Human immunodeficiency virus type 1 (HIV-1) still causes a chronic infection that affects millions of individuals worldwide. The infection remains incurable and presents a huge challenge for treatment, as it tends to disable a patient’s immune system. Although the current HIV-1 treatment regime possesses the ability to reduce the viral load to undetectable limits, complete eradication of the virus cannot be achieved while latent HIV-1 reservoirs go unchallenged. These viral reservoirs are established early on during HIV-1 infection and are a major hurdle since they remain unaffected by antiretroviral drugs and have the ability to replenish systemic infections once treatment is interrupted. Further ailments with the highly active antiretroviral therapy (HAART) include issues such as the cumbersome lifelong treatment, development of drug resistant strains of HIV-1 and adverse side effects. Contrarily, early diagnosis of the HIV-1 infection and HIV-1 treatment is a major challenge in resource-limited countries. The current available diagnostic tools for HIV-1 infection have shown to be highly accurate in monitoring CD4+ T lymphocyte count and viral load measurements. However, these tests such as enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) which are highly efficient, are usually very expensive with complex operation, time consuming, require skilled personnel and training that makes them incompatible for the application in resource-limited areas. Therefore, this raises the urgent need for developing an HIV point of care (POC) diagnostic tool that is label-free, highly specific and sensitive as well as therapeutic modalities, which can be used to address the previously mentioned challenges. Much research has been conducted to resolve these problems but to date, there has not been application of laser and/or photonics in HIV research. Therefore, in this thesis a femtosecond laser was used in HIV infected cells for targeted antiretroviral drug delivery while preserving their viability. For the first time according to our knowledge, antiretrovirals (ARVs) that target all the life stages of the HIV-1 life cycle were utilized and they proved to be significant in reducing HIV-1 infection. Furthermore, through the employment of a continuous wave laser at 640 nm, for the first time, surface plasmon resonance was conducted to facilitate label-free detection of HIV-1. Success of these laser based technologies will open doors for incorporation in POC HIV diagnostic tools for the detection and treatment monitoring of HIV in resource-limited settings. / Physics / Ph. D. (Physics)

Indiana University-Purdue University Indianapolis (IUPUI) / With effective antiretroviral therapy (ART), cardiovascular diseases (CVD), are emerging as a major cause of morbidity and death in the aging population with HIV infection. Although this increase in CVD could be partially explained by the toxic effects of combined anti-retroviral therapy (ART), more recently, HIV infection has emerged as an independent risk factor for CVD. However, it is unclear how HIV can contribute to CVD in patients on ART, when viral titers are low or non-detectable. Here, we provide several lines of evidence that HIV-Nef, produced in infected cells even when virus production is halted by ART, can lead to endothelial activation and dysfunction, and thus may be involved in CVD. We demonstrate that HIV-infected T cell-induced endothelial cell activation requires direct contact as well as functional HIV-Nef. Nef protein from either HIV-infected or Nef-transfected T cells rapidly transfers to endothelial cells while inducing nanotube-like conduits connecting T cells to endothelial cells. This transfer or transfection of endothelial cells results in endothelial apoptosis, ROS generation and release of monocyte attractant protein-1 (MCP-1). A Nef SH3 binding site mutant abolishes Nef-induced apoptosis and ROS formation and reduces MCP-1 production in endothelial cells, suggesting that the Nef SH3 binding site is critical for Nef effects on endothelial cells. Nef induces apoptosis of endothelial cells through both NADPH oxidase- and ROS-dependent mechanisms, while Nef-induced MCP-1 production is NF-kB dependent. Importantly, Nef can be found in CD4 positive and bystander circulating blood cells in patients receiving virally suppressive ART, and in the endothelium of chimeric SIV-infected macaques. Together, these data indicate that Nef could exert pro-atherogenic effects on the endothelium even when HIV infection is controlled and that inhibition of Nef-associated pathways may be promising new therapeutic targets for reducing the risk for cardiovascular disease in the HIV-infected population.

