Magister Public Health - MPH / The introduction of antiretroviral therapy (ART) brought new hope to HIV patients as it has transformed a fatal disease to a chronic manageable condition. In 2009 there were over 920,000 Malawians infected with HIV and 110,000 new infections. Malawi like other countries in the sub-Saharan Africa has made great strides in ensuring access to ART. The government of Malawi introduced free antiretroviral therapy (ART) in June 2004. By 2010, a total of 250,987 patients in the country were receiving ART. The success of ART requires, amongst others, a sustained adherence rate to medication of more than 95% to prevent viral replication and the development of drug resistant HIV strains. Identifying the factors that influence adherence is essential for the long-term success of public ART programmes. This study explored patient, socio-economic, cultural, and religious and health systems factors that influence adherence to ART in Zomba district in Malawi. An explorative qualitative study was conducted amongst ART patients and health workers in four health facilities in Zomba district of the Southern Region of Malawi. Data collection was through individual in-depth interviews with 25 ART patients and semi-structured key informant interviews with 13 health workers that were actively involved in the ART programme. Data was audio-recorded and transcribed verbatim. Thematic and content analysis of transcribed data was done. The study found high individual commitment, having social support from family and friends and continuous good counselling to be facilitators to adherence to ART. HIV-related stigma and discrimination, none disclosure of HIV status, lack of partner support, travelling to attend funerals and religious beliefs were noted barriers to adherence. Health system factors such as congestion in the clinic, negative staff attitudes and a lack of privacy at the pharmacy were also identified as barriers to clinic attendance and keeping appointments. Although pill burden was not mentioned, patients reported drug reactions as a barrier to adherence. Although there is good road network in the district, transport cost was still mentioned as a hindrance to treatment adherence. Treatment success was reported to be both a facilitator and a barrier to adherence. HIV-related stigma and discrimination among people need to be addressed to increase support to PLWHIV and encourage disclosure of HIV status. The improvement of the socio-economic status of ART patients needs to be addressed to reduce dependence on support from other people and provide money to make follow-up appointments. The health systems need to reduce clinic congestion and waiting times so that patients are not deterred from accessing ART.

In this thesis, some issues about the human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) have been addressed by concentrating on the stochastic modelling of the dynamics of the viruses. The aim of this thesis is to determine parameters such as the mean number of free HIV, infectious free HIV and non-infectious free HIV which are essential in determining incubation period of the virus, the disease progression of an infected individual and the efficacy of the treatment used. This thesis comprises of six chapters. The first two chapters are introductory to the viruses and reasons why HIV-1 is given priority over HIV-2 are given. The pathogenesis of the virus is addressed. This is because knowledge of the pathogenesis and strains of the virus has become essential in the study of HIV in vivo dynamics which is still paving ways into extensive research of the ways to contain the disease better. In chapter three the distribution functions of the HIV incubation period and seroconversion time are determined via stochastic models by building on previous work of Lui et al. (1988) and Medley et al. (1988). Also AIDS incidence projection was done using the Backcalculation method. Chapter four deals with the formulation of stochastic model of the dynamics of HIV in an infected individual. Two stochastic models are proposed and analysed for the dynamics of the viral load in a HIV infected person and the multiplication process of the virions inside an infected T4 cell. Also a numerical illustration of the stochastic models derived is given. In chapter five, the T4 cell count which is considered one of the markers of disease progression in HIV infected individual is examined. WHO has recently advocated that countries encourage HIV infected individuals to commence antiretroviral treatments once their T4 cell count is 350 cells per ml of blood. This is because when the T4 cell count is low, the T4 cells are unable to mount an effective immune response against antigens (and any such foreign matters in the body) and consequently, the individual becomes susceptible to opportunistic infections and lymphomas. We developed a stochastic catastrophe model to obtain the mean, variance and covariance of the uninfected, infected and lysed T4 cells; also the amount of toxin produced in a HIV infected person from the time of infection to the present time is derived. A numerical illustration of the correlation structure between uninfected and infected T4 cells, and infected and lysed T4 cells is portrayed. Antiretrioviral treatments were introduced while we await a cure. Treatment with single drug failed due to the fact that HIV evolved rapidly because of its high replication rate. Thus drug resistance to single therapeutic treatment in HIV infected individuals has promoted research into combined treatments. In chapter six a stochastic model under combined therapeutic treatment is derived. Mean numbers of free HIV, infectious free HIV and non-infectious free HIV are obtained. Variance and co-variance structures of our parameters were obtained unlike in previous work of Perelson et al. (1996), Tan and Xiang (1999). / Thesis (PhD)--University of Pretoria, 2009. / Statistics / unrestricted

