Global ETD Search

1	Modelling the epidemiology and management of HIV / AIDS in the era of HAART Fang, Yongxiang January 2001 (has links) No description available. 610 Highly active anti-retroviral therapy
2	Preeclampsia in HIV Positive Pregnant Women on Highly Active Anti-retroviral Therapy: A Matched Cohort Study Boyajian, Talar 15 December 2010 (has links) Background: Some studies have suggested that the risk of preeclampsia in HIV positive pregnant women has increased since the use of HAART became routine. There is also a concern that HIV positive women on HAART have a higher risk of adverse fetal outcomes compared to HIV negative women. Methods: In this matched retrospective cohort study, the risk of preeclampsia and adverse fetal outcomes was examined in 91 HIV positive pregnant women receiving HAART and 273 HIV negative pregnant women. Multivariate logistic regression models were used to adjust for confounding factors. Results: The risk of preeclampsia and preterm birth did not differ significantly between HIV positive and HIV negative women. HIV treated with HAART was an independent predictor for giving birth to a low birthweight baby. Conclusions: HIV positive women on HAART do not have a higher risk of preeclampsia. They do however have a higher risk for lower birthweight infants. Human immunodeficiency virus preeclampsia Highly Active Anti Retroviral Therapy low birthweight pregnancy 0380
3	Preeclampsia in HIV Positive Pregnant Women on Highly Active Anti-retroviral Therapy: A Matched Cohort Study Boyajian, Talar 15 December 2010 (has links) Background: Some studies have suggested that the risk of preeclampsia in HIV positive pregnant women has increased since the use of HAART became routine. There is also a concern that HIV positive women on HAART have a higher risk of adverse fetal outcomes compared to HIV negative women. Methods: In this matched retrospective cohort study, the risk of preeclampsia and adverse fetal outcomes was examined in 91 HIV positive pregnant women receiving HAART and 273 HIV negative pregnant women. Multivariate logistic regression models were used to adjust for confounding factors. Results: The risk of preeclampsia and preterm birth did not differ significantly between HIV positive and HIV negative women. HIV treated with HAART was an independent predictor for giving birth to a low birthweight baby. Conclusions: HIV positive women on HAART do not have a higher risk of preeclampsia. They do however have a higher risk for lower birthweight infants. Human immunodeficiency virus preeclampsia Highly Active Anti Retroviral Therapy low birthweight pregnancy 0380
4	Response to Pneumococcal-Polysaccharide Vaccine PPV23 in HIV-Positive Individuals Iyer, Anita Sridhar January 2015 (has links) No description available. Biomedical Research Immunology Microbiology
5	Intervenção nutricional previne alterações do perfil lipídico em indivíduos HIV-Positivo que iniciam terapêutica anti-retroviral : um ensaio clínico randomizado Lazzaretti, Rosmeri Kuhmmer January 2007 (has links) Introdução: A Terapia Anti-Retroviral combinada (TARV) em indivíduos infectados com HIV-1 está associada ao desenvolvimento de dislipidemia, que é caracterizada por hipertrigliceridemia e hipercolesterolemia. As diretrizes atuais recomendam dieta e exercício físico como primeira intervenção para indivíduos HIV-1 com dislipidemia secundária aos anti-retrovirais, mas não há evidências clínicas com estudos randomizados que sustentem estas recomendações. Objetivo: Avaliar a influência da intervenção nutricional no desenvolvimento de dislipidemia em indivíduos com HIV-1 que iniciam TARV. Métodos: Indivíduos em acompanhamento regular e que preencheram os critérios de inclusão (necessidade de iniciar terapia anti-retroviral, idade >=18 anos e aceitar participar do estudo) e exclusão (gestantes, doença oportunista