Submitted by Jorge Silva (jorgelmsilva@ufrrj.br) on 2017-06-02T19:41:02Z No. of bitstreams: 1 2015 - Thuany Christine Lessa de Azevedo Vieira.pdf: 2529622 bytes, checksum: e7159cd09d3d218f61d6f6cee88a775e (MD5) / Made available in DSpace on 2017-06-02T19:41:02Z (GMT). No. of bitstreams: 1 2015 - Thuany Christine Lessa de Azevedo Vieira.pdf: 2529622 bytes, checksum: e7159cd09d3d218f61d6f6cee88a775e (MD5) Previous issue date: 2015-04-15 / FAPERJ / During the last decade, the antiretroviral therapy (ART) contributed to the reduction of the mortality and morbidity among HIV-1 affected people. However, the therapeutic flaw related to the appearance of resistence to the retrovirals due to the mutations and/or the not adherence to the antiretroviral therapy, is a problem of public health. It becomes of extreme importance, the comprehension of the resistence patterns and the mechanism related to them, enabling the choice of a suited therapeutic treatment that considers the mutation frequency, the quantity of viral particles and CD4+ cells among subtypes B and C. Therefore, the goal of the paper is to develop a model based on computational intelligence to help make decisions and give a better support to the clinic practice and research for those who deal with the pati-ents. 923 samples were used for thus study, obtained together with the Laboratory of Molecu-lar Virology of the Federal University of Rio de Janeiro, that belongs to the genotyping net-work of the Health Ministry. Initially, it was done a study of the profile of the mutations of subtypes B and C. To do so, it was made a cut of the patients that entered from 1998 on, with mutation frequency in the protease equal or greater than 5% and submitted to only one HA-ART therapy with just one protease inhibitor, Nelfinavir (NFV), or without any kind of prote-ase inhibitor. Through these studies, it was possible to observe that the subtype C has a diffe-rent character from subtype B, not only when it comes to the CV and CD4+ level but also the numbers of mutations in the protease gene, this fact emphasizes the necessity of specific tre-atments, from health professionals, for each subtype Key-words: antiretroviral treatment, HIV, Artificial Neural Network. / Durante a ?ltima d?cada a terapia antirretroviral (TARV) contribuiu para a redu??o da taxa de mortalidade e morbidade entre as pessoas infectadas pelo HIV-1. Contudo, a falha terap?utica relacionada ao surgimento de resist?ncias aos retrovirais em fun??o das muta??es e/ou pela n?o ades?o ? terapia antirretroviral ? um problema de sa?de p?blica. Torna-se de fundamental import?ncia a compreens?o dos padr?es de resist?ncias e dos mecanismos a eles associados, possibilitando a escolha de um tratamento terap?utico apropriado que considere a frequ?ncia de muta??o, quantidade de part?culas virais (CV) e c?lulas CD4+ entre os subtipos B e C. Portanto, o objetivo desse trabalho ? desenvolver um modelo baseado em intelig?ncia computacional para auxiliar a tomada de decis?o e proporcionar melhor suporte a pr?tica cl?-nica e de pesquisa daqueles que lidam diretamente com pacientes. Foram utilizadas 923 amos-tras para esse estudo, obtidas juntos ao Laborat?rio de Virologia Molecular da Universidade Federal do Rio de Janeiro pertencente ? rede de genotipagem do Minist?rio da Sa?de. Inicial-mente foi realizado um estudo do perfil de muta??es dos subtipos B e C. Para tal foi feito um corte com pacientes com entrada no sistema a partir de 1998, com frequ?ncia de muta??es na protease maior ou igual a 5% e submetidos a uma ?nica terapia HAART com apenas um ini-bidor de protease, Nelfinavir (NFV), ou sem nenhum inibidor de protease. Foram realizadas 50 simula??es para cada um dos subtipos usando as posi??es da sequ?ncia da protease como dados entrada juntamente com as taxas de carga viral e CD4+. Atrav?s dos estudos foi poss?-vel observar que o subtipo C possui car?ter diferenciado do subtipo B tanto em n?vel de CV e CD4+ quanto ao n?mero de muta??es no gene da protease, fato esse que enfatiza a necessida-de de tratamentos espec?ficos para cada subtipo pelos profissionais da sa?de. Al?m disso, o modelo demonstrou um desempenho satisfat?rio, possuindo um bom ?ndice de acertos.

