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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.
11

Working memory profiles of children with the Human Immunodeficiency Virus (HIV) : a comparison with controls.

McKillop, Brittany 23 July 2014 (has links)
With 10% of the population being infected with Human Immunodeficiency Virus (HIV), South Africa has the highest number of infections in the world (StatsSA, 2013). HIV results in cognitive and motor deficits in children as the severe compromise of the immune system leads to neurodevelopmental dysfunction peri-natally (Ruel, Boivin, Boal, Bangirana, Charlebois, & Havlir, 2011). Neurocognitive deficits affect overall general intellectual abilities and include difficulties with attention and speed of information processing, verbal language, executive –abstraction, complex-perceptual motor function, memory and motor and sensory function (Dawes & Grant, 2007). Developmentally, it is evident that working memory provides a crucial interface between perception, attention, memory and action (Baddeley, 1996; Baddeley 2003). Therefore the purpose of the study was to investigate the working memory profiles of both an HIV positive children and a control sample, on cognitive tasks (Automated Working Memory Assessment), general intellect tasks (Raven’s Colored Progressive Matrices) and language competence tasks (Sentence Repetition Test). The current study compared 26 HIV positive children (mean age = 6.58 years) to 26 matched controls (mean age = 6.73 years). It was found that both non-verbal IQ and language proficiency were correlated to HIV status and thus were used as covariates in the study. MANCOVA’s were conducted on the data and produced findings that showed that there were only significant differences in visuo-spatial short-term memory between the two groups. Furthermore, it was also found that there were significant differences between the groups on nonverbal IQ and language proficiency. Therefore, the results showed that HIV may have an overall effect on non-verbal ability and language proficiency and a few aspects of working memory such as visuo-spatial short-term memory. Together with future studies focused on larger sample sizes and children who are not currently on HAART, early developmental interventions can be formulated to assist South African HIV-infected children so that the neurocognitive effects are lessened and their overall lifestyle is improved.
12

The knowledge of pregnant women about polymerase chain reaction HIV testing of infants in the Molemole Municipality of the Capricorn District, Limpopo Province

Ramoraswi, Sophy Ramadimetja January 2013 (has links)
Thesis (M.Cur.) --University of Limpopo, 2013 / All pregnant women who seek antenatal health care at the public clinics are offered HIV counselling and testing. Those who agree to test and who test positive, often fail to bring their infants for polymerase chain reaction (PCR) HIV testing after delivery, despite the fact that they have been advised to do so during delivery. There are very few studies which have assessed the women’s knowledge with regard to the PCR HIV testing of infants. In this study; a qualitative, exploratory, and descriptive methodology was applied to explore and describe the knowledge of pregnant women with regard to PCR HIV testing of infants in the Molemole Municipality of the Limpopo Province, Capricorn District. Purposive sampling was used and semi-structured interviews were conducted until saturation of data was reached. Qualitative data analysis design of Marshall and Rossman was used. The study indicated that the participants had knowledge with regard to the PCR HIV testing of infants. The nurse and lay counsellors knew about the different modes of prevention of mother-to-child transmission (PMTCT) and they used every contact opportunity with pregnant women to share its benefits. Mother to mother support groups for HIV positive pregnant and lactating women should be established for continuous support and counselling with the purpose of achieving an HIV-free generation.
13

Experiences of caregivers working with children living with HIV/AIDS.

Naidu, Nemsha. January 2005 (has links)
The present study aims to explore the experiences of caregivers working with children living with HIV/AIDS in the context of a children's home. While there has been research conducted on family members as well as community based caregivers of people living with HIV/AIDS, there has been a paucity of research on caregivers of children living with HIV/AIDS in Children's homes. There is a strong need to address this area of deficit in order to identify and tackle areas of difficulty as well as rewarding aspects to enhance the caregiving experience This pilot study adopted the interpretive research paradigm, is qualitative in nature and utilized in depth interviews as a means of data collection. Four women working as caregivers at the children's home were interviewed and the data obtained was analysed using thematic content analysis. The present study highlights the positive as well as the negative aspects of caregiving from the perspective of the caregivers. While caregivers identify the difficulties that they face as a result of caregiving, they also acknowledge the rewards that they attain from their line of work. Furthermore the present study emphasises the coping strategies employed by the caregivers on a personal and an organisational level as well as the resources that aid coping and the constraints against utilising the coping resources. In addition issues of attachment and detachment associated with caring for children, that are particularly pertinent to these non -familial caregivers have been explored. / Thesis (M.A.)-University of KwaZulu-Natal, Durban, 2005.
14

The spectrum of HIV related nephropathy in KwaZulu-Natal : a pathogenetic appraisal and impact of HAART.

