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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
381

Antimycobacterial treatment among children at start of antiretroviral treatment and antimycobacterial treatment after starting antiretroviral treatment among those who started antiretroviral treatment without antimycobacterial treatment at a tertiary antiretroviral paediatric clinic in Johannesburg, South Africa

Chivonivoni, Tamuka January 2010 (has links)
Magister Public Health - MPH / Background: Although clinicians encounter antimycobacterial treatment in Human mmunodeficiency (HIV)-infected children as one of the most common treatments coadministered with antiretroviral treatment (ART), quantitative data on the extent of antimycobacterial treatment among HIV-infected children at the time of commencement of ART and at different times during ART is scarce. The baseline risk factors associated with being on both ART and antimycobacterial treatments are not known and it remains to be elucidated how the different exposure factors impact on the antimycobacterial treatment-free survival of children who begin ART without antimycobacterial treatment.Objectives: To describe the prevalence of antimycobacterial treatment among children at the time of starting ART and the antimycobacterial treatment-free survival after starting ART. Design: A retrospective cohort study based on record reviews at the Harriet Shezi children&lsquo;s clinic (HSCC).Population: HIV-infected children less than fifteen years of age presumed ART naïve started on ART at HSCC.Analysis: A descriptive analysis of the prevalence of antimycobacterial treatment at time of start of ART was done. Kaplan Meier (KM) survival curves were used to determine the antimycobacterial treatment-free survival and logistic regression was used to analyze the association between baseline factors and future antimycobacterial treatment among children who had no antimycobacterial treatment at time of start of ART. Results: The prevalence of antimycobacterial treatment at the time of starting ART was 518/1941 (26.7%, 95% confidence interval (CI): 24.7-28.7). Among children who started ART without antimycobacterial treatment, the KM cumulative probability of antiretroviral and antimycobacterial (ART/antimycobacterial) co-treatment in the first 3 months of starting ART was 4.6% (95% CI: 4.1- 5.2), in the first 12 months it was 18.1% (95% CI: 17.0-19.2) and in the first 24 months of starting ART it was 24% (95% CI: 21.9-25.1). Survival analysis suggested that children with high baseline viral load, advanced World Health Organization (WHO) stage of disease, very low normalized weight for age (waz) and very young age (less than one year) at start of ART had significantly reduced antimycobacterial treatment-free survival (log rank p < 0.05) in the first two years of starting ART. In the logistic regression model, age less than one year {Odds ratio (OR): 3.7 (95% CI: 2.2-6.0; p <0.0001)} and very low weight for age Z-score (waz < -3) {OR; 2.2 (95% CI: 1.4-3.6; p = 0.0015)} were the two critical risk factors independently associated with future antimycobacterial treatment. Conclusions: Antimycobacterial treatment is extremely common among HIV-infected children at the time of starting ART and early after starting ART and the incremental risk of being on ART/antimycobacterial co-treatment decreases with time on ART. The results emphasize the need for a heightened and careful alertness for mycobacterial events especially among children starting ART with severe malnutrition and those who start ART at age less than one year. The results further suggest that it is probably optimal to start ART in children before their nutritional status has deteriorated severely in the course of the HIV disease so that they get protection against mycobacterial events by early ART. / South Africa
382

Prédire et estimer l’impact d’un programme d’intervention sur l’incidence du VIH, district de Ndhiwa, Kenya / Predicting and estimating the potential impact of multiple interventions on HIV incidence, Ndhiwa sub-county, Kenya

