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

Thesis (M.C.T.M. (Clinical Tropial Medicine))--Mahidol University, 2006. / LICL has E-Thesis 0012 ; please contact computer services. LIRV has E-Thesis 0012 ; please contact circulation services.

A research report submitted to the faculty of Health Sciences, University of the Witwatersrand in partial fulfillment of the requirements for the Master of Science Degree in Epidemiology. / Antiretroviral therapy (ART) recommendations among HIV – infected pregnant women have been revised several times by the World Health Organization (WHO). Option B+, which is the latest recommendation continues to be rolled out in several countries across the globe but mostly in sub-Saharan Africa. Retention in care and adherence to antiretroviral (ARV) drugs taken by these women remains unclear in this new program. We assessed ability to stay in care (retention) and adherence to ART among HIV – infected women starting life-long treatment during pregnancy and after, at an HIV care and treatment clinic in Ifakara Tanzania. Our study provided an opportunity to understand the trends in adherence to ART and retention in care for this population. Methods We analyzed data of HIV-infected pregnant women registered and starting ART for the first time in the Kilombero and Ulanga Antiretroviral Cohort in 2009 and 2010 with a follow up period of up to two years to 2011 and 2012 respectively. Adherence was by patient self-report (PSR) and was sufficient (good) if the woman took all the prescribed pills of the issued batch or insufficient (poor) if she missed two or more pills. Women that missed two or more consecutive scheduled visits to the clinic were not retained while those that honored their scheduled visits were retained in care. Two sample t test and Wilcoxon rank sum test were used to test predictor outcome associations for continuous variables while Pearson’s and Fisher’s exact tests were used for categorical ones. Hazard ratios of each predictor variable were calculated using Cox regression. Student No: 737395 Page v Results A total of 1,282 HIV – infected women were registered in KIULARCO between 2009 and 2010. Fifty (50) were pregnant and started life-long ART upon registration in this period. Of these, 25 (50%) were registered in 2009 and the other 25 (50%) in 2010. Slightly more than half, 52.2% had CD4 cell counts above 350cells/mm3. Almost half, 49% of the women were registered in their final (third) pregnancy trimester. About 82% were in WHO stage one and 60% of all the 50 women were initiated on AZT/3TC/EFV regimen. Only 5.7% had secondary education while the rest had primary or no education at all. Of the women that reported their partners HIV state, 54.5% had partners that had never tested for HIV. Adherence for all participants was reported as sufficient (good) for the entire period the women were in care. No one had insufficient (poor) adherence. Retention in care was higher during pregnancy than after delivery. Generally, loss to follow up was 40%. About 30% were lost during pregnancy and the majority, 70% lost after they had delivered their babies. There was no evidence to prove that any of the factors studied independently predicted non retention. The most likely time to non retention was six months after delivery. Conclusions Our study, despite small sample size, shows that among women diagnosed HIV – infected and starting life-long ART during pregnancy (Option B+), adherence to ART is sufficient and retention in care similar during and after pregnancy. Counseling on the importance of staying in care especially around the first few months after delivery should be emphasized at ANC.

