similar to that of other medical specialties, including 2 years of general internal medicine training and 2 years of specific training. The clinical activity and services provided by Infectious Diseases units in Spanish hospitals is similar to that in other countries. In this article, training programs, clinical activity and scientific activities in Infectious Diseases in the different countries is reviewed.

Within the Multicenter Project on Tuberculosis Research performed in Spain in 1996-1997, the Bajo Deba Area reported the highest incidence of tuberculosis in the Basque Country. We analyzed the clinical and epidemiological characteristics of the tuberculosis population diagnosed in our area during the period of 1995 to 2006.Ambispective, observational study.A total of 584 patients were diagnosed with tuberculosis. The disease affected the respiratory tract in 509 cases and other sites in 75 cases. The mean annual incidence rate of tuberculosis was 64.5 cases per 100 000 inhabitants (91.6 in 1995-1998; 34.9 in 2003-2006). The mean annual incidence rate of smear-positive patients was 20.7 cases per 100 000 inhabitants (33.8 in 1995-1998; 12.9 in 2003-2006). The 15 to 24-year-old group was the most highly affected during the period of 1995 to 1998 (mean annual incidence rate 199.4 cases per 100 000); in contrast, the75-year-old group was the most highly affected during the period of 2003 to 2006 (121.1 cases per 100 000 inhabitants). Fifty-three patients were co-infected by HIV (9%) (yearly mean of 11.6% in 1995-1998 and 7% in 2003-2006). Löwenstein culture was positive in 431 cases (73.8%). Resistance to isoniazid was detected in 1.4% out of a total of 287 strains tested, and multidrug resistance was not observed. Nine patients were immigrants (1.5%). Treatment completion was greater in our area (505 patients, 86.4%), as compared to that recorded in the Guipuzcoa province during the same period (1956 of 2525 patients, 77.5%) (P.01).The Bajo Deba Area presented a high incidence of tuberculosis in the 1995 to 2006 period. Epidemiological trends showed a progressive decrease in the number of tuberculosis patients, with a shift from younger to older persons as the most highly affected age group. The impact of drug resistance and immigration was negligible on tuberculosis rates. The percentage of microbiologically confirmed cases was high. Treatment completion was satisfactory.

To evaluate the effectiveness and tolerability of a simplification regimen with tenofovir DF (TDF), lamivudine (3TC), and efavirenz (EFV) in HAART-experienced HIV-1-infected subjects with sustained viral suppression.Patients with HIV-1 RNA200 copies/mL during the previous 6 months and who switched their current twice-daily or three-times-daily HAART to a simplified once-daily regimen of TDF (300 mg), 3TC (300 mg), and EFV (600 mg) were included.154 patients (70% males, mean age 42 years) were included. Previous HAART included a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen in 55% of the patients and a thymidine analog in 87%. The percentage of patients with viral load200 copies/mL in the intent-to-treat (ITT) data set was 83% at 6 months and 75% at 12 months (98% and 96%, respectively, in the on-treatment [OT] analysis). Five patients (3%) were identified as virologic failures according to the study protocol. The mean CD4 T-cell count increased significantly 12 months after simplification (from 570 to 632 cells/mm3; p.01). At 12 months, mean triglyceride levels decreased from 233 to 170 mg/dL (p.01) and mean cholesterol levels decreased from 205 to 189 mg/dL (p.01). Thirty-three patients (21%) discontinued the study treatment prior to completing the 12-month follow-up.Simplification to a once-daily regimen containing TDF, 3TC, and EFV is virologically and immunologically effective, well-tolerated, and safe with benefits in the lipid profile in the majority of patients.

We present two cases of P. falciparum malaria in visitors to tourist resorts on the East Coast of the Dominican Republic, traditionally believed to be an area without risk of malaria. In both patients the malaria was severe (with 20% parasitization in one) and there was a long interval between the onset of symptoms and diagnosis. These cases are possibly related (along with a further 17 reports by the Centers for Disease Control and Prevention) to an increase in the population of Anopheles sp as a consequence of increased rainfall and floods provoked by a hurricane in September 2004, as well as to the presence of a semi-immune population (Haitian immigrants working in the construction and tourist sectors). Both physicians and patients should be aware of this outbreak so that adequate precautions can be taken and early diagnoses can be made.

