<p>Background: Although clinicians encounter antimycobacterial treatment in Human mmunodeficiency (HIV)-infected children as one of the most common treatments coadministered with antiretroviral treatment (ART), quantitative data on the extent of antimycobacterial treatment among HIV-infected children at the time of commencement of ART and at different times during ART is scarce. The baseline risk factors associated with being on both ART and antimycobacterial treatments are not known and it remains to be elucidated how the different exposure factors impact on the antimycobacterial treatment-free survival of children who begin ART without antimycobacterial treatment.Objectives: To describe the prevalence of antimycobacterial treatment among children at the time of starting ART and the antimycobacterial treatment-free survival after starting ART. Design: A retrospective cohort study based on record reviews at the Harriet Shezi children&lsquo / s clinic (HSCC).Population: HIV-infected children less than fifteen years of age presumed ART na&iuml / ve started on ART at HSCC.Analysis: A descriptive analysis of the prevalence of antimycobacterial treatment at time of start of ART was done. Kaplan Meier (KM) survival curves were used to determine the antimycobacterial treatment-free survival and logistic regression was used to analyze the association between baseline factors and future antimycobacterial treatment among children who had no antimycobacterial treatment at time of start of ART. Results: The prevalence of antimycobacterial treatment at the time of starting ART was 518/1941 (26.7%, 95% confidence interval (CI): 24.7-28.7). Among children who started ART without antimycobacterial treatment, the KM cumulative probability of antiretroviral and antimycobacterial (ART/antimycobacterial) co-treatment in the first 3 months of starting ART was 4.6% (95% CI: 4.1- 5.2), in the first 12 months it was 18.1% (95% CI: 17.0-19.2) and in the first 24 months of starting ART it was 24% (95% CI: 21.9-25.1). Survival analysis suggested that children with high baseline viral load, advanced World Health Organization (WHO) stage of disease, very low normalized weight for age (waz) and very young age (less than one year) at start of ART had significantly reduced antimycobacterial treatment-free survival (log rank p &lt / 0.05) in the first two years of starting ART. In the logistic regression model, age less than one year {Odds ratio (OR): 3.7 (95% CI: 2.2-6.0 / p &lt / 0.0001)} and very low weight for age Z-score (waz &lt / -3) {OR / 2.2 (95% CI: 1.4-3.6 / p = 0.0015)} were the two critical risk factors independently associated with future antimycobacterial treatment. Conclusions: Antimycobacterial treatment is extremely common among HIV-infected children at the time of starting ART and early after starting ART and the incremental risk of being on ART/antimycobacterial co-treatment decreases with time on ART. The results emphasize the need for a heightened and careful alertness for mycobacterial events especially among children starting ART with severe malnutrition and those who start ART at age less than one year. The results further suggest that it is probably optimal to start ART in children before their nutritional status has deteriorated severely in the course of the HIV disease so that they get protection against mycobacterial events by early ART.</p>

<p>Background: Although clinicians encounter antimycobacterial treatment in Human mmunodeficiency (HIV)-infected children as one of the most common treatments coadministered with antiretroviral treatment (ART), quantitative data on the extent of antimycobacterial treatment among HIV-infected children at the time of commencement of ART and at different times during ART is scarce. The baseline risk factors associated with being on both ART and antimycobacterial treatments are not known and it remains to be elucidated how the different exposure factors impact on the antimycobacterial treatment-free survival of children who begin ART without antimycobacterial treatment.Objectives: To describe the prevalence of antimycobacterial treatment among children at the time of starting ART and the antimycobacterial treatment-free survival after starting ART. Design: A retrospective cohort study based on record reviews at the Harriet Shezi children&lsquo / s clinic (HSCC).Population: HIV-infected children less than fifteen years of age presumed ART na&iuml / ve started on ART at HSCC.Analysis: A descriptive analysis of the prevalence of antimycobacterial treatment at time of start of ART was done. Kaplan Meier (KM) survival curves were used to determine the antimycobacterial treatment-free survival and logistic regression was used to analyze the association between baseline factors and future antimycobacterial treatment among children who had no