Sarcoma de Kaposi en personas que viven con VIH-SIDA en un hospital público de referencia en Perú / Kaposi's sarcoma in people living with HIV/aids in a public referral hospital in Peru

RESUMEN El sarcoma de Kaposi (SK) es el cáncer más frecuente en las personas que viven con VIH. Las investigaciones sobre esta condición son escasas en la región, por lo que, el objetivo de este artículo fue describir las características demográficas, clínicas y terapéuticas de los pacientes con VIH que desarrollaron SK en el Hospital Cayetano Heredia entre el 2000 y 2018. Se identificaron 129 casos de SK, con una mediana de edad de 33 años, con predominio en varones con el 92% (119/129), y en su mayoría hombres que tienen sexo con hombres (HSH). La mediana de tiempo desde el diagnóstico de VIH hasta el del SK fue de cinco meses, asociado con un recuento de linfocitos CD4 de 64 células/µL (RIC: 33-185) al momento del diagnóstico de SK. El compromiso cutáneo fue el más común; sin embargo, al menos la mitad de ellos también tuvo la forma visceral.

ABSTRACT Kaposi's sarcoma (KS) is the most frequent cancer in people living with HIV. Research on this condition is scarce in the region, therefore, this article aimed to describe the demographic, clinical and therapeutic characteristics of patients with HIV who developed KS at the Cayetano Heredia Hospital between 2000 and 2018. A total of 129 KS cases were identified, with a median age of 33 years, predominantly males with 92% (119/129), and mostly men who have sex with men (MSM). The median time from HIV diagnosis to KS diagnosis was five months, associated with a CD4 lymphocyte count of 64 cells/μL (IQR: 33-185) at KS diagnosis. Cutaneous involvement was the most common presentation; however, at least half also had the visceral form.

Presentación del síndrome de Wernicke-Korsakoff secundario a encefalitis por citomegalovirus, a propósito de un caso / Wernicke-Korsakoff syndrome secondary to cytomegalovirus encephalitis: A case report

Resumen El citomegalovirus (CMV) es uno de los microorganismos oportunistas con mayor prevalencia en pacientes inmunocomprometidos, aunque su reactivación ha descendido después de la introducción de la terapia antirretroviral altamente activa (Highly Active Antiretroviral Therapy, HAART). En las coinfecciones, la encefalitis se ha reportado como una de las condiciones más frecuentes. Se presenta el caso de un paciente adulto joven con infección por virus de la inmunodeficiencia humana (HIV) que tuvo un rápido deterioro neurológico evidenciado en síntomas y signos clínicos clásicos del síndrome de Wernicke-Korsakoff y que no presentaba factores de riesgo para deficiencia de tiamina. En las imágenes de la resonancia magnética cerebral, se detectaron hallazgos típicos del síndrome, y se identificó citomegalovirus (CMV) en el líquido cefalorraquídeo. Con el tratamiento específico para el CMV, se logró el control de los síntomas, aunque hubo secuelas neurológicas que mejoraron. Este es uno de los pocos casos reportados a nivel mundial de síndrome de Wernicke secundario a encefalitis por citomegalovirus.

Abstract Cytomegalovirus (CMV) is one of the opportunistic microorganisms with the highest prevalence in immunocompromised patients. Reactivation has decreased after the introduction of highly active antiretroviral therapy (HAART). Encephalitis has been reported in the coinfection as one of the most frequent presentations. We present the case of a young adult patient with HIV infection and rapid neurological deterioration due to classic clinical symptoms and signs of the Wernicke-Korsakoff syndrome, with no risk factors for thiamine deficiency, with images by nuclear magnetic resonance typical of the syndrome, and identification of cytomegalovirus in cerebrospinal fluid. The specific treatment for CMV managed to control the symptoms with neurological sequelae in progression towards improvement. This is one of the few cases reported in the literature of Wernicke syndrome secondary to cytomegalovirus encephalitis.

Merkel cell carcinoma in an immunosuppressed patient

Abstract Merkel cell carcinoma is an uncommon neuroendocrine carcinoma with a rising incidence and an aggressive behavior. It predominantly occurs in older patients, with onset occurring at a mean age of 75-80 years. Recognized risk factors are ultraviolet sunlight exposure, immunosuppression, and, more recently, Merkel cell polyomavirus. We report a case of Merkel cell carcinoma in a young HIV positive patient with Merkel Cell polyomavirus detected in the tumor.

Angiosarcoma in HIV-negative patients is not associated with HHV-8

Abstract: BACKGROUND: Angiosarcoma is an aggressive, malignant neoplasm of vascular or lymphatic origin. Herpes virus 8 (HHV-8) is a member of the herpes family with a tropism for endothelial cells and it has been proven to induce vascular neoplasms, such as Kaposi's sarcoma. The role of HHV-8 in the pathogenesis of angiosarcoma has not been well defined. OBJECTIVE: To investigate the relationship between the presence of HHV-8 and angiosarcoma. METHODS: In this study, the team investigated the relationship between the presence of HHV-8, as determined by polymerase chain reaction, and angiosarcoma, using samples from patients with epidemic Kaposi's sarcoma as controls. RESULTS: While all control cases with epidemic Kaposi's sarcoma were positive for HHV-8, none of the angiosarcoma cases was. CONCLUSION: These findings support most previous studies that found no association between HHV-8 and angiosarcoma.