This consensus document is an update of antiretroviral therapy (ART) recommendations for adult patients infected with the human immunodeficiency virus (HIV).To formulate these recommendations, a panel composed of members of the Grupo de Estudio de Sida (GESIDA; AIDS Study Group) and the Plan Nacional sobre el Sida (PNS; Spanish AIDS Plan) reviewed the advances in current understanding of the pathophysiology of HIV, the safety and efficacy findings from clinical trials, and the results from cohort and pharmacokinetic studies published in biomedical journals or presented at scientific meetings over the last years. Three levels of evidence were defined according to the source of the data: randomized studies (level A), cohort or case-control studies (level B), and expert opinion (level C). The decision to recommend, consider or not recommend ART was established in each of these situations.ART consisting of at least three drugs is currently the initial treatment of choice for chronic HIV infection. These regimens should include 2 NRTI + 1 NNRTI or 2 NRTI + 1 PI. Initiation of ART is recommended in patients with symptomatic HIV infection. In asymptomatic patients, initiation of ART is recommended on the basis of CD4+ lymphocyte counts per L and plasma viral load, as follows: 1) Therapy should be started in patients with CD4+ counts of200 cells/microL; 2) Therapy should be started in most patients with CD4+ counts of 200-350 cells/microL, although it can be delayed when CD4+ count persists at around 350 cells/microL and viral load is low; and 3) Initiation of therapy can be delayed in patients with CD4+ counts of350 cells/microL. The initial objective of ART is to achieve an undetectable viral load. Adherence to therapy plays an essential role in maintaining the antiviral response. Because of the development of cross resistance, therapeutic options are limited when ART fails. Genotype studies are useful in these cases. Toxicity is a limiting factor in the use of ART, although the benefits outweigh the risks. In addition, the criteria for the use of ART are discussed in situations of acute infection, pregnancy, and post-exposure prophylaxis, and in the management of co-infection of HIV with HCV or HBV.CD4+ lymphocyte count is the most important reference factor for initiating ART in asymptomatic patients. The large number of available drugs, the increased sensitivity of tests to monitor viral load, and the possibility to determine viral resistance is leading to a more individualized approach to therapy.

To describe the epidemiological characteristics of new cases of HIV infection diagnosed from 1997-2001 and compare them with AIDS cases (1991-2001).Data were retrospectively collected on new cases of HIV infection detected in the Basque Country (1997-2001) and were compared with AIDS cases (1991-2001).A total of 912 new cases of HIV infection were diagnosed. In 299 of the new cases (32.8%), HIV and AIDS were diagnosed simultaneously. The most common mechanism of transmission was heterosexual transmission, followed by intravenous and homo/bisexual transmission. Significant epidemiological differences (p0.001) were found with regard to AIDS cases.Sexual transmission has replaced intravenous drug use as the most common mechanism of HIV transmission. A large percentage of patients were simultaneously diagnosed with HIV and AIDS, indicating the need for new prevention strategies.

To provide an update of guidelines from the Spanish AIDS Study Group (GESIDA) and the National AIDS Plan (PNS) committee on the prevention of opportunistic infections in adult and adolescent HIV-infected patients.These consensus recommendations have been produced by a group of experts from GESIDA and/or the PNS after reviewing the earlier document and the scientific advances in this field in the last years. The system used by the Infectious Diseases Society of America and the United States Public Health Service has been used to classify the strength and quality of the data.This document provides a detailed review of the measures for the prevention of infections caused by viruses, bacteria, fungi and parasites in the context of HIV infection. Recommendations are given for preventing exposure and for primary and secondary prophylaxis for each group of pathogens. In addition, criteria are established for the withdrawal of prophylaxis in patients who respond well to highly active antiretroviral therapy (HAART).HAART is the best strategy for the prevention of opportunistic infections in HIV-positive patients. Nevertheless, prophylaxis is still necessary in countries with limited economic resources, in highly immunodepressed patients until HAART achieves beneficial effects, in patients who refuse to take or who cannot take HAART, in those in whom HAART is not effective, and in the small group of infected patients with inadequate recovery of CD4+ T lymphocyte counts despite good inhibition of HIV replication.

