RESUMO. O tratamento antirretroviral tem aumentado significativamente a sobrevida de pacientes contaminados pelo HIV-1. Entretanto, com o aumento da sobrevida, observam-se frequentemente alterações cognitivas associadas ao HIV nessa população. As manifestações clínicas das alterações do HIV podem variar em decorrência de diversos aspectos, entre eles a via de transmissão do vírus. Diversos estudos têm apontado alterações neurológicas prematuras em pacientes contaminados por via vertical, enquanto a manifestação de danos cognitivos em adultos pode levar um tempo maior. Objetivo: O objetivo deste estudo foi verificar a prevalência das alterações cognitivas em pacientes com HIV via transmissão vertical após a era da terapia antirretroviral altamente ativa e o desempenho cognitivo desses pacientes comparado ao de um grupo de pacientes contaminados por via sexual. Métodos: Foram avaliados 48 pacientes, sendo 25 com transmissão vertical e 23 com transmissão sexual no período entre maio de 2013 e fevereiro de 2015, no Instituto de Infectologia Emílio Ribas. Foram aplicados testes neuropsicológicos para avaliar o desempenho cognitivo, escalas para avaliar sintomas de ansiedade e depressão e questionário sociodemográfico. Resultados: Os resultados demonstraram que a frequência de comprometimento cognitivo em pacientes contaminados via transmissão vertical foi maior do que naqueles contaminados via transmissão sexual. Conclusões: Essas descobertas sugerem que os efeitos deletérios do vírus HIV na formação do sistema nervoso central repercutem de forma mais acentuada do que em pacientes que o adquiriram após a vida adulta.

ABSTRACT. Antiretroviral treatment has significantly increased the survival of patients infected with HIV-1. However, with increased survival, cognitive changes associated with HIV are frequently observed in this population. The clinical manifestations of HIV changes can vary as a result of several aspects, including the virus transmission route. Several studies have pointed out premature neurological changes in vertically infected patients, while the manifestation of cognitive damage in adults may take a longer time. Objective: The aim of this study was to verify the prevalence of cognitive changes in patients with HIV via vertical transmission after the highly active antiretroviral therapy and the cognitive performance of these patients compared to a group of sexually infected patients. Methods: A total of 48 patients were evaluated, 25 with vertical transmission and 23 with sexual transmission, between May 2013 and February 2015 at the Institute of infectology Emilio Ribas. Neuropsychological tests were applied to assess cognitive performance, scales to assess symptoms of anxiety and depression, and sociodemographic questionnaire. Results: The results demonstrate that the frequency of cognitive impairment in vertically transmitted patients was higher than in sexually transmitted patients. Conclusions: These findings suggest that the deleterious effects of the HIV virus on the development of the central nervous system reverberate more strongly than in patients who acquire it after adulthood.

ABSTRACT Human immunodeficiency virus (HIV)-associated neurocognitive disorders are the main cause of cognitive decline and dementia in people living with HIV (PLHIV). However, extensive workup should be done in patients with rapidly progressive dementia (RPD) and HIV, especially when secondary infection in the central nervous system (CNS) is ruled out. Sporadic Creutzfeldt-Jakob disease (sCJD) is the main cause of RPD in non-HIV patients. It is a fatal neurodegenerative condition caused by prions that mainly affects elderly patients. Our objective is to describe two cases of PLHIV presenting with controlled infections and sCJD, and to review the literature. Our patients were younger than expected for sCJD and one of them had a longer disease course. As aging is expected to occur earlier in PLHIV, sCJD must be excluded in younger PLHIV presenting with RPD and without CNS infection.

ABSTRACT The human T cell lymphotropic virus type 1 (HTLV-1) is the first human retrovirus discovered. Since then, it has spread worldwide and is mainly associated with adult T cell leukemia/lymphoma (ATLL) and HTLV1-associated myelopathy (HAM). Its relationship, however, with other types of cancer is controversial. We describe the case of a patient presenting with small cells lung epidermoid carcinoma who had recently developed HAM, and a review of the literature related to these conditions. This is the first case of this type of lung cancer, the same of the first description in the literature, associated with HAM outside Japan.