Lesiones orales asociadas con la enfermedad del virus de inmunodeficiencia humana en pacientes adultos, una perspectiva clínica / Oral lesions associated with human immunodeficiency virus disease in adult patients, a clinical perspective

Among the clinical manifestations which may occur in HIV/AIDS patients, oral lesions are relevant because there are easily accessible and usually the diagnosis is made through clinical features. Some oral manifestations are strongly related with HIV/AIDS patients indicating infection and progression to AIDS and also allow monitoring the success or failure of using antiretroviral therapy. The massive introduction of antiretroviral therapy has changed the morbidity and mortality, frequency, type of clinical manifestation and the timing of the classic opportunistic complications. The aim of this review is to provide an updated of the classical clinical features of the most frequent and relevant HIV/AIDS oral manifestations, considering the fundamental clinical features for their diagnosis.

Dentro de las manifestaciones que pueden aparecer en los pacientes con infección por VIH/SIDA, las lesiones de la cavidad oral tienen gran relevancia debido a que son fácilmente accesibles y por lo general su diagnóstico se efectúa a través de signos clínicos. Además, algunas manifestaciones orales están fuertemente relacionadas con el síndrome por lo que indican sospecha de infección y progresión a etapa SIDA y permiten monitorizar el éxito o fracaso de la terapia anti-retroviral empleada. La introducción masiva de la terapia anti-retroviral ha modificado la morbi-mortalidad, la frecuencia, el tipo de manifestación clínica y el momento de aparición de las clásicas complicaciones oportunistas. El objetivo de esta revisión es entregar las características clínicas clásicas actualizadas de aquellas manifestaciones orales asociadas a la infección por VIH/SIDA que son más frecuentes y que tienen mayor relevancia clínica, considerando las características fundamentales para su diagnóstico.

JC virus/human immunodeficiency virus 1 co-infection in the Brazilian Amazonian region

Abstract JC virus (JCV) is a member of the Polyomaviridae family and is associated to a severe disease known as progressive multifocal leukoencephalopathy, PML, which is gradually increasing in incidence as an opportunistic infection among AIDS patients. The present study aimed to investigate the occurrence of JCV among HIV-1 carriers including their types and molecular subtypes and the possible association with disease. Urine samples from 66 HIV-1 infected subjects were investigated for the presence of the virus by amplifying VP1 (215 bp) and IG (610 bp) regions using the polymerase chain reaction. JCV was detected in 32% of the samples. The results confirmed the occurrence of type B (subtype Af2); in addition, another polyomavirus, BKV, was also detected in 1.5% of samples of the HIV-1 infected subjects. Apparently, there was no significant difference between mono- (HIV-1 only) and co-infected (HIV-1/JCV) subjects regarding their TCD4+/TCD8+ lymphocyte counts or HIV-1 plasma viral load. Self admitted seizures, hearing and visual loses were not significantly different between the two groups.

Human herpesvirus 8 (HHV-8) detected by nested polymerase chain reaction (PCR) in HIV patients with or without Kaposi's sarcoma. An analytic cross-sectional study / Herpesvírus humano 8 (HHV-8) detectado por reação da polimerase em cadeia do tipo nested PCR em pacientes HIV-positivos com ou sem sarcoma de Kaposi. Um estudo transversal analítico

CONTEXT AND OBJECTIVE: Kaposi's sarcoma (KS) is a common neoplastic disease in AIDS patients. The aim of this study was to evaluate the frequency of human herpesvirus 8 (HHV-8) infection in human immunodeficiency virus (HIV)-infected patients, with or without KS manifestations and correlate HHV-8 detection with KS staging. DESIGN AND SETTING: Analytic cross-sectional study conducted in a public tertiary-level university hospital in Ribeirão Preto, São Paulo, Brazil. METHODS: Antibodies against HHV-8 lytic-phase antigens were detected by means of the immunofluorescence assay. HHV-8 DNA was detected in the patient samples through a nested polymerase chain reaction (nested PCR) that amplified a region of open reading frame (ORF)-26 of HHV-8. RESULTS: Anti-HHV-8 antibodies were detected in 30% of non-KS patients and 100% of patients with KS. Furthermore, the HHV-8 DNA detection rates observed in HIV-positive patients with KS were 42.8% in serum, 95.4% in blood samples and 100% in skin biopsies; and in patients without KS, the detection rate was 4% in serum. Out of the 16 serum samples from patients with KS-AIDS who were classified as stage II, two were positive (12.5%); and out of the 33 samples from patients in stage IV, 19 (57.6%) were positive. CONCLUSION: We observed an association between HHV-8 detection and disease staging, which was higher in the serum of patients in stage IV. This suggests that detection of HHV-8 DNA in serum could be very useful for clinical assessment of patients with KS and for monitoring disease progression.

