Made available in DSpace on 2014-06-12T18:31:41Z (GMT). No. of bitstreams: 2 arquivo8071_1.pdf: 858986 bytes, checksum: 9df2c957ba9deda2147047654f1862b1 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2004 / Tendo em vista que são poucos os trabalhos na literatura que falam sobre os fatores que levam a falha terapêutica, em pacientes submetidos ao tratamento anti-retroviral, e em particular no estado de Pernambuco, fomos motivados a realizar o presente estudo no qual o objetivo foi descrever o resultado ao tratamento anti-retroviral de pacientes com AIDS. O desenho do estudo foi descritivo do tipo serie de casos, a população de estudo foram indivíduos maiores de 13 anos de idade, com diagnóstico de AIDS (baseado na definição Brasileira de Casos de AIDS em adultos do Ministério de Saúde), atendidos no ambulatório de Doenças Infecciosas e Parasitárias do Hospital das Clínicas da Universidade Federal de Pernambuco. No período de fevereiro 2002 a agosto de 2003 . Sessenta e nove pacientes foram incluídos e acompanhados, dos quais, sete foram excluídos por falta de dados de CD4+ e Carga viral. Na primeira avaliação, os pacientes foram classificados segundo os critérios de Caracas e CDC modificado, preenchidos questionários, a carga viral quantificada pelo método NASBA e os CD4+ foram realizados por citometria de fluxo. Esses exames foram colhidos ao início, 4, 8 e 12 meses de terapia .Entre os pacientes estudados a maioria era do sexo masculino 41 (59,4%), com idade media entre 30 e 39 anos 28(40,6%). Vente e sete pacientes (39,1%) tinha de 4 A 7 anos de estudo, 62% dos pacientes eram heterossexuais, o tempo de acompanhamento médio foi de 12 meses, e 82,6% eram portadores de AIDS de acordo com os critérios de CDC. Observou-se uma marcada redução da Carga viral a partir do 4 mês de terapia a < 400 cópias/ml e ao final dos 12 meses de tratamento anti-retroviral a maioria tinha CD4+>200 células/mm3 Dos 69 pacientes acompanhados 48 (69,6%) apresentavam boa resposta ao tratamento e 14 (20,4% foi o percentual de falha terapêutica. A terapia mais utilizada (72,5%) foi:2 ITRN+1 ITRNN e os três esquemas mais utilizados foram; Zidovudina +Lamivudina + Efavirenz; Estavudina+ Lamivudina + Efavirenz ; Zidovudina +Lamivudina +Nelfinavir . Não houve associação entre o esquema utilizado, as condições socioeconômicas e demográficas; a adesão, mudança de regime e a categoria de exposição com falha terapêutica. HAART foi efetivo no 69,6%. As condições sócio-econômicas, demográficas e clínicas, imunológicas, virológicas e esquemas terapêuticos utilizados não se mostraram associadas a falha terapêutica, neste corto período

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ABSTRACT The formulation and approval of the Operational Plan for Comprehensive Care, Management and Treatment for HIV/AIDS in 2003 was a major victory for the roll-out of anti-retroviral therapy (ART) in the public sector in South Africa. Since its initiation in 2004, the ART Programme has expanded rapidly and realised considerable gains in prolonging life. However, it has also faced major constraints and implementation has been uneven across provinces. This study investigates the impact of organisational capacity upon levels of adherence to ART in two public sector sites in Gauteng. The study uses the Chronic Care Model (CCM) proposed by Edward Wagner (2004). The CCM identifies four major components as crucial to effective clinical outcomes for the management of chronic care. These factors are (1) prepared proactive practice teams; (2) delivery systems design; (3) decision support; and (4) clinical information systems. Both sites demonstrated different strengths and constraints. Strengths included the presence of motivated champions leading the ART service, positive patient-provider relationships, shifting of tasks to lower level health workers to deal with the shortage of skilled staff, good relationships with non-governmental organisations and the innovation to deal with challenges in a way that does not compromise the quality of care provided to patients using the CCMT service. Overall constraints that were identified in the two facilities include the shortage of skilled staff, burn-out among staff, a shortage of space, inconsistent data collection and interpretation, as well as poor integration and collaboration between local and provincial government in relation to the shared responsibility for the provision of Tuberculosis (TB) treatment and other related CCMT services. Despite these barriers, levels of adherence exceeded 85% in both sites.