ativa, deficiência mental, diabetes melito, uso de drogas que alteram o perfil lipídico, hipolipemiantes ou drogas ilícitas), foram selecionados no ambulatório de HIV/AIDS do Hospital de Clínicas de Porto Alegre (Brasil). Os pacientes foram randomizados para receberem orientação nutricional para uma reeducação alimentar antes de iniciar a terapia anti-retroviral, e posteriormente orientação trimestral enfocando as dislipidemias, baseada no National Cholesterol Education Program (NCEP), (n = 43), durante 12 meses, ou para um grupo controle que recebeu a mesma orientação nutricional basal, porém sem seguimento orientado (n = 40). Perfil lipídico, índice de massa corporal (IMC) e razão cintura/quadril foram avaliados a cada três meses. Dados foram analisados por intenção de tratar, usando modelo linear misto Após a randomização as características basais foram semelhantes entre os grupos. Resultados: A intervenção dietoterápica propiciou uma redução nas calorias totais (média ± DP: de 2662 ± 614 para 2281 ± 512 kcal/dia) e o no percentual de gorduras (de 31 ± 7 para 21 ± 3%) ingerido, enquanto que o grupo controle aumentou a ingestão de calorias (de 2594 ± 550 para 2806 ± 653 kcal/dia) e não houve mudanças no percentual de gordura ingerido. O IMC manteve-se constante no grupo intervenção enquanto que no grupo controle aumentou significativamente (23,5 ± 3 para 24,2 ± 3 e 23,3 ± 3 para 26,2 ± 4; p < 0,001, respectivamente). A razão cintura/quadril aumentou em ambos os grupos, porém mais acentuadamente no grupo controle (0,86 ± 0,06 para 0,89 ± 0,06 e 0,86 ± 0,05 para 0,91 ± 0,06; p = 0,049, respectivamente). O colesterol total (de 151 ± 29 mg/dl para 190 ± 33 mg/dl) e o LDL-C (de 85 ± 24 mg/dl para 106 ± 31 mg/dl) aumentaram significativamente no grupo controle e permaneceram inalterados no grupo intervenção. Os níveis plasmáticos de triglicerídeos reduziram no grupo intervenção (135 ± 67 mg/dl para 101 ± 42 mg/dl) e aumentaram no controle (134 ± 70 mg/dl para 160 ± 76 mg/dl). Após 12 meses de acompanhamento, 21% dos indivíduos que receberam intervenção nutricional apresentaram níveis lipídicos compatíveis com dislipidemia comparados com 68% (p < 0,001) no grupo controle. Conclusão: O estudo demonstra que a intervenção nutricional previne dislipidemia associada à TARV em indivíduos infectados com HIV-1 em início de tratamento. / Background: Treatment of HIV-1-infected individuals with Highly Active Anti- Retroviral Therapy (HAART) is associated with dyslipidemia, which is characterized by hypertriglyceridemia and hypercholesterolemia. Current guidelines recommend diet and exercise as first step intervention for HIV-1-infected individuals with HAART-related dyslipidemia, but there is no evidence from randomized trials to support this recommendation. Objective: To evaluate the effects of dietary intervention on the development of dyslipidemia in HIV-1 infected individuals who are started on HAART. Methods: Eighty-three HIV-1- infected patients naive from previous treatment were randomized to receive HAART with dietary intervention (n = 43) or HAART without dietary intervention (controls, n = 40) for 12 months. Dietary intervention, according to the National Cholesterol Education Program, was given every 3 months. Before and after intervention, 24 h food records, body mass index, weight/hip ratio, and lipid profile were obtained. Data were analyzed by intention to treat, using mixed-effects models. Results: After randomization, groups had similar characteristics. Dietary intervention resulted in reduction in total caloric intake (mean ± SD: from 2,662 ± 14 to 2,281 ± 512 kcal/day) and percentage of fat intake (from 31 ± 7 to 21 ± 3% of calories), while controls increased caloric intake (from 2,594 ± 550 to 2,806 ± 653 kcal/day), with no change in percentage of fat intake. Body mass index stayed in the group intervention while