The researcher investigated the knowledge, attitudes and experiences of people living with the Human Immunodeficiency Virus (HIV) towards antiretroviral treatment (ART) and who are accessing antiretroviral treatment at a public health clinic in Limpopo, South Africa. A qualitative method was used. The research findings revealed five themes: experiences, social support, knowledge, attitudes, unemployment and economic themes of the study. Factors reported influencing optimum adherence were the inability of the patients to take medication at work, laziness of the patients to collect medication, unemployment, economic hardship, poverty and lack of knowledge of employers regarding HIV/AIDS. / Health Studies / M.A. (Social Behaviour Studies in HIV and AIDS)

AIM The purpose of this study was to explore and describe factors that contribute to the non-initiation of Antiretroviral Therapy (ART) amongst Pre-Antiretroviral Therapy eligible patients and to make recommendations for health care workers to enhance early initiation of pre-ART-eligible patients for primary health care facilities in Swaziland. METHOD A qualitative design was applied in rural primary health care (PHC) facilities in the Hhohho region of Swaziland. The target population for this study included nurses who have successfully completed the National Nurse Led Antiretroviral Therapy Initiation in Swaziland (NARTIS) training, and who actively initiated ART to eligible patients in rural PHC facilities. Data was collected through semi-structured interviews and field notes. Purposive, convenient sampling was applied. Eleven respondents were interviewed for the study, and data was collected until data saturation was reached. Data from transcripts and field notes was analysed and categorised with thematic analysis through Tesch’s open coding process. RESULTS The study identified the following three predominant themes: 1) systematic enablers of prompt ART initiation, 2) barriers to prompt ART initiation, 3) sources of support. Categories included public health care (PHC) factors, community level factors, the interdependence of the health care system, patient centred barriers, individual patient agency, and NARTIS nurse support. CONCLUSION The recommendations for health care workers that emerged from the study included continued HIV treatment scale-up and decentralisation to grass roots levels, aggressive treatment prioritisation among pre-ART patients, building the capacity of the local health care system and continued research initiatives. It is hoped that recommendations emerging from the findings of this study will have positive implications for programming and practice regarding the initiation of ART for eligible pre-ART patients in Swaziland. / Health Studies / M. PH.

Adolescence is a significant period of change in physical and psychosocial development of human beings. Being HIV positive and growing up on a dynamically multifaceted HAART treatment, adds to the complexity of adolescence. This study was aimed at exploring the nature of experiences of adolescents who are on long-term Highly Active Antiretroviral Therapy (HAART) in Tembisa, Gauteng province. The study is based on a qualitative research method using in-depth semi-structured open-ended interviews and a focus group for data collection. The sample consisted of seven individual adolescent participants, three parents, guardians and caregivers, as well as 11 health care professionals. The thematic data analysis and the phenomelogical analysis methods were used to analyse data qualitative data while descriptive statistics were used to analyse quantitative biographical data. The study findings cover the negative and positive experiences and the perceived role of HAART treatment over a long period of time. The predominant themes identified from adolescent participants were disclosure of HIV positive status and the stigma surrounding a positive status, early childhood experience of parental death, challenges of taking HAART treatment, factors influencing adherence and non-adherence to HAART treatment, and lastly, the impact of religion on HAART treatment adherence. The findings suggest that adolescents who are on HAART treatment over an extended period of time experience drug fatigue. Drug fatigue has far-reaching implications for the health of an adolescent, as it has a higher likelihood that poor adherence or even complete refusal to take HAART treatment will occur. Poor adherence or refusal to take HAART treatment will most likely lead to cross infection and further spread of HIV and AIDS. A recommendation was made to include the establishment of a youth and adolescent-friendly centre by the hospital – one that is designated for the provision of tailored adolescent services and sensitive to adolescent developmental stages so as to minimise the likelihood of infected adolescents falling through the health care cracks. The introduction of a hospital-based school, an education unit run by dedicated and qualified facilitators focusing on aiding hospitalised learners with catch-up scholarly programmes, was a further recommendation. It was further recommended that reproductive health care needs of adolescents who grow up on HAART treatment be given attention in further research. / Psychology / Ph.D. (Psychology)