Trata-se de um estudo transversal, de abordagem qualitativa e quantitativa que teve por objetivo avaliar os aspectos referentes à adesão irregular aos antirretrovirais por pessoas vivendo com HIV/aids. O estudo foi aprovado pelo Comitê de Ética da Escola de Enfermagem de Ribeirão Preto e pela Unidade de Pesquisa Clínica do Hospital das Clínicas de Ribeirão Preto. A coleta de dados ocorreu no período de outubro de 2017 a abril de 2018, em duas unidades de internação especializadas em tratamento das pessoas com HIV/aids, de um hospital público do interior paulista sendo organizada em duas etapas: Aplicação do questionário elaborado pelo pesquisador e consulta ao prontuário eletrônico. A partir disso, a entrevista semiestruturada foi gravada e posteriormente transcrita e revisada pelo próprio pesquisador. Os dados quantitativos coletados foram organizados em planilhas do Microsoft® Office Excel 2011 for Windows. Logo após, os dados foram transferidos para o banco de dados definitivo e analisados por meio do software IBM®SPSS, versão 23.0 for Windows. A análise e processamento dos dados qualitativos foram realizados pela Classificação Hierárquica Descendente com base fundamentada no Discurso do Sujeito Coletivo. Identificou-se que a adesão irregular aos antirretrovirais está intimamente ligada a aspectos do contexto social, econômico e cultural em que estão inseridas as PVHA. Apesar do tratamento no Brasil ser gratuito, as questões financeiras mencionadas têm relação com o cotidiano da vida social e exercem influência no uso regular do medicamento. Participaram do estudo 50 indivíduos hospitalizados. A média de idade dos pacientes foi de 42 anos e a média do tempo de diagnóstico de HIV foi de 12 anos. Analisando as características clínicas, percebeu-se que 86,4% dos indivíduos tinham mais de cinco anos de diagnóstico e mantinham parceria afetiva sexual (84,6%) em relação aos que não mantinham (81,1%). Outras condições foram relatadas: necessidade de apoio familiar; uso de álcool e outras drogas e dificuldades com a adaptação à apresentação medicamentosa. As principais dificuldades enfrentadas por pessoas vivendo com HIV/aids hospitalizadas e que estão em adesão irregular são os efeitos adversos causados pelo medicamento, os problemas financeiros, o estigma social e familiar e o uso de álcool e drogas. Mais de 80% dos participantes apresentaram diagnóstico de HIV há mais de cinco anos. / This is a cross-sectional, qualitative and quantitative study whose objective was to evaluate the aspects related to irregular adherence to antiretrovirals by people living with HIV / AIDS. The study was approved by the Ethics Committee of the Ribeirão Preto School of Nursing and the Clinical Research Unit of the Ribeirão Preto \"Hospital das Clínicas\". The data of collection took place from October 2017 to April 2018, in two hospitalization units specialized in the treatment of people with HIV / AIDS, from a public hospital in the interior of São Paulo. It was organized in two stages: Application of the questionnaire prepared by the researcher and consult the electronic medical record. From this, the semi-structured interview was recorded and later transcribed and revised by the researcher himself. The quantitative data collected was organized into Microsoft® Office Excel 2011 for Windows spreadsheets. Shortly after the data was transferred to the definitive database and analyzed using IBM®SPSS software, version 23.0 for Windows. The analysis and processing of the qualitative data were performed by the Descending Hierarchical Classification based on the Discourse of the Collective Subject. It has been identified that irregular adherence to antiretrovirals is closely linked to aspects of the social, economic and cultural context in which PLWHA are inserted. Although the treatment in Brazil is free, the mentioned financial issues are related to the daily life of social life and influence the regular use of the drug. Fifty hospitalized individuals participated in the study. The mean age of the patients was 42 years and the average time of diagnosis of HIV was 12 years. Analyzing the clinical characteristics 86.4% of the individuals had more than five years of diagnosis maintained a sexual affective partnership (84.6%) compared to those who did not maintain (81.1%). Other conditions were reported: need for family support; use of alcohol and other drugs and difficulties with adaptation to drug presentation. The main difficulties faced by people living with HIV / AIDS who are hospitalized and who are in irregular adherence are the adverse effects caused by the drug, financial problems, social and family stigma, alcohol and drug use. More than 80% of participants had been diagnosed with HIV for more than five years.

Thesis (M.Sc.)--Memorial University of Newfoundland, 2005. / Includes bibliographical references.

Thematic Paper (M.C.T.M. (Clinical Tropical Medicine))--Mahidol University, 2007. / LICL has E-Thesis 0024 ; please contact computer services. LIRV has E-Thesis 0024 ; please contact circulation services.