in the group control it increased significantly (from 23,5 ± 3 to 24,2 ± 3 and 23,3 ± 3 to 26,2 ± 4; p < 0,001, respectively) The waist/hip ratio increased in both groups, however more strongly in the group control (from 0,86 ± 0,06 to 0,89 ± 0,06 and 0,86 ±0,05 to 0,91 ± 0,06; p = 0,049, respectively). Plasma cholesterol (from 151 ± 29 to 190 ± 33 mg/dl) and LDL-C-cholesterol (from 85 ± 24 to 106 ± 31 mg/dl) increased in the controls and were unchanged in the dietary intervention group. Plasma triglycerides were reduced by dietary intervention (from 135 ± 67 to 101 ± 42 mg/dl) and increased in controls (from 134 ± 70 to 160,76 mg/dl). After one year follow-up, 21% of patients who received dietary intervention had lipid profile compatible with dyslipidemia, while 68% (p < 0.001) of controls had dyslipidemia. Conclusion: This randomized trial demonstrates that dietary intervention prevents dyslipidemia associated with HAART in HIV-1-infected individuals. Terapia nutricional HIV Lipídeos Dislipidemias HIV/AIDS Highly active anti-retroviral therapy Nutrition Dyslipidemia
6	Intervenção nutricional previne alterações do perfil lipídico em indivíduos HIV-Positivo que iniciam terapêutica anti-retroviral : um ensaio clínico randomizado Lazzaretti, Rosmeri Kuhmmer January 2007 (has links) Introdução: A Terapia Anti-Retroviral combinada (TARV) em indivíduos infectados com HIV-1 está associada ao desenvolvimento de dislipidemia, que é caracterizada por hipertrigliceridemia e hipercolesterolemia. As diretrizes atuais recomendam dieta e exercício físico como primeira intervenção para indivíduos HIV-1 com dislipidemia secundária aos anti-retrovirais, mas não há evidências clínicas com estudos randomizados que sustentem estas recomendações. Objetivo: Avaliar a influência da intervenção nutricional no desenvolvimento de dislipidemia em indivíduos com HIV-1 que iniciam TARV. Métodos: Indivíduos em acompanhamento regular e que preencheram os critérios de inclusão (necessidade de iniciar terapia anti-retroviral, idade >=18 anos e aceitar participar do estudo) e exclusão (gestantes, doença oportunista ativa, deficiência mental, diabetes melito, uso de drogas que alteram o perfil lipídico, hipolipemiantes ou drogas ilícitas), foram selecionados no ambulatório de HIV/AIDS do Hospital de Clínicas de Porto Alegre (Brasil). Os pacientes foram randomizados para receberem orientação nutricional para uma reeducação alimentar antes de iniciar a terapia anti-retroviral, e posteriormente orientação trimestral enfocando as dislipidemias, baseada no National Cholesterol Education Program (NCEP), (n = 43), durante 12 meses, ou para um grupo controle que recebeu a mesma orientação nutricional basal, porém sem seguimento orientado (n = 40). Perfil lipídico, índice de massa corporal (IMC) e razão cintura/quadril foram avaliados a cada três meses. Dados foram analisados por intenção de tratar, usando modelo linear misto Após a randomização as características basais foram semelhantes entre os grupos. Resultados: A intervenção dietoterápica propiciou uma redução nas calorias totais (média ± DP: de 2662 ± 614 para 2281 ± 512 kcal/dia) e o no percentual de gorduras (de 31 ± 7 para 21 ± 3%) ingerido, enquanto que o grupo controle aumentou a ingestão de calorias (de 2594 ± 550 para 2806 ± 653 kcal/dia) e não houve mudanças no percentual de gordura ingerido. O IMC manteve-se constante no grupo intervenção enquanto que no grupo controle aumentou significativamente (23,5 ± 3 para 24,2 ± 3 e 23,3 ± 3 para 26,2 ± 4; p < 0,001, respectivamente). A razão cintura/quadril aumentou em ambos os grupos, porém mais acentuadamente no grupo controle (0,86 ± 0,06 para 0,89 ± 0,06 e 0,86 ± 0,05 para 0,91 ± 0,06; p = 0,049, respectivamente). O colesterol total (de 151 ± 29 mg/dl para 190 ± 33 mg/dl) e o LDL-C (de 85 ± 24 mg/dl para 106 ± 31 mg/dl) aumentaram significativamente