PhD (Advanced Nursing Sicence) / Department of Advanced Nursing Science

MPH / Department of Public Health / Background: South Africa presently has a very high HIV burden. It has adopted the UNAIDS “90-90-90 targets” to curb its HIV burden. This target aims to attain sustained viral suppression in 90% of all persons receiving antiretroviral therapy. This is supported by several studies. Studies to observe if patients are achieving and sustaining viral suppression in Limpopo, South Africa, are few. Objective: To investigate the viral and immunologic responses of patients in Vhembe District to highly active antiretroviral therapy (HAART) between the 1st of January 2004 and 31st of July 2016. Methodology: This was a retrospective medical record review conducted in Vhembe District in rural Limpopo. It included the medical records of 1247 individuals from Thohoyandou Community Health Centre. Analysis was done using SPSS 24.0. To model the factors associated with virologic and immunologic responses, each independent variable was tested for association with the dependent variable (viral suppression and CD4 count increase of ≥ 50 cells/μL from baseline to 6 months). The independent variables included age, year of initiation, gender, marital status, baseline BMI, haemoglobin, clinical stage and estimated creatinine clearance. The Pearson Chi square (X2) was used for all categorical independent variables and