Ramsuran, Duran. January 2012 (has links)
Sub-Saharan Africa bears 70% of the global HIV burden with KwaZulu-Natal (KZN) identified as the epicenter of this pandemic. HIV related nephropathy (HIVRN) exceeds any other causes of kidney diseases responsible for end stage renal disease, and has been increasingly recognized as a significant cause of morbidity and mortality. There is nonetheless a general lack of surveillance and reporting for HIVRN exists in this geographical region. Consequentially, the aim of this study was to outline the histopathogical spectrum of HIVRN within KZN. Moreover, from a pathology standpoint, it is important to address whether HIVRN was a direct consequence of viral infection of the renal parenchyma or is it a secondary consequence of systemic infection. Additionally, an evaluation of the efficacy of Highly Active Anti-Retroviral Therapy (HAART) in combination with angiotensin converting enzyme inhibitors (ACE-I) was performed via a genetic appraisal of localized replication of HIV-1 in the kidney, ultrastructural review and immunocytochemical expression of a podocyte maturity and proliferation marker pre and post-HAART. Blood and renal biopsies were obtained from 30 children with HIV related nephropathy pre- HAART, followed-up clinically for a period of 1 year. This cohort formed the post-HAART group. Clinical and demographic data were collated and histopathology, RT-PCR, sequencing, immunocytochemistry and transmission electron microscopy was performed. The commonest histopathological form of HIVRN in children (n = 30) in KZN was classical focal segmental glomerular sclerosis (FSGS) presented in 13(43.33%); mesangial hypercellularity 10(30%); mesangial, HIV associated nephropathy 3(11%) and minimal change disease 2(6.67%). Post-HAART (n = 9) the predominant pathology was mesangial hypercellularity 5(55.56%); FSGS 3(33.33%) and sclerosing glomerulopathy 1(11.11%). This study also provides data on the efficacy of HAART combined with ACE-I. The immunostaining pattern of synaptopodin, Ki67 and p24 within the glomerulus expressed as a mean field area percentage was significantly downregulated in the pre-HAART compared to the post-HAART group respectively (1.14 vs. 4.47%, p = 0.0068; 1.01 vs.4.68, p < 0.001; 4.5% vs 1.4%, p = 0.0035). The ultrastructural assessment of all biopsies conformed to their pathological appraisal however, features consistent with viral insult were observed. Latent HIV reservoirs were observed within the podocyte cytoplasm but was absent in mesangial or endothelial cells. Real-Time polymerase chain reaction assays provided evidence of HIV-1 within the kidney. Sequence analysis of the C2-C5 region of HIV-1 env revealed viral diversity between renal tissue to blood. In contrast to a collapsing type of FSGS that occurs in adults, the spectrum of paediatric nephropathy in treatment-naive children within KwaZulu-Natal was FSGS with mesangial hypercellularity. Additionally, our study demonstrates podocyte phenotype dysregulation pre- HAART and reconstitution post therapy. Evidence of ultrastructural viral reservoirs within epithelial cells is supported by a genetic appraisal confirming the ubiquitous presence of HIV DNA in renal tissue. Moreover, sequence analysis showed viral evolution and compartmentalization between renal viral reservoirs to blood. Finally, the interplay of viral genes and host response, influenced by genetic background, may contribute to the variable manifestations of HIV-1 infection in the kidney in our paediatric population. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2012.
15

Growth patterns and nutrition-related problems of infants under one year attending Red Cross Children's Hospital's antiretroviral clinic and the knowledge, attitudes, beliefs and practices of their caregivers, concerning infant feeding