no grupo controle e permaneceram inalterados no grupo intervenção. Os níveis plasmáticos de triglicerídeos reduziram no grupo intervenção (135 ± 67 mg/dl para 101 ± 42 mg/dl) e aumentaram no controle (134 ± 70 mg/dl para 160 ± 76 mg/dl). Após 12 meses de acompanhamento, 21% dos indivíduos que receberam intervenção nutricional apresentaram níveis lipídicos compatíveis com dislipidemia comparados com 68% (p < 0,001) no grupo controle. Conclusão: O estudo demonstra que a intervenção nutricional previne dislipidemia associada à TARV em indivíduos infectados com HIV-1 em início de tratamento. / Background: Treatment of HIV-1-infected individuals with Highly Active Anti- Retroviral Therapy (HAART) is associated with dyslipidemia, which is characterized by hypertriglyceridemia and hypercholesterolemia. Current guidelines recommend diet and exercise as first step intervention for HIV-1-infected individuals with HAART-related dyslipidemia, but there is no evidence from randomized trials to support this recommendation. Objective: To evaluate the effects of dietary intervention on the development of dyslipidemia in HIV-1 infected individuals who are started on HAART. Methods: Eighty-three HIV-1- infected patients naive from previous treatment were randomized to receive HAART with dietary intervention (n = 43) or HAART without dietary intervention (controls, n = 40) for 12 months. Dietary intervention, according to the National Cholesterol Education Program, was given every 3 months. Before and after intervention, 24 h food records, body mass index, weight/hip ratio, and lipid profile were obtained. Data were analyzed by intention to treat, using mixed-effects models. Results: After randomization, groups had similar characteristics. Dietary intervention resulted in reduction in total caloric intake (mean ± SD: from 2,662 ± 14 to 2,281 ± 512 kcal/day) and percentage of fat intake (from 31 ± 7 to 21 ± 3% of calories), while controls increased caloric intake (from 2,594 ± 550 to 2,806 ± 653 kcal/day), with no change in percentage of fat intake. Body mass index stayed in the group intervention while in the group control it increased significantly (from 23,5 ± 3 to 24,2 ± 3 and 23,3 ± 3 to 26,2 ± 4; p < 0,001, respectively) The waist/hip ratio increased in both groups, however more strongly in the group control (from 0,86 ± 0,06 to 0,89 ± 0,06 and 0,86 ±0,05 to 0,91 ± 0,06; p = 0,049, respectively). Plasma cholesterol (from 151 ± 29 to 190 ± 33 mg/dl) and LDL-C-cholesterol (from 85 ± 24 to 106 ± 31 mg/dl) increased in the controls and were unchanged in the dietary intervention group. Plasma triglycerides were reduced by dietary intervention (from 135 ± 67 to 101 ± 42 mg/dl) and increased in controls (from 134 ± 70 to 160,76 mg/dl). After one year follow-up, 21% of patients who received dietary intervention had lipid profile compatible with dyslipidemia, while 68% (p < 0.001) of controls had dyslipidemia. Conclusion: This randomized trial demonstrates that dietary intervention prevents dyslipidemia associated with HAART in HIV-1-infected individuals. Terapia nutricional HIV Lipídeos Dislipidemias HIV/AIDS Highly active anti-retroviral therapy Nutrition Dyslipidemia
7	Intervenção nutricional previne alterações do perfil lipídico em indivíduos HIV-Positivo que iniciam terapêutica anti-retroviral : um ensaio clínico randomizado Lazzaretti, Rosmeri Kuhmmer January 2007 (has links) Introdução: A Terapia Anti-Retroviral combinada (TARV) em indivíduos infectados com HIV-1 está associada ao desenvolvimento de dislipidemia, que é caracterizada por hipertrigliceridemia e hipercolesterolemia. As diretrizes atuais recomendam dieta e exercício físico como primeira intervenção para indivíduos HIV-1 com dislipidemia secundária aos anti-retrovirais, mas não há evidências clínicas com estudos randomizados que sustentem estas