Interleukin-l0 (IL-10) helps to limit the duration of potentially harmful inflammatory responses but has also been implicated in the persistence of a number of chronic viral infections. This thesis aimed to investigate the phenotype and function of mv -specific IL-l0-producing cells in chronic HIV-I infection, and the effect of IL-10 blockade on responses to candidate HIV -I vaccines. A cytokine capture assay was used to determine the HIV -specific cellular sources of IL- 10 in PBMC from 55 chronically infected individuals. A rare subset of CD8+ T cells was found to be the major HIV -I Gag-specific IL-10-producing population; these cells were restricted to ART-naive individuals and did not express the regulatory T cell markers CD25 or FoxP3 but could co-express IFN-y. A proportion of the population (median 48% and 9% respectively) expressed the P7 chain of the gut-homing integrin a4p7 and the chemokine receptor CXCR3, which mediates lymphocyte migration to sites of inflammation. Experimental depletion of Gag-specific IL-10+ CD8+ T cells did not affect T cell activation, or the production of cytokines such as IL-2 or IFN-y during short-term culture. However, depletion was associated with a significant increase in CD38 expression on CDI4+ monocytes, a trend towards increased HLA-DR expression on the same cells, and a significant increase in the concentration of the pro-inflammatory cytokine IL-6 in culture supernatants. There was also a significant increase in the number of HIV-infected (p24 antigen+) CD4+ T cells in cultures depleted of Gag- specific IL-10+ CD8+ T cells after 3 days, indicating that this population may contribute to control of viral replication. In order to determine the effect of IL-10 blockade on vaccine immunogenicity, IL-10R blocking antibody was administered to BALB/c mice prior to immunisation with two mV-I candidate vaccines, HIVA and HIVconsv. IL-10R blockade resulted in a trend towards increased IFN-y production by CD8+ T cells in response to the dominant H (Env) and P (Pol) epitopes of HIV A, and a significant increase in IFN-y ELISPOT responses to the subdominant Gl (Gag) epitope of HIV consv in vitro. Collectively, these data suggest that IL-10 producing cell populations may play critical but different roles in chronic infection and vaccination. Further research into how the timing of IL-10 responses affects disease outcome may allow IL-IO blockade to be explored as a therapeutic strategy in humans

The health care industry in Nigeria is increasingly grappling with challenges of meeting end users’ requirements and expectations for quality antiretroviral therapy (ART) service provision. This study sought to explore and describe the quality of antiretroviral therapy in public health facilities in Nigeria and the perceptions of the end users. A descriptive qualitative research design was used in the study in order to generate ideas from end users for improving quality of ART service provision, and prompt additional research activities. Unstructured focus group discussions were conducted with end users (n=64) in 6 locations across the 6 geopolitical zones of Nigeria. Data was analysed using the framework approach because it reflects the original accounts and observations of the end users and the Weft QDA version 1.0.1 software to validate the results. Findings revealed that end users were satisfied with uninterrupted antiretroviral drug supplies, courtesy treatment, volunteerism of support group members and quality counselling services. End users expect public health facilities to accept diagnostic results from collaborating facilities, implement continuous quality improvement (CQI), maintain clean and adequate health infrastructure, reduce end user waiting time, reduce stigma, comprehensively assess end users during each clinic visit and ensure uninterrupted ART services. They also expect effective collaboration between healthcare providers and support group members, to enhance the quality of life of people living with HIV (PLHIV). End users identified the following as quality gaps in ART service provision: weak health facility leadership, non-attractive ART service infrastructure, frequently interrupted laboratory services, demotivated and inadequate health care workers, long waiting time, interrupted medicine supplies and inadequate procedure for complaints management. In conclusion, the following recommendations were proffered: deploy and train additional health care workers, integrate ART into regular health services, improve supply chain management of health commodities, and reduce end user overload in clinics. Finally, a best practice guideline for the provision of end user focused ART service provision was developed. / Health Studies / D.Litt. et Phil. (Health Studies)

The health care industry in Nigeria is increasingly grappling with challenges of meeting end users’ requirements and expectations for quality antiretroviral therapy (ART) service provision. This study sought to explore and describe the quality of antiretroviral therapy in public health facilities in Nigeria and the perceptions of the end users. A descriptive qualitative research design was used in the study in order to generate ideas from end users for improving quality of ART service provision, and prompt additional research activities. Unstructured focus group discussions were conducted with end users (n=64) in 6 locations across the 6 geopolitical zones of Nigeria. Data was analysed using the framework approach because it reflects the original accounts and observations of the end users and the Weft QDA version 1.0.1 software to validate the results. Findings revealed that end users were satisfied with uninterrupted antiretroviral drug supplies, courtesy treatment, volunteerism of support group members and quality counselling services. End users expect public health facilities to accept diagnostic results from collaborating facilities, implement continuous quality improvement (CQI), maintain clean and adequate health infrastructure, reduce end user waiting time, reduce stigma, comprehensively assess end users during each clinic visit and ensure uninterrupted ART services. They also expect effective collaboration between healthcare providers and support group members, to enhance the quality of life of people living with HIV (PLHIV). End users identified the following as quality gaps in ART service provision: weak health facility leadership, non-attractive ART service infrastructure, frequently interrupted laboratory services, demotivated and inadequate health care workers, long waiting time, interrupted medicine supplies and inadequate procedure for complaints management. In conclusion, the following recommendations were proffered: deploy and train additional health care workers, integrate ART into regular health services, improve supply chain management of health commodities, and reduce end user overload in clinics. Finally, a best practice guideline for the provision of end user focused ART service provision was developed. / Health Studies / D.Litt. et Phil. (Health Studies)