RESUMO Apesar da síndrome de HAM / TSP clássica ser a perturbação neurológica mais atribuída, alguns distúrbios neurológicos denominados “menores” são vistos em portadores “assintomáticos” de HTLV-1. Esses distúrbios, incluindo alterações cognitivas já observadas em descrições de casos clínicos e estudos, podendo constituir uma verdadeira síndrome clínica intermediária (SI) entre o estado assintomático e mielopatia. O objetivo deste estudo foi investigar a presença de déficits cognitivos em pacientes portadores do vírus HTLV-1 diagnosticados classicamente como assintomáticos. Métodos Foram avaliadas 54 pessoas, sendo 35 assintomáticos, 19 com alterações neurológicas menores (avaliados por um neurologista) e 25 HTLV-1 negativo. Os instrumentos utilizados foram: Inventário Beck de Depressão, Escala de Atividades de Vida Diária de Lawton e uma completa bateria neuropsicológica. A aplicação destes instrumentos de avaliação foi realizada de forma cega, ou seja, a avaliadora não sabia a condição clinica do paciente. Resultados A maioria dos participantes era do sexo feminino (n = 57, 72,21%), com idade média de 52.34 anos (DP = 14,29) e escolaridade média de 9.70 anos (DP = 4,11). Discussão Avaliando o desempenho cognitivo nos três grupos, foi possível observar que os participantes classificados com SI, apresentaram menores escores brutos, quando comparados, com os pacientes com classificação assintomática e grupo controle e, em relação à memória episódica auditiva de evocação imediata (p < 0,01) (p = 0,01) e tardia. Conclusão Diante dos resultados foi possível concluir que os pacientes com SI apresentam comprometimento de memória quando comparado com os outros grupos, sendo possível, ser este um dos sintomas para auxiliar na classificação da síndrome.

Background Although classical human T-cell lymphocyte virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis syndrome is the most frequent HTLV-1-associated neurological disorder, some “minor” neurological disorders can be seen in “asymptomatic” carriers. These disorders, including cognitive alterations already described in clinical cases and studies, may constitute an intermediate syndrome (IMS) between the asymptomatic state and myelopathy. The aim of this study was to investigate the presence of cognitive deficits in patients with HTLV-1 virus, who usually are diagnosed as asymptomatic. Methods A total of 54 HTLV-1-infected patients were evaluated, 35 asymptomatic and 19 with minor neurological alterations (evaluated by a neurologist); 25 HTLV-1-seronegative individuals served as controls. The instruments used were: Beck’s Depression Inventory, Lawton’s Daily Life Activity Scale, and a complete neuropsychological battery. The application of these evaluation instruments was performed blindly, with the evaluator neuropsychologist not knowing the clinical condition of the patient. Results Most of the participants in this cohort, including seronegative controls, were female (n = 57, 72.21%), their mean age was 52.34 years (SD = 14.29) and their average schooling was 9.70 years (SD = 4.11). Discussion Participants classified with IMS had lower gross scores when compared with both the patients classified as asymptomatic and with the control group, and when tested for auditory episodic memory of immediate (p < 0.01), and late (p = 0.01), recall. Conclusion Patients with IMS presented with memory impairment when compared with asymptomatic patients and seronegative individuals; this is one of the symptoms that aids in the classification of the syndrome.

ABSTRACT This study evaluated the impact of urinary incontinence (UI) on sexuality, body image, mood, and quality of life of patients with myyelopathy associated with HTLV-1/tropical spastic paraparesis (HAM/TSP). The sample consisted of 31 HAM/TSP outpatients, of both sexes, followed-up at the Emílio Ribas Infectology Institute. The following instruments were used: sociodemographic questionnaire, Hospital Anxiety and Depression Scale (HAD), Body Image Assessment Scale, Sexual Quotient Female (QS-F) and Male (QS-M) Versions, King's Health Questionnaire (KHQ), and Revised OSAME Motor Disability Score. Data analysis was performed using descriptive statistics and the Mann-Whitney U-test was used for group comparison. The presence of UI was reported by 13 (41.9%) patients. Based on the quality of life questionnaire, patients with UI had a significant impact in the following domains: incontinence impact, daily life activities limitation, physical and social limitations, social relations, emotions, sleep and disposition, and severity measurements. Most participants had no anxiety (21; 67.7%) or depression symptoms (18; 58.1%). Regarding the sexual coefficient, 13 (41.9%) participants had sexual dissatisfaction. Conclusion: UI is common in HTLV-1 patients and may cause serious impairment in quality of life, with social, psychological and hygienic consequences. Nonetheless, there are few studies on this subject and their impact on mood and sexuality.

