HIV RNA viral load and CD4+ T-cell counts in HIV-infected pregnant women with and without treatment discontinuation in early pregnancy.

BACKGROUND: In pregnant women taking antiretroviral treatment at conception treatment may be transiently stopped for safety concerns. Limited data are available on the consequences of such discontinuations. METHODS: We used data from a national study to compare different treatment pathways during pregnancy. Overall, 321 women were evaluated and classified into three groups: women not on treatment at conception and who started treatment during pregnancy (starters; n=91); women on treatment at conception who temporarily discontinued treatment during first trimester (discontinuers; n=114); and women on treatment at conception who maintained treatment (continuers; n=116). RESULTS: At conception, the three groups had similar CD4+ T-cell counts (499, 495 and 470 cells/mm3, respectively; P>0.10); starters had significantly higher median HIV RNA levels at conception (5,690 copies/ml) compared with both continuers (58 copies/ml, P<0.001) and discontinuers (49 copies/ml, P<0.001). Continuers maintained undetectable HIV RNA at all pregnancy trimesters, while discontinuers showed at first and second trimester transient negative effects on HIV (4,776 and 386 copies/ml, respectively) and CD4+ T-cell levels (376 and 392 cells/mm3, respectively), which were reversed at last trimester (52 copies/ml and 432 cells/mm3, respectively). No significant differences were observed among the groups in HIV RNA and CD4+ T-cell counts at third trimester, preterm delivery, low birth weight or mode of delivery. The number of cases of HIV transmission and birth defects were too limited to allow comparisons. CONCLUSIONS: Early discontinuation of antiretroviral treatment in pregnancy produces transient virological and immunological effects without precluding the achievement of a good viral suppression at the end of pregnancy; no clinical consequences were observed.

Análise da Viabilidade de Uso do FNIRS em Atividades Educacionais com Crianças e Jovens com Deficiência Intelectual e Autismo / Analysis of FNIRS Usability in Educational Activities with Children and Young People with Intellectual Disability and Autism

RESUMO: Métodos em neurociência cognitiva podem auxiliar o planejamento educacional de docentes no contexto da Educação Especial, por favorecerem práticas personalizadas que valorizem a velocidade individual de aprendizagem de estudantes com transtorno do espectro do autismo (TEA) e/ou deficiência intelectual (DI). Assim sendo, este estudo objetivou verificar a viabilidade de uso da Espectroscopia Funcional de Infravermelho Próximo (fNIRS) em situação naturalística clínica com crianças e jovens com TEA e/ou DI durante tarefas de ensino. Ademais, o estudo buscou identificar as estratégias de treino para que as crianças e os jovens utilizassem o equipamento durante a realização da atividade. Sete estudantes com diagnóstico de TEA e/ou DI foram treinados com atividades de matemática, leitura e expressividade emocional, de acordo com seus respectivos currículos educacionais prévios. Cada participante foi exposto a duas tarefas em cada atividade, uma na qual já apresentava domínio e outra que necessitava de apoio para emitir uma resposta independente. Os resultados indicaram a viabilidade de uso do fNIRS nesse contexto natural da criança e do jovem e forneceram medidas implícitas para além das medidas observacionais de acerto e erro na tarefa. Esta é uma importante demonstração da viabilidade do uso do fNIRS em experimentos no contexto da Educação Especial.

ABSTRACT: Methods in cognitive neuroscience can assist educational planning of teachers in the context of Special Education, as they favor personalized practices that value individual students with Autism Spectrum Disorder (ASD) and/or Intellectual Deficiency (ID). Therefore, this study aimed to verify the feasibility of using functional near-infrared spectroscopy (fNIRS) in clinical naturalistic situation with children and young people with ASD and/or ID during teaching tasks. In addition, the study sought to identify training strategies so that children and young people use the equipment during the activity. Seven students diagnosed with ASD and/or ID were trained with mathematics, reading and emotional expressiveness, according to their respective previous educational curricula. Each participant was exposed to two tasks in each activity, one in which he/she already had a domain and one that needed support to issue an independent response. The results indicated the feasibility of using fNIRS in this natural context of the child and the young student and provided implicit measures beyond the observational arrangement measures and task error. This is an important demonstration of the feasibility of using fNIRS in experiments in the context of Special Education.

Toscana virus infections in northern Italy: laboratory and clinical evaluation.

Toscana virus (TOSv) is a neurotropic arthropod-borne virus that causes meningitis in the Mediterranean basin during the summer months. A total of 120 patients suffering from acute aseptic meningitis between July 1 and October 31, 2010 in northern Italy were evaluated. Eighteen of them (15%) were in the acute stage of TOSv disease.

Case report: primary infection by human herpesvirus 6 variant a with the onset of myelitis.