Magister Public Health - MPH / Background: The advent of antiretroviral therapy (ART) has significantly redefined the course of the HIV pandemic making HIV, a chronic illness rather than a death sentence. To maximize the efficacy of ART in improving survival rates of HIV/AIDS patients, lowering the incidence of opportunistic infections, reducing HIV transmission and minimizing the possibilities of developing drug resistance, long-term retention in care is critical. In South Africa, poor retention in care of 32% has been noted in women who were initiated on ART during pregnancy as compared to 13% in non-pregnant women initiated on ART. However, little is known in Swaziland about the retention in care in women who were initiated on ART during pregnancy and the factors that influence retention in care among this category of women. Aim: To determine the factors associated with poor retention in care among women initiated on ART during pregnancy at King Sobhuza II Public Health Unit (PHU) in Swaziland. Methodology: A quantitative, retrospective cohort review of 316 medical records of women who were initiated on ART during pregnancy from January 2012 to December 2013 was conducted. A data extraction sheet was used to collect data from the files of patients who were initiated on ART during pregnancy. The dataset was imported into IBM SPSS Statistic 20 Software for analysis. Bi-variate analysis was done to determine risk factors associated with retention in ART care at ART initiation and on the last ART refill visit. Kaplan-Meier analysis was used to determine retention in care at 6, 12, 24 and 36 months. Cox proportional hazards models were then used to determine factors associated with poor retention. Results: The overall retention rate of women who were initiated on ART during pregnancy at the PHU after a median duration on ART of 25.80 months [interquartile range (IQR): 16.70 – 30.98] of follow up was 74.1% (n=316). Most women initiated on ART during pregnancy (52.4%) became lost to follow up after giving birth as compared to 47.6% who became lost to follow up before giving birth. After 6 months on ART, the lost to follow up rate was 16.5% (n=316); but increased to 20.9% (n=316), 23.5% (n=243) and 26.9% (n=52) after 12, 24 and 36 months respectively. On the ART initiation visit, the factors associated with retention in care for pregnant women included being married, having the partner on ART, disclosing one’s HIV status to the partner, not drinking alcohol, being a non-smoker and reporting no financial challenges. In addition, on the last ART refill visit, the risk factors for retention in care for women initiated on ART during pregnancy were having the ART regimen changed, having regular CD4 cell count done, rise in CD4 cell count, good adherence on ART and use of contraceptive other than the condom for family planning after delivery. Conclusion: The retention in care for women who were initiated on ART during pregnancy was found to be lower than in the general adult population. However, the study findings on retention in care are similar to what has been found in other settings. The factors influencing poor retention also mirror those found in the other parts of sub-Saharan Africa. Whilst decentralisation of ART services improves ART coverage it should be coupled with strategies aimed at improving patient retention.