Made available in DSpace on 2014-06-12T16:31:31Z (GMT). No. of bitstreams: 2 arquivo6104_1.pdf: 2722623 bytes, checksum: 100943884ef723a587b163b073e5b200 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2005 / O efavirenz é, atualmente no Brasil, o medicamento mais utilizado no tratamento da AIDS, primeira escolha como anti-retroviral inibidor da transcriptase reversa, associado à outros fármacos antiretrovirais. Foi realizada caracterização físico-química do efavirenz, procedendo a certificação da matéria-prima de três fornecedores. Foi realizada validação do método analítico para doseamento da matéria-prima e comprimidos de efavirenz, seguindo os requisitos definidos na Resolução RE-899 (Brasil, 2003). Foram desenvolvidos comprimidos revestidos de efavirenz 600 mg. Os núcleos foram obtidos utilizando a técnica de compressão por via úmida. Foram realizados testes físicos e físico-químicos dos comprimidos obtidos. Todos os resultados estavam de acordo com o preconizado nas Farmacopéias Oficiais. O revestimento gastrossolúvel obtido utilizou Opadry Y-1-7000 como polímero. Este polímero foi disperso em água (revestimento aquoso), vantagem em relação aos revestimentos orgânicos, evitando possível presença de resíduos de solventes orgânicos como diclorometano, isopropanol e outros. Foram avaliados ganho de peso, características e aspectos macroscópicos do revestimento, além dos testes farmacopéicos exigidos para os comprimidos revestidos. Além do desenvolvimento de comprimidos revestidos de liberação imediata, realizou-se desenvolvimento farmacotécnico de comprimidos de liberação prolongada de efavirenz, utilizando como matrizes Hidroxipropil metilcelulose HPMC- (Methocel&#63194;), em concentrações que variaram entre 10-20%, e etilcelulose (Ethocel&#63194;) em concentração de 20% na formulação, sendo avaliado diferentes processos de obtenção e o perfil de liberação in vitro. Algumas formulações demonstraram rápida hidratação e intumescimento quando em contato com o meio de dissolução, com baixo teor de erosão. Foi observada uma diminuição da liberação de efavirenz com o aumento do porcentual do polímero (HPMC) na formulação. Os comprimidos com 20% de HPMC na composição, tiveram perfil de liberação mais adequado com liberação de 100% do fármaco em 14 horas

Magister Public Health - MPH / HRQOL of HAART recipients at the Kagera region hospital was generally lower than that of the general population. However, their general health perceptions and mental health status were comparable to those of the general population, suggesting effectiveness of HAART in improving some subjective experiences of HIV morbidity. Chronic diseases were the main factor negatively affecting HRQOL of recipients.

