The thesis work entails a bench-to-bedside translational research approach to the development of pediatric fixed dose combination of zidovudine/lamivudine/nevirapine (60/30/50mg) orally disintegrating tablets. A simple and cost-effective, direct compression method was used. Preformulation studies that included analytical and bio-analytical assay development, excipient selection and characterization of drug-excipient interaction for initial formulation were conducted. Response surface methodology was utilized to optimize the formulation in terms of disintegration time and crushing strength. Stable ODT tablet was developed with desired friability (< 1%), reasonable crushing strength, disintegration time (< 30sec) and other quality attributes such as potency and dissolution. An open label randomized two-way cross-over bioequivalence of the product (with approved IRBs), conducted in 24 healthy adult volunteers, indicated the product to be bioequivalent with the innovators. 90% C.I of the point estimates of PK parameters evaluated were in the range of 80-125% as specified by FDA. / Mylan School of Pharmacy and the Graduate School of Pharmaceutical Sciences; / Pharmaceutics / MS; / Thesis;

No description available.

Magister Public Health - MPH / Background:HIV is a worldwide pandemic with an estimated 2.5 million children under the age of 15 living with HIV in the world in 2009. Children account for approximately 14% of all HIV-related deaths around the world. Several studies have shown that the use of antiretroviral drugs greatly improve the lives of HIV-1 infected individuals, however, most of these studies report on outcomes of ART programmes in developed world and for adult patients. Very few settings have published outcomes of paediatric ART programmes.Objectives This research was aimed at describing the long term (at least one year) treatment outcome of HIV-1 infected children in the HIV/AIDS Prevention Group (HAPG) program in Bela-Bela in the Limpopo province of South Africa.Study design and methods: A quantitative approach involving a retrospective cohort design was used for the study. The study included all children under the age of 15 that were enrolled in the HATG treatment programme in Bela-Bela between February 2004 and December2009.Immunological, virological, clinical outcomes and loss to follow-up were determined for this cohort. Mortality and survival was also determined. Results: The median age of children in this study was 5 years (IQR: 2-7) with 14% (10/71) of them being less than 18 months. Median CD4 count at commencement of ART, viral load and weight were 358 cells/mm3 (IQR 203.5-, 125673 RNA copies/μL (IQR 58094-328424.5) and 14.5Kg (IQR: 11.0-18.35) respectively. CD4 counts and weight showed increase within the study period, and there was also a decline in viral load. Loss to follow-up was 7.04% while mortality was 19% with 21.43% of mortality cases being children who were ≤18months. Mortality occurred within the first year of ART initiation and occurred in cases that had advanced disease.Conclusion: This study shows that the ART program in Bela-Bela has a positive outcome on HIV positive children.The high mortality rate was due to children starting ART at an advanced disease stage. Despite the good outcome, it is recommended that a system be put into place that will aid in identifying children at an early stage of the disease and treatment initiated promptly.

No description available.

Cardiovascular diseases (CVDs) are the leading causes of death globally. Recent studies show that CVDs are one of the major causes of morbidity and mortality in people living with HIV/AIDS (PLWHA). HIV symptoms arise as our body tries to fight off the virus but as our immune system weakens as CD4 T cells are targeted. As these T cells diminish in quantity, it leaves the body susceptible to other infections, which is why ARV drug treatment is used. NRTIs are common drug treatments for these viruses as they inhibit the enzyme reverse transcriptase. Unfortunately, these NRTIs are known to cause dilated cardiomyopathy, while protease inhibitors are known to cause increased cardiovascular mortality and heart failure. Treatment of these side effects is crucial since millions of people are on these ARV drug treatments. Therefore, we analyzed RNA sequencing data of neonatal ventricular cardiomyocytes treated with ARV's to determine the regulatory pathway of upregulated/downregulated genes associated with the ARV treatment. It was seen that many of the upregulated genes such as PSEN and PSENEN2 were mitophagy control genes, and most of the downregulated genes were from complexes I-IV of the oxidative phosphorylation chain. Based on the genomic data, we hypothesized that increasing the expression of these downregulated genes could potentially reduce mitochondrial dysfunction and bring back the functionality of the complexes. Research has shown that rapamycin treatment can potentially reduce the effects of mitochondrial dysfunction, and tests were conducted to see how much expression changed. Another indicator of mitochondrial dysfunction is the detection of ROS, and this project aims to see how rapamycin will affect the presence of these ROS.