La majorité des infections par le VIH de l’enfant sont acquises par transmission de la mère à l’enfant en période périnatale. Le fait que le système immunitaire des nourrissons soit « immature » par certains aspects et le fait que le virus transmis ait déjà échappé au contrôle de l’environnement immunitaire maternel, génétiquement proche de celui de l’enfant, sont probablement responsables du risque important que l’évolution naturelle soit extrêmement rapide lorsque l’infection est acquise en tout début de vie. En l’absence d’un traitement antirétroviral, la réplication virale va en effet se maintenir à un niveau très élevé pendant les premières années de vie chez tous les enfants et jusque 25% d’entre eux vont évoluer jusqu’au stade SIDA ou le décès durant leur 1ère année de vie. L'utilisation des traitements antirétroviraux puissants actuellement disponibles permet de réduire drastiquement la réplication virale et a profondément modifié le pronostic de l’infection par le VIH. D’une infection inéluctablement fatale, elle est devenue une affection chronique peu ou pas évolutive pour autant que le traitement antirétroviral soit pris de façon ininterrompue. Dans ce travail, nous présentons les résultats d’une étude prospective qui incluait les patients chez qui un traitement antirétroviral efficace était débuté pour la première fois. Nous avons pu démontrer que le nombre de lymphocytes CD4+ naïfs était d’autant plus rapidement reconstitué après l’initiation d’un traitement antiviral que celui-ci avait été débuté jeune. Non seulement les patients restauraient leurs nombres de cellules CD4+, et leurs cellules CD4+ naïves en particulier, mais des tests plus fonctionnels des lymphocytes (réponses lymphoprolifératives aux mitogènes) montraient également une nette amélioration sous traitement antirétroviral. Malgré cela, certaines anomalies, et en particulier l’activation des lymphocytes CD8+ persistaient après un an de traitement.Dans une étude cross-sectionnelle ayant inclus 46 patients, nous avons ensuite démontré qu’un traitement antirétroviral de longue durée débuté lorsque l’immunodépression est déjà sévère permet de récupérer des réponses lymphoprolifératives semblable à celles des progresseurs lents, y compris contre un antigène spécifique du VIH ce qui n’est généralement pas le cas chez les adultes. Toutefois, des altérations dans la sécrétion des cytokines en réponse à un mitogène (la phytohémagglutinine) persistent, et la sécrétion de cytokines après stimulation par un antigène spécifique du VIH est biaisée vers une réponse de type Th2, montrant encore une fois que si les capacités d’immunorestauration des enfants sont très importantes, des anomalies immunitaires persistent même après un traitement de longue durée lorsque le traitement est débuté à un stade avancé dans l’évolution de la maladie.Dans le contexte de l’absence d'espoir d'atteindre l'éradication du virus par la seule utilisation des drogues antirétrovirales, la caractérisation du phénotype des patients « non progresseurs » prend tout son sens. Nous avons donc axé notre travail suivant sur la caractérisation des patients chez qui la maladie progresse lentement et qui gardent une réplication virale basse sans prendre de traitement antirétroviral. Ces patients ont une faible activation et une faible différentiation de leurs lymphocytes CD4+ et un profil particulier de réponses CD4 vis-à-vis de la protéine Gag du VIH.Enfin, la dernière partie du travail décrit les bénéfices de ces traitements lorsqu’ils sont administrés très précocement (dans les 2 mois après la naissance) et le devenir à long terme de ces enfants en se basant sur la cohorte suivie au sein du CHU Saint-Pierre. L’histoire naturelle de l’infection par le VIH de l’enfant contaminé par sa mère est en effet caractérisée par une évolution bi-modale. Trois quarts des enfants infectés vont avoir une évolution comparable aux patients infectés à l’âge adultes, mais le dernier quart aura une évolution beaucoup plus rapide menant au développement d’une affection classant l’enfant au stade SIDA ou au décès dans la première année de vie. De plus, à cet âge, il y a un large recouvrement entre les valeurs des taux de lymphocytes CD4+ des enfants qui vont évoluer rapidement ou plus lentement. Nous avons participé activement à la démonstration qu’un traitement antirétroviral très précoce est très bien supporté par les nourrissons, est capable d’empêcher la réplication virale de façon durable et réduit la quantité de DNA proviral intracellulaire prévenant de ce fait les manifestations cliniques ou biologiques de l’infection. Alors que les adultes infectés par le VIH expriment quasi toujours des anticorps contre le VIH, même lorsqu’ils sont traités très précocement par une trithérapie, les enfants traités précocement deviennent souvent séronégatifs. Ils perdent les anticorps spécifiques contre le VIH transmis durant la grossesse mais n’en sécrètent pas par la suite, alors qu’ils peuvent les synthétiser dès que le traitement antirétroviral est interrompu. Ces patients traités très précocement ont un profil particulier caractérisé par un système immunitaire non altéré par l’infection par le VIH mais aussi par l’absence de défenses spécifiques contre ce virus et un réservoir viral très faible. / Doctorat en Sciences médicales (Médecine) / info:eu-repo/semantics/nonPublished