CONTEXTO E OBJETIVO: Sarcoma de Kaposi (SK) é uma doença neoplásica comum em pacientes com aids. O objetivo deste estudo foi avaliar a frequência da infecção por herpesvírus humano 8 (HHV-8) em pacientes infectados por HIV, com ou sem SK e associar a detecção do HHV-8 com o estadiamento do SK. TIPO DE ESTUDO E LOCAL: Estudo transversal analítico realizado em hospital universitário público terciário de Ribeirão Preto, São Paulo, Brasil. MÉTODOS: Anticorpos contra antígenos de fase lítica do HHV-8 foram detectados por imunofluorescência. O DNA viral de HHV-8 foi detectado em amostras de pacientes pela reação em cadeia da polimerase do tipo nested (nested PCR), que amplificou uma região do fragmento de leitura aberta (ORF)-26 do HHV-8. RESULTADOS: Anticorpos anti-HHV-8 foram detectados em 30% dos pacientes sem SK e 100% dos com SK. Além disso, a detecção de HHV-8 DNA observada em pacientes HIV-positivos com SK foi de 42,8% no soro, 95,4% em amostras de sangue e 100% em biópsias de pele, e em pacientes sem SK foi de 4% no soro. Das 16 amostras de soro de pacientes com SK-AIDS classificados como estádio II, duas foram positivas (12,5%) e, das 33 amostras de pacientes no estádio IV, 19 (57,6%) foram positivas. CONCLUSÃO: Observamos associação entre a detecção do HHV-8 e o estadiamento da doença, que foi maior no soro de pacientes no estágio IV. Isso sugere que a detecção do HHV-8 no soro poderia ser muito útil para a avaliação clínica de pacientes com SK e para o monitoramento da progressão da doença.

Antigenemia y reacción de polimerasa en cadena en tiempo real en el diagnóstico de enfermedad por citomegalovirus en adultos con virus de inmunodeficiencia adquirida / Antigenemia and real time polymerase chain reaction for diagnosis of cytomegal ovirus disease in HIV infected adults

Background: Cytomegalovirus (CMV) infection is frequent in HIV adults. It is unknown usefulness of quantitative methods for diagnosing the CMV disease in Chilean patients. Aim: To determine the performance of antigenemia and real time polymerase chain reaction (rtPCR) in the diagnosis of CMV disease in Chilean HIV adults. Method: Detection of CMV by viral isolation (AVR), antigenemia and quantitative rtPCR in HIV adults. Results: The 102 adults with suspected CMV disease had lower LTCD4 count and higher HIV viral load than 77 patients without suspicion (p < 0.05). Antigenemia and PCR were positive in 47 (46.1%) and 37 (36.3%) adults with clinical suspicion and in 2 (2.6%) and 4 (5.2%) of 77 without suspicion. The sensitivity, specificity, positive and negative predictive value of antigenemia and RPCtr were 92%, 80%, 72% and 95% and 72%, 95%, 92% and 80%, respectively. The cutoff values were ≥ lcell (+) and ≥ 5.5 log10 copies/2 x 10(6) cells. CMV was isolated in 6/179 patients (3.4%), all symptomatic. Conclusión: Positivity of antigenemia and rtPCR are similar for diagnosing CMV disease in Chilean HIV adults. AVR is inappropriate as a gold standard for its low performance.

Introducción: La infección por citomegalovirus (CMV) es frecuente en adultos con virus de inmunodeficiencia humana (VIH). No se ha establecido la utilidad de los métodos cuantitativos para diagnosticar enfermedad por CMV en pacientes chilenos. Objetivo: Determinar la positividad de antigenemia y reacción de polimerasa en cadena en tiempo real (RPC-TR) en el diagnóstico de enfermedad por CMV en adultos chilenos con infección por VIH. Metodología: Se detectó CMV mediante aislamiento viral rápido (AVR), antigenemia y reacción de polimerasa en cadena en tiempo real (RPC-TR) cuantitativa en adultos infectados por VIH, con y sin sospecha de enfermedad por CMV. Resultados: El recuento de LT CD4 fue menor y mayor la carga de VIH en 102 sintomáticos respecto a 77 asintomáticos (p < 0,05). La antigenemia y la RPC-TR fueron positivas en 46 y 36% de los enfermos y en 3 y 5% de los asintomáticos respectivamente. La sensibilidad, especificidad, valor predictor positivo y negativo de la antigenemia y la RPC-TR fueron 92%, 80%, 72% y 95% y 72%, 95%, 92% y 80%, respectivamente. Los valores de corte fueron ≥ 1 núcleo (+) y ≥ 5,5 log10 copias/2 x 10(6) céls. Se aisló CMV en 3,4%, todos los sintomáticos. Conclusión: La antigenemia y la RPC-TR tienen una positividad similar para diagnosticar enfermedad por CMV en adultos chilenos con infección por VIH. El AVR es inapropiado como referencia por su baja positividad.

MENINGOENCEPHALITIS DUE TO VARICELLA ZOSTER VIRUS IN AIDS PATIENTS. REPORT OF ELEVEN CASES AND REVIEW OF THE LITERATURE / Meningoencefalite pelo vírus varicela-zoster em pacientes com AIDS. Relato de onze casos e revisão da literatura

Neurological complications of varicella-zoster virus (VZV) are infrequent and include various clinical pictures. The reactivation of VZV in patients with AIDS is generally associated with an acute and severe meningoencephalitis. We report the epidemiological, clinical and virological data from 11 consecutive patients with diagnosis of HIV/AIDS and central nervous system (CNS) involvement due to VZV. All patients were male and seropositive for HIV. The primary risk factor for HIV infection was unprotected sexual contact. The median of CD4 T cell count was 142 cells/µL. All of them presented signs and symptoms of meningoencephalitis. Six patients (54.5%) presented pleocytosis; they all showed high CSF protein concentrations with a median of 2.1 g/dL. Polymerase chain reaction of cerebrospinal fluid specimen was positive for VZV in all of them and they were treated with intravenous acyclovir at doses of 30/mg/kg/day for 21 days. Overall survival was 63% (7 of 11 patients). The four dead patients had low cellular counts in CSF, below the median of this parameter. VZV should be included among the opportunistic pathogens that can involve CNS with a diffuse and severe meningoencephalitis in patients with advanced HIV/AIDS disease.