Note: / Clinical chemistry is a medical discipline whose aim is to diagnose and assess disease by analysis of biological specimens. Modem laboratories can perform several hundred different tests using many different methods developed over the last century. The classical, more traditional assays are typically labour-intensive, not multiplexed (only measure one analyte or disorder per assay), expensive, require a long turnaround time, and may not provide adequate sensitivity and specificity. Developments in mass spectrometry (MS) and related technologies over the last two decades have provided solutions for many if not all of these shortcomings. While MS based applications have not yet been widely implemented in clinical chemistry laboratories, current developments will encourage the replacement of traditional methods as well as the expansion of clinically diagnostic endpoints. Indeed, modem MS can be used to simultaneously analyze and quantitate multiple biomarkers in a single analysis. Currently, no other technique exists that can provide a comparable multiplexed analysis. In this thesis, current MS and related technologies were developed and applied to several important but distinct clinical chemistry applications. [...] / La chimie clinique est une discipline medicale qui a pour but de diagnostiquer la presence et la progression d'une maladie par l'analyse d'echantillons biologiques. Les laboratoires modemes peuvent executer des centaines d'analyses en utilisant plusieurs methodes developpees au courrant des cent demieres annees. Les essaisc1assiques, et plus traditionnels, sont souvent laborieux, non multiplexe (mesurent seulement un analyte par essai), cher, exige un long temps de rotation et risque de ne pas fournir une specificite adequate. Pendant les deux dernieres decennies, les developpements dans Ie domaine de la spectrometrie de masse (MS) et les technologies rattachees ont foumi des solutions a plusieurs, pour ne pas dire tous, manques retrouves dans les methodes d'analyse traditionnelles.

Thesis (Ph. D.)--University of Alabama at Birmingham, 2008. / Title from first page of PDF file (viewed Sept. 16, 2008). Includes bibliographical references.

Submitted by Biblioteca da Faculdade de Farmácia (bff@ndc.uff.br) on 2018-01-12T13:36:10Z No. of bitstreams: 1 Lívia Gonçalves dos Santos.pdf: 1966028 bytes, checksum: ce4f6a062e6fcea35758f69235302a88 (MD5) / Made available in DSpace on 2018-01-12T13:36:10Z (GMT). No. of bitstreams: 1 Lívia Gonçalves dos Santos.pdf: 1966028 bytes, checksum: ce4f6a062e6fcea35758f69235302a88 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Doenças crônicas, como a aids, estão associadas ao emprego de grande número medicamentos, sendo importante monitorar e acompanhar do uso dos mesmos. Sistemas informatizados para dispensação de medicamentos podem ser usados como fonte de informação e avaliação do uso e da posse de medicamentos. Este estudo teve como objetivos investigar a terapia antirretroviral (ARV) utilizada por pacientes acompanhados em um hospital universitário no estado do Rio de Janeiro a partir do Sistema de Controle Logístico de Medicamentos (SICLOM), caracterizar o perfil dos usuários atendidos no local bem como discutir o uso de indicadores logísticos de posse de ARV. Foi realizado um estudo de utilização de medicamentos do tipo prescrição-indicação, seccional, observacional a partir dos registros de dispensação de farmácia. Foram incluídos pacientes que iniciaram o uso de ARV entre janeiro e dezembro de 2014 (virgens de tratamento ou troca de ARV), maiores de 18 anos, de ambos os sexos, com cadastro ativo no SICLOM. Gestantes e pacientes que não tinham mais vínculo com a Unidade Dispensadora de Mecicamentos (UDM) foram excluídos. A coleta de dados sócio demográficos e clínicos foi realizada por meio do uso do SICLOM. Para calcular a posse dos medicamentos foram usados os indicadores PDC (do inglês Proportion of Days Covered) e CR (do inglês Compliance Rate). A análise incluiu descrição da população estudada, distribuições de frequência e medidas estatísticas de resumo das variáveis selecionadas. Dos 77 pacientes estudados, 60% eram homens. A média de idade foi 42,3 anos (± 13,2 anos) e o tempo médio de uso de ARV foi de 7,3 anos (± 6,2 anos). A maior parte da população estudada estava em uso de ARV de primeira linha terapêutica e 35% eram virgens de tratamento. A maioria das trocas de esquema terapêutico não foi justificada. Não foi verificada associação estatística entre as variáveis sócio demográficas e clínicas e a posse de ARV. A posse de ARV apresentou média acima de 80% por ambos os indicadores. Os indicadores PDC e CR permitiram avaliar a posse de medicamentos da terapia ARV e o SICLOM permitiu o conhecimento do perfil dos pacientes atendidos no referido hospital, bem como os medicamentos usados por essa população. Recomenda-se o uso de CR para avaliar a posse de ARV a partir dos dados do SICLOM / Chronic diseases such as AIDS are associated with the use of many medications and monitoring the use of these drugs is very important. Drug pickups could be used as a source of information and evaluation of the use and possession of drugs. The aim of this study was to evaluate the possession for antiretroviral drugs (ART), the socio demographics and clinics factors associated with medicine use for people living with HIV/Aids (PLHA) from a University Hospital in Rio de Janeiro state. It was conducted as a prospective drug utilization study, sectional and descriptive, realized through pharmacy dispensing records obtained from the National System of Logistic Control of Antiretroviral Medicines (SICLOM). Two logistic measures defined by literature, PDC (Proportion of Days Covered) and CR (Compliance Rate) were used for ascertaining the possession of ART. All PLHA, both male and female, with active and updated refill records (treatment naïve and PLVA who switched the drug regimen) was included since they were >18 years of age. Pregnant and people who had no more connection with pharmacy were excluded. Clinic and demographic information were performed using SICLOM. To calculate possession drug regimen we used two refill adherence measures, Proportion of Days Covered (PDC) and Compliance Rate (CR). The analysis included description of the study population, frequency distributions and measures, summary statistics of the selected variables. Of the 77 patients, 60% were male. The mean age was of 42.4 years and the average time of ARV use was 7.3 years (± 6.2 years). Of ART schemes employed in this hospital, the most corresponded to a first line treatment and a minority was naïve of treatment (35%). The possession rate was above 80% in both measures (PDC or CR). The switches were not justified. The PDC and CR indicators allowed us to evaluate the possession of antiretroviral treatment and SICLOM allowed us to know the profile of the patients treated at the same hospital as well the drugs used by this population. The use of CR is recommended to evaluate the possession of ARV from SICLOM data