Wasserfall, Estelle 12 1900 (has links)
Thesis (MNutr)--Stellenbosch University, 2011. / ENGLISH ABSTRACT: Introduction A paucity of data exists regarding growth patterns and nutrition-related problems in infants (<12 months) on antiretroviral treatment (ART) and the infant feeding knowledge, beliefs, attitude and practices of their caregivers. Aim To describe the growth and nutrition-related problems of infants (<12 months) attending the Antiretroviral (ARV) clinic at Red Cross Children’s Hospital, as well as the knowledge, attitudes, beliefs and practices of their caregivers concerning infant feeding. Methods A cross-sectional, descriptive study was conducted with census sampling. Thirty infants and 31 caregivers were included in the sample. Anthropometric measurements were performed and interviewer-administered questionnaires were utilised to obtain the knowledge, attitude, beliefs and practices of the caregivers. The mean Z-score of each measurement as well as the weight-for-age, length-for-age, weight-forlength and bodymass index-for-age for each infant were determined, analysed, interpreted and described according to the World Health Organisation (WHO) growth standards for children. Results Thirty-nine percent (n=11) of the mothers (n=28) did not receive infant feeding counselling prior to delivery, while only 9 (32%) received the minimum number of at least 4 sessions, as prescribed by the Department of Health. It was not assessed whether the counselling occurred before delivery. The mean age of the infants was 6.9 (SD 3.3) months. Eighty-three percent (n=25) had an opportunistic infection prior to data collection. Twenty-three percent (n=7) were underweight-forage and 40% (n=12) of the infants were stunted. Vomiting and diarrhoea were the most common nutrition-related problems experienced. A statistical significant positive correlation (p=0.003) was found between an infant’s duration on ART and W/A z-score. Only two caregivers were breastfeeding at the time of data collection, but 34% (n=10) of the other caregivers had at some stage breastfed their infant. Formula feeding practices were poor. Sixty-two percent (n=18) were not preparing the feeds correctly and only six (21%) were correctly cleaning and sterilising the bottles. Thirty-nine percent (n=11) of the infants were not receiving an adequate amount of milk per day. Sixty-five percent (n=11) of the infants (>six months) did not receive a diet the previous day which met the minimum WHO dietary diversity indicator and only 18% (n=3) received a minimum acceptable diet. Caregivers had an average knowledge concerning infant feeding. Thirteen percent (n=4) knew the correct definition of exclusive breast- or formula feeding. Sixty-eight percent (n=21) did not know what mixed feeding meant, or the dangers associated with it. Most caregivers (n=25, 81%) knew that oral rehydration solution had to be given when infants developed diarrhoea, but only 48% (n=15) knew how to prepare it and only 6% (n=2) knew how to administer it. Seventy-five percent (n=9) of caregivers did not know what should be done when experiencing breast problems. Sixty-four percent (n=19) of the caregivers believed that if a HIV-positive woman breastfeeds she would definitely transmit HIV to her infant. Conclusion The infant sample showed a variety of erratic growth patterns with a high prevalence of underweight and stunting. Infant feeding knowledge of caregivers was average, but not deemed sufficient to translate into appropriate, safe and optimal infant feeding practices. The breastfeeding prevalence was low. Formula preparation, feeding and hygiene practices were poor and dietary intake of infants was not optimal. The quality and quantity of HIV infant feeding counselling sessions received at antenatal clinic visits were poor and need to