South Africa and the province of KwaZulu-Natal (KZN) has one of the greatest HIV burdens in the world with an estimated 5.7 mHIion people living with HIV/AIDS. One of the interventions that the government introduced to address this situation was the provision of antiretroviral treatment (ART) to those individuals that are eligible for HIV treatment in order to reduce the morbidity and mortality. Despite widespread availability of ART in KZN, children do not access ART to the extent that adults do, and therefore continue to die because of HIV and AIDS. This qualitative study explored the psychosocial and health system factors that influence paediatric access to ART in KZN from parents and caregivers perspectives. The ecological theory and the social cognitive theory was used to formulate an interview schedule used in conducting the in-depth interviews with adults (parents or guardians) who were bringing their children for ARTservices and those attending these services themselves and not their children at Edendale and King Edward Hospitals in KZN. Purposive sampling was used to select clients for interviews and thematic was done in accordance with the aims and objectives of the study. A total of 42 participants were interviewed in this study. The low uptake of child ART was found to be influenced by several psychosocial and economic factors such as the poor knowledge about ART, stigma and disclosure associated with HIV, extent of support provided by parents/caregivers, parent's own ART was a determinant for bringing children for ART, use of traditional / alternative medicines, disintegrated families, especially the issue of multiple caregivers, complexity of paediatric ART, poor referrals of children from community institutions, unsatisfactory service at clinics, and some health policy and legislation with respect to health care for HIV-infected children that had an unintended effect of restricting child access to ART as well as poverty related Issues. Improving knowledge and self-efficacy related to ART, prevention of mother to child transmission ofHIV, re-training of health workers on child issues and addressing stigma and discrimination and other psychosocial and institutional problems and logistics could help to improve the low paediatric uptake of ART. / Thesis (M.A.)-University of KwaZulu-Natal, Durban, 2009.

M.A. (Psychology) / The Acquired Immunodeficiency Syndrome (AIDS) has become one of the major challenges that the health care system has had to face and will continue to present a significant health challenge well into the 21st century. Up to the present time no effective treatment method has been found as the retroviral agents typically only cause a temporary inhibition of the progression of the Human Immunodeficiency Virus (HlV) and not a permanent cessation of the activity ofthe virus. Psychosocial approaches to the management of HlV have been moderately successful, but more successful then the retroviral agents during the HIV but non Clinical stage. Considering the proportions of the HlV disease, there are few studies in South-Africa, that describe the therapeutic effects of a stress management package consisting of aerobic exercise, group-based cognitive behavioural therapy and relaxation training on mood state changes of asymptomatic and early symptomatic HIV sufferers. Psychological measures, like depression and anxiety have been found to be associated with lowered immune responsivity, thus enhancing the underlying immunodeficiency found in HlV/AIDS sufferers. Past research has also illustrated the benefits that may be derived from aerobic exercise on the physiological mechanisms of the body. The intention of this research, was therefore to further reinforce the positive effects of aerobic exercise by using a biopsychosocial approach in the treatment of HIV, leading to an overall improvement in the immunological status, depression and distress levels of HlV patients, as well as their ability to cope with the disease. The study took place within the context of a wider project, forming a component of the AIDS research conducted by Prof. E.Wolff (Rand Afrikaans University). The study assessed the relevance of this intervention for the South African Setting.