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-01-21T14:37:18Z No. of bitstreams: 1 rouzelimariacoelhopereira.pdf: 1227583 bytes, checksum: 6bf30204887e8bad003a4c456764d51c (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-01-25T18:46:30Z (GMT) No. of bitstreams: 1 rouzelimariacoelhopereira.pdf: 1227583 bytes, checksum: 6bf30204887e8bad003a4c456764d51c (MD5) / Made available in DSpace on 2016-01-25T18:46:30Z (GMT). No. of bitstreams: 1 rouzelimariacoelhopereira.pdf: 1227583 bytes, checksum: 6bf30204887e8bad003a4c456764d51c (MD5) Previous issue date: 2014-07-29 / A expansão da terapia antirretroviral (TARV) vem contribuindo significativamente para a contínua diminuição de novos casos de HIV em todo o mundo. A TARV, além de reduzir o risco de transmissão do vírus, permite que os portadores do HIV tenham maior sobrevida e com mais qualidade. No entanto, apesar da elevada eficácia deste tratamento a efetividade do mesmo tem sido prejudicada em virtude das dificuldades encontradas pelos pacientes em cumpri-lo adequadamente. Sendo assim, estimular a adesão à TARV com a promoção do uso racional de antirretrovirais, participação de uma equipe multidisciplinar na assistência, entre outras medidas faz-se uma necessidade iminente. Assim, o presente estudo objetivou estabelecer a relação entre cada classe terapêutica usada nos tratamentos de HIV em pacientes assistidos pelas Unidades de Dispensação de Medicamentos (UDM) do Centro de Atenção à Saúde da Universidade Federal de Juiz de Fora (UFJF) e o comportamento de adesão aos mesmos, na tentativa de identificar fatores que levam a não adesão ao tratamento e propor ações que promovam o uso racional dos medicamentos. Os dados relativos ao perfil sociodemográfico e dispensação de antirretrovirais a 291 pacientes atendidos na UDM entre janeiro de 2009 e dezembro de 2010 e a evolução destes pacientes em 2013, foram analisados descritivamente e pelo teste do qui-quadrado empregando o software Statistical Package for the Social Sciences (SPSS) versão 14. Os mesmos pacientes foram reavaliados em 2013, a fim de se observar o desfecho terapêutico e a evolução dos pacientes participantes deste estudo. O perfil dos pacientes foi traçado como sendo a maioria do sexo masculino, na faixa etária entre 41 e 50 anos, solteiros, com 8 a 11 anos de estudo e residentes em Juiz de Fora. A maioria dos pacientes (60,8%) foi considerada como não aderentes ao tratamento a associação zidovudina + lamivudina + efavirenz foi a mais precrita (39,9% dos pacientes). A maior frequência de adesão (57,6%) se deu com as terapias compostas por inibidor de transcriptase reversa nucleosídeo-nucleotídeo + inibidor da transcriptase reversa não nucleosídeo. O maior índice de não adesão (64,3%) se deu entre os pacientes que usavam a composição inibidor de transcriptase reversa nucleosídeo-nucleotídeo + inibidor de protease .A reavaliação feita em 2013 revelou que 8,6% dos pacientes do inicio do estudo abandonaram o tratamento após 2011 e não houve diferença significativa entre este abandono e a não adesão observada na primeira fase do estudo. Também, não houve diferença significativa no número de óbitos e na mudança de tratamento comparando-se o grupo dos aderentes e não aderentes. Dos 291 pacientes, 87,3% deram seguimento à TARV, mesmo aqueles cujas retiradas de medicamentos eram irregulares na primeira fase do estudo. Os demais abandonaram o tratamento ou evoluíram à óbito. Diante do alto índice de não adesão (60,8%) encontrado na UDM, ressalta-se a importância de se estimular a realização de