A case of primary infection by human herpesvirus 6 (HHV-6) variant A in a 54-year-old woman, which occurred at the same time as the onset of encephalomyelitis, is reported. The correlation between the two events is discussed. It is speculated that, during the early phase of the infection, the HHV-6 spread to the central nervous system and triggered a pathogenic process that initially developed without symptoms. When the neurological disorders appeared, HHV-6 had already established a latent state: only the virus carried by infected blood cells was detected in the cerebrospinal fluid.

Clinical pharmacokinetics of nelfinavir and its metabolite M8 in human immunodeficiency virus (HIV)-positive and HIV-hepatitis C virus-coinfected subjects.

In order to evaluate the potential risk of nelfinavir (NFV) accumulation in human immunodeficiency virus (HIV)-hepatitis C virus (HCV)-coinfected patients with liver disease, we investigated the concentrations of NFV and M8, the active metabolite of NFV, in plasma HIV-positive (HIV+) patients coinfected with HCV. A total of 119 HIV+ subjects were included in our study: 67 HIV+ patients, 32 HIV+ and HCV-positive (HCV+) patients without cirrhosis, and 20 HIV+ and HCV+ patients with cirrhosis. Most of the enrolled patients (chronically treated) were taking NFV at the standard dosage of 1,250 mg twice a day. To assay plasma NFV and M8 concentrations, patients underwent serial plasma samplings during the dosing interval at steady state. Plasma NFV and M8 concentrations were measured simultaneously by a high-performance liquid chromatography method with UV detection. The HIV+ and HCV+ patients with and without cirrhosis had significantly lower NFV oral clearances than the HIV+ and HCV-negative individuals (28 and 58% lower, respectively; P < 0.05), which translated into higher areas under the concentration-time curves for cirrhotic and noncirrhotic patients. The NFV absorption rate was significantly lower in cirrhotic patients, resulting in a longer time to the maximum concentration in serum. The mean ratios of the M8 concentration/NFV concentration were significantly lower (P < 0.05) in HIV+ and HCV+ subjects with cirrhosis (0.06 +/- 0.074) than in the subjects in the other two groups. The mean ratios for M8 and NFV were not statistically different between HIV+ and HCV-negative patients (0.16 +/- 0.13) and HIV+ and HCV+ patients without cirrhosis (0.24 +/- 0.17), but the interpatient variability was high. Our results indicate that the pharmacokinetics of NFV and M8 are altered in HIV+ and HCV+ patients, especially those with liver cirrhosis. Therefore, there may be a role for therapeutic drug monitoring in individualizing the NFV dosage in HIV-HCV-coinfected patients.

Limited sampling strategy for the estimation of systemic exposure to the protease inhibitor nelfinavir.

Therapeutic drug monitoring (TDM) of antiretroviral drugs has been proposed as a means of optimizing response to highly active antiretroviral therapy (HAART) in HIV infection because suboptimal exposure to these agents may lead to the development of resistant viral strains and subsequent therapeutic failure. The area under the curve (AUC), though considered to make the best estimate of total drug exposure, requires repeated blood sampling. The authors investigated the predictability of individual nelfinavir (NFV) concentrations at different time points for the AUC and tried to find the best sampling time for the abbreviated AUC to predict NFV total body exposure. A total of 99 NFV AUC0-12h values were measured in 99 patients receiving a 1250-mg oral dose twice a day. Venous blood samples were collected at baseline (predose, 0) and 1, 2, 3, 4, 5, 6, 8, and 12 hours postdose. A stepwise forward-selection, multiple-regression technique was chosen to assess the relative importance of single and combination concentration time points to predict the AUC calculated from the entire pharmacokinetic profile. Data were split into a development set and a validation set. The development set contained 49 randomly selected HIV patients. Of these, 22 HIV patients were coinfected with HCV, 7 with and 15 without cirrhosis. One-point predictors provided the lowest prediction precision, but predictive performance improved after the first 2 hours postdose. Plasma concentrations at 0 and 4 hours after the oral dose were most predictive if 2 variables were used in the regression equation. The AUC could be estimated from data for these 2 samples by using the following equation: AUC0-12 = 3.0 + 2.7 (C0) + 6.4 (C4), r = 92. The predictive performance of 2-point predictors at 0 and 4 hours (C0 + C4) was validated by comparing their ability to predict the full AUC in a validation set representative of HIV/HCV patients (n = 28) and HIV/HCV patients, with (n = 8) and without (n = 14) cirrhosis. The results showed a mean bias ranging from +2.7% in HIV/HCV patients to -6.0% in HCV coinfection with cirrhosis. The authors conclude that this result is clinically significant. The limited sampling strategy (LSS) described could be used in clinical practice for the easy assessment of the total exposure to NFV in HIV/HCV patients, both with and without cirrhosis.