be addressed. / AFRIKAANSE OPSOMMING: Inleiding Daar is 'n tekort aan data oor groeipatrone en voedingsverwante probleme by babas (<12 maande) op antiretrovirale behandeling asook die babavoedingkennis, -oortuigings, -houdings en -praktyke van hul versorgers. Doelwit Om ondersoek in te stel na die groei- en voedingsverwante probleme by babas (<12 maande) in die antiretrovirale kliniek by Rooikruis-kinderhospitaal, sowel as die babavoedingkennis, - oortuigings, -houdings en -praktyke van hul versorgers. Metodes 'n Beskrywende dwarssnitstudie is met sensussteekproefneming onderneem. Dertig babas en 31 versorgers is by die steekproef ingesluit. Antropometriese metings was gedoen en onderhoude was met behulp van vraelyste gevoer ten einde inligting oor die versorgers se kennis, houdings, oortuigings en praktyke te bekom. Elke baba se gemiddelde z-telling per meting sowel as die gewig-vir-ouderdom, lengte-vir-ouderdom en liggaamsmassa-indeks-vir-ouderdom was volgens die Wêreldgesondheidsorganisasie (WGO) se groeistandaarde vir kindersbepaal, ontleed, vertolk en beskryf. Resultate Altesaam 39% (n=11) van die moeders (n=28) het nie voor die bevalling voorligting oor babavoeding ontvang nie, terwyl slegs 9 (32%) die Departement van Gesondheid se voorgeskrewe minimum 4 sessies, deurloop het. Dit was nie bepaal of hierdie sessies voor die bevalling ontvang was nie. Die gemiddelde ouderdom van die babas was 6,9 (standaardafwyking 3,3) maande. 'n Totaal van 83% (n=25) het voor data-insameling 'n opportunistiese infeksie gehad, 23% (n=7) was ondergewig-vir-ouderdom, en 40% (n=12) van die babas se lengtegroei was ingekort. Die algemeenste voedingsverwante probleme was braking en diarree. Daar blyk 'n statisties beduidende positiewe korrelasie (p=0.003) te wees tussen die duur van die baba se antiretrovirale behandeling en sy/haar gewig-vir-ouderdom-z-telling. Slegs twee versorgers het hul babas ten tyde van die studie geborsvoed, hoewel 34% (n=10) van die versorgers in 'n stadium geborsvoed het. Voedingspraktyke met die gee van melkformule was swak. Altesaam 62% (n=18) het die melkformule verkeerd aangemaak en slegs ses (21%) het die bottels behoorlik skoongemaak en gesteriliseer. Nege-en-dertig persent (n=11) van die babas het te min melk per dag ontvang. Vyf-en-sestig persent (n=11) van die babas (>6 maande) se melkinname die vorige dag het nie aan die minimum WGO aanbevole dieetdiversiteitsaanwyser voldoen nie, en slegs 18% (n=3) het 'n minimum aanvaarbare dieet gevolg. Versorgers se kennis ten opsigte van babavoeding was gemiddeld, met net 13% (n=4) wat die korrekte omskrywing van eksklusiewe bors- of formulevoeding geken het. 'n Totaal van 68% (n=21) het nie geweet wat gemengde voeding beteken of watter gevare dit inhou nie. Die meeste versorgers (n=25, 81%) het geweet dat orale rehidrasie oplossing toegedien moet word wanneer babas aan diarree ly, maar slegs 48% (n=15) het geweet hoe om dit aan te maak en 'n skrale 6% (n=2) hoe om dit toe te dien. Vyf-en-sewentig persent (n=9) van die versorgers het nie geweet wat om te doen as hulle probleme met hul borste ervaar nie. Altesaam 64% (n=19) van die versorgers het geglo dat 'n MIV-positiewe vrou definitief haar baba MIV sal gee indien sy hom/haar sou borsvoed. Samevatting Die steekproef babas het 'n verskeidenheid onreëlmatige groeipatrone getoon en baie was ondergewig of het ook dwerggroei getoon. Versorgers se kennis van babavoeding was gemiddeld, maar nie voldoende om tot toepaslike, veilige en optimale babavoedingspraktyke aanleiding te gee nie. Die voorkoms van borsvoeding was laag. Melkformulevoorbereiding, - voeding en -higiëne was swak, en babas se voedinginname was nie ideaal nie. Die gehalte van en hoeveelheid voorligting oor MIV-babavoeding met besoeke aan voorgeboorteklinieke was swak en moet aangespreek word.
16