A thesis submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg in fulfilment of the requirements for the degree of Doctor of Philosophy. Johannesburg, 28 May 2018. / Since their discovery, protease inhibitors continue to be an essential component of antiretroviral treatment for human immunodeficiency virus type 1 (HIV-1). However, the development of resistance to protease inhibitors remains one of the most significant challenges in the fight for sustained viral suppression in those infected with HIV-1. Studies show that specific mutations arising within the HIV-1 gag and protease genes can lead to the development of resistance. In this research, a South African HIV-1 subtype C Gag-protease variant (W1201i) was investigated. This variant was considered due to the presence of a mutation and insertion (N37T↑V), located within the hinge region of the protease enzyme. Moreover, the variant displayed the following polymorphisms: Q7K, I13V, G16E, M36T, D60E, Q61E, I62V and M89L. Genotyping of W1201i Gag revealed a previously unreported MSQAG insertion between the CA/p2 and p2/NC cleavage sites. Additionally, a mutation and insertion (I372L↑M), and multiple polymorphisms (S369N, S371N, I373M and G377S) were discovered within the p2/NC cleavage site. Single-cycle phenotypic assays were performed to determine the drug susceptibility and replication capacity of the variant. The results show that the mutations present in the N37T↑V protease conferred a replicative advantage and reduced susceptibility to lopinavir, atazanavir and darunavir. Interestingly, the mutations in W1201i Gag were found to modulate both replication capacity and protease inhibitor susceptibility. In silico studies were performed to understand the physical basis for the observed variations. Molecular dynamics simulations showed that the N37T↑V protease displayed altered dynamics around the hinge and flap region and highlighted the amino acids responsible for the observed fluctuations. Furthermore, induced fit docking experiments showed that the variant bound the iv protease inhibitors with fewer favourable chemical interactions than the wild-type protease. Collectively, these data elucidate the biophysical basis for the selection of hinge region mutations and insertions by the HI virus and show that protease, as well as Gag, needs to be evaluated during resistance testing. / EM2018

Thesis presented in partial fulfilment for the degree of Master of Management (in the field of Public Sector Monitoring and Evaluation) to the Faculty of Commerce, Law, and Management, University of the Witwatersrand 2016 / The purpose of this research was to assess outcomes of the antiretroviral treatment intervention in Mankweng. The antiretroviral treatment intervention was conceived with the aim to reduce HIV transmission through viral load suppression. Literature has shown that viral load is used as a tool to measure the performance of the intervention and studies on viral load outcomes in rural settings of Limpopo are limited. For this reason, the research was focused on viral load suppression with the aim of (1) determining the proportion of adults with viral load suppression among people taking antiretroviral treatment for 12 months, and (2) identifying factors associated with failure to achieve viral load suppression among people on antiretroviral treatment for 12 months. Binomial logistic regression model was used to identify factors associated with failure to suppress viral load. This study used the theory of change to interpret its findings as well as theories of behavioural planning and self-regulation models to understand the logic that underpins the theory of change. The findings revealed that the majority (78%) of adults achieved viral load suppression, and a quarter of the individuals failed to suppress the viral load. There was no significant difference in baseline characteristics between people who achieved viral load suppression and those who did not. In addition, males, with a low CD4 and opportunistic illnesses when in the primary disease stages were more likely to fail to suppress the viral load. Moreover, people who were initiated on a 3-pill containing treatment and do not have social support were also likely to fail to achieve viral load suppression. Although the study showed a trend of likelihood towards failure to achieve viral load suppression, the estimates were not statistically significant. Theoretical arguments from this study suggest that failure to achieve viral load was attributed to poor adherence to treatment. This is supported by the logic that underpins the theory of change, in which the assumption of adherence was possibly violated. However, the results chain framework highlighted that the implementation of the intervention was effective as it led to good outcomes and an effective intervention. Drawing all this together, the study highlights the need for intensified adherence counseling during treatment in order to improve the performance of the intervention. Author: Ramatsobane Johanna Ledwaba, Thesis Title: Outcomes of the antiretroviral treatment intervention in Mankweng, Johannesburg, March 2016 / GR2018

The HIV/AIDS pandemic has implications at every level of social functioning. It affects individuals, families, communities and organisations. The burden of caring for those exposed, affected and infected is vast, but one of the most significant developments which have the potential to reduce disease burden is antiretroviral therapy. Antiretroviral therapy (ART) is complex and difficult to administer, and requires a learning process which is mediated through a number of means. Vygotskian theory was utilised to better understand the process of adherence through mediated learning, and as a framework for explaining compliance. In this study, mediated learning occurs both in the context of the clinic staff and the clinic attendees, and the caregivers and the child. Therefore Vygotsky‟s theory offers useful insight into this process. This qualitative study aimed to research the factors which contribute to ART adherence in a small sample of HIV positive children who are attending a local clinic. Eight child-caregiver dyads were interviewed, and drawings utilised to better understand child and caregiver factors which contribute to compliance. There were a number of psychosocial factors identified which contribute to compliance, or lack thereof, including social support, stigma, medication fatigue, disclosure, access difficulties, psychoeducation, and motivation. A number of qualitative differences were also identified between children who knew their HIV status and those who did not. These differences emerged primarily through the analysis of the child participants‟ drawings and there appeared to be a number of inter- and intrapersonal benefits to disclosure. The factors identified in this study, if better understood, can inform interventions to improve compliance on ART. / Thesis (M.Soc.Sci.)-University of KwaZulu-Natal, Pietermaritzburg, 2010.