Thesis (MPH.) -- University of Limpopo, 2019 / Virological failure occurs when the viral load fails to supress to undetectable limit and immunological failure is when the immune system fails to improve with the CD4 count remaining low on clients on antiretroviral drugs. These being markers of poor adherence to antiretroviral drugs or treatment failure. Upon routine blood-monitoring of students on antiretroviral drugs, the researcher noticed that some students’ viralload levels were not suppressing and their immune system was not improving. The purpose of the study was to identify the experiences of those students whose viral load is not suppressing and their immune system not improving. The objective was to identify and describe the experiences of students with immunological and virological failure on antiretroviral drugs at the University of Limpopo. A qualitative, explorative and descriptive study design was used. Convenience purposive sampling method was adopted. Using a semi-structured interview guide, face-toface interviews were conducted on 10 students on antiretroviral drugs at the Student Health and Wellness Centre, University of Limpopo. Techs’ method was used to analyse data. Guba’s model for establishing trustworthiness was used. The study yielded the following themes: Disclosure, stigma, antiretroviral drugs packaging, side effects of antiretroviral drugs and service delivery. The study concluded that students are afraid to take their treatment for fear of stigmatisation and disclosure is still a problem. Students tend to forfeit taking drugs when studying for examinations due to side effects of the drugs. It is recommended that service delivery and antiretroviral drugs packaging be user friendly. Key words: Disclosure, stigma, side effects, antiretroviral drugs packaging and antiretroviral drugs.

The study explores pertinent issues around a comprehensive provision of antiretroviral drugs to HIV positive pregnant women in South Africa from a human rights perspective. Although these drugs have been proven to significantly reduce the transmission of HIV from a pregnant mother to her newborn baby/babies at birth, the South African government for over five years refused to roll them out in the public health sector. Reasons that were provided in this regard were multifaceted and have included claims regarding their alleged toxicity, potential side effects, huge cost, inadequate infrastructure, etc until March 2004 when it announced to start a national rollout program. It is in light of this that the study sets out to explore some of the key positions within the government and amongst activist groups on the health rights of HIV positive pregnant women, and how these different positions have evolved in response to each other. In particular, the paper aims at examining how discourses of human rights were employed, and how they have impacted on the Social Work discipline. It further focuses on developing a Social Work perspective on the human rights of HIV positive pregnant women in South Africa, thereby contributing to the discipline’s professional value base and body of knowledge, which inform, inter alia, its advocacy role and social action approach. The research project was embedded in a theoretical framework often referred to as ‘standpoint research’. An archival study of local and international literature and policy documents was conducted. This was complemented with a limited qualitative study. Semi-structured interviews were conducted with a purposive sample of five interviewees representing a cross-section of positions on the topic. This data was analyzed using a three step coding procedure that allowed for categorizing, connecting, and systematically relating the gathered data to each other and to the reviewed literature. The research findings indicate that the South African government’s absence of consistency and apparent lack of political will to rollout the drugs have contributed to the deterioration of the right of HIV positive pregnant women to access health care services. The role of civil society organizations in helping to realize, promote and protect the health and related human rights of this group is emphasized. It was also found that the different strategies employed to this end speak well to Social Work’s value base, and some of its methods and approaches to practice. Social Work is therefore well placed to join and support those efforts of other segments of civil society that have been investigated in this paper. The paper concludes by making recommendations towards, inter alia, the need for the South African government to adhere to the values enshrined in the country’s Constitution; to work closely and transparently with different organs of civil society; and simultaneously implement the said ARV rollout program while building and strengthening its infrastructural capacity. The various roles Social Work could, and should, assume with regards to improving the human rights of HIV positive pregnant women in this regard are also highlighted.