Factors contributing to paediatric HIV diclosure by caregivers

Van der Meulen, Christine January 1900 (has links)
Due to the increasing availability of ART (antiretroviral therapy),HIV is starting to be seen as a chronic disease. This has several effects on families, one of which is the need to disclose their HIV status to children who were born with the illness. Potential barriers and available support structures with regards to paediatric HIV disclosure need to be considered before specific guidelines can be given to caretakers and health care providers. This study aimed to explore and describe the patterns of paediatric HIV disclosure or non-disclosure using a sample of caretakers or parents of children/adolescents who were born with HIV. The Disclosure Decision Making Model (DDMM) was used as a framework to understand the decision-making process that leads to either disclosure or non-disclosure. Qualitative data was gathered by means of in-depth, semi-structured interviews, conducted in English. Ten participants were recruited from a community health care centre that offers HIV counselling and testing in the Nelson Mandela Bay Health District. Data gathered was transcribed and analysed using thematic analysis. Lincoln and Guba’s model was used to determine the trustworthiness of the data. The two themes that emerged from the study were (1) caretakers wish to disclose HIV status to the child but identified barriers to doing this and, (2) caretakers identified factors that helped them to disclose the child’s status. This study provides a more in-depth understanding of the factors that influence disclosure in a resource-limited setting in the Eastern Cape.
17

A chronic care coordination model for HIV-positive children requiring antiretroviral therapy

Williams, Margaret January 2013 (has links)
The human immunodeficiency virus / acquired immune deficiency syndrome pandemic (HIV/AIDS) continues to increase in prevalence worldwide, particularly in South Africa. There is a concurrent and distinct increase in the prevalence of HIV/AIDS and HIV-related diseases in the paediatric population in South Africa, particularly those using public sector health services, with a corresponding increase in morbidity and mortality rates (Abdool Karim & Abdool Karim, 2010:363), which impacts greatly on paediatric healthcare services. Adding to this, the provision of paediatric antiretroviral care has numerous stumbling blocks, not least of which is lack of decentralisation of facilities to provide treatment. There is the additional shortage of staff, which includes staff that are comfortable dealing with children, lack of training programmes on the provision of antiretroviral therapy to children, and minimal on-site mentorship of staff regarding HIV/AIDS disease in children. This lack of capacity in the healthcare system means that not all of those who require treatment will be able to access it, and this is particularly pertinent to paediatric patients (Meyers et al., 2007:198). Therefore the purpose of this research was to develop a nursing model that would assist healthcare professionals, in particular professional nurses, to optimise the comprehensive treatment, care and support for HIV-positive children who require antiretroviral therapy at PHC clinics. To achieve the purpose of this study, a theory-generating design based on a qualitative, explorative, descriptive and contextual approach was implemented by the researcher to gain an understanding of how the healthcare professionals and parents/caregivers of HIV-positive children experienced the comprehensive treatment, care and support provided at primary healthcare clinics. The information obtained was used to develop a chronic care coordination model for the optimisation of comprehensive treatment, care and support for HIV-positive children requiring antiretroviral therapy. The study design comprised the following four steps: Step One of the research design focused on the identification, classification and definition of the major concepts of the study. This involved describing and selecting the research population and the sampling process prior to conducting the field work which comprised in-depth interviews with two groups of participants, namely healthcare professionals and parents/caregivers who accompany their HIV-positive children to PHC clinics in order to receive antiretroviral therapy. Step Two of the research design focused on the development of relationship statements in order to bring clarity and direction to the understanding of the phenomenon of interest. Step Three of the design concentrated on the development and description of the chronic care coordination model for optimising comprehensive treatment, care and support for HIV-positive children who require antiretroviral therapy in order to ensure a well-managed child on ART. A visual representation of the structure of the model for chronic care coordination was given and described as well as a detailed description of the process of the model. Step Four was the last step of the research design and its focus was the development of guidelines for the operationalisation of the model for chronic care coordination for the optimisation of comprehensive treatment, care and support for HIV-positive children requiring antiretroviral therapy at PHC clinics. Guidelines and operational implications for each of the five sequential steps of the model were developed. The evaluation criteria of Chinn & Kramer (2008:237‒248) were used to evaluate the model. It is therefore concluded that the researcher succeeded in achieving the purpose for this study because a chronic care coordination model that is understandable, clear, simple, applicable and significant to nursing practice has been developed for use by healthcare professionals, particularly professional nurses, in order to optimise the comprehensive treatment, care and support for HIV-positive children requiring antiretroviral therapy at primary healthcare clinics.
18