Thesis (MFamMed)--Stellenbosch University, 2015. / ENGLISH SUMMARY: Background: Sub Saharan Africa is home to approximately two thirds of the world’s population of HIV positive individuals. In view of the socioeconomic challenges of the region governments have provided antiretroviral therapy free to improve chances of survival among patients. However, adherence to antiretroviral therapy is recognised as more important in predicting patient survival. Aim: The study aimed to describe the prevailing factors that influence adherence to antiretroviral therapy. Methods: The study design was carried out using three methods of data collection. Focus group discussions, semi structured interviews and a questionnaire format. Setting: This study has been conducted among adult patients attending the Dora Nginza Hospital Adult wellness clinic. Results: The methods highlighted factors that influence antiretroviral therapy revealing psychosocial factors – lack of family support, not wanting to take medicines in front of people outside the home; patient factors – co morbidities that disturb patient adherence to therapy, a lack of trust in the patient-care giver relationship, fear of the drug side effects; socioeconomic factors – patients’ inability to afford food or transport costs to clinic appointments. In the semi structured interviews, 25% of patients self reported on poor adherence while in the questionnaire 5% of patients reported poor adherence. In assessing the effect of adherence to therapy on CD4 count and viral load there was a general increase in CD 4 count and a drop in viral load indicating clinical improvement in patients on therapy. Recommendation: There is a need for clinicians developing a health relationship with patients to facilitate adherence. The interventions designed to help patients in adherence to therapy should involve the patients in question in the designing of these interventions. Conclusion: Adherence monitoring is an important aspect of managing patients on antiretroviral therapy. The factors highlighted are similar to findings of other studies in similar contexts i.e. resource poor settings. / AFRIKAANSE OPSOMMING: Opsomming nie beskikbaar.

M.A. (Public Management and Governance) / This study starts with an introduction and background, and this is followed by a statement of the research problem, research rationale, research objectives, research design, research methodology and the data collection methods. A list of acronyms will be provided, as well as an overview of chapters, conclusions, and acknowledgements. “Around 5.7 million in 2009 had contracted HIV and AIDS and in the preceding year 250,000 South Africans died due to HIV/AIDS related diseases. All age categories and gender are prone to contracting the disease and the resultant loss of life has had a devastating effect on the workforce. Death due to this disease has caused loss of income and family disintegration” (Sottile 2013:2). In 2010, some 280,000 South Africans died of HIV/AIDS. In the decade up to 2010, between 42% and 47% of all deaths among South Africans were HIV/AIDS-related deaths (Sottile 2013:2). Mlambo et al (2011:1) further say that “The Human Sciences Research Council estimates that 10.9% of all South Africans have HIV/AIDS. Additionally, the Central Intelligence Agency estimates that 310,000 individuals died in South Africa from HIV/AIDS in the year 2009”. A study in 2003 made a comparison on two scenarios, an HIV/AIDS scenario and a no-HIV/AIDS scenario and this was based on the annual growth rates between 2002 and 2015. The finding was that “real growth in GDP would be 0.6% lower than if there were no HIV/AIDS, but per-capita growth in GDP would be 0.9% higher. Growth in population would have been 1.5% lower, and growth of the labour force would be 1.2% lower, but the unemployment rate would be 0.9% lower as well” (Avert.Org 2010:2). Different HIV/AIDS prevention strategies are being implemented in South Africa. The focus in this study is on male medical circumcision (hereafter MMC), which is the removal of all or part of the foreskin on the penis. It can either be performed surgically in hospitals or at initiation schools. Initiation schools perform the procedure as a traditional rite of passage from boyhood to manhood, and this is referred to as traditional male circumcision (TMC). This practice has up till now been performed purely for traditional or religious purposes, but it can no longer be viewed only as such. It should, instead, also be seen as a measure to curb the spread of the HIV/AIDS pandemic. A number of observational studies (which will be referenced later) found that circumcised men had smaller chances of contracting HIV infection compared with uncircumcised men...