A dissertation submitted to Faculty of Health Sciences, University of the Witwatersrand, in fulfilment of the requirements for the degree of Master of Science in Medicine, Johannesburg, June 2018 / It is well known that antiretroviral (ARV) drug resistant variants of HIV-1 can be sexually transmitted. Several studies have shown that in resource-rich geographical locations as many as 15-20% of individuals are newly infected with HIV-1 containing at least one drug resistant mutation. In contract, resource limited geographical locations, such as Sub-Saharan Africa, have shown prevalences in the range of 5 to 10%. Since the ART rollout in these resource-limited locations are generally not well monitored with virological genotyping, the transmission of drug resistant HIV-1 is likely to increase, with significant clinical and public health consequences. HIV-1 transmission is characterised by the transmission of a single founder virus, or narrow spectrum of founder viruses, that develop into the viral quasispecie. It is unlikely that drug resistant virus will coexist with wild type (wt) virus, in the case of non-drug resistance transmission. However, initiating in ARV treatment, drug non-adherence may select of ARV drug resistance mutations and may subsequent lead to treatment failure. Drug resistant virus may be transmitted to a new host, as drug resistant mutations do not appear to hamper transmission efficiency of the mutated virus. Several studies have shown that transmitted drug resistance mutations (TDRMs) persist either as the dominant species or as minority variants, or revert to wild type over time, in the absence of drug pressure. It is generally acknowledged that many drug resistance mutations decrease the replicative capacity of HIV-1, and thus reversion confers a potential survival advantage. Because of the emergence of wild type variants from TDRM quasispecies requires evolution and back-mutation, the rate at which individual TDRMs become undetectable may vary substantially. Contradictory findings of persistence versus reversion of TDRMs have been reported, and may be attributed to the fact that minority variants are difficult to detect by conventional population based Sanger sequencing, and patient numbers studied are small. Consequently, individuals infected with HIV-1 harbouring TDRM have a higher chance of failing their first-line therapy. Understanding the population dynamics of transmitted drug resistant HIV-1 in the absence of drug pressure is essential for clinical management and public health strategies. The individuals identified with TDRMs from the IAVI-Early Infections Cohort (Protocol C) provides a unique research opportunity to address the aforementioned issue. This study describes III the evolutionary mechanisms of ARV drug resistant HIV-1 after transmission to a new host to provide insight into persistence and/or rates of reversion to wild type. TDRMs initially identified by Price et al. (2011) in the IAVI-Early Infections Cohort (Protocol C) using population-based Sanger sequencing (the current diagnostic gold standard), were confirmed in this study by newer ultra-deep next generation sequencing (NGS) technology on the Illumina Miseq platform. Longitudinal samples were made available for individuals in which transmitted drug resistance were identified, and we also sequenced using NGS on the Illumina Miseq platform. Additional minority variants (present at <20% of the sequenced viral population) were identified by NGS. This study found a large percentage of TDRMs to persist for a significant amount of time after transmission to a new, drug naïve host, in the longitudinal samples. The level of persistence, or rate of reversion of TDRMs, appear to be subject to the type of resistance (NRTI, NNRTI or PI), level of resistance the mutation confers, as well as the combination of mutations that are cotransmitted. Findings of this study highlight the importance of drug resistance screening prior to ART initiation, as well as the importance of the drug resistance screening assay sensitivity. As rates of transmitted drug resistance are increasing in developing countries of which the IAVI-Early Infections Cohort (Protocol C) are composed of, understanding the population dynamics of transmitted drug resistant HIV-1 in the absence of drug pressure is essential for clinical management, public health strategies and informing future vaccine design. / XL2018

ABSTRACT The number of people in immediate need of anti-retroviral treatment (ART) in the southern African region continues to significantly exceed the capacity of health systems to provide it. Approaches to this complex rationing dilemma have evolved in different directions. The ethical concepts of fairness and equity have been suggested as a basis guiding rationing or patient selection processes for ART. The purpose of the study was to examine whether or not such concepts had relevance or operative value for a treatment team providing ART in rural Lesotho. Using an exploratory, single case study design the study found that while concepts of fairness and equity were relevant to the work of the treatment team, patient selection practices did not necessarily reflect what these concepts entail. The idea of fairness as a structured, formalized selection process did not figure in the approach to ART provision at St. Charles. A less formal, ‘first-come-first-served’ approach was adopted. While there was knowledge amongst some team members that social, economic or geographic conditions inhibit individuals and groups from gaining access to ART and that this was inequitable, it was felt that there was little they could do to try to mediate the impact of these conditions. The study findings pose importance questions about the approach to ART programming in resource constrained settings. The findings also question the relevance of trying to achieve fairness and equity when the gap between need for care and capacity to provide it remains so large.