As complicações neurológicas do vírus varicela-zoster (VVZ) são pouco frequentes e incluem vários quadros clínicos. A reativação do VVZ em pacientes com AIDS é geralmente associada com meningoencefalite aguda e grave. Nós relatamos os dados epidemiológicos, clínicos e virológicos de onze pacientes consecutivos com diagnóstico de HIV/AIDS e comprometimento do sistema nervoso central (SNC) devido ao VVZ. Todos os pacientes eram do sexo masculino e soropositivos para HIV. O principal fator de risco para a infecção pelo HIV foi o contato sexual sem proteção. A mediana da contagem de células CD4 T foi de 142 cel/µL. Todos apresentavam sinais e sintomas devido à meningoencefalite. Seis pacientes (54,5%) apresentaram pleiocitose; todos apresentaram hiperproteinorraquia com mediana de 2,1 g/dL. A reação em cadeia da polimerase de amostra do líquido cefalorraquidiano foi positiva para VVZ em todos eles. Todos os pacientes foram tratados com aciclovir por via intravenosa em doses de 30 mg/kg/dia durante 21 dias. A sobrevida global foi de 63% (sete de 11 pacientes). Os quatro pacientes mortos tiveram uma escassa resposta celular no LCR abaixo da mediana para este parâmetro. O VVZ deve ser incluído entre os patógenos oportunistas que podem comprometer o SNC com meningoencefalite difusa e grave em pacientes com doença avançada por HIV/SIDA.

Late emergence of A594V and L595W mutations related to ganciclovir resistance in a patient with HCMV retinitis and long-term HIV progression

The emergence of ganciclovir (GCV) resistance during the treatment of human cytomegalovirus (HCMV) infection is a serious clinical challenge, and is associated with high morbidity and mortality. In this case report, we describe the emergence of two consecutive mutations (A594V and L595W) related to GCV resistance in a patient with HCMV retinitis and long-term HIV progression after approximately 240 days of GCV use. Following the diagnosis of retinitis, the introduction of GCV did not result in viral load reduction. The detected mutations appeared late in the treatment, and we propose that other factors (high initial HCMV load, previous GCV exposure, low CD4+ cell count), in addition to the presence of resistance mutations, may have contributed to the treatment failure of HCMV infection in this patient.

Lack of associaiion between herpesvirus detectin in saliva and gingivitis in hhiv‑infected children / Ausência de associação entre a detecção de herpesvírus na saliva e gengivite em crianças infectadas pelo HIV

The aims of this study were to compare the detection of human herpesviruses (HHVs) in the saliva of HIV-infected and healthy control children, and to evaluate associations between viral infection and gingivitis and immunodeficiency. Saliva samples were collected from 48 HIV-infected and 48 healthy control children. Clinical and laboratory data were collected during dental visits and from medical records. A trained dentist determined gingival indices and extension of gingivitis. Saliva samples were tested for herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella zoster virus (VZV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) by nested polymerase chain reaction assays. Thirty-five HIV-infected and 16 control children had gingivitis. Seventeen (35.4%) HIV-infected children and 13 (27%) control children were positive for HHVs. CMV was the most commonly detected HHV in both groups (HIV-infected, 25%; control, 12.5%), followed by HSV-1 (6.2% in both groups) and HSV-2 (HIV-infected, 4.2%; control, 8.3%). The presence of HHVs in saliva was not associated with the presence of gingivitis in HIV-1-infected children (p = 0.104) or healthy control children (p = 0.251), or with immunosuppression in HIV-infected individuals (p = 0.447). Gingivitis was correlated with HIV infection (p = 0.0001). These results suggest that asymptomatic salivary detection of HHVs is common in HIV-infected and healthy children, and that it is not associated with gingivitis.

Os objetivos deste estudo foram detectar a presença de herpesvírus humanos (HHVs) na saliva de crianças infectadas pelo HIV, em comparação com controles saudáveis e avaliar a associação entre infecção viral, gengivite e imunodeficiência. Para este fim, foram colhidas amostras de saliva de 48 crianças HIV-positivas e 48 controles saudáveis. O índice gengival e extensão de gengivite foram determinados por um dentista treinado. Informações clínicas e laboratoriais foram obtidas durante a consulta odontológica e dos registros médicos. As amostras de saliva foram testadas para detecção de vírus herpes simplex tipos 1 e 2 (HSV-1 e HSV-2), vírus da varicela-zoster (VVZ), vírus Epistein-Barr (EBV) e citomegalovírus (CMV) através de nested-PCR. Trinta e cinco crianças HIV-positivas e 16 crianças do grupo controle apresentavam gengivite. Dezessete (35,4%) crianças HIV-positivas e 13 (27%) crianças controle testaram positivo para a presença de HHVs. CMV foi o vírus mais comum detectado em ambos os grupos (25% HIV-positivas e 12,5% de controle), seguido por HSV-1 (6,2% de ambos os grupos) e HSV-2 (4,2% HIV-positivas e 8,3% de controle). Não houve associação entre a detecção de HHVs na saliva e a presença de gengivite em ciranças HIV-positivas (p = 0.104) ou crianças saudáveis (p = 0,251), ou com imunossupressão em indivíduos HIV-positivos (p = 0,447). Foi observada uma correlação entre a infecção por HIV e a presença de gengivite (p = 0,0001). Os resultados sugerem que a detecção salivar assintomática de HHVs é comum entre crianças HIV-positivas e crianças saudáveis, e não está associada à gengivite.