recomendações. Objetivo: Avaliar a influência da intervenção nutricional no desenvolvimento de dislipidemia em indivíduos com HIV-1 que iniciam TARV. Métodos: Indivíduos em acompanhamento regular e que preencheram os critérios de inclusão (necessidade de iniciar terapia anti-retroviral, idade >=18 anos e aceitar participar do estudo) e exclusão (gestantes, doença oportunista ativa, deficiência mental, diabetes melito, uso de drogas que alteram o perfil lipídico, hipolipemiantes ou drogas ilícitas), foram selecionados no ambulatório de HIV/AIDS do Hospital de Clínicas de Porto Alegre (Brasil). Os pacientes foram randomizados para receberem orientação nutricional para uma reeducação alimentar antes de iniciar a terapia anti-retroviral, e posteriormente orientação trimestral enfocando as dislipidemias, baseada no National Cholesterol Education Program (NCEP), (n = 43), durante 12 meses, ou para um grupo controle que recebeu a mesma orientação nutricional basal, porém sem seguimento orientado (n = 40). Perfil lipídico, índice de massa corporal (IMC) e razão cintura/quadril foram avaliados a cada três meses. Dados foram analisados por intenção de tratar, usando modelo linear misto Após a randomização as características basais foram semelhantes entre os grupos. Resultados: A intervenção dietoterápica propiciou uma redução nas calorias totais (média ± DP: de 2662 ± 614 para 2281 ± 512 kcal/dia) e o no percentual de gorduras (de 31 ± 7 para 21 ± 3%) ingerido, enquanto que o grupo controle aumentou a ingestão de calorias (de 2594 ± 550 para 2806 ± 653 kcal/dia) e não houve mudanças no percentual de gordura ingerido. O IMC manteve-se constante no grupo intervenção enquanto que no grupo controle aumentou significativamente (23,5 ± 3 para 24,2 ± 3 e 23,3 ± 3 para 26,2 ± 4; p < 0,001, respectivamente). A razão cintura/quadril aumentou em ambos os grupos, porém mais acentuadamente no grupo controle (0,86 ± 0,06 para 0,89 ± 0,06 e 0,86 ± 0,05 para 0,91 ± 0,06; p = 0,049, respectivamente). O colesterol total (de 151 ± 29 mg/dl para 190 ± 33 mg/dl) e o LDL-C (de 85 ± 24 mg/dl para 106 ± 31 mg/dl) aumentaram significativamente no grupo controle e permaneceram inalterados no grupo intervenção. Os níveis plasmáticos de triglicerídeos reduziram no grupo intervenção (135 ± 67 mg/dl para 101 ± 42 mg/dl) e aumentaram no controle (134 ± 70 mg/dl para 160 ± 76 mg/dl). Após 12 meses de acompanhamento, 21% dos indivíduos que receberam intervenção nutricional apresentaram níveis lipídicos compatíveis com dislipidemia comparados com 68% (p < 0,001) no grupo controle. Conclusão: O estudo demonstra que a intervenção nutricional previne dislipidemia associada à TARV em indivíduos infectados com HIV-1 em início de tratamento. / Background: Treatment of HIV-1-infected individuals with Highly Active Anti- Retroviral Therapy (HAART) is associated with dyslipidemia, which is characterized by hypertriglyceridemia and hypercholesterolemia. Current guidelines recommend diet and exercise as first step intervention for HIV-1-infected individuals with HAART-related dyslipidemia, but there is no evidence from randomized trials to support this recommendation. Objective: To evaluate the effects of dietary intervention on the development of dyslipidemia in HIV-1 infected individuals who are started on HAART. Methods: Eighty-three HIV-1- infected patients naive from previous treatment were randomized to receive HAART with dietary intervention (n = 43) or HAART without dietary intervention (controls, n = 40) for 12 months. Dietary intervention, according to the National Cholesterol Education Program, was given every 3 months. Before and after intervention, 24 h food records, body mass index, weight/hip ratio, and lipid profile were obtained. Data were analyzed by intention to treat, using mixed-effects models. Results: After randomization, groups had similar