Blaizot, Stéphanie 03 December 2015 (has links)
Bien que le nombre annuel de nouvelles infections au VIH diminue régulièrement depuis le milieu des années 1990, celui-ci reste élevé, en particulier en Afrique sub-Saharienne. L’organisme médical international Médecins Sans Frontières (MSF) a sélectionné quatre sites à hautes incidence et prévalence, dont un situé dans le district de Ndhiwa, au Kenya. La prévalence chez l’adulte a été estimée à 24% (d’après l’enquête en population NHIPS menée en 2012 par MSF-Epicentre). MSF espère, après une combinaison d’interventions sur le terrain, observer en temps réel une baisse de l’incidence de l’infection par le VIH. Dans la première partie, différents aspects de l’infection par le VIH et les questions actuelles sont présentés. Dans la seconde partie, notre objectif était d’estimer l’incidence de l’infection par le VIH à Ndhiwa à l’aide de différentes approches sélectionnées et appliquées aux données de NHIPS. Cet indicateur est essentiel pour déterminer la dynamique de l’épidémie, identifier les groupes de la population les plus à risque, et pour planifier des interventions de santé. Dans la dernière partie, notre objectif portait sur la modélisation à court terme de l’épidémie de VIH/SIDA dans le district de Ndhiwa. Dans un premier temps, nous avons proposé une méthodologie pour la modélisation de l’épidémie de VIH/SIDA associant l’estimation des paramètres d’un modèle et la prédiction de l’évolution de l’épidémie selon celui-ci, utilisant des données locales. Cette méthodologie a ensuite été appliquée aux interventions de santé envisageables par MSF-Epicentre, à l’aide de simulations déterministes et stochastiques / Although the annual number of new HIV infections has been decreasing since the middle of the 1990s’, it remains high, and particularly in sub-Saharan Africa. Epicentre, in collaboration with “Médecins Sans Frontières”, is planning a strategy to reduce HIV incidence in several areas of high prevalence and incidence rates, such as Ndhiwa sub-county (Nyanza Province, Kenya). In this sub-county, the adult HIV prevalence was estimated at 24% in 2012 (Ndhiwa HIV Impact in Population Survey, NHIPS, 2012). In the first part of this thesis, various aspects of HIV infection as well as current issues are given. In the second part, our objective is to estimate HIV incidence in Ndhiwa sub-county using several distinct approaches. In the last part, we focus on the mathematical modeling of the spread of the HIV infection to the short term. Firstly, we develop a framework for using the same data for estimation and prediction. Secondly, the potential impacts of multiple interventions on HIV incidence in Ndhiwa sub-county are studied using our framework and performing deterministic and stochastic simulations
383

Identifying, recording and monitoring adverse effects associated with antriretroviral treatment

Mulinge, Florence Muthoni January 2010 (has links)
South Africa, with an estimated 5.7 million people living with HIV, continues to have one of the largest epidemics in the world. The introduction of HAART resulted in prolonged and improved quality of life of many infected patients. However, adverse effects caused by these drugs have become a major concern as they affect the adherence of patients and in some cases even result in the death of patients. Although much research has been and is still being conducted in the area of understanding, preventing and management of ARV adverse effects, there is still a need for patients to be actively involved in self-monitoring for adverse effects. This will assist health care professionals in early identification of serious or potentially serious ARV effects. This study aimed at evaluating the usefulness of strategies developed and employed in the identification, recording and monitoring of adverse effects. The study was conducted with patients receiving HAART from a private HIV and AIDS clinic in Uitenhage, Eastern Cape, South Africa. The research project was approved by the Nelson Mandela Metropolitan University Research and Ethics Committee and the research site. This was an experimental, randomized controlled study carried out over a period of three months (August to October 2009), with a sample size of 160 patients divided into four study groups of 40 patients each. Two monitoring strategies, namely an ARV adverse effect monitoring tool and a patient self-monitoring diary were developed and used for the identification and recording of adverse effects. The four study groups included a Control group, a Tool group, a Diary group and a Tool-Diary group. Willing patients, after signing an informed consent form, were randomly assigned to one of the four groups by participating health care workers at the study site. Data was retrieved from the patient files by the researcher. Descriptive statistical analysis of the findings of the study was conducted using SPSS®. One hundred and forty nine patients were included in the final data analysis. Of the 80 diaries handed out to patients, only 33 were returned and due to errors only 31 were suitable for analysis. Monitoring tools were completed and analysed for 36 patients. The tool was found to be more effective in identifying adverse effects of a physical nature (such as peripheral neuropathy and lipodystrophy) than the usual methods of monitoring employed by the clinic, whilst the diary, used alone, was found to be less effective. Use of the tool and diary combined resulted in the most significant identification and recording of central nervous system related adverse effects and physical adverse effects. However due to the low return rate of the diaries and the majority of the monitoring tool not being completed in many instances the results of this study may not be generalisable. The study results did however suggest that combining the tool and the diary methods of adverse effect identification, yielded the most favourable results when compared to each method alone. This may be attributed to the fact that the tool is useful in identifying objective symptoms and the diaries subjective symptoms, particularly in instances where the patients forget to report their symptoms to healthcare professional whilst at the clinic. The diaries were also reported to improve adherence for more than 90 percentage (n=31) of the patients. More research would be needed in order to verify the exact significance of the tool and the diary in identifying and recording adverse effects and symptoms of adverse effects.
384