ResumenObjetivoDescribir las características epidemiológicas de los nuevos diagnósticos de infección por el VIH en el período 1997- 2001 y comparlas con los casos de sida (1991-2001).MétodosSe han recogido retrospectivamente los datos de las nuevas infecciones por el VIH ocurridas en el País Vasco (1997-2001) y se han comparado con los casos de sida (1991- 2001).ResultadosSe han diagnosticado 912 nuevas infecciones por el VIH. El diagnóstico de VIH coincidió con el de sida en 299 (32,8%) de las nuevas infecciones. Las relaciones heterosexuales han sido el mecanismo de transmisión más frecuente, seguido de la transmisión por vía parenteral y las relaciones homosexuales y bisexuales, con diferencias significativas (p < 0,001) respecto a los casos de sida.ConclusionesLa transmisión sexual ha reemplazado al consumo de drogas por vía parenteral como mecanismo más frecuente de transmisión del VIH. Hay un alto porcentaje de pacientes con diagnóstico simultáneo de VIH y sida. Estos datos indican la necesidad de realizar nuevas estrategias de prevención.SummaryObjectiveTo describe the epidemiological characteristics of new cases of HIV infection diagnosed from 1997-2001 and compare them with AIDS cases (1991-2001).MethodsData were retrospectively collected on new cases of HIV infection detected in the Basque Country (1997-2001) and were compared with AIDS cases (1991-2001).ResultsA total of 912 new cases of HIV infection were diagnosed. In 299 of the new cases (32.8%), HIV and AIDS were diagnosed simultaneously. The most common mechanism of transmission was heterosexual transmission, followed by intravenous and homo/bisexual transmission. Significant epidemiological differences (p < 0.001) were found with regard to AIDS cases.ConclusionsSexual transmission has replaced intravenous drug use as the most common mechanism of HIV transmission. A large percentage of patients were simultaneously diagnosed with HIV and AIDS, indicating the need for new prevention strategies.

We analyzed survival rates, neurologic function, and prognostic factors for 118 consecutive patients with acquired immunodeficiency syndrome-associated progressive multifocal leukoencephalopathy (PML) treated with highly active antiretroviral therapy (HAART) in 11 hospitals throughout Spain. Seventy-five patients (63.6%) remained alive for a median of 114 weeks (2.2 years) after diagnosis of PML. Neurologic function of the survivors was categorized as cure or improvement in 33, stabilization or worsening in 40, and unknown in 2. The baseline CD4+ cell count was the only variable found with prognostic significance. The odds ratio of death was 2.71 (95% confidence interval, 1.19-6.15) for patients with CD4+ cell counts of100 cells/microL, compared with patients who had CD4+ cell counts ofor =100 cells/microL. One-third of patients with PML died despite receipt of HAART; neurologic function improved in approximately one-half of the survivors. A CD4+ cell count of100 cells/microL was associated with higher mortality.