characteristics. Dietary intervention resulted in reduction in total caloric intake (mean ± SD: from 2,662 ± 14 to 2,281 ± 512 kcal/day) and percentage of fat intake (from 31 ± 7 to 21 ± 3% of calories), while controls increased caloric intake (from 2,594 ± 550 to 2,806 ± 653 kcal/day), with no change in percentage of fat intake. Body mass index stayed in the group intervention while in the group control it increased significantly (from 23,5 ± 3 to 24,2 ± 3 and 23,3 ± 3 to 26,2 ± 4; p < 0,001, respectively) The waist/hip ratio increased in both groups, however more strongly in the group control (from 0,86 ± 0,06 to 0,89 ± 0,06 and 0,86 ±0,05 to 0,91 ± 0,06; p = 0,049, respectively). Plasma cholesterol (from 151 ± 29 to 190 ± 33 mg/dl) and LDL-C-cholesterol (from 85 ± 24 to 106 ± 31 mg/dl) increased in the controls and were unchanged in the dietary intervention group. Plasma triglycerides were reduced by dietary intervention (from 135 ± 67 to 101 ± 42 mg/dl) and increased in controls (from 134 ± 70 to 160,76 mg/dl). After one year follow-up, 21% of patients who received dietary intervention had lipid profile compatible with dyslipidemia, while 68% (p < 0.001) of controls had dyslipidemia. Conclusion: This randomized trial demonstrates that dietary intervention prevents dyslipidemia associated with HAART in HIV-1-infected individuals. Terapia nutricional HIV Lipídeos Dislipidemias HIV/AIDS Highly active anti-retroviral therapy Nutrition Dyslipidemia
8	Assessment of health-related quality of life of adult highly active anti-retroviral therapy recipients at the Kagera Regional Hospital Tanzania. Magafu, Mgaywa. 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style="font-size: 10pt / font-family: &quot / Times New Roman&quot / ,&quot / serif&quot / ">Background: The care and treatment for people with HIV/AIDS (PLWHA) at the Kagera regional hospital began in February 2005. It is important to evaluate quality of life (QOL) of highly active anti-retroviral therapy (HAART) recipients periodical to assess HAART&rsquo / s effectiveness. This study aimed to assess the health-related QOL (HRQOL) of HAART recipients and determine factors associated with it, two years after the programme had started at the kagera regional hospital in Tanzania. Results: The HRQOL of HAART recipients was generally lower than that of the general population. However, the general health perceptions (p=0.191) and mental health (p=0.161) means score of HAART recipients were not different from those of the Tanzanian general population. About 89% of the HAART recipients reported better health than in the previous years. Chronic diseases were associated with lower HRQOL of HAART recipients independently of other factors. HAART recipients with chronic diseases co-morbidity were more likely to score below the general population&rsquo / s mean score for mental health (p=0.007). While the effect of chronic diseases on HRQOL among those who recorded CD4+ cell increase was negative (OR=13.6,95%CI=3.7 / 49.9), there was no effect on those who did not have such an increase. Adherence to ARVs and CD4+ cell count were not associated with HRQOL. &nbsp / &nbsp / &nbsp / &nbsp / &nbsp / &nbsp / <span style=""> <o:p></o:p></span></span></p> <p style="margin-bottom: 0.0001pt / line-height: normal / " class="MsoNormal"><span style="font-size: 12pt / font-family: &quot / Times New Roman&quot / ,&quot / serif&quot / "><o:p>&nbsp / </o:p></span></p> <span style="font-size: 12pt / font-family: &quot / Times New Roman&quot / ,&quot / serif&quot / "><span style="">&nbsp / </span><span style="">&nbsp / </span><span style="">&nbsp / </span><span style="">&nbsp / </span><span style=""> </span><o:p></o:p></span></p> <p>&nbsp / </p> HIV/AIDS People living with HIV/AIDS Highly active anti-retroviral therapy care and treatment anti-retroviral therapy Kagera regional hospital Tanzania.