Agentes patógenos responsables de trastornos gastrointestinales en sujetos infectados con VIH / Enteropathogens responsible of gastrointestinal disorders in HIV patients

Los trastornos gastrointestinales o TGI son afecciones debilitantes muy comunes en individuos infectados con el virus de inmunodeficiencia humana (VIH), que pueden conducir a muerte. Numerosos agentes etiológicos y mecanismos patofisiológicos han sido propuestos causar esta afección. A pesar del uso de terapia antirretroviral, que ha reducido enormemente la prevalencia de TGI en estos pacientes, patógenos entéricos como virus, bacterias, parásitos y hongos logran actuar todavía como agentes oportunistas. Citomegalovirus, adenovirus, calicivirus, astrovirus, rotavirus, enterovirus, picobirnavirus y algunos más recientemente descritos, como bocavirus y Aichi virus han sido detectados en pacientes con VIH. Sin embargo, a excepción del citomegalovirus, hay muy poca certeza acerca del papel que juegan algunos de ellos en estas afecciones. Varias especies de Criptosporidium, microsporidos, Salmonella, micobacterias atípicas y Campylobacter jejuni han sido reconocidos también como una importante causa de TGI en estos pacientes. La progresiva incorporación de técnicas inmunoenzimáticas y moleculares, cada vez más sensibles para la detección de antígenos, anticuerpos y agentes patógenos en heces ha mejorado el diagnóstico de las diarreas y contribuido a esclarecer la importancia etiológica de algunos microorganismos en los pacientes inmunocompetentes. En Venezuela existen algunos datos acerca de la prevalencia de patógenos entéricos en pacientes inmunodeficientes infectados con VIH. La identificación del agente etiológico responsable de TGI podría ser de gran utilidad para el manejo y tratamiento de estos pacientes, para quienes la enteritis viral es una manifestación morbosa que reduce la calidad de vida y ocasiona un elevado gasto en salud pública.

Gastrointestinal disorders or GID are debilitating conditions common in individuals infected by the human immunodeficiency virus (HIV), capable of leading to death. Numerous etiological agents and pathophysiological mechanisms have been involved in this status. Although the use of highly active antiretroviral therapy (HAART) in many countries has greatly reduced the prevalence of gastrointestinal infections, enteric pathogens such as bacteria, parasites, fungi and viruses may still act as opportunist agents in these patients. Cytomegalovirus, adenovirus, calicivirus, astrovirus, rotavirus, enterovirus, picobirnavirus and some more recently described, like bocavirus and Aichi virus, have been detected in HIV patients. However, except for cytomegalovirus, which is an established etiological agent of GID in these patients, the role of the other viruses remains unclear. Several species of Cryptosporidium, microsporidia, Salmonella, atipical mycobacteria and Campylobacter jejuni, have also been recognized as important causes of GID in HIV patients. The progressive incorporation of increasingly sensitive immunological and molecular assays for antigen, antibody and pathogens detection from faeces, has improved the diagnosis of diarrhea and contributed to clarify the etiological significance of some microorganisms in immunocompetent patients. In Venezuela, some information is available about the prevalence of enteric pathogens in immunocompromised patients infected with HIV. The identification of the etiologic agent responsible for this condition may be useful for the management and treatment of these patients, for whom viral enteritis is a disease, which reduces their quality of life and causes a high public health spending.

Current status of herpesvirus identification in the oral cavity of HIV-infected children

INTRODUCTION: Some viruses of the Herpesviridae family are frequently the etiologic agents of oral lesions associated with HIV. The aim of this study was to identify the presence of herpes simplex virus types 1 and 2 (HSV-1, HSV-2), Varicella Zoster virus (VZV), Epstein-Barr virus (EBV), human cytomegalovirus (HCMV), human herpesvirus type 6, type 7 and type 8 (HHV-6, HHV-7 and HHV-8) in the oral cavity of HIV-infected children/adolescents and verify the association between viral subtypes and clinical factors. METHODS: The cells of oral mucosa were collected from 50 HIV infected children/adolescents, 3-13 years old (mean age 8.66). The majority (66%) of selected were girls, and they were all outpatients at the pediatric AIDS clinic of a public hospital in Rio de Janeiro. Nested-PCR was used to identify the viral types. RESULTS: Absence of immunosuppression was observed in 66% of the children. Highly active antiretroviral therapy (HAART) was used by 72.1% of selected and moderate viral load was observed in 56% of the children/adolescents. Viral types were found in 86% of the children and the subtypes were: HSV-1 (4%), HSV-2 (2%), VZV (4%), EBV (0%), HCMV (24%), HHV6 (18%), HHV-7 (68%), HHV8 (0%). CONCLUSIONS: The use of HAART has helped to reduce oral lesions, especially with herpes virus infections. The health professionals who work with these patients should be aware of such lesions because of their predictive value and the herpes virus can be found circulating in the oral cavity without causing lesions.