To provide an update of recommendation on antiretroviral treatment (ART) in HIV-infected adults.Methods. These recommendations have been agreed by consensus by a committee of the spanish AIDS Study Group (GESIDA) and the National AIDS Plan. To do so, advances in the physiopathology of AIDS and the results on efficacy and safety in clinical trials, cohort and pharmacokinetics studies published in biomedical journals or presented at congresses in the last few years have been reviewed. Three levels of evidence have been defined according to the data source: randomized studies (level A), case-control or cohort studies (level B) and expert opinion (level C). Whether to recommend, consider, or not to recommend ART has been established for each situation.Currently, ART with combinations of at least three drugs constitutes the treatment of choice in chronic HIV infection. In patients with symptomatic HIV infection, initiation of ART is recommended. In asymptomatic patients initiation of ART should be based on the CD41/mL lymphocyte count and on the plasma viral load (PVL): a) in patients with CD41 lymphocytes200 cells/mL, initiation of ART is recommended; b) in patients with CD41 lymphocytes between 200 and 300 cells/mL, initiation of ART should, in most cases, be recommended; however, it could be delayed when the CD41 lymphocyte count remains close to 350 cells/mL and the PVL is low, and c) in patients with CD41 lymphocytes350 cells/mL, initiation of ART can be delayed. The aim of ART is to achieve an undetectable PVL. Adherence to ART plays a role in the durability of the antiviral response. Because of the development of cross-resistance, the therapeutic options in treatment failure are limited. In these cases, genotypic analysis is useful. Toxicity limits ART. The criteria for ART in acute infection, pregnancy and postexposure prophylaxis and in the management of coinfection with HIV and hepatitis C and B virus are controversial.The current approach to initiating ART is more conservative than in previous recommendations. In asymptomatic patients, the CD41 lymphocyte count is the most important reference factor for initiating ART. Because of the considerable number of drugs available, more sensitive monitoring methods (PVL) and the possibility of determining resistance, therapeutic strategies have become much more individualized.

Objectives: To evaluate the safety and effectiveness of once-daily didanosine and nevirapine plus twice-daily stavudine versus twice-daily administration of all three drugs. Methods: This open-label, randomized, multicentre study enrolled 94 antiretroviral-naive patients with chronic HIV infection, CD4+ cell counts > 500 × 10 6 cells/l, and viral loads > 5000 copies/ml. Patients were treated with either 40 mg stavudine (twice daily) plus 400 mg didanosine (once daily) and 400 mg nevirapine (once daily) or 40 mg stavudine (twice daily) plus 200 mg didanosine (twice daily) and 200 mg nevirapine (twice daily). Results: After 12 months, 68% of patients who received twice-daily didanosine and nevirapine had viral loads < 200 copies/ml in the intention-to-treat and 79% in the on-treatment analysis, respectively. The corresponding values for patients treated with didanosine and nevirapine, taken once-daily, were 73 and 85%. The percentages of patients in each group with viral loads < 5 copies/ml at 12 months were 40% (once daily ) and 45% (twice daily) for the intention-to-treat analysis. Five of 11 patients (45%) with plasma viral loads < 5 copies/ml at 12 months had detectable virus in tonsillar tissue. Genotypic resistance to nevirapine was noted in seven of the 14 patients with detectable viral load at month 12. Mean changes in CD4+ cell counts for patients treated with stavudine plus once- or twice-daily didanosine and nevirapine were 154 and 132 × 10 6 cells/I, respectively. Treatment was interrupted due to adverse events in seven patients (8%) (four who received once-daily didanosine and nevirapine and three treated with twice-daily doses). Conclusions: The combination of twice-daily stavudine plus once-daily didanosine and nevirapine was as safe and well tolerated as twice-daily administration of all three agents. Both regimens were equally effective in reducing viral loads and in increasing CD4+ cell counts.

Se presentan 2 casos de paludismo por Plasmodium falciparum en viajeros a centros turisticos de la costa este de Republica Dominicana, considerados clasicamente como libres de riesgo de paludismo. En ambos casos, se trato de pacientes con paludismo grave (con una parasitacion del 20% en uno de ellos), con un tiempo largo entre el inicio de la sintomatologia y el diagnostico. Es posible que estos casos (junto con otros 17 comunicados por los Center for Disease Control and Prevention [CDC]) esten relacionados con un aumento en la poblacion de Anopheles sp. como consecuencia del aumento de lluvias e inundaciones provocados por el paso de un huracan en septiembre de 2004, junto con la existencia de poblacion semiinmune (inmigrantes haitianos trabajando en la construccion y el sector turistico). Es muy importante que tanto los medicos como los pacientes sean conscientes de este brote para facilitar la toma adecuada de precauciones y un diagnostico precoz.

Although mucocutaneous candidiasis is a common occurrence in HIV-infected patients, candidal meningitis is uncommon. We report 3 cases of candidal meningitis in HIV-positive patients, all intravenous drug abusers, and we discuss the clinical course and outcome, the treatment with fluconazole and possible prophylaxis.