9	Assessment of health-related quality of life of adult highly active anti-retroviral therapy recipients at the Kagera Regional Hospital Tanzania. Magafu, Mgaywa. 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style="font-size: 10pt / font-family: &quot / Times New Roman&quot / ,&quot / serif&quot / ">Background: The care and treatment for people with HIV/AIDS (PLWHA) at the Kagera regional hospital began in February 2005. It is important to evaluate quality of life (QOL) of highly active anti-retroviral therapy (HAART) recipients periodical to assess HAART&rsquo / s effectiveness. This study aimed to assess the health-related QOL (HRQOL) of HAART recipients and determine factors associated with it, two years after the programme had started at the kagera regional hospital in Tanzania. Results: The HRQOL of HAART recipients was generally lower than that of the general population. However, the general health perceptions (p=0.191) and mental health (p=0.161) means score of HAART recipients were not different from those of the Tanzanian general population. About 89% of the HAART recipients reported better health than in the previous years. Chronic diseases were associated with lower HRQOL of HAART recipients independently of other factors. HAART recipients with chronic diseases co-morbidity were more likely to score below the general population&rsquo / s mean score for mental health (p=0.007). While the effect of chronic diseases on HRQOL among those who recorded CD4+ cell increase was negative (OR=13.6,95%CI=3.7 / 49.9), there was no effect on those who did not have such an increase. Adherence to ARVs and CD4+ cell count were not associated with HRQOL. &nbsp / &nbsp / &nbsp / &nbsp / &nbsp / &nbsp / <span style=""> <o:p></o:p></span></span></p> <p style="margin-bottom: 0.0001pt / line-height: normal / " class="MsoNormal"><span style="font-size: 12pt / font-family: &quot / Times New Roman&quot / ,&quot / serif&quot / "><o:p>&nbsp / </o:p></span></p> <span style="font-size: 12pt / font-family: &quot / Times New Roman&quot / ,&quot / serif&quot / "><span style="">&nbsp / </span><span style="">&nbsp / </span><span style="">&nbsp / </span><span style="">&nbsp / </span><span style=""> </span><o:p></o:p></span></p> <p>&nbsp / </p> HIV/AIDS People living with HIV/AIDS Highly active anti-retroviral therapy care and treatment anti-retroviral therapy Kagera regional hospital Tanzania.
10	gp120 Immunogen Design And Characterization Chakraborty, Kausik 06 1900 (has links) (PDF) HIV-1 is the causative agent for AIDS and has been a major focus of research for the past two decades. Though there is a combination therapy in place known as the “Highly Active Anti-Retroviral Therapy” (HAART), its usefulness is confounded by the generation of escape mutants, a host of side effects, and its prohibitive cost. The most useful alternative would be the prevention of infection by vaccination. Vaccine research has been focused on the use of recombinant protein sub-units of the virus or combinations thereof to elicit a neutralizing response against the virus. These approaches have mostly resulted in a failure to generate broadly cross reactive neutralizing response against primary strains of the virus. The work reported herein is aimed at designing a rigidified version of gp120/gp120 derivatives and understanding the scope of the various antigenic regions in gp120 in generating a neutralization response. Chapter one discusses some general features of the virus and the immune system. The general nature of AIDS, its spread and its immunological characteristics are also described in this chapter. Chapter two discusses the design and NMR structural analysis of gp120 bridging sheet peptide mimics in methanol and water. The structure of gp120 can be loosely divided into two domains (the outer domain and the inner domain) that are linked together by a discontinuous four stranded antiparallel beta sheet known as the bridging sheet. The bridging sheet is known to overlap with the coreceptor binding site of gp120 and hence is a suitable target for designing virus-entry inhibitors. 