Ophthalmic manifestations of HIV in the highly active antiretroviral therapy era / Manifestaciones oftálmicas del VIH en la era de la terapia antiretroviral altamente activa

HIV-related eye disease can be classified as retinal HIV microangiopathy, opportunistic infections, neuro-ophthalmic manifestations and unusual malignancies. There is a 52-100% lifetime accumulative risk of HIV patients developing eye problems. Seventy-seven per cent of patients with ocular manifestations of HIV had CD4 counts < 200 cells/µL. Cytomegalovirus (CMV) is the most prevalent opportunistic infection, however, Africa has a low incidence of this, and more commonly squamous cell carcinoma, compared to the western hemisphere. Due to highly active antiretroviral therapy (HAART), the anti-CMV therapy may be discontinued if the CD4+ T cell count is > 100 cells/µL for a minimum of three months. Despite HAART, patients with a CD4 count < 50 cells/µL have a similar risk of developing CMV retinitis as compared to the pre-HAART era. Opportunistic infections include CMV, herpetic retinopathy (progressive outer retinal necrosis - PORN), less commonly toxoplasmosis, pneumocystis and cryptococcus. Malignancies associated with HIV include Kaposi's sarcoma and conjunctival squamous cell carcinoma. Cranial nerve palsies, optic disc swelling and atrophy are characteristic neuro-ophthalmic features. They usually occur secondary to meningitis/encephalitis (from cryptococcus and tuberculosis). With the advent of HAART, new complications have developed in CMV retinitis: immune recovery uveitis (IRU) and cystoid macula oedema (CMO). Immune recovery uveitis occurs in 71% of patients if HAART is started before the induction of the anti-CMV treatment. However, this is reduced to 31% if HAART is started after the induction treatment. Molluscum contagiosum and Kaposi's sarcoma can spontaneously resolve on HAART. Highly active anti-retroviral therapy has reduced the frequencies of opportunistic infections and improved the remission duration in HIV patients.

Las enfermedades oculares relacionadas con el VIH pueden clasificarse como microangiopatía retiniana por VIH, infecciones oportunistas, manifestaciones neuro-oftálmicas, y tumores inusuales. Hay un riesgo acumulativo de por vida de 52-100% de que los pacientes con VIH desarrollen problemas oculares. Setenta y siete por ciento de los pacientes con manifestaciones oculares por VIH tenían conteos de CD4 < 200 células/µL. El citomegalovirus (CMV) es la infección oportunista más frecuente. Sin embargo, África tiene una baja incidencia de CVM, siendo en cambio más común el carcinoma de células escamosas, en comparación con el hemisferio occidental. Debido a la terapia antiretroviral altamente activa (TAAA), la terapia anti-CMV puede suspenderse si el conteo de células CD4+ T es > 100 células/µL por un mínimo de tres meses. A pesar de la terapia TAAA, los pacientes con un conteo de CD4 < 50 células/µL tienen un riesgo similar de desarrollar retinitis por CMV en comparación con la era pre-TAAA. Las infecciones oportunistas incluyen CMV, retinopatía herpética (necrosis retiniana progresiva externa - PORN), y menos comúnmente toxoplasmosis, pneumocistosis, y cryptococcus. Los tumores malignos asociados con el VIH incluyen el sarcoma de Kaposi y el carcinoma de células escamosas de conjuntiva. La parálisis del nervio craneal, la inflamación del disco óptico, así como la atrofia, son características neuro-oftálmicas típicas. Generalmente se presentan de forma secundaria en los casos de meningitis, encefalitis (cryptococcus y tuberculosis). Con el advenimiento de TAAA, se han desarrollado nuevas complicaciones de la retinitis por CMV, a saber, la uveitis por recuperación inmunológica (IRU por su sigla en inglés) y el edema macular cistoide (EMC). La uveitis por recuperación inmunológica ocurre en 71% de los pacientes si la terapia TAAA se comienza antes de la inducción del tratamiento anti-CMV. Sin embargo, esta cantidad se reduce a un 31% si TAAA se inicia después del tratamiento de inducción. El molusco contagioso y el sarcoma de Kaposi pueden desaparecer espontáneamente con el TAAA. La terapia anti-retroviral altamente activa ha reducido las frecuencias de las infecciones oportunistas, y mejorado la duración de la remisión en pacientes con VIH.

High prevalence of the simultaneous excretion of polyomaviruses JC and BK in the urine of HIV-infected patients without neurological symptoms in São Paulo, Brazil / Alta prevalência de excreção simultânea de poliomavírus JC e BK na urina de pacientes HIV+ sem sintomas neurológicos em São Paulo, Brasil

OBJECTIVE: To evaluate the prevalence of the urinary excretion of BKV and JCV in HIV-infected patients without neurological symptoms. METHODS: Urine samples from HIV-infected patients without neurological symptoms were tested for JC virus and BK virus by PCR. Samples were screened for the presence of polyomavirus with sets of primers complementary to the early region of JCV and BKV genome (AgT). The presence of JC virus or BK virus were confirmed by two other PCR assays using sets of primers complementary to the VP1 gene of each virus. Analysis of the data was performed by the Kruskal-Wallis test for numerical data and Pearson or Yates for categorical variables. RESULTS: A total of 75 patients were included in the study. The overall prevalence of polyomavirus DNA urinary shedding was 67/75 (89.3%). Only BKV DNA was detected in 14/75 (18.7%) urine samples, and only JCV DNA was detected in 11/75 (14.7%) samples. Both BKV and JCV DNA were present in 42/75 (56.0%) samples. CONCLUSION: In this study we found high rates of excretion of JCV, BKV, and simultaneous excretion in HIV+ patients. Also these results differ from the others available on the literature.