antimycobacterial treatment at time of start of ART. Results: The prevalence of antimycobacterial treatment at the time of starting ART was 518/1941 (26.7%, 95% confidence interval (CI): 24.7-28.7). Among children who started ART without antimycobacterial treatment, the KM cumulative probability of antiretroviral and antimycobacterial (ART/antimycobacterial) co-treatment in the first 3 months of starting ART was 4.6% (95% CI: 4.1- 5.2), in the first 12 months it was 18.1% (95% CI: 17.0-19.2) and in the first 24 months of starting ART it was 24% (95% CI: 21.9-25.1). Survival analysis suggested that children with high baseline viral load, advanced World Health Organization (WHO) stage of disease, very low normalized weight for age (waz) and very young age (less than one year) at start of ART had significantly reduced antimycobacterial treatment-free survival (log rank p &lt / 0.05) in the first two years of starting ART. In the logistic regression model, age less than one year {Odds ratio (OR): 3.7 (95% CI: 2.2-6.0 / p &lt / 0.0001)} and very low weight for age Z-score (waz &lt / -3) {OR / 2.2 (95% CI: 1.4-3.6 / p = 0.0015)} were the two critical risk factors independently associated with future antimycobacterial treatment. Conclusions: Antimycobacterial treatment is extremely common among HIV-infected children at the time of starting ART and early after starting ART and the incremental risk of being on ART/antimycobacterial co-treatment decreases with time on ART. The results emphasize the need for a heightened and careful alertness for mycobacterial events especially among children starting ART with severe malnutrition and those who start ART at age less than one year. The results further suggest that it is probably optimal to start ART in children before their nutritional status has deteriorated severely in the course of the HIV disease so that they get protection against mycobacterial events by early ART.</p>

Magister Public Health - MPH / Background: Although clinicians encounter antimycobacterial treatment in Human mmunodeficiency (HIV)-infected children as one of the most common treatments coadministered with antiretroviral treatment (ART), quantitative data on the extent of antimycobacterial treatment among HIV-infected children at the time of commencement of ART and at different times during ART is scarce. The baseline risk factors associated with being on both ART and antimycobacterial treatments are not known and it remains to be elucidated how the different exposure factors impact on the antimycobacterial treatment-free survival of children who begin ART without antimycobacterial treatment.Objectives: To describe the prevalence of antimycobacterial treatment among children at the time of starting ART and the antimycobacterial treatment-free survival after starting ART. Design: A retrospective cohort study based on record reviews at the Harriet Shezi children&lsquo;s clinic (HSCC).Population: HIV-infected children less than fifteen years of age presumed ART naïve started on ART at HSCC.Analysis: A descriptive analysis of the prevalence of antimycobacterial treatment at time of start of ART was done. Kaplan Meier (KM) survival curves were used to determine the antimycobacterial treatment-free survival and logistic regression was used to analyze the association between baseline factors and future antimycobacterial treatment among children who had no antimycobacterial treatment at time of start of ART. Results: The prevalence of antimycobacterial treatment at the time of starting ART was 518/1941 (26.7%, 95% confidence interval (CI): 24.7-28.7). Among children who started ART without antimycobacterial treatment, the KM cumulative probability of antiretroviral and antimycobacterial (ART/antimycobacterial) co-treatment in the first 3 months of starting ART was 4.6% (95% CI: 4.1- 5.2), in the first 12 months it was 18.1% (95% CI: 17.0-19.2) and in the first 24 months of starting ART it was 24% (95% CI: 21.9-25.1). Survival analysis suggested that children with high baseline viral load, advanced World Health Organization (WHO) stage of disease, very low normalized weight for age (waz) and very young age (less than one year) at start of ART had significantly reduced antimycobacterial treatment-free survival (log rank p < 0.05) in the first two years of starting ART. In the logistic regression model, age less than one year {Odds ratio (OR): 3.7 (95% CI: 2.2-6.0; p <0.0001)} and very low weight for age Z-score (waz < -3) {OR; 2.2 (95% CI: 1.4-3.6; p = 0.0015)} were the two critical risk factors independently associated with future antimycobacterial treatment. Conclusions: Antimycobacterial treatment is extremely common among HIV-infected children at the time of starting ART and early after starting ART and the incremental risk of being on ART/antimycobacterial co-treatment decreases with time on ART. The results emphasize the need for a heightened and careful alertness for mycobacterial events especially among children starting ART with severe malnutrition and those who start ART at age less than one year. The results further suggest that it is probably optimal to start ART in children before their nutritional status has deteriorated severely in the course of the HIV disease so that they get protection against mycobacterial events by early ART. / South Africa