The introduction of antiretroviral drugs (ARVs) in 1996 transformed the treatment of HIV and AIDS, improving the quality and greatly prolonging the lives of many infected people. HIV (Human Immunodeficiency Virus) is the virus that is believed to cause AIDS. AIDS (Acquired Immune Deficiency Syndrome) is the collection of illnesses or symptoms that ultimately results in death. Antiretroviral (ARVs) drugs or Highly Active Antiretroviral Therapy (HAART) is the treatment that has been applied to combat the HI virus in a bid to slow down the progression of AIDS and ultimately prolong the life of the infected individual. The study aimed to explore and describe the factors contributing to adherence and non-adherence to ARVs in individuals on treatment. A sample of 81 individuals who have been on ARV and HAART treatment for six months or more was used. The methodology used was exploratory-descriptive and the data obtained was quantitative in nature. A biographical questionnaire and questionnaire with questions aimed at ascertaining the possible factors that contribute to individuals either adhering to or defaulting on their treatment, such as side effects and cost of treatment, was administered. The data obtained was analysed by means of descriptive statistics and frequency counts. The results of the study showed that the sample had a fairly high level of adherence. The factors that could undermine adherence were identified as lack of support, as familial and health provider support acts as a motivator to adhere; substance abuse as it can lead to forgetting to take treatment; unemployment and poverty, as these can lead to an inability to return for follow up clinic visits or failure to have food to take with the pills; and the type of treatment regimen whereby the more complex the treatment is the more likely it is that adherence will be difficult to maintain. Suggestions were made as to future research involving antiretroviral therapy (ART). Finally the limitations as well as the value of the research were outlined.

The human immunodeficiency virus (HIV) is one of the most common and dreaded diseases of the 21th century. Today, the disease is still spreading with increasing incidence. “Since the beginning of the epidemic, almost 75 million people have been infected with the HIV virus and about 36 million people have died of HIV. Globally, 35.3 million [32.2–38.8 million] people were living with HIV at the end of 2012” (http://www.who.int/gho/hiv/en/). Several studies have been conducted on herbs under a multitude of ethnobotanical grounds. The use of medicinal plants for the management of HIV has become a common practice especially, in the Eastern Cape Province of South Africa (Wilfred Otang Mbeng, 2013 PhD thesis, UFH). At the beginning of this programme, an ethnomedicinal survey of plants used for the management of HIV infection was carried out in targeted areas of the Province and information on the names of plants, the parts and the methods of preparation were collected. The survey revealed that 18 species representing 12 families were found to be commonly used for the management of HIV, as well as other opportunistic diseases such as tuberculosis, diabetes mellitus, sores, high blood pressure, etc. Carpobrotus edulis was selected for this research because it was the most frequently used in the Province. The foliar micro morphological contents of the plant, its phytochemical and antioxidant activity, in vitro antimicrobial activity, inhibitory effect against HIV-1 protease and reverse transcriptase, mechanisms of action and cytotoxicity were investigated. In terms of the foliar micro morphological contents in plants, an electron microscopy scanning (SEM) was completed. Investigation revealed that both glandular tricomes and calcium oxalate crystals (CaOX) were observed. Consequently, it is hypothesized that the bioactive therapeutic compounds secreted by C. edulis may be produced in the glandular trichomes. An investigation of phytochemical content of the plant extracts (C. edulis) was completed using four solvent extracts (hexane, acetone, ethanol and water). Results of the phytochemical analysis showed that proanthocyanidins (86.9 ± 0.005%) where highest in the aqueous extract with phenolics at 55.7 ± 0.404% in acetone extract, tannin at 48.9 ± 0.28% in ethanol extract, while the hexane extract had the highest levels of flavonoids (0.12 ± 0.05%) and flavonols (0.12 ± 0.05%). Antioxidant studies of the various extracts revealed that aqueous and ethanol extracts were found to be the best solvents for antioxidant activity in C. edulis leaves. GC-MS analysis of the essential oil from C. edulis leaves revealed that the essential oil contained at least 28 compounds. These included, in order of abundance: Oxygenated monoterpenes (36.61%); fatty acids esters (19.25%); oxygenated diterpenes (19.24%); monoterpenes (10.6%); sesquiterpenes (3.58%); and diterpenes (1.43%). Similarly, a GC-MS analysis of the crude hexane, acetone and ethanol extracts from C. edulis leaves identified a total of 59 compounds. Of the 59 compounds, 12 major phyto-metabolites that are active against infectious diseases were identified. To comfirm the potential use of C. edulis to treat infectious disease, antifungal activity of the crude essential oil extract and the four solvent extracts were tested against Candida albicans, Candida krusei, Candida glabrata, Candida rugosa and Cryptococcus neoformans strains. The essential oil extract was found to be the most active against all the fungal strains tested and performed better than the four extracts used various solvents used to extract (hexane, acetone, ethanol and water) the C. edulis leaves were tested for antibacterial and anti HIV-1 reverse transcriptase (RT) activity. The results indicated that both gram-positive and gram-negative isolates were inhibited by the extracts (hexane, acetone and ethanol) but antimicrobial activity was observed for the water extract. The lowest minimum inhibitory concentration values were obtained for the ethanol extract, followed by acetone and hexane extracts. No inhibition of HIV-1 reverse transcriptase was observed for any of the leaf extracts, even up to concentrations of 16 mg/ml. The potential inhibitory activities of the various solvent extracts against HIV-1 protease were evaluated at four different concentrations (16, 1.6, 0.16 and 0.016 mg/ml). Results indicated that the water extract showed almost 100% inhibition of HIV-1 protease activity, with an IC50 of 0.86 mg/ml leaf extract. Other solvent extracts (hexane, acetone and ethanol) however, did not show any inhibition activity above that observed for the DMSO control. The metabolic components in the water extract were subjected to LC-MS/MS analysis, which identified at least 91 compounds present in the water extract. Further studies involving the molecular modelling need to be carried out to confirm the inhibitory potential of these compounds. The cytotoxicity of the water extract of C. edulis leaves was also screened using human Chang liver cells at concentrations ranging bewteen 0.005 mg/ml and 1 mg/ml. Results indicated that the water extracts were not toxic. In conclusion the results from this study support the use of water extracts of C. edulis leaves by traditional healers to treat HIV infections and have identified possible mechanisms of action of the water extracts of C. edulis.

