A thesis submitted in partial fulfilment of tine requirements for the Degree of Master of Technology: Biomedical Technology, Durban University of Technology, 2007. / In 2004, it was reported that KwaZulu-Natal had the greatest number of HIV infected people, approximately 1.8 million people, of whom an estimated 450 000 were in need of antiretroviral drug therapy based on their Cluster of Differentiation 4 (CD4) counts and clinical status. Studies on the success of antiretroviral drugs in improving the quality of life in HIV infected individuals have been extensively performed and published. However, there are no published data on the effect that immune boosters have in improving the quality of life in such persons. Considering the side effects, toxicity, multi-drug regimens and drug resistance problems associated with antiretroviral therapy, alternative or supplementary therapies may play an important role in improving the quality of life in HIV infected people. Such therapy might help in situations where some patients who qualify for antiretroviral treatment are unable to access them because of several reasons such as long waiting lists, travelling costs, unwilling to take antiretroviral drugs, etc. Some patients have reservations in taking antiretroviral drugs. The stigma associated with the disease may be a major factor. The aim of this study was to investigate the change in the immune status of HIV infected patients that were on the Inochi New Medicine immune booster, as well as, to assess the safety and efficacy of this immune booster in improving the patients’ quality of life. / M

Thesis (M.Tech.: Biomedical Technology)-Dept. of Biomedical Technology, Durban University of Technology, 2007 xxiii, 244 leaves / In 2004, it was reported that KwaZulu-Natal had the greatest number of HIV infected people, approximately 1.8 million people, of whom an estimated 450 000 were in need of antiretroviral drug therapy based on their Cluster of Differentiation 4 (CD4) counts and clinical status. Studies on the success of antiretroviral drugs in improving the quality of life in HIV infected individuals have been extensively performed and published. However, there are no published data on the effect that immune boosters have in improving the quality of life in such persons. Considering the side effects, toxicity, multi-drug regimens and drug resistance problems associated with antiretroviral therapy, alternative or supplementary therapies may play an important role in improving the quality of life in HIV infected people. Such therapy might help in situations where some patients who qualify for antiretroviral treatment are unable to access them because of several reasons such as long waiting lists, travelling costs, unwilling to take antiretroviral drugs, etc. Some patients have reservations in taking antiretroviral drugs. The stigma associated with the disease may be a major factor. The aim of this study was to investigate the change in the immune status of HIV infected patients that were on the Inochi New Medicine immune booster, as well as, to assess the safety and efficacy of this immune booster in improving the patients’ quality of life.

[Truncated abstract] In the last ten years regulator T (Tr) cells have re-emerged as an integral part of the immune system. Research in this field has rapidly demonstrated the role of these cells in the maintenance of immune homeostasis and their involvement in disease. Tr cells are generated in the thymus as a normal part of the developing immune system. Furthermore, antigen-specific Tr cells are induced in the periphery by a mechanism which is yet to be completely elucidated, but is likely to involve dendritic cells. Tr cells play an important role in autoimmune disease, transplantation tolerance, cancer. Most recently Tr cell involvement has been demonstrated in a growing number of infectious diseases. Tr cell induction was reported in Friend Virus infection at the commencement of this study, and subsequent to publication of our findings have also been identified in FIV and HIV. Murine AIDS (MAIDS) is a fatal chronic retroviral infection induced in susceptible strains of mice by infection with BM5d, a replication defective virus, in a viral mixture which is designated LP-BM5. The manipulation of Tr cells detailed in this thesis and the related publication represent the first reported therapy utilising targeted removal of Tr cells. Chapter 1 summarises the literature relevant to this study up to November 2004. Chapter 2 details the materials and methodologies used in this work. Chapter 3 investigates whether Tr cells are involved in the development of murine AIDS, particularly in the early stages of infection. The data presented in this chapter provides evidence of a population of CD4+ Tr cells which express CD25 on their cell surface and secrete TGF-β, some IL-10 and low levels of IL-4 are induced following infection with LP-BM5. These cells were found to arise by day 12 post infection (pi) by flow cytometry and immunosuppressive cytokine expression was found to peak at day 16 pi indicating a role in the early stages of disease progression. Chapter 4 investigates the effect of therapeutically targeting these induced Tr cells using the antimitotic agent Vinblastine during their induction period. The efficacy of treatment was found to be time dependent and was shown to abrogate disease progression maximally when given at day 14 pi. Treatment with anti-CD4 monoclonal antibody was also found to be efficacious at day 14 pi and confirmed the identity of the Tr cells as being CD4+ T cells. Adoptive transfer studies demonstrated that the return of these cells to a successfully treated host results in renewed MAIDS progression, confirming their role in disease progression