Challenges faced by mothers with human immunodeficiency virus positive children in Pietersburg Hospital, Limpopo Province South Africa

Segoale, Nare Okney January 2020 (has links)
Thesis(M.A.(Nursing)) -- University of Limpopo, 2020 / The purpose of the study was to identify and explore the challenges faced by mothers with HIV positive children and who were admitted to Pietersburg Hospital, Limpopo Province, South Africa, during the period of study. A qualitative research methodology was used in the study based on exploratory and descriptive designs. The population for the study included all mothers of children who are HIV positive and had been admitted to the Paediatric Ward of Pietersburg Hospital, Limpopo Province, during the period of study. Non-probability purposive sampling was used to draw a sample of twelve (12) HIV positive participants from the research population. Data was collected from twelve participants through the use of semi-structured in-depth interviews, guided by an interview schedule. Fields notes were captured for non-verbal communication and a voice recorder was used to capture all the audio record of the interview sessions. Ethical clearance for the study was obtained from Turfloop Research Ethics Committee (TREC); and permission to collect data at the Pietersburg Hospital was obtained from the Limpopo Department of Health as well as the hospital’s Chief Executive Officer and from the Operational Manager of the Paediatric Ward. The findings from the study indicated that mothers of HIV positive children experienced numerous psychosocial and economic challenges on a daily basis. These challenges include accepting their own and their children’s HIV positive status; and also disclosing the status to their children. They also had to deal with opportunistic infections that the HIV positive children are more susceptible to, as well as challenges of ensuring that their children did not default on the medication schedules. Poverty and the lack of finances to pay for the various special needs of HIV positive children were also other key challenges experienced by the mothers. In light of these findings the study recommends the need for HIV/AIDS education, support from families and significant others as well as from the government. The study also recommends that well-coordinated and integrated inter-departmental intervention programmes are required to help mothers cope with their challenges.
19

Perceptions of nurses on disclosure of children's HIV positive status in Addis Ababa, Ethiopia

Yenealem Tadesse Woldemariam 08 1900 (has links)
A quantitative, descriptive, explorative survey was conducted to explore and describe nurses’ perceptions of disclosure to children of their HIV positive status in Addis Ababa. 100 nurses working in six conveniently sampled health centres participated by completing a self-administered questionnaire. The findings revealed that the majority of participants were of the opinion that children have the right to know their HIV status, participate in their own treatment, and that disclosure contributes towards improved adherence. Forty-one of the participants said that it is nurses’ role to support caregivers in the disclosure process. But 56.3% felt they lacked the training to disclose to children that they are infected with HIV. Accordingly, it is recommended that relevant and applied training is required to equip nurses with the knowledge and skills to disclose to children their status. The importance of nurses’ proactive role in disclosure to children of their HIV status needs to be emphasised. / Health Studies / M.A. (Public Health)
20

Cellular immunity, immune activation and regulation in HIV-1 infected mother-child pairs : what are the determinants of protective immunity.