Atualmente, a Leucemia Linfocítica Crônica (LLC) pode ser dividida em dois grupos: um com mutações somáticas no gene da região variável da cadeia pesada da imunoglobulina (MIgVH) e outro sem mutações (NMIgVH). Alguns estudos mostraram que a expressão de CD38 na superfície das células B de LLC pode estar correlacionada com o estado mutacional do gene VHIg, entretanto, esses controversos. Estudos recentes mostraram que a expressão da proteína tirosina quinase Zap-70 está melhor associada com o estado mutacional do gene IgVH. O objetivo deste estudo foi avaliar a expressão de Zap-70 e CD38, por citometria de fluxo, nas células CD19+ de pacientes com LLC e correlacioná-los com o estádio clínico (EC), sobrevida livre de tratamento (SLT) e sobrevida global (SG). A expressão de Zap-70 e CD38 foi avaliada, em 144 de pacientes com LLC classificados nos estádios clínicos A, B e C de acordo com os critérios de Binet: 59 (41%) do EC-A, 38 (26%) do EC-B e 47 (33%) do EC-C. Foi observada menor positividade para Zap-70 e CD38 nos pacientes do EC-A do que nos EC-B e C. Quando avaliada a SLT nos pacientes do EC-A, os casos Zap-70+ assim como os CD38+ apresentaram menor SLT. A média de SG dos pacientes Zap-70+ e CD38+ foi menor quando comparado com os Zap-70- e CD38- entretanto quando correlacionada com o EC não foi observada diferença estatisticamente significante entre a expressão desses marcadores e o EC-A, B ou C. Pela analise combinada de CD38 e Zap-70, dividimos os pacientes em dois grupos (Zap-70-/CD38- e Zap-70+ ou CD38+). Observamos que a expressão positiva desses dois marcadores estava associada ao EC, uma vez que a grande maioria dos pacientes dos estádios B (74%) e C (66%) expressam Zap-70 ou CD38. Entretanto, os pacientes do EC-A, Zap-70+ ou CD38+, apresentaram SG menor quando comparado com os Zap-70-/CD38-. Essa diferença não foi observada nos pacientes do EC-B e do EC-C. Também foi observada menor SLT nos pacientes no EC-A, Zap-70+ ou CD38+. Esses resultados sugerem que análise combinada de Zap-70 e CD38 podem ser empregadas na avaliação dos pacientes do EC-A para se acompanhar a evolução clinica desse grupo de pacientes. Porém, estudos adicionais devem ser realizados para se validar a utilização clínica desses marcadores. / Actually, chronic lymphocytic leukemia (CLL) can be divided in two subsets: one with somatically mutated immunoglobulin heavy-chain variable-region genes (MIgVH) and other with unmutated sequences. (UMIgVH). Some studies have shown that CD38 expression in CLL cells are correlated with IgVH mutational status. However, the value of CD38 as surrogate IgVH mutational status is controversial. Recent studies, have found that Zap-70 protein tyrosine kinase expression is strongly associated with the mutational status IgVH. The aim of this study was to evaluate the Zap-70 and CD38 expression, for flow cytometry, in CD19+ LLC cells and correlate with the Binet’s staging system, treatment-free survival (TFS) and a overall survival (OS). Zap-70 and CD38 was evaluated, in 144 CLL patients that was classified in A, B and C Binet’s staging system: 59 (41%) in stage A, 38 (26%) in B and 47 (33%) in C. We observed low Zap-70 and CD38 expression in stage A patients than in stage B and C cases. When we analyzed the TFS in stage A patients Zap-70+ and CD38+ patients showed shorter TFS than Zap-70- and CD38-. Then we observed that the OS of Zap-70+ and CD38+ patients was, also, shorter than Zap-70- and CD38- cases. However, statistical differences was not found when Zap-70 and CD38 expression was correlated with stage A, B or C Binet’s staging system. To understand the associated Zap-70 and CD38 expression, we divided the CLL patients in two subgroups (Zap-70-/CD38 - and Zap-70+ or CD38+). We observed that CD38+ or Zap-70+ was associated Binet’s staging system, once most of stage B (74%) and C (66%) patients are Zap-70+ or CD38+. However, stage A patients, Zap-70+ or CD38+, showed shorter OS than Zap-70-/CD38-. These differences were not observed in stage B and C patients. Shorter TFS was also observed in the Zap-70+ or CD38+ stage A patients. These results suggest that combined analysis of Zap-70 and CD38 can be used to evaluate stage A patients to observe the clinical evolution of the disease. Nevertheless, other studies must be carried to confirm the clinical use of these markers.