A não adesão ao tratamento anti-retroviral implica no risco de falha terapêutica e queda da qualidade de vida. Objetivos. Estimar os níveis da adesão aos medicamentos anti-retrovirais (ARVs) na prática clínica e analisar fatores associados. Avaliar a concordância entre adesão auto-referida e as concentrações plasmáticas dos medicamentos ARV, numa sub-amostra. Métodos. Estudo de corte transversal, incluindo crianças e adolescentes não institucionalizadas, com idade entre um a 20 anos, atendidas no Instituto de Infectologia Emílio Ribas/São Paulo. Utilizou-se questionário estruturado e, para um sub-grupo, coletou-se sangue para dosagens plasmáticas de Efavirenz. Resultados. Dos 262 participantes do estudo, 40,1% não apresentaram adequada adesão aos ARVs, tomando até 89% das doses prescritas para o dia da entrevista e três anteriores. Os fatores que se mostraram associados à não adesão após o ajuste no modelo de regressão logística múltipla foram: ter dificuldades em usar ARVs por esquecer de tomar, residir com os avós, referir dificuldades em lidar com o tratamento ARV e como fator protetor, participar de atividades multiprofissionais. Foi demonstrada diferença significativa entre as médias das concentrações plasmáticas de Efavirenz para o grupo com e sem adesão adequada. Tendo como referência a mensuração da concentração plasmática do Efavirenz, o método da adesão auto-referida apresentou baixa sensibilidade e alta especificidade, sendo moderada a proporção de concordância entre os dois métodos (Kappa: 0,41). Conclusões. A dosagem das concentrações plasmáticas poderia ser incorporada na rotina de atendimento para acompanhamento da adesão ao Efevirenz. Considerando a baixa adesão aos medicamentos ARVs, torna-se importante estabelecer estratégias de acompanhamento envolvendo os fatores modificáveis associados à não adesão. / Non-adherence to anti-retroviral treatment results in therapeutic flaw risks and lower quality of life. Objectives: To evaluate the levels of adherence to anti-retroviral medicine (ARV) in clinical practice as well as to analyze associated factors. To evaluate conformity between self-reported adherence and plasmatic concentrations of ARV medicine in a subsample. Methods: A cross-sectional study, including non-institutionalized children and adolescents, ages from 1 to 20 years, who were assisted at the Infectology Institute Emílio Ribas / São Paulo. A structured questionnaire was used and, in one of the sub-groups, blood was collected for plasmatic dosages of Efavirenz. Results: Of the 262 study participants, 40,1% didn't not adhere to the ARVs, taking up to 89% of the prescribed doses for the interview day and for the three previous days. The factors which were linked to non-adherence after adjustment in the multiple logistics regression model were: difficulties in using ARVs due to forgetfulness, live with grandparents, difficulties with ARV treatment and as a protecting factor, participate in multiprofessional activities. As far as the Efavirenz there was a significant difference between the plasmatic concentrations of the groups with and without appropriate adherence. Using the plasmatic concentration of Efavirenz dosage as a reference, the self-reported adherence method had low sensibility and high specificity, and the conformity rates between the two methods were moderated (Kappa: 0, 41). Conclusion: The plasmatic concentrations dosages could be incorporate in the follow-up routine for adherence to Efevirenz. If we take in consideration the low adherence to ARVs, it will be important to establish follow-up strategies involving the modifiable factors associated to non-adherence.