Magister Pharmaceuticae - MPharm / South Africa faces a huge Human Immunodeficiency Virus (HIV) burden with more than 400,000 children currently on antiretroviral therapy (ART). Studies on lipid and haematological profile changes in paediatrics are of particular interest since these children are exposed to ART in the course of a developmentally significant period and will possibly have longer collective exposure to ART. As such, monitoring for adverse effects, including lipid and haematological abnormalities, is essential for curtailing morbidity and mortality rates of children on ART. There is a dearth of studies assessing lipid and haematological abnormalities in the South African paediatric population on ART where genetic differences, co-morbidities, malnutrition and use of traditional medicines, all influence the safety profile of a drug. The goal of this study was twofold: Firstly to identify a suitable parameter for assessing lipid and haematological abnormalities in paediatrics on Antiretroviral (ARV) treatment using available secondary data and secondly, to assess prescriber adherence to routine monitoring tests in the ART guidelines. This study was a retrospective review of secondary data obtained from 168 patient clinical records at a Community Health Centre in the Cape Metropole, Western Cape and corresponding laboratory data from the National Health Laboratory Service (NHLS) database. Appropriate cholesterol, triglyceride, haemoglobin and neutrophil test results were compared against the standard reference ranges/values. The Chi-Squared test identified associations between total cholesterol (TC) /triglycerides and haemoglobin (Hb)/neutrophil and other independent variables. Evaluation of health care provider adherence to routine monitoring tests was assessed against relevant national ARV management guidelines. There was a paucity of baseline data for all laboratory markers and infrequent follow-up tests were ordered by healthcare providers. This precluded the measurement of changing lipid and haematological levels and an alternative parameter, viz., the highest available laboratory test value for each marker per patient, was assessed against reference values/ranges. Only nine out of the 36 (25%) patients on an AZT regimen had any Hb or neutrophil laboratory tests performed and 23 and two out of 97 (24% and 2%) patients, respectively, on a protease inhibitor (PI) had a TC and triglyceride laboratory test performed. Anaemia was detected in 45.5 % of children below five years of age, in 21.7% between ages of six and 11 and in 65.5 % between 12 and 14 years of age. Neutropenia was detected in 25.6% of children below five years of age and in 50% aged between six and 11. Hypercholesterolemia was found in 13.1% of patients. The only statistically statistical associations were found between the TC and CD4 count in children aged six to 14 years (χ2=5.000; p=0.025) and between neutrophil counts and viral load in children aged six to 14 years (χ2=6.4532; p=0.0240). A significant association was also found between Hb levels and viral load (χ2=7.000; p=0.008). In the absence of baseline test results and routine monitoring of haematological and lipid profiles, this study presents a potential alternative marker for assessing lipid and haematological abnormalities using the highest level of neutrophil, Hb, TC and triglycerides recorded for each patient.

>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).

Purpose: The main objective of the current study was to investigate and monitor the auditory status in a group of adult patients with AIDS receiving antiretroviral therapy (ART) and other therapies in a hospital outpatient clinic in Gauteng, South Africa. Specific objectives included estimating the prevalence of hearing loss and the presence of other otologic effects over and above hearing impairment (tinnitus, aural fullness, disequilibrium, and so forth); assessing the type, degree and configuration of the hearing loss; exploring the type of hearing symptom onset; documenting case history data such as signs and symptoms of each participant and identifying any associations between obtained signs and symptoms and hearing loss; documenting the names of all medications used and their possible impact on hearing function (specifically ototoxicity monitoring of ART); and comparing the results of the experimental group to those of a control group.