OBJETIVO: Avaliar a prevalência de excreção urinaria de vírus JC (VJC) e vírus BK (VBK) em pacientes HIV+ sem sintomas neurológicos. MÉTODOS: Amostras de urina de pacientes HIV+ sem sintomas neurológicos foram testados para a presença de VJC e VBK através da técnica de PCR. As amostras foram triadas para a presença de poliomavírus com par de primers complementares a região precoce do genoma do VBK e do VJC (AgT). A presença foi confirmada através de dois outros ensaios de PCR dirigidos a região do gene VP1 de ambos os vírus. A análise estatística foi realizada com auxílio do teste de Kruskal-Wallis para dados numéricos e Pearson ou Yater para variáveis categóricas. RESULTADOS: Ao todo foram inclusos no estudo 75 pacientes. A prevalência geral de excreção de poliomavírus na urina foi de 67/75 (89,3%). O DNA do vírus VBK foi detectado em 14/75 (18,7%) das amostras de urina, e o DNA do VJC foi detectado em 11/75 (14,7%) das amostras testadas. Ambos os vírus estavam presentes simultaneamente em 42/75 (56%) das amostras de urina. CONCLUSÃO: Encontramos, no presente estudo, uma alta taxa de excreção de VJC, VBK e excreção simultânea em pacientes HIV+. Ainda, esses resultados diferem de outros disponíveis na literatura.

JC virus-associated central nervous system diseases in HIV-infected patients in Brazil: clinical presentations, associated factors with mortality and outcome

INTRODUCTION: Several presentations of neurologic complications caused by JC virus (JCV) in human immunodeficiency virus (HIV)-infected patients have been described and need to be distinguished from the "classic" form of progressive multifocal leukoencephalopathy (PMl). The objectives of this study were: 1) to describe the spectrum and frequency of presentations of JCV-associated central nervous system (CNS) diseases; 2) identify factors associated with in-hospital mortality of patients with JCV-associated CNS disease; and 3) to estimate the overall mortality of this population. MATERIAL AND METHODS: This was a retrospective study of HIV-infected patients admitted consecutively for JCVassociated CNS diseases in a referral teaching center in São Paulo, Brazil, from 2002 to 2007. All patients with laboratory confirmed JCV-associated CNS diseases were included using the following criteria: compatible clinical and radiological features associated with the presence of JCV DNA in the cerebrospinal fluid. JCV-associated CNS diseases were classified as follows: 1) classic PMl; 2) inflammatory PMl; and 3) JC virus granule cell neuronopathy (GCN). RESULTS: We included 47 cases. JCV-associated CNS diseases were classified as follows: 1) classic PMl: 42 (89%); 2) inflammatory PMl: three (6%); and 3) JC virus GCN: four (9%). Nosocomial pneumonia (p = 0.003), previous diagnosis of HIV infection (p = 0.03), and imaging showing cerebellar and/or brainstem involvement (p = 0.02) were associated with in-hospital mortality. overall mortality during hospitalization was 34%. CONCLUSIONS: Novel presentations of JCV-associated CNS diseases were observed in our setting; nosocomial pneumonia, previous diagnosis of HIV infection, and cerebellar and/or brainstem involvement were associated with in-hospital mortality; and overall mortality was high.

Evaluation of GBV-C / HVG viremia in HIV-infected women / Avaliação da viremia por GBV-C/HGV em mulheres infectadas pelo HIV

The present study aimed at standardizing a real-time quantitative polymerase chain reaction assay to evaluate the presence of GBV-C/HGV RNA. A "TaqMan" assay using primers and probe derived from the 5¢ NCR region was developed and validated. Two hundred and fifty-three plasma samples from HIV-infected women were tested for GBV-C viremia and antibody against the envelope protein 2. GBV-C RNA was detected in 22.5 percent of the patients whereas the antibody was identified in 25.3 percent of the cohort. Detection of viral RNA and of antibodies was mutually exclusive. Viral loads showed a mean of 1,777 arbitrary units / mL, being 1.1 and 13,625 arbitrary units / mL respectively the lowest and highest values measured. We conclude that the real-time quantitative polymerase chain reaction method developed is appropriate for the investigation of GBV-C RNA since it was shown to be highly specific and sensitive, as well as requiring few steps, preventing contamination and providing additional information as to the relative viremia of carriers, a parameter that must be included in studies evaluating the co-factors influencing the clinical outcome of HIV/AIDS.

Este estudo teve como objetivo o desenvolvimento de método de PCR em Tempo Real para a determinação da viremia do vírus GBV-C. Ensaio baseado em primers e sonda "TaqMan" derivados da região 5' não-codificante deste vírus foi padronizado, validado e aplicado em uma série de 253 amostras de plasma de pacientes HIV+. Além do PCR em tempo real, as amostras foram submetidas a um ensaio imunoenzimático anti-E2 e a um nested-PCR. Das 253 amostras testadas, 64 foram positivas para o anticorpo anti-E2 (25,3 por cento), enquanto 57 amostras foram concordantemente RNA positivas pelo nested-PCR e PCR em tempo real (22,5 por cento), perfazendo um índice total de exposição de 48 por cento (25.3 + 22.5). A carga viral teve média de 1.777 UA/mL (13.625 - 1.1UA/mL). Foi obtida metodologia simples, rápida e de boa sensibilidade e especificidade, permitindo a quantificação do RNA do vírus GBV-C com reprodutibilidade. A metodologia permite a análise simultânea de grande número de amostras, sendo apropriada para estudos clínicos. A prevalência de exposição a este agente na população feminina HIV+ estudada é alta, provavelmente decorrente da via sexual comum de transmissão dos agentes.