Atualmente, a Leucemia Linfocítica Crônica (LLC) pode ser dividida em dois grupos: um com mutações somáticas no gene da região variável da cadeia pesada da imunoglobulina (MIgVH) e outro sem mutações (NMIgVH). Alguns estudos mostraram que a expressão de CD38 na superfície das células B de LLC pode estar correlacionada com o estado mutacional do gene VHIg, entretanto, esses controversos. Estudos recentes mostraram que a expressão da proteína tirosina quinase Zap-70 está melhor associada com o estado mutacional do gene IgVH. O objetivo deste estudo foi avaliar a expressão de Zap-70 e CD38, por citometria de fluxo, nas células CD19+ de pacientes com LLC e correlacioná-los com o estádio clínico (EC), sobrevida livre de tratamento (SLT) e sobrevida global (SG). A expressão de Zap-70 e CD38 foi avaliada, em 144 de pacientes com LLC classificados nos estádios clínicos A, B e C de acordo com os critérios de Binet: 59 (41%) do EC-A, 38 (26%) do EC-B e 47 (33%) do EC-C. Foi observada menor positividade para Zap-70 e CD38 nos pacientes do EC-A do que nos EC-B e C. Quando avaliada a SLT nos pacientes do EC-A, os casos Zap-70+ assim como os CD38+ apresentaram menor SLT. A média de SG dos pacientes Zap-70+ e CD38+ foi menor quando comparado com os Zap-70- e CD38- entretanto quando correlacionada com o EC não foi observada diferença estatisticamente significante entre a expressão desses marcadores e o EC-A, B ou C. Pela analise combinada de CD38 e Zap-70, dividimos os pacientes em dois grupos (Zap-70-/CD38- e Zap-70+ ou CD38+). Observamos que a expressão positiva desses dois marcadores estava associada ao EC, uma vez que a grande maioria dos pacientes dos estádios B (74%) e C (66%) expressam Zap-70 ou CD38. Entretanto, os pacientes do EC-A, Zap-70+ ou CD38+, apresentaram SG menor quando comparado com os Zap-70-/CD38-. Essa diferença não foi observada nos pacientes do EC-B e do EC-C. Também foi observada menor SLT nos pacientes no EC-A, Zap-70+ ou CD38+. Esses resultados sugerem que análise combinada de Zap-70 e CD38 podem ser empregadas na avaliação dos pacientes do EC-A para se acompanhar a evolução clinica desse grupo de pacientes. Porém, estudos adicionais devem ser realizados para se validar a utilização clínica desses marcadores. / Actually, chronic lymphocytic leukemia (CLL) can be divided in two subsets: one with somatically mutated immunoglobulin heavy-chain variable-region genes (MIgVH) and other with unmutated sequences. (UMIgVH). Some studies have shown that CD38 expression in CLL cells are correlated with IgVH mutational status. However, the value of CD38 as surrogate IgVH mutational status is controversial. Recent studies, have found that Zap-70 protein tyrosine kinase expression is strongly associated with the mutational status IgVH. The aim of this study was to evaluate the Zap-70 and CD38 expression, for flow cytometry, in CD19+ LLC cells and correlate with the Binet’s staging system, treatment-free survival (TFS) and a overall survival (OS). Zap-70 and CD38 was evaluated, in 144 CLL patients that was classified in A, B and C Binet’s staging system: 59 (41%) in stage A, 38 (26%) in B and 47 (33%) in C. We observed low Zap-70 and CD38 expression in stage A patients than in stage B and C cases. When we analyzed the TFS in stage A patients Zap-70+ and CD38+ patients showed shorter TFS than Zap-70- and CD38-. Then we observed that the OS of Zap-70+ and CD38+ patients was, also, shorter than Zap-70- and CD38- cases. However, statistical differences was not found when Zap-70 and CD38 expression was correlated with stage A, B or C Binet’s staging system. To understand the associated Zap-70 and CD38 expression, we divided the CLL patients in two subgroups (Zap-70-/CD38 - and Zap-70+ or CD38+). We observed that CD38+ or Zap-70+ was associated Binet’s staging system, once most of stage B (74%) and C (66%) patients are Zap-70+ or CD38+. However, stage A patients, Zap-70+ or CD38+, showed shorter OS than Zap-70-/CD38-. These differences were not observed in stage B and C patients. Shorter TFS was also observed in the Zap-70+ or CD38+ stage A patients. These results suggest that combined analysis of Zap-70 and CD38 can be used to evaluate stage A patients to observe the clinical evolution of the disease. Nevertheless, other studies must be carried to confirm the clinical use of these markers.