Moodley-Govender, Eshia S. 01 November 2013 (has links)
Background: Prevention of Mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) remains a significant challenge in resource-poor settings despite the advances in antiretroviral (ARV) treatment. HIV-1 infected individuals are able to achieve viral control naturally, however the underlying mechanisms of immunological control in children remains poorly understood. This study was conducted from 2006 to 2010 to investigate correlates of immune control in HIV-1 clade C infected mother-child pairs in the absence of ARVs. Genotypic and phenotypic viral characteristics, cellular immune responses to HIV-1 and host genetics were characterized and correlated with clinical markers of disease progression. Materials and Methods: To achieve the objectives of the study, three cohorts of mother-child pairs were investigated. The first cohort included 60 untreated mother-child pairs and a further ten uninfected children as controls. The second cohort comprised of ARV treated pairs (n=60). The third cohort consisted of 374 mothers and 374 children (infected, exposed uninfected, HIV negative). Plasma viral loads and absolute CD4+ T cell counts were routinely performed in all three cohorts. HIV-specific CD8+ T cell responses were analyzed by interferon gamma (IFN-γ) enzyme linked immunosorbent spot (ELISpot) assays. Viral replicative fitness was assessed using a green fluorescent protein reporter cell line (GFP).Multi-parameter flowcytometry allowed for the investigation of T cell regulation, exhaustion and activation using CD127/CD25, TIM-3/PD-1 and HLA-DR/CD38 markers respectively. IL-10 promoter single nucleotide polymorphisms (SNPs) at positions -592 and -1082 were determined by TaqMan allelic discrimination assays. Plasma IL-10 levels were measured using a luminex assay. Results: To describe the CTL responses elicited to various regions of the HIV proteome in HIV-infected treatment naïve children. Sixty children under one year of age in the untreated cohort were analyzed for CTL responses spanning the HIV genome, for which only 30 had detectable responses. There was no significant difference in viral load between respondersand non-responders (p=0.2799). The responders predominantly targeted Nef (49%), Gag (17%) and Env (14%) regions. Markers of T cell exhaustion and regulation and theirrelationship to markers of disease progression, were next investigated as these parameters may explain the inability of T cells to effectively control HIV infection. T cell phenotyping compared treated, untreated and uninfected subgroups. In infected children, CD8+ T cells were significantly higher for both the inhibitory marker TIM-3 (p=0.001) and exhaustion marker PD-1 (p=0.0001) compared to uninfected children. Median expression of TIM-3 was higher on CD8+ T cells (46%) compared to CD4+ T cells (20%). TIM-3 and PD-1 expression on T cells were maintained at high levels over time. The frequency of absolute Tregs (p=0.0225) were found to be significantly higher in untreated compared to treated children. HLA-DR+CD38+ on CD8+ T cells were significantly up-regulated in untreated children compared to treated (p=0.002) and uninfected children (p=0.0177). HLA-DR+CD38+ was also significantly higher in children less than 6 months compared to older children on CD4+ (p=0.0437) and CD8+ T cells (p=0.00276). Interestingly, we observed a significant negative correlation between magnitude of CTL response and CD25+CD127- (p=0.0202; r=-0.7333) as well as HLA-DR+CD38+ (p=0.0408; r=-0.5516) on CD8+ T cells. IL-10 is an important immunoregulatory cytokine that has been shown to affect the outcome of chronic viral infections. IL-10 polymorphisms have previously been associated with IL-10 levels and HIV-1 outcomes in adults. Polymorphisms associated with different levels of IL-10 production and their relationship with transmission, markers of disease progression and immune responses were next investigated in this mother-child HIV transmission setting. Genetic analysis of IL-10 in cohort three revealed that HIV-1 acquisition was not associated with either IL10 -592 (AA/CA vs CC) or IL10 -1082 (AA/AG vs GG) single nucleotide polymorphisms (SNPSs). There was a significant association between IL10 -1082 and HIV-1 transmission (p=0.0012). No correlation was observed between IL10 -592 (p=0.4279) or IL10 -1082 SNPs (p=0.6361) and mortality rates in children. IL10 -592C was associated with an elevated magnitude of IFN-γ CD8+ T cell response compared to IL10 -529A (p=0.0071). We found a significant positive correlation between IL-10 plasma levels and viral loads (p=0.0068; r=0.4759) and the ages of the children (p=0.0312; r=0.1737). Conclusion: CD8+ T cell responses and viral fitness did not explain differences in disease progression in selected HIV-1 untreated clade C transmission pairs. T cell activation and regulatory markers influence CTL immune responses resulting in poor clinical outcome. IL10 -1082 polymorphisms may be used as a predictor of HIV-1 transmission. The association between increased IL-10 plasma levels and high viral loads suggest that IL-10 contributes to immune dysfunction in paediatric HIV-1 infection. This study has extended our understanding of immunological and genetic correlates of mother-to-child transmission and disease outcome in ARV naïve (naturally controlling) and HIV treated infected children. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2011.

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