ABSTRACT Objective: We evaluated the association between cognitive deficits and leukocyte telomere length (LTL) in HIV-1-infected individuals. Design: 73 HIV-1-infected patients undergoing neuropsychological evaluation and 91 healthy controls were included in this study. Fifteen HIV-1 positive patients did not have cognitive disorders whereas 26 had asymptomatic neurocognitive disorder (ANI), 13 presented mild to moderate neurocognitive disorder (MND), and 10 had HIV-associated dementia (HAD). Methods: DNA from the peripheral blood of HIV-1-infected patients was used for measurement of telomere length by real-time PCR. HIV-1 viral load was determined in blood. Results: LTL decreased with age in healthy controls (p=0.0001). Regardless of the HIV status, age-matched LTL from HIV patients, including those with ANI and MND, were shortened in comparison to the healthy control group (p=0.0073); however, no association was found among the HIV-1-infected individuals with cognitive deficits (p=0.01). In addition, no gender-related association with LTL was observed (p=0.80), smoking, physical exercise, and plasma viral load were not correlated to telomere length (p=0.66). Conclusions: We concluded that leukocyte telomere length may not be a marker of cellular senescence in individuals with HIV infection and neurocognitive disorders.

ABSTRACT Um aumento expressivo da incidência de alterações cognitivas em pacientes com AIDS/HIV vem ocorrendo, assim três categorias de acometimento cognitivo foram propostas: comprometimento cognitivo assintomático (ANI) e alteração cognitiva leve/moderada (MND) que correspondem às formas leves e intermediárias; e demência associada ao HIV (HAD), a forma mais grave. O termo HIV-associated neurocognitive disorders (HAND) é uma denominação genérica que engloba as três categorias de acometimento. A aplicação de métodos de neuroimagem agregou grande avanço no entendimento das alterações neurológicas do HIV, promovendo maior confiabilidade na exclusão de patologias associadas e diagnóstico mais precoce. Diante disso, as alterações ou características específicas de neuroimagem podem ser em breve incorporadas aos critérios de classificação da HAND, o que será de grande valor no seu manejo, inclusive no auxílio para a otimização de esquemas antirretrovirais de alta penetração no SNC.

ABSTRACT A significant increase in the incidence of cognitive impairment in HIV/AIDS patients has been continuously observed. Consequently, three classification categories of cognitive impairment have been proposed: asymptomatic neurocognitive impairment (ANI) and mild neurocognitive disorder (MND), that correspond to the mild and intermediate forms, and HIV-associated dementia (HAD) for the most severe cases. HIV-associated neurocognitive disorders (HAND) is a broad term that encompasses these three categories. Moreover, the application of neuroimaging methods has led to a major breakthrough in understanding of the neurological changes in HIV, providing greater reliability in the exclusion of associated diseases and allowing earlier diagnosis. Therefore, abnormalities and/or specific neuroimaging elements may soon be incorporated into the HAND classification criteria, which will be of great value in the management of these diseases, including in the optimization of high CNS penetration antiretroviral regimens.

The HAM/TSP caused by HTLV-1 infection usually affects patients to disabling states, and sometimes can lead them to paraplegia presenting symptoms of depression and anxiety, impacting on quality of life. Objective: The purpose of this study was to evaluate the frequency of depression and anxiety and its impact on quality of life in HTLV-1-infected TSP/HAM patients. Material and Methods: This was a cross-sectional study including 67 asymptomatic (control group) and 63 with TSP/HAM subjects. The instruments used were a demographic questionnaire, scales for anxiety and depression diagnosis (BDI and BAI), questionnaire for the assessment of Quality of Life of the World Health Organization (WHOQOL-Brief) and neurological scale to measure the disability level (Osame's Disability Status Scale). All patients had HTLV-I diagnosis by serological and molecular approaches, monitored at Instituto de Infectologia Emílio Ribas from May 2008 to July 2009. Data were analyzed statistically by frequencies, the Mann-Whitney test and the Spearman correlation test. Data among groups were analyzed and correlated with functional and severity aspects. Results: The results showed that patients with HAM/TSP compared to asymptomatic carriers had higher rates of depression (p < 0.001) and anxiety (p < 0.001), and impairment on quality of life in the areas of: dissatisfaction with health (p < 0.001), physical (p < 0.001) and the environment (p = 0.003). The main factors that correlated with levels of depression and anxiety and the domains of the WHOQOL-brief were: education, family income and social class. Conclusion: A well conducted evaluation and counseling may help in treatment, for a better quality of life of these patients.