Philosophiae Doctor - PhD / AIDS is considered a pandemic causing millions of deaths worldwide and a cure for this disease is still not available. Failure to implement early treatments due to the poor diagnostic methods and ineffective therapeutic regimens to treat HIV patients to achieve complete viral eradication from the human body has encouraged the escalation of this disease at an exponential rate. Though the current treatment regimens (High Active Antiretroviral Therapy) have aided in increasing the lifespan of HIV patients, it still suffers from some shortcomings such as adverse side effects and non-eradication of the virus. Thus, there is a need for a non-toxic therapeutic regimen to stop further infection of HIV-infected patients. Antimicrobial Peptides (AMPs) are naturally occurring peptides which are components of the first line of defence of many organisms against infections and have been proven to be promising therapeutic agents against HIV. The use of AMPs as anti-microbial agents is due to the fact that most AMPs have a net positive charge and are mostly hydrophobic molecules. These features allow AMPs to be site directed electro-statistically to the mostly negatively charged pathogens. In a previous study, a number of novel anti-HIV AMPs was identified using a predictive algorithm Profile Hidden Markov Models (HMMER). The AMP's threedimensional structures were predicted using an in-silico modelling tool I-TASSER and an insilico protein-peptide interaction study of the AMPs to HIV protein gp120 was performed using PatchDock. Five AMPs were identified to bind gp120, at the site where gp120 interacts with CD4 to prevent HIV invasion and HIV replication. Therefore, the aims of this research were to perform in-silico site-directed mutation on the parental anti-HIV AMPs to increase their binding affinity to the gp120 protein, validate the anti-HIV activity of these peptides and confirm the exclusivity of this activity by testing possible anti-bacterial and anti-cancer activities of the AMPs. Firstly, the five parental anti-HIV AMPs were used to generate mutated AMPs through insilico site-directed mutagenesis. The AMPs 3-D structures were determined using I-TASSER and the modelled AMPs were docked against the HIV protein gp120 using PatchDock. Secondly, an "in house" Lateral Flow Device (LFD) tool developed by our industrial partner, Medical Diagnostech (Pty) Ltd, was utilised to confirm the in-silico docking results. Furthermore, the ability of these AMPs to inhibit HIV-1 replication was demonstrated and additional biological activities of the peptides were shown on bacteria and cancer cell lines. In an effort to identify AMPs with increased binding affinity, the in-silico results showed that two mutated AMPs Molecule 1.1 and Molecule 8.1 bind gp120 with high affinity, at the point where gp120 bind with CD4. The molecular binding however showed that only Molecule 3 and Molecule 7 could prevent the interaction of gp120 protein and CD4 surface protein of human cells, in a competitive binding assay. Additionally, the testing of the anti-HIV activity of the AMPs showed that Molecule 7, Molecule 8 and Molecule 8.1 could inhibit HIV-1 NL4-3 with maximal effective concentration (EC₅₀) values of 37.5 μg/ml and 93.75 μg/ml respectively. The EC₅₀ of Molecule 8.1 was determined to be around 12.5 μg/ml. This result looks promising since 150 μg/ml of the AMPs could not achieve 80% toxicity of the human T cells, thus high Therapeutics Index (TI) might be obtained if 50% cytotoxic concentration (CC₅₀) is established. Further biological activity demonstrates that Molecule 3 and Molecule 7 inhibited P. aeruginosa completely after 24 hours treatment with peptide concentrations ranging from 0.5 mg/ml to 0.03125 mg/ml. Nevertheless, moderate inhibition was observed when CHO, HeLa, MCF-7 and HT-29 were treated with these peptides at peptides concentration of 100 μg/ml. The ability of these AMPs to block the entrance of HIV via the binding to CD4 of the host cells is a good concept since they pave the way for the design of anti-HIV peptide-based drugs Entry Inhibitors (FIs) or can be exploited in the production microbicide gels/films to suppress the propagation of the virus. / DST-NIC/Mintek