The aim of pharmaceutical development is to design a quality product and the manufacturing process to deliver the product in a reproducible manner. The development of a new and generic formulation is based on a large number of experiments. Statistics provides many tools for studying the conditions of formulations and processes and enables us to optimize the same while being able to minimize our experimentation. The purpose of this study was to apply experimental design methodology (DOE) and multivariate analysis to the development and optimization of tablet formulations containing 150 mg lamivudine manufactured by direct compression.

Background: Clinical management of dyslipidemia is challenging, particularly hypertriglyceridemia in patients with HIV-infection. Changing combined anti-retroviral therapy (CART) and the use of lipid-lowering drugs have proven useful in treating dyslipidemia in HIV infected patients Objective: To assess the efficacy of lipid lowering drugs (LLDs) and/or CART switching, in the management of HIV-associated dyslipidemia Design: A retrospective, longitudinal cohort study Setting: Phidisa HIV research project, 6 sites in South Africa, period April 2008 and April 2011 Patients: HIV positive South African National Defence Force (SANDF) members and their dependents; who are on CART and are 18 years or older. Four hundred and forty eight participants with dyslipidemia had non-fasted, total serum cholesterol ≥ 8.0mmol/l, serum triglyceride levels ≥4.52 mmol/l and naïve to lipid lowering drugs at baseline. Measurements: Mean change over time of total serum cholesterol and serum triglyceride in the following treatment strategies were used: exercise and dietary advice, lipid-lowering drugs (statins or fibrates or both), CART switches separately and combined lipid lowering drug with ART switch was measured using panel data with first–order autoregressive-response and xtabond. Results: The mean age for a total of 448 participants was 39.9 years; males were 87%, females were only 13%. The participants contributed to 1861 follow-up visits. CD4 count was normally distributed with the baseline mean value of 402 cells/mm3 (18.5%). Mean change over time for total serum cholesterol and triglycerides increased by 0.099 mmol/l (p=0.007) and 0.248 mmol/l (p=0.018) respectively, with an increase in body mass index while an increase in CD4 cell percent decreased mean over time for total serum cholesterol by 0.045 mmol/l (p=0.002). Our hypothesis was confirmed when lipid lowering drugs and ART switch combined treatment strategy even more decrease in the mean total serum cholesterol and triglycerides levels over time by 0.754 mmol/l (p<0.001) and 2.073 mmol/l (p<0.001) respectively compared to the exercise and dietary advice treatment strategy. Our findings showed that combined treatment strategy maintained a decrease in both the mean total serum cholesterol and triglycerides levels over time of 0.283 mmol/l (p=0.038) and 0.941 mmol/l (p=0.016) respectively, when compared to lipid lowering drugs; the mean serum triglycerides over time were also reduced by 0.486 mmol/l (p=0.048) when the combined treatment strategy was compared to CART switch only. Furthermore combined treatment strategy of lipid lowering drugs with ART switch showed significant virological suppression by decreasing log of viral load, 0.486 (p<0.001) when compared to the exercise and dietary advice group. Conclusions: Combining lipid lowering drugs and ART switching as a treatment strategy in the management of HIV-associated dyslipidemia is effective in lowering the mean over time of both total serum cholesterol and triglycerides when compared to exercise and dietary advice strategy, while maintaining virological suppression. / Dissertation (MSc)--University of Pretoria, 2015. / tm2015 / School of Health Systems and Public Health (SHSPH) / MSc / Unrestricted