A não adesão ao tratamento anti-retroviral implica no risco de falha terapêutica e queda da qualidade de vida. Objetivos. Estimar os níveis da adesão aos medicamentos anti-retrovirais (ARVs) na prática clínica e analisar fatores associados. Avaliar a concordância entre adesão auto-referida e as concentrações plasmáticas dos medicamentos ARV, numa sub-amostra. Métodos. Estudo de corte transversal, incluindo crianças e adolescentes não institucionalizadas, com idade entre um a 20 anos, atendidas no Instituto de Infectologia Emílio Ribas/São Paulo. Utilizou-se questionário estruturado e, para um sub-grupo, coletou-se sangue para dosagens plasmáticas de Efavirenz. Resultados. Dos 262 participantes do estudo, 40,1% não apresentaram adequada adesão aos ARVs, tomando até 89% das doses prescritas para o dia da entrevista e três anteriores. Os fatores que se mostraram associados à não adesão após o ajuste no modelo de regressão logística múltipla foram: ter dificuldades em usar ARVs por esquecer de tomar, residir com os avós, referir dificuldades em lidar com o tratamento ARV e como fator protetor, participar de atividades multiprofissionais. Foi demonstrada diferença significativa entre as médias das concentrações plasmáticas de Efavirenz para o grupo com e sem adesão adequada. Tendo como referência a mensuração da concentração plasmática do Efavirenz, o método da adesão auto-referida apresentou baixa sensibilidade e alta especificidade, sendo moderada a proporção de concordância entre os dois métodos (Kappa: 0,41). Conclusões. A dosagem das concentrações plasmáticas poderia ser incorporada na rotina de atendimento para acompanhamento da adesão ao Efevirenz. Considerando a baixa adesão aos medicamentos ARVs, torna-se importante estabelecer estratégias de acompanhamento envolvendo os fatores modificáveis associados à não adesão. / Non-adherence to anti-retroviral treatment results in therapeutic flaw risks and lower quality of life. Objectives: To evaluate the levels of adherence to anti-retroviral medicine (ARV) in clinical practice as well as to analyze associated factors. To evaluate conformity between self-reported adherence and plasmatic concentrations of ARV medicine in a subsample. Methods: A cross-sectional study, including non-institutionalized children and adolescents, ages from 1 to 20 years, who were assisted at the Infectology Institute Emílio Ribas / São Paulo. A structured questionnaire was used and, in one of the sub-groups, blood was collected for plasmatic dosages of Efavirenz. Results: Of the 262 study participants, 40,1% didn't not adhere to the ARVs, taking up to 89% of the prescribed doses for the interview day and for the three previous days. The factors which were linked to non-adherence after adjustment in the multiple logistics regression model were: difficulties in using ARVs due to forgetfulness, live with grandparents, difficulties with ARV treatment and as a protecting factor, participate in multiprofessional activities. As far as the Efavirenz there was a significant difference between the plasmatic concentrations of the groups with and without appropriate adherence. Using the plasmatic concentration of Efavirenz dosage as a reference, the self-reported adherence method had low sensibility and high specificity, and the conformity rates between the two methods were moderated (Kappa: 0, 41). Conclusion: The plasmatic concentrations dosages could be incorporate in the follow-up routine for adherence to Efevirenz. If we take in consideration the low adherence to ARVs, it will be important to establish follow-up strategies involving the modifiable factors associated to non-adherence.

Magister Public Health - MPH / Background Nigeria accounted for 2.95 million of the 22 million people globally living with HIV in 2008. In 2010, the HIV prevalence increased to 3.1 million, with 1.5 million people requiring anti-retroviral treatment (ART). ART is effective if patients adhere to treatment (taking 95% or more of drugs as prescribed) over a sustained period. Taking less than 95% of the medication can lead to drug resistance and treatment failure, which have dire individual and public health consequences. This study described adherence to ART and the factors that constrain and motivate adherence among patients on ART at the University of Abuja Teaching Hospital in the Federal Capital Territory (FCT), Nigeria. Methodology An observational, descriptive and analytical, cross-sectional survey of adherence among 502 adult ART patients (254 women and 248 men) from the University of Abuja Teaching Hospital was conducted. I collected sociodemographic and clinical characteristics of participants, and barriers and facilitators to adherence. For the prescription refill data, I utilized the updated pharmacy refill records from the ART dispensary. Bivariate and multivariate analysis was performed to analyse the factors that influence adherence to ART. Results Participants in this study had been on therapy for a mean of 43±27 months. Total optimal self-reported adherence over the previous three days (not missing a dose, taking correct doses in the correct frequency and correct schedule) was 53.6%, compared with 62.5% adherence calculated by prescription refill. However, most (80.3%) participants achieved virologic suppression at a level of <400 copies/μl3. Reported barriers to adherence were: forgot (43%); travelled away from home (21%); ran out of medication (16%); busy at work (13%); lack of food (5%) and medication snatched by armed robbers (2%). Self-reported adherence over the previous three days was positively associated with age and viral load. Younger respondents (under 30 years) were 3 times more likely to adhere to their regimen compared with those older than 30 years (OR = 2.5; 95% CI = 1.26-4.61; p =