Magister Artium (Child and Family Studies) - MA(CFS) / HIV patients face an array of social and psychological problems, such as depression, which can affect their quality of life. Moreover, HIV infection is also linked to psychological distress such as anxiety. In addition, avoidant emotion-focused strategies such as acceptance, wishful thinking and self-blame are associated with higher levels of psychological distress in persons with HIV. Current health services in the city of Cairo, Egypt, are not adapted to provide advice and psychological support to people living with HIV to aid in the development of problem-solving skills to cope with the stress of living with HIV. The purpose of this study was to examine the relationship between quality of life, psychological distress and the coping strategies of persons living with HIV/AIDS in Cairo, Egypt. A quantitative methodology with a cross-sectional correlational design was adopted in this study. Data collection entailed questionnaires that consisted of four sections: Demographics, Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), Depression, Anxiety, Stress Scales (DASS) and the Cope Inventory. The sample consisted of 202 HIV/AIDS participants who access the National AIDS Program (NAP). The data were analysed using the Statistical Program for Social Science V23 (SPSS). The results are provided using descriptive and inferential statistics. The findings of the study show that in terms of the prevalence of psychological distress, the moderate scales were stress and depression, while the severe scale was anxiety. The most prevalent of coping styles was emotion-focused coping, specifically in terms of acceptance and religion. In terms of the prevalence of quality of life, the highest scores were for family and social relationships, while the lowest scores were for sexual drive and leisure time activities. The findings also show that psychological distress and certain coping styles such as substance use negatively predicted quality of life of patients with HIV/AIDS. Positive predictors included coping styles such as venting, positive reframing, humour, acceptance and religion.

Master of Public Health - MPH / Background: HIV has reached epidemic proportions globally with Sub-Saharan Africa carrying the greatest burden (71%). It is estimated that there are 37 million people world-wide infected with HIV, and an estimated 6.8 million live in South Africa. Globally there were 2.1 million adolescents living with HIV in 2014. Improved access to Antiretrotiviral Therapy (ART) has led to a steep decline in HIV incidence and HIV-related mortality. Yet despite these successes in terms of HIV treatment outcomes, HIV-related mortality amongst adolescents has increased. Adolescents are defined by the WHO as individuals between 10 and 19 years old. WHO states that adolescents have poorer access to ART, are at a higher risk of disengaging from care and have special needs to keep them motivated to remain in care. The uptake of adolescents into the South African ART programme is low and those that are enrolled into the programme have poorer adherence than their adult counterparts. Aim: The aim of the study was to explore the factors that influence adherence to ART amongst adolescents in a primary health care clinic in a low socio-economic, urban setting in Cape Town. Methodology: An exploratory qualitative design was employed where data was collected through two key informant interviews with staff from an urban primary health care clinic. Four focus group discussions and eight individual in-depth interviews were held with adolescents and young people who accessed ART at this health facility. Audio data was digitally recorded and transcribed verbatim. Data was analyzed using content analysis. Results: The study identified school commitments, strained teacher-pupil relationships, negative household dynamics and ill-treatment by non-biological caregivers as major reported barriers to adherence. In addition, poor service delivery, missing and misplaced files and long waiting times came under major criticism. Fear of intended or unintended disclosure of HIV status, perceived stigma and discrimination, treatment fatigue and having unstructured lives, profoundly influenced ART adherence. Finally, having a strong support system, disclosing to a trustworthy person and having goals and ambitions served as motivators to remain adherent to ART. Conclusions: This study highlighted the complexity of ART adherence amongst this age group due to school factors, social factors, health services factors, therapy related factors and patient factors. Interventions to improve adherence should aim to address treatment fatigue, disclosure, household dynamics, service delivery factors, as well as the impact of school commitments and symptoms of depression on ART adherence amongst adolescents.