Given the pathophysiology associated with the Human Immunodeficiency Virus (HIV) and the reported predilection for frontal circuitries and deep white matter, one might expect that executive dysfunction forms part of the neurocognitive profile of people living with HIV. However, such deficits have mainly been reported for adults living with HIV. Adolescence is a period where significant growth and refinement of executive functioning occurs and therefore specific research focused on HIV-positive adolescents is needed. Adolescence is also a developmental period where poor adherence to Antiretroviral Therapy (ART) persists despite marked increases in the national roll out of ART in South Africa, which has significantly decreased HIV-related morbidity and mortality rates. Poor adherence is not only a threat to the efficacy of ART but is also linked to the emergence of drug-resistant HIV strains and identified as a key contributor in the persistence of some cognitive impairments among people living with HIV. Studies show that executive dysfunction can undermine adherence to ART particularly in adolescents, whose frontal lobes are still developing. The first aim of this study was to compare the executive function profile of a group of HIV positive adolescents with that of a matched HIV negative control group. Using P. Anderson's (2002) model, executive functions were considered along the four subdomains: attentional control, processing speed, cognitive flexibility and goal setting. A second aim of the study was to investigate the relationship between executive function and levels of adherence to ART amongst the HIV positive adolescents in the sample. This cross sectional, between-groups study used a comprehensive neuropsychology test battery which was sorted into composite domains to investigate differences in executive functioning between the two study groups of adolescents aged between 14 to 16 (n = 22 in each group) using t-tests. Correlation coefficients were further computed to establish association between adherence and executive functioning. Apart from processing speed (p = 0.42, after the removal of outliers), there were no significant between-group differences in executive functioning outcomes that emerged between the HIV-positive and HIV-negative groups. The neuropsychological test scores for both groups were largely in the borderline range. Correlations between adherence and executive functioning outcomes did not yield any significant associations for each of the executive function domains. The lack of significant between-group differences may be explained by the mitigating effects of ART in the CNS in the HIV-positive group. However, consideration should be given to social factors as these may be important mediators of cognition and may therefore confound neuropsychological performance outcomes for both groups. Although the findings in the current study did not conclusively provide evidence for the role of executive functions in adherence, given the noted limitations, further studies with larger samples should confirm such outcomes.

This research presents a proposal for the assessment of technology to manage antiretroviral treatment. The system called Cell-Life has been successfully tested at a pilot site in Gugulethu, Cape Town from September 2002 till date and offers a cost-effective solution for adherence monitoring, side effect management, effective home based care and reducing pill count dependence at the clinic. With the aid of the Cell-Life SIM card menu (please see Appendix A, page 63) on a cell-phone the therapeutic counsellor is equipped with a live-link to the clinic or doctor while visiting patients. The menu allows entering data about the patient's drug adherence, side effects and symptoms, scheduling visits to the clinic and alert messages. The data is sent using short message service (SMS) and stored in a database, which can be accessed via the Internet by a doctor who will receive a complete report on the patient's status quo. The main benefits of the system lie in creating a communication link between the clinic/doctor and the therapeutic counsellor at minimal cost. Another benefit is the collection of reliable data relating to drug adherence and the minimising of human error through preset menu options on the phone. The pilot study has shown that management of anti-retroviral therapy is possible in resource-constraint urban settings. But for a provincial or national rollout of the Cell-Life system, the challenge is the lack of the required infrastructure, technology, personnel and logistics for effective operation of the Cell-Life systems specifically in the rural areas of South Africa. This research investigated the availability of the Cell-Life requirements in the Western Cape. The findings showed that the Cell-Life systems could be implemented in the health regions investigated across the Western Cape. It was also shown that an in depth needs assessment study is required before implementing the Cell-Life system in any community.