A hearing profile of persons infected with acquired immune deficiency syndrome (AIDS)

De Lange, Maria 08 August 2008 (has links)
With the worldwide increase in numbers of individuals infected with the human-immune deficiency virus (HIV) and acquired immune deficiency syndrome (AIDS), the need for more information became essential. The devastating influences and fatal outcome of this disease is inevitable. These individuals are confronted with mortality and various disabling conditions. One of these disabling conditions is the possible development of a hearing loss. Loss of hearing sensitivity related to HIV/AIDS is only one of numerous effects the virus may have on humans and their quality of life. Therefore increased awareness of HIV/AIDS and the influences of this disease is inevitable for the modern audiologist. The precise nature and the extent of the influence that HIV/AIDS and antiretroviral therapy (ART) has on the hearing ability of a person are unknown to date. Even though a relationship between hearing loss, HIV/AIDS and the administration of relevant medication is expected, no clear explanation is available to provide the public or clinicians with the necessary information on assessments, interventions and aural rehabilitation techniques. Without being able to identify the specific cause, symptoms and place of lesion of the hearing loss, it will be difficult to ensure appropriate monitoring and treatment. Information regarding the influences of HIV/AIDS and ART on hearing sensitivity had to be established to ensure appropriate intervention and rehabilitation options. The first part of this research project reviews the evidence available regarding the possible influences of HIV/AIDS on hearing. Throughout the research a cross-sectional design with quantitative and qualitative approaches were followed comprising of a structured interview, basic and specialized audiometric battery to obtain the necessary case history, as well as results for these different audiological tests that were conducted. The specialised tests included immittance measurements, distortion-product otoacoustic emission (DPOAE) and auditory brainstem response (ABR). The results of this study were discussed in terms of the three sub aims in accordance with the different audiological tests that were conducted. The results indicated that those participants with ART exposure had a significantly higher incidence of hearing loss. The pure tone averages were mainly found within normal limits but decreased with the progression of the final stages of HIV/AIDS. The high and low frequencies of the audiogram were often affected with loss of hearing sensitivity suggesting the presence of a high and low frequency slope. The final three stages of HIV/AIDS had a significantly higher incidence of bilateral hearing loss. ART exposure were associated with more severe degrees of hearing loss. The DPOAE and ABR indicated that cochlear and retro-cochlear damage existed often among these participants. Only 20% participants had abnormal tympanograms suggestive of conductive pathology. The results revealed that the type of pathology varied across the stages of HIV/AIDS. The conclusions and implications of this study are discussed. Recommendations incorporate the development of HIV/AIDS awareness campaigns that includes audiological information on the possible influences, where to refer or where to seek assistance; issues regarding the improvement of the modern audiologists’ knowledge in terms of the management of the audiological needs of individuals with HIV/AIDS and the application of these results in the industrial setting to utilize when they consider granting compensation claims. / Dissertation (MCommunication Pathology)--University of Pretoria, 2008. / Speech-Language Pathology and Audiology / unrestricted
385

Avaliação de parâmetros funcionais respiratórios em pacientes adultos infectados pelo HIV / Evaluation of functional respiratory parameters in HIV infected adult patients