A thesis submitted to the Faculty of Humanities, University of the Witwatersrand, Johannesburg, in fulfillment of the requirements for the degree of Doctor of Philosophy, July, 2017 / This thesis explores the rearticulation of subjectivity in the context of the struggle for antiretroviral therapy in South Africa, and also in the contemporary era of treatment accessibility for HIV and AIDS. Two sub-aims are investigated: the first concerns exploring how, and with what consequences, subjectivity was deployed in the contestations that characterized the South African ‘AIDS war’; the second concerns inquiring into the intelligibility of subjectivity in public and everyday consciousness in the post-AIDS war period. Integrating qualitative analyses with the theoretical lens of an analytics of governmentality, the data set includes policy-related archival materials, a popular HIV advice column and interviews with people living with HIV and on antiretroviral therapy. The thesis brings into sharp focus the adumbration of the right to health with rational decision-making, dignity and autonomy. Much more than a way of organizing interests, advocating for the right to treatment - to prevent the transmission of HIV from mother to child and to slow-down HIV spread - was a strategy of effecting a rationality-cum-affective transfiguration of a widespread helplessness and despair into self-reliance and hope. At the level of public and everyday consciousness, self-government on antiretroviral therapy lies at the intersection of knowledge, self-care and self-management. However, such a subjective positionality is not adopted unproblematically, or even sustained indefinitely, owing to the relative weight of other disparate requirements upon oneself from day to day. What emerged out of the epic battle for antiretroviral therapy, undergirding the prevailing current public and policy orientation to antiretroviral therapy care, was the combination of an optimistic rationality and a hopeful affectivity for the potential of fashioning an HIV-positive subjectivity, contiguously responsibilized and self-responsibilizing. At the experiential level of living on ARVs, where autonomy is synonymous with self-regulation, the thesis demonstrates that self-responsibility is also an unpredictable and fluid undertaking of navigating the affective tumult of hopefulness, uncertainty, sacrifice and tension. / XL2018