Introduction: Decentralization of antiretroviral therapy (ART) services faces decreasing quality when increasing ART coverage. This study compares nurse initiated and managed patients to doctor managed patients under these circumstances, using retention in care as a crude measure of quality of care. Methods: This was an observational retrospective cohort study. A simple data abstraction tool was used to collect baseline patient data from medical records of HIV positive patients (N=871) initiating ART at Mbabane Government Hospital and four of its outreach clinics, between 1st January and 30th June 2011. Descriptive summary statistics and comparison of the two cohorts using multivariate analysis was done. Results There was no statistically significant difference in retention rates between the doctors and nurses cohorts at 69.1% and 70.9%, respectively (P was 0.56). After adjusting for sex, haemoglobin, CD4 cell count, weight and WHO stage, the odds of being retained in care were similar between the two groups, adjusted OR: 1.11(95% CI: 0.72, 1.69), with a p value of 0.64. Haemoglobin and weight were positively associated with retention in care, while male sex was negatively associated with retention in care. Discussion: The similar retention rates between the two cohorts suggest that in terms of retention in care the service provided by the nurses was comparable to that provided by doctors. This is important to ART program managers as they scale-up ART decentralization. Conclusion: Task-shifting of ART initiation from doctors to nurses is feasible as nurse initiated and managed antiretroviral therapy is comparable to doctor initiated and managed treatment. / Dissertation (MSc)--University of Pretoria, 2014. / gm2014 / Clinical Epidemiology / unrestricted

Magister Public Health - MPH / Background: HIV/AIDS affects the health of millions of people world wide. According to the Joint United Nations Program on HIV/AIDS [UNAIDS], the number of people living with HIV globally has risen from 26 million in 2001 to 33.2 million in 2007. It is estimated that 2.5 million people were newly infected with HIV in 2007. The introduction of anti-retroviral therapy [ART] has brought hope to millions of people living with HIV and AIDS. More recently, the increased availability of treatment in many countries including Namibia has dramatically improved survival rates and lowered the incidence of opportunistic infections among HIV patients. Adherence to antiretroviral therapy (ART) is a fundamental attribute of excellent clinical HIV care and a key aspect in determining the effectiveness of treatment. Strict adherence to ART is vital to maintain low viral load and to prevent the development of drug resistant virus. Poor adherence is one of the key obstacles to successful ART for HIV positive patients. Literature has shown that there are various factors that hinder adherence to ART such as patient, service, community, family, socio-economic and work-related factors. Aim: This study aimed to describe the experiences of patients in the ART programme at Katutura State Hospital, Communicable Disease Clinic (CDC), in the Khomas region of Namibia and to explore factors that contribute to poor adherence. / South Africa

Magister Public Health - MPH / In the era of AIDS, food and nutrition are becoming more of a priority for many households and communities. This is more so now that treatment is available for people infected with HIV and AIDS. Food and nutrition are fundamentally intertwined with HIV transmission and the impacts of AIDS. Evidence of the ways in which food insecurity and malnutrition may interfere with the effectiveness of antiretroviral therapy is well documented. Aim: The purpose of the study was to inform improvements in food security interventions for PLWHA through an investigation of existing food security interventions in the Khomas Region, Namibia. / South Africa

Magister Public Health - MPH / The study utilized a qualitative case study design to explore the problem of poor access to ART in Benue State. PLWHAs, policy makers, program managers and health workers were involved in an effort to describe the factors influencing access to ART in the State. Semi structured interviews, exit interviews and focus group discussions were used. To analyse the findings, categorization was done into facilitators and barriers to access, in addition to the ways respondents believe these barriers can be overcome. Other sub-themes were also identified and sorted. Themes were linked to direct quotes from the respondents. Additional literature review was done to review available information on the themes identified. Facilitators of access included free cost and increased number of sites; beneficial effects of ART; disclosure, membership in a support group and having a treatment partner. Barriers included stigma and discrimination; hunger, poverty, transportation and opportunity costs; hospital factors; non-disclosure; inaccurate knowledge and perceptions about HIV and ART; certain religious beliefs and advice; coverage, capping of services and fear of non-availability of ART. In addition to stigma, patients bypass closer ART access points to further away hospitals because of business opportunities; financial assistance; perceived better standard of care and hope that a cure, when found, will be more accessible to patients in bigger hospitals. / South Africa