Passos, Ana Isabela Morsch, 1985- 07 July 2011 (has links)
Orientador: Maria Luiza Moretti / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-18T15:05:39Z (GMT). No. of bitstreams: 1 Passos_AnaIsabelaMorsch_M.pdf: 2317515 bytes, checksum: 2a34cbc644c6ec0279e1f66cf58ccf4a (MD5) Previous issue date: 2011 / Resumo: A função pulmonar, em pacientes infectados pelo vírus da imunodeficiência humana (HIV), tem sido associada com a redução nos parâmetros de ventilação pulmonar. Métodos: Foi realizado estudo do tipo corte transversal para avaliar a função pulmonar de pacientes com aids atendidos em ambulatórios de doenças infecciosas. Foram avaliados dados de espirometria, pressão inspiratória máxima (PImáx) e pressão expiratória máxima (PEmáx). Também foram coletados, através de prontuários médicos, dados clínicos, demográficos e laboratoriais. Resultados: Os dados de PImáx e PEmáx foram avaliados em 73 pacientes, o exame de espirometria foi avaliado em 54 pacientes. O tempo médio de infecção pelo HIV (em anos) foi semelhante para os homens (8,5 ± 5,1) e mulheres (10,4 ± 4,2, p = 0,13) e o tempo médio de utilização da terapia antiretroviral foi de 8,5 ± 4,1 anos para as mulheres e 7,7 ± 4,1 anos para os homens (p = 0,46). Os valores de PImáx e PEmáx foram abaixo do previsto em 38 (52%) e 25 (34%) pacientes, respectivamente. O uso do tenofovir e a presença de tosse, no momento em que o teste foi realizado, foram independentemente associados com PEmáx abaixo do valor previsto. Valores elevados de creatinoquinase foram associados com o uso prolongado de terapia antiretroviral (9,6 ± 4,1 anos versus 7,4 ± 3,9 anos, p = 0,05). Os valores de capacidade vital forçada (CVF) se apresentaram reduzidos em 14 (26,4%) pacientes e foi independentemente associado com risco cardiovascular intermediário ou alto (p = 0,002) e com murmúrio vesicular reduzido à ausculta pulmonar (p = 0,047). Os valores de volume expiratório forçado no primeiro segundo (VEF1) foram significativamente menores nos pacientes com tempo prolongado de tabagismo (p = 0,019) e risco cardiovascular intermediário ou alto (p = 0,003). A redução da relação VEF1/CVF foi associada com o tabagismo (p = 0,041). Conclusão: Nas medidas de PImáx e PEmáx, 38 (52,1%) e 25 (34,2%) pacientes apresentaram resultados abaixo do previsto. O exame de Espirometria foi considerado normal em 45 pacientes. Houve diagnóstico de distúrbio obstrutivo e restritivo em um (1,9%) e 8 (14,8%) pacientes. O uso de Tenofovir e a presença de tosse foram independentemente associadas à PEmáx abaixo do previsto. Pacientes com menores valores de CVF foram os com maior risco cardiovascular e murmúrio vesicular diminuído à ausculta pulmonar. Pacientes com menores valores de VEF1 foram aqueles com maior tempo de tabagismo e maior risco cardiovascular. A variável independentemente associada a valores reduzidos de VEF1/CVF foi tabagismo / Abstract: Background: Pulmonary function, in HIV infected patients, has been associated with reduction in pulmonary ventilation parameters Methods: We conducted a sectional study to evaluate the pulmonary function of AIDS patients cared for in the infectious diseases ambulatories. Maximal inspiratory (MIP) and expiratory (MEP) pressures and spirometry were assessed. Clinical, demographic and laboratorial data were also evaluated. Results: MIP and MEP were assessed in 73 and spirometry in 54 patients. The mean time of HIV infection (in years) was similar for men (8.5+5.1) and women (10.4±4.2; p= .13) and the mean time of use of antiretroviral therapy (ART) was 8.5±4.1 years for women and 7.7±4.1 years for men (p= .46). MIP and MEP values were not normal in 38 (52%) and 25 (34%) patients, respectively. The use of tenofovir (TVF) and presence of cough, by the time the test was performed, were independently associated MEP below the predictive value. Elevated CK values were associated with prolonged time ARV usage (9.6±4.1 years vs 7.4±3.9 years; p= .05). FVC was reduced in 14 (26.4%) patients and was independently associated with high and/or intermediate cardiovascular risk (p= .002), and those with reduced vesicular murmur in auscultation (p= .047). FEV1 was significantly lower in patients with prolonged time of smoking (p= .019) and high and/or intermediate cardiovascular risk (p= .003). Reduced FEV1/FVC ratio was associated with smoking (p= .041). Conclusions: In measurements of MIP and MEP, 38 (52.1%) and 25 (34.2%) patients had results below forecast. The spirometry test was considered normal in 45 patients. There was a diagnosis of obstructive and restrictive ventilation disorder in one (1.9%) and 8 (14.8%) patients. The use of tenofovir and cough were independently associated with lower than expected MEP. Patients with lower values of FVC had the highest cardiovascular risk and reduced breath sounds on pulmonary auscultation. Patients with lower values of FEV1 were those with longer duration of smoking and increased cardiovascular risk. The variable independently associated with lower values of FEV1/FVC was smoking / Mestrado / Ciencias Basicas / Mestre em Clinica Medica
386