>Magister Scientiae - MSc / The viral Integrase (IN) protein is an essential enzyme of all known retroviruses, including HIV-1. It is responsible for the insertion of viral DNA into the human genome. It is known that HIV-1 is highly diverse with a high mutation rate as evidenced by the presence of a large number of subtypes and even strains that have become resistant to antiretroviral drugs. It remains inconclusive what effect this diversity in the form of naturally occurring polymorphisms/variants exert on IN in terms of its function, structure and susceptibility to IN inhibitory antiretroviral drugs. South Africa is home to the largest HIV-1 infected population, with (group M) subtype C being the most prevalent subtype. An investigation into IN is therefore pertinent, even more so with the introduction of the IN strand-transfer inhibitor (INSTI) Dolutegravir (DTG).

The human immunodeficiency virus (HIV)-hepatitis C virus (HCV) coinfection is one of the most common coinfections across the globe. There are over 2 million people living with both HIV and HCV worldwide. In the United States, HIV-HCV coinfections present a huge public health issue. There are several risk factors associated with developing this coinfection. One of the greatest risk factors is injection drug use and the practice of sharing needles. With the advent of the opioid epidemic, the number of people contracting both infections have skyrocketed. Despite the large prevalence rate, people with HIV-HCV coinfections can be treated for both infections. Medical professionals have begun successfully controlling HIV infections through antiretroviral therapies and treatments. These HIV regimens have worked well to increase the cluster of differentiation 4 (CD4) cell counts to manageable levels in many patients. Clinicians have used several different HIV medications that are easily categorized into five separate categories: nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase strand transfer inhibitors, protease inhibitors, and C-C chemokine receptor type 5 (CCR5) antagonists. Of these medications, nucleoside reverse transcriptase inhibitors and protease inhibitors have been commonly used with direct-acting antivirals. Like antiretroviral treatments, these direct-acting antivirals (or HCV regimens) have been largely successful in reducing HCV ribonucleic acid (RNA) levels and effectively “curing” the HCV infection. However, some serious complications occurred in several cases because of drug-drug interactions between antiretroviral and direct-acting antiviral medications. This study was dedicated (1) to exploring the many benefits that these medications have for coinfected patients and (2) to analyzing the significant consequences of these drug-drug interactions. To achieve both goals, a review of various research studies, websites, and textbooks was instigated through PubMed, Google Scholar, and the Boston University library system. The resulting research studies spanned a period from the 1980s to the 2010s. The implications from these sources suggest that more extensive testing of medications, regimens, and drug combinations is needed to allow for a more individualized and simplified HIV-HCV treatment plan for each patient. Additional testing may also lead to more generalizable findings that could be applied to a large swath of the population in the United States.

Magister Public Health - MPH / With the improvements in the effectiveness and availability of antiretroviral therapy (ART), perinatally infected children are surviving to adolescence and emerging as a significant sub-population living with HIV/AIDS in Zimbabwe. Adolescents, aged 10-19 years, face unique challenges related to adherence to chronic medication due to this period of vulnerability that is characterised by decreased parental support and supervision, decreased inhibition, increased risk-taking, and immature judgement. It is widely reported that poor adherence to ART leads to viral rebound, disease progression and drug resistance, in addition to increasing the risk of transmitting resistant strains of HIV to others. It is imperative to determine the factors that influence ART adherence among HIV positive adolescents so that effective interventions can be put in place. The current study described the factors that are associated with adherence to ART among HIV positive adolescents in Zimbabwe.

Magister Commercii (Information Management) - MCom(IM) / South Africa has one of the largest HIV and AIDS burdens in the world, with an estimated7.52 million people living with HIV in 2018. The antiretroviral therapy (ART) programme is the biggest and most costly programme in the country, with 3.7 million people enrolled as of 2017. The success of antiretroviral therapy is dependent on adherence to medication and long-term retention in care. It has been reported that support groups can improve the treatment adherence of patients and their retention in care. However, enrolment in adherence support groups is voluntary, and the abovementioned success thereof is dependent on the commitment of the patient to active participation in the group. It is estimated that about 80% of adults and young people own at least one mobile phone, which makes this technology suitable to improve communication and enhance interaction amongst support group members.