pesquisas de novos fármacos e formas farmacêuticas mais eficazes, com menos efeitos colaterais e economicamente viáveis para TARV e, por fim, subsidiar a elaboração dos consensos em terapia ARV e protocolos de Assistência Farmacêutica em DST/HIV/AIDS. / The expansion of antiretroviral therapy (ART) has contributed significantly to the ongoing decline in new HIV cases worldwide. Besides reducing the risk of transmitting the virus, antiretroviral therapy allows HIV patients to survive longer and have a better quality of life. However, despite the high efficacy of this treatment, its effectiveness has been hampered given the difficulties patients experience in properly adhering to it. Therefore, encouraging the adherence to ART by promoting rational use of antiretrovirals, as well as the participation of a multidisciplinary team in such care, among other measures, is an imminent need. Thus, the present study aimed to establish the relationship between each therapeutic class used in HIV treatments in patients assisted by the Drug Dispensing Units (UDM) of the Secondary Service Center of the Federal University of Juiz de Fora, state of Minas Gerais (UFJF-MG) as well as patients’ adherence behavior, in an attempt to identify factors which lead to non-adherence to the treatment and to propose actions in order to promote the rational use of medicines. Data concerning the socio demographic and the dispensation of ARVs to 291 patients assisted by the DMU between January 2009 and December 2010 and the evolution of these patients in 2013 were analyzed by means of descriptive statistics and the chi-square test by using the Statistical Package for the Social Sciences (SPSS) version 14. The same patients were reassessed in 2013 in order to observe the therapeutic outcomes and patients’ progress with regards to their participation in this study. The profile of patients was outlined as being most man, aged between 41 and 50 years old, single, with 8-11 years of study and living in the city of Juiz de Fora, state of Minas Gerais, Brazil. Most patients (60.8%) were considered as non-adherent to the treatment and the combination zidovudine + lamivudine + efavirenz was the most prescribed (39.9% of patients). The highest rate of adherence (57.6%) occurred with therapies composed of nucleotide-nucleotide reverse transcriptase inhibitor + non-nucleoside reverse transcriptase inhibitor. The highest rate of non-adherence (64.3%) occurred among patients using nucleotide-nucleotide reverse transcriptase inhibitor + protease inhibitor. The reassessment done in 2013 revealed that 8.6% of patients from the beginning of the study dropped out of treatment after 2011 and there was no significant difference between abandonment and non-adherence observed in the first phase of the study. Also, there was no significant difference in the number of deaths and treatment changes when compared with the group of patients who adhered and the ones who did not adhere to the treatment. Out of the 291 patients, 87.3% adhered to the ART, even those whose medication withdrawals were irregular in the first phase of the study. The others either dropped out of treatment or developed to death. Given the high rate of non-adherence (60.8%) found in the UDM, the importance of encouraging the development of studies on more effective new drugs and dosage forms, with fewer side effects and that are economically viable, and finally, to subside the elaboration of consensus regarding ARV therapy and Pharmaceutical Care protocols for STD / HIV / AIDS should be emphasized.