17b, a neutralizing antibody isolated from an infected individual, is known to bind to this region of gp120. Our aim in this part of the work was to design a four stranded antiparallel beta sheet, based on the sequence of the bridging sheet, that would contain most of the residues involved in 17b binding. NMR and CD studies confirmed that the peptide was well structured in methanol but the structure was largely lost on addition of aqueous solvent. A small population of the peptide was found to be well-folded in aqueous solution. Chapter three discusses the design and characterization of a gp120-CD4D12 single chain. It is well known that the conformation of gp120 changes upon binding CD4 to expose cryptic epitopes, known as CD4i epitopes. In this work we report the generation of a single chain gp120-CD4 construct that has the cryptic epitopes exposed. The construct bound to 17b, a conformation specific antibody against the bridging sheet of gp120, a cryptic epitope, as well as a non-covalent complex of gp120:CD4D12. There was also very insignificant secondary structural change in gp120 upon complex formation with CD4D12 as observed by CD spectroscopy. Immunological studies with DNA and protein vaccination in guinea-pigs indicated that though 17b like antibodies are generated after immunization, they did not contribute towards the neutralization of primary isolates of the virus. It was also observed that it was the anti-CD4D12 antibodies that were responsible for the neutralization by the sera. These studies indicated towards the inability of the bridging sheet to generate effective neutralization response in case of vaccination with gp120/CD4 complexes. Chapter four discusses the design of a mimic of the gp120/CD4 complex. Since it was seen from our previous work that gp120/CD4 complexes generate a large fraction of antiCD4 antibodies and hence are unsuitable for vaccination purposes, we generated a construct with the minimal binding region of CD4. The small fragment of CD4 spanning from 21st residue to 64th residue was inserted in the V1/V2 loop of gp120. The insertion site was designed based on the region of gp120 closest to this fragment and capable of tolerating insertions. This protein did not bind to 17b as well as gp120/CD4 complex but showed a higher binding compared to full length gp120. Further immunological characterization with this protein revealed that it was not capable of generating neutralizing antibodies against the virus. Chapter five discusses the design and execution of a SPR based solution phase competition experiment to find the solution phase binding constant of CD4 and CD4 analogs to gp120. A major problem during the analysis of binding data obtained by SPR is the accurate determination of Rmax, a parameter needed to obtain an accurate equilibrium dissociation constant. In this chapter we have developed a binary as well as a ternary solution phase SPR based assay to accurately determine a solution phase equilibrium binding constant. The binding constants were determined for gp120 binding to CD4D12 and other CD4 analogs. To confirm the validity of the assay, a control antigen:antibody interaction whose equilibrium dissociation constant has been determined by other methods has been used as a test case. Chapter six discusses the design and characterization of V3 peptides inserted in the loop regions of E. coli Thioredoxin (Trx). Trx has earlier been used to display random peptide libraries between the 33rd and the 34th residue. We have constructed three constructs where the peptide has been inserted between the 33rd and 34th residue, between the 74th and 75th residue and between the 84th and 85th residue. The insertion between 74th and 75th position (74V3Trx) was found to be superior to the other two and would be a suitable alternative for display of a random peptide library. The binding of these constructs to 447-52D, a V3 peptide specific antibody was characterized. These were also characterized immunologically, and 74V3Trx was found to generate weakly neutralizing activity against the MN strain of HIV-1. Competition experiments with 447-52D with these sera indicated that there were antibodies generated that could compete out 447-52D binding to gp120 but not in sufficient concentration to provide broad neutralization. Appendix 1 discusses the rational design of disulfides to stabilize proteins based on the analysis of naturally occurring disulfides. In our attempts to design a rigidified version of gp120 we had designed disulfides in gp120 based on its crystal structure. Many of these were disulfides that would span antiparallel adjacent strands. In order to improve the design principles, we analyzed naturally occurring disulfides that span antiparallel adjacent strands and characterized them in terms of their positional preference in a beta sheet. It was found that these disulfides mostly occur on edge strands and are found exclusively between non-hydrogen bonded registered pairs of adjacent antiparallel strands. Mutagenesis on Thioredoxin was performed to verify our results. It was found that disulfides designed between the non-hydrogen bonded pairs of antiparallel strands could significantly stabilize the protein whereas the ones between hydrogen bonded pairs destabilized the protein. Human Immunodeficiency Virus (HIV) Immunogenetics HIV-1 gp120 HIV (Viruses) gp120-CD4D12 gp120-M9 HIV Vaccine Design gp120 Molecular Biology

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