BACKGROUND: Cerebral toxoplasmosis (CT) continues to cause significant morbidity and mortality in human immunodeficiency virus (HIV)-infected patients in Brazil. In clinical practice, the initial diagnosis is usually presumptive and alternative diagnosis tools are necessary. Our objective was to evaluate whether the detection of high titers of IgG anti-Toxoplasma gondii and T. gondii DNA in blood samples are associated with the diagnosis of CT. METHODS: In this case-control study we included 192 patients with HIV-1 infection: 64 patients with presumptive CT (cases) and 128 patients with other diseases (controls). Blood samples to perform indirect immunofluorescense reaction (IFI) to detect anti-T. gondii IgG antibodies and polymerase chain reaction (PCR) were collected before or within the first three days of anti-Toxoplasma therapy. Two multivariate logistic regression models were performed: one including the variable qualitative serology and another including quantitative serology. RESULTS: In the first model, positive IgG anti-T. gondii (OR 4.7, 95% CI 1.2-18.3; p = 0.027) and a positive T. gondii PCR result (OR 132, 95% CI 35-505; p < 0.001) were associated with the diagnosis. In the second model, IgG anti-T. gondii titres > 1:1024 (OR 7.6, 95% CI 2.3-25.1; p = 0.001) and a positive T. gondii PCR result (OR 147, 95% CI 35-613; p < 0.001) were associated with the diagnosis. CONCLUSIONS: Quantitative serology and molecular diagnosis in peripheral blood samples were independently associated with the diagnosis of CT in HIV-infected patients. These diagnostic tools can contribute to a timely diagnosis of CT in settings where Toxoplasma infection is common in the general population.

Antes da introdução da terapia anti-retroviral altamente efetiva (HAART), a retinite por CMV era uma complicação comum em pacientes com doença por HIV avançada e a terapia era bem estabelecida e consistia em uma fase de indução com ganciclovir para controlar a infecção, seguida por uma manutenção por toda a vida, para evitar e retardar as recidivas. Para determinar a segurança da retirada da terapia de manutenção para retinite por citomegalovírus em pacientes com recuperação imunológica após o HAART, 35 pacientes com retinite por CMV tratados com terapia de manutenção, com contagem de células CD4+ maiores que 100 células/mm³ por no mínimo três meses, mas a maioria dos pacientes apresentava esses valores por mais de seis meses e carga viral < 30.000 cópias/mL, foram avaliados prospectivamente para a recorrência de doença por CMV. A terapia de manutenção foi retirada na inclusão e os pacientes foram monitorados no mínimo 48 semanas por avaliações clínicas e oftalmológicas e pela determinação de marcadores de viremia para CMV (antigenemia). Contagens de CD4+ e CD8+ e níveis de RNA de HIV no plasma. Métodos linfoproliferativos foram realizados em 26/35 pacientes. RESULTADOS: Dos 35 pacientes incluídos no estudo, somente um teve reativação da retinite por CMV confirmada, no dia 120 do seguimento. Nenhum paciente teve testes de antigenemia positivos. Nenhuma correlação entre os ensaios linfoproliferativos e contagens de CD4+ foi observada. CONCLUSÃO: Descontinuação da terapia de manutenção para retinite por CMV é segura para aqueles pacientes com recuperação imune quantitativa após HAART.

BACKGROUND: Before the introduction of highly active antiretroviral therapy (HAART), CMV retinitis was a common complication in patients with advanced HIV disease and the therapy was well established; it consisted of an induction phase to control the infection with ganciclovir, followed by a lifelong maintenance phase to avoid or delay relapses. METHODS: To determine the safety of CMV maintenance therapy withdrawal in patients with immune recovery after HAART, 35 patients with treated CMV retinitis, on maintenance therapy, with CD4+ cell count greater than 100 cells/mm³ for at least three months, but almost all patients presented these values for more than six months and viral load < 30000 copies/mL, were prospectively evaluated for the recurrence of CMV disease. Maintenance therapy was withdrawal at inclusion, and patients were monitored for at least 48 weeks by clinical and ophthalmologic evaluations, and by determination of CMV viremia markers (antigenemia-pp65), CD4+/CD8+ counts and plasma HIV RNA levels. Lymphoproliferative assays were performed on 26/35 patients. RESULTS: From 35 patients included, only one had confirmed reactivation of CMV retinitis, at day 120 of follow-up. No patient returned positive antigenemia tests. No correlation between lymphoproliferative assays and CD4+ counts was observed. CONCLUSION: CMV retinitis maintenance therapy discontinuation is safe for those patients with quantitative immune recovery after HAART.

Neurological dysfunction as the first manifestation of AIDS has been found in 10 to 20% of symptomatic human immunodeficiency virus infections. However, stroke has rarely been reported in AIDS patients. The most common causes of cerebral infarction in AIDS are central nervous system infections: toxoplasmosis, cryptococcal meningitis and tuberculosis. Potential vascular mechanisms for cerebral infarction and transient neurological deficits among AIDS patients include deposition of antigen-antibody complexes with vasculitis and infarction, and a direct toxic effect of a viral antigen or infectious agent on vascular endothelium. The role of cryptococcal meningitis in vasculopathy is still not clear. We report a case of cerebral infarction in an HIV-infected patient, with cryptococcal meningitis as the first manifestation of AIDS.