Human polyomaviruses JC and BK in the urine of Brazilian children and adolescents vertically infected by HIV

The aim of this study was to characterize the urinary excretion of the BK (BKV) and JC (JCV) human polyomaviruses in a cohort of human immunodeficiency virus (HIV)-infected children and adolescents. One hundred and fifty-six patients were enrolled: Group I included 116 HIV-infected children and adolescents [median age = 11.4 years (y); range 1-22 y]; Group II included 40 non-HIV-infected healthy controls (median age = 11.37 y; range 7-16 y). Single urine samples from both groups were screened for the presence of JCV and BKV DNA by polymerase chain reaction at enrolment. The overall rate of JCV and BKV urinary excretion was found to be 24.4 percent and 40.4 percent, respectively (n = 156). Group I had urinary excretion of JCV and BKV in 27.6 percent and 54.3 percent of subjects, respectively. In contrast, Group II showed positive results for JCV in 17.5 percent of subjects and for BKV in 12.5 percent of subjects (p Pearson JCV = 0.20; p Pearson BKV < 0.0001). In Group I, there was no association between JCV/BKV shedding and age, gender or CD4 values. Patients with an HIV viral load < 50 copies/mL had a lower excretion of BKV (p < 0.001) and a trend of lower JCV excretion (p = 0.07). One patient in Group I (1/116, 0.9 percent) showed clinical and radiological features consistent with progressive multifocal leukoencephalopathy, suggesting that children with HIV/polyomavirus coinfection should be kept under surveillance.

Acute meningoencephalomyelitis due to varicella-zoster virus in an AIDS patient: report of a case and review of the literature / Meningoencefalomielite aguda pelo vírus varicela-zoster em um paciente com AIDS: relato de um caso e revisão da literatura

Varicella-zoster virus (VZV) meningoencephalomyelitis is a rare but severe neurological complication of VZV reactivation in immunocompromised patients. We report the case of an HIV-infected individual who developed an acute and severe meningoencephalomyelitis accompanied by a disseminated cutaneous eruption due to VZV. The presence of VZV DNA in cerebrospinal fluid was confirmed by polymerase chain reaction (PCR) technique. The patient started undergoing an intravenous acyclovir therapy with a mild recovery of neurological manifestations. Varicella-zoster virus should be included as a cause of acute meningoencephalomyelitis in patients with AIDS. Early diagnosis followed by specific therapy should modify the rapid and fulminant course for this kind of patients.

A meningoencefalomielite pelo vírus varicela-zoster (VVZ) é uma complicação neurológica rara mas grave da reativação do VVZ em pacientes imunocomprometidos. Nós relatamos o caso de um indivíduo infectado por HIV que desenvolveu uma meningoencefalomielite aguda e grave acompanhada por uma erupção cutânea por causa do VVZ. A presença do DNA do VVZ no líquor foi confirmada pela técnica de reação em cadeia da polimerase (PCR). O paciente iniciou uma terapia intravenosa com aciclovir com uma leve recuperação das manifestações neurológicas. O vírus varicela-zoster deve ser incluído como uma causa de meningoencefalomielite nos pacientes com AIDS. O diagnóstico precoce seguido por terapia específica pode modificar o curso rápido e fulminante deste tipo de pacientes.

Genotypical diversity of HIV clades and central nervous system impairment / Diversidade genotípica dos subtipos de HIV e comprometimento do sistema nervoso central

The central nervous system (CNS) and the immune system are considered major target organs for HIV infection. The neurological manifestations directly related to HIV are acute viral meningitis, chronic meningitis, HIV associated dementia, vacuolar myelopathy and involvement of the peripheral nervous system. Changes in diagnosis and clinical management have changed the aspect of HIV infection so that it is no longer a fatal disease, and has become a chronic disease requiring sustained medical management. After HAART the incidence of most opportunistic infections, including those affecting the CNS, has dropped markedly. Some studies suggest that neurological involvement of infected patient occur with different frequency, depending on HIV subtype involved in the infection. Subtype C may have reduced neuroinvasive capacity, possibly due to its different primary conformation of HIV transactivating regulatory protein (Tat), involved in monocyte chemotaxis. This review focus on physiopathologic aspects of HIV infection in CNS and its correlation with HIV clades.

O sistema nervoso central (SNC) e o sistema imunológico são considerados os principais órgãos alvo na infecção pelo HIV. As manifestações neurológicas diretamente relacionadas ao HIV são meningites virais aguda e crônica, demência associada ao HIV, mielopatia vacuolar e envolvimento do sistema nervoso periférico. Mudanças no diagnóstico e sobrevida têm mudado o aspecto da infecção pelo HIV, não mais considerada uma doença fatal e sim crônica. Após HAART, a incidência da maioria das doenças oportunistas, incluindo aquelas que afetam o SNC, reduziu-se significativamente. Alguns estudos sugerem que o envolvimento de pacientes infectados ocorre com frequência diferente, dependendo do subtipo de HIV. O subtipo C apresenta uma capacidade reduzida de neuroinvasão, possivelmente devido a conformação primária da sua proteína reguladora da transativação (Tat), que perde sua capacidade quimiotáxica. Esta revisão aborda aspectos fisiopatológicos da infecção do HIV no SNC e subtipos de HIV.