Strategies utilized by professional nurses in the primary health care facilities regarding adherence of patients to antiretroviral theraphy, Capricorn District, Limpopo Province South Africa

Phashe, M. L. January 2015 (has links)
Thesis (MPH.) -- University of Limpopo, 2015 / The success of antiretroviral therapy for HIV infection through widespread and resounding has been limited by inadequate adherence to its unforgiving regimens especially over a long term. While health care professionals may not be able to predict adherence, they can help overcome barriers to adherence and take steps to improve it. The aim of the study was to explore and describe the strategies that are utilised by professional nurses in the primary health care facilities regarding adherence to antiretroviral therapy, Capricorn District, Limpopo Province, South Africa. A qualitative research approach was used to describe the strategies that are utilised by professional nurses in the primary health care facilities in the Capricorn District Limpopo Province, referring to Mankweng Hospital. The descriptive qualitative design was used. Unstructured interviews were used to collect data until saturation was reached. Informed consent was obtained prior the data collection. The data was analysed qualitatively using Tesch’s open coding method. 18 (eighteen) professional nurses working in the primary health care facilities participated in the study. The findings revealed that the strategies utilised by professional nurses in the primary health care facilities to improve adherence to ART were described. Information and education, health worker and adherence guidelines, use of adherence partner or treatment buddy, addressing religious beliefs, communication skills, community mobilisation and continuous counselling, were the strategies that were utilised by professional nurses in the primary health care facilities to improve adherence of patients to ART.
387

An Equitable Framework for Antiretroviral Therapy and COVID-19 Vaccine Allocation Strategies in Botswana

Park, Yhesaem 12 August 2021 (has links)
The HIV/AIDS epidemic and the COVID-19 pandemic have ruined many people's lives. Antiretroviral therapy (ART) has controlled the HIV/AIDS epidemic and COVID-19 vaccine is expected to ease confusion caused by the pandemic. However, the supply of health-resource falls far short of the demand in resource-constrained countries; thus, decision-making about resource allocation should be discussed. Botswana, as a resource-constrained country with a high prevalence of HIV, needs to construct its own framework for ART allocation. We propose an equitable framework for ART and COVID-19 vaccine allocation in Botswana based upon the egalitarian principle, which provides each individual has an equal chance of receiving them. We use a spatial mathematical model of treatment accessibility with an equity objective function, and sequential quadratic programming is used to address the nonlinear programming model. Considering Botswana's current health infrastructure, our strategy brings the most equal health outcomes. However, the disparity of accessibility still exists between rural and urban areas even from our equitable strategy. We present proposals that can increase the accessibility of rural areas using sensitivity analysis. Our work can be applied to different contexts, especially in sub-Saharan Africa.
388

Relationship between the presence of metabolic syndrome and electrocardiographic abnormalities in HIV patients with HAART in a level III hospital, Lima - Peru

Taza Caroy, Jaime Enzo, Vilchez Muñoz, Renzo Alberto 28 February 2021 (has links)
Introduction: Antiretroviral Therapy (ARVT) has been related to some elements of Metabolic Syndrome (MS). Likewise, there exists a high prevalence of alterations on the electrocardiogram (ECG) in people with HIV. Objective: Evaluate the association between MS and alterations in the ECG in HIV patients who received ARVT. Methodology: A consecutive non-randomized cross-sectional study was developed in which patients from the Infectious Disease Service of the Arzobispo Loayza National Hospital were evaluated from January 2019 to April 2020. Survey data, clinical history, clinical examination and a 12-lead ECG were performed to each participant. Alterations in the ECG were classified with the Minnesota code. For SM, NCEP-ATP III 2005 criteria was used. Results: 63 patients were included, the mean age was 38,78 years (SD: 9,23). 25 participants presented electrocardiographic alteration, being 24 minor alterations and 5 major alterations. 27 from the 63 patients (42,9%) had MS. Association was found between MS and ECG alterations in the adjusted model by sex, age, smoking, time with HIV, time with ARVT and use of another medication, with a relative prevalence (RP) value of 2,17 (IC=95% 1,21-3,90) (p=0,009). Conclusion: Although association between the presence of MS and ECG alterations in the HIV population was found, due to the low power of the study, it is recommended to manage the results with caution. / Introducción: La Terapia Antirretroviral de Gran Actividad (TARGA) se ha relacionado con elementos del Síndrome Metabólico (SM). Asimismo, existe una alta prevalencia de alteraciones en el electrocardiograma (ECG) en personas con VIH. Objetivo: Evaluar la asociación entre el SM y las alteraciones en el ECG en pacientes VIH que recibieron TARGA. Metodología: Se desarrolló un estudio transversal con muestreo no aleatorio de tipo consecutivo en el que se evaluó a pacientes del Servicio de Infectología del Hospital Nacional Arzobispo Loayza en el período enero 2019 - abril de 2020. Se incluyeron datos de encuesta, historia clínica, examen clínico y un ECG de 12 derivaciones fue realizado a cada participante. Las alteraciones en el ECG se clasificaron con el código de Minnesota y para SM se utilizaron criterios de NCEP-ATP III 2005. Resultados: Un total de 63 pacientes fueron incluidos, cuya edad media fue 38,78 años (DE: 9,23). Asimismo, 25 (39,68%) participantes presentaron alteraciones electrocardiográficas, obteniendo 24 participantes con alteraciones menores y 5 con mayores. La prevalencia de SM fue de 27 de 63 (42,9%). Se halló asociación entre SM y alteración en el ECG con una prevalencia relativa (PR) de: 2,17 (IC=95% 1,21-3,90) (p=0,009) al ajustar por sexo, edad, tabaquismo, tiempo con VIH, tiempo con TARGA y uso de otra medicación. Conclusión: Aunque se halló asociación entre SM y alteraciones en ECG en población VIH, debido a la baja potencia del estudio se recomienda tomar con cautela estos resultados. / Tesis
389

The biopsychosocial factors influencing HIV/AIDS patient adherence to antiretroviral therapy (ART) : a social work study

Spies, Margaretha 11 August 2008 (has links)
The study emanates from the need to identify the biopsychosocial factors that influence patients’ adherence to antiretroviral therapy (ART) within the South African context The specific goal of the study was to explore these in order to make recommendations to enhance service delivery. Applied research was conducted, with its primary task being to stimulate thought and action concerning the challenges faced by patients who are on ART. In order to gather comprehensive data, the researcher engaged in a combination of the qualitative and quantitative approaches. For the qualitative case study the researcher made use of semi-structured interviews, utilizing the non-probability sampling method, aiming to understand and interpret the meaning that the multidisciplinary team accorded to matters of antiretroviral treatment. For the quantitative part of the study the probability random sampling method was made use of for the quantitative descriptive survey. Questionnaires were employed to collect data from 201 patients already on antiretroviral medication. The conclusions, which were drawn from the research findings, identified challenges to adherence to ART: the study confirmed that since the advent of combination antiretroviral therapy (HAART), HIV/AIDS has been transformed into a manageable and chronic condition, and has undoubtedly extended and improved the quality of life for people living with HIV/AIDS. However, it also confirmed that ART, is a complex intervention, which is accompanied by severe biopsychosocial implications, requiring near-perfect adherence in order to prevent the development of resistance. The impact that the various psychosocial needs of millions of HIV/AIDS people living on ART will have on current social structures and services, will tax the available professional social services, particularly the social work profession. The social correlation of HIV/AIDS and poverty is endorsed by the findings, confirming that the high level of unemployment, coupled with families who are headed by women and who receive little support, lead to almost total dependency on social security. The findings further indicate a specific relationship between socio-economic circumstances and the ability to adhere to ART. Empowering HIV/AIDS patients, to be able to adhere to ART, is therefore indicated, as is the further need for a regulator of HIV/AIDS support services, in order to protect and promote high standards of service delivery, especially counselling. / Thesis (DPhil)--University of Pretoria, 2007. / Social Work and Criminology / DPhil / unrestricted
390

Compartmentalization, adaptive evolution and therapeutic response of HIV-1 in the gastrointestinal tract (GIT) of African patients infected with Subtype C: implications for the enhancement of therapeutic efficacy

Mahasha, Phetole Walter January 2014 (has links)
Background: Due to its continuous exposure to food antigens and microbes, the gastrointestinal tract (GIT) is in a constant state of low level immune activation and contains an abundance of activated CCR5+CD4+ T lymphocytes, the primary target HIV-1. As a result, the GIT is a site of intense viral replication and severe CD4+ T cell depletion, a process that begins during primary HIV-1 infection and continues at a reduced rate during chronic infection in association with increased production of pro-inflammatory cytokines, a breakdown in the epithelial barrier, microbial translocation, systemic immune activation and the continued recruitment and infection of new target cells. AntiRetroviral Therapy (ART) is only partially effective in reversing these pathogenic changes. Despite the importance of the GIT in HIV-1 pathogenesis, and as a reservoir of persistent virus during ART, little is known about the diversity of HIV-1 in the GIT, or how different tissues in the GIT respond to ART. Objectives: Primary objectives of this thesis were to: 1) characterize the diversity of HIV-1 RNA variants in different parts of the GIT; 2) determine whether there is compartmentalized evolution of HIV-1 RNA variants in the GIT and whether these variants are likely to have different biological properties; 3) investigate the impact of ART on immune restoration in the GIT. Methods: A prospective study of the duodenum, jejunum, ileum and colon of African AIDS patients with chronic diarrhea and/or weight loss, sampled before and during 6 months of ART. RNA extracted from gut biopsies was reverse transcribed and PCR amplified. Env and gag PCR fragments were cloned, sequenced and subjected to extensive phylogenetic analysis; pol PCR fragments were analyzed for drug resistance. CD4+, CD8+ and CD38+CD8+ T cells levels in biopsies collected at baseline (duodenum, jejunum, ileum and colon) and after 3 (duodenum) and 6 (duodenum and colon) months of ART were quantified by flow cytometry and immunohistochemistry, plasma and tissue VL by the Nuclisens assay. Results: Viral diversity varied in different regions of the GIT with env HIV-1 RNA variants being significantly more diverse than gag variants. Gag HIV-1 RNA variants were widely dispersed among all tissue compartments. Some env variants formed tight monophyletic clusters of closely related viral quasispecies, especially in the colon, a finding that is suggestive of compartmentalized viral replication and adaptive evolution. CD4+ T cell and VL levels were significantly lower, while CD8+ including activated CD38+CD8+ T cell levels were higher in the duodenum and jejunum versus the colon. After 6 months of ART, a significant but incomplete recovery of CD4+ T cells was observed in the colon but not in the duodenum. Failed restoration of CD4+ T cells in the duodenum was associated with non-specific enteritis and CD8+ T cell activation. Conclusions: These results advance our understanding of the GIT as a host-pathogen interface by providing new insights into the diversity, evolution and dissemination of HIV-1 variants in the GIT. Strategies aimed at decreasing immune activation, especially in the small intestine, may be highly beneficial in enhancing the therapeutic efficacy of ART. / Thesis (PhD)--University of Pretoria, 2014. / lk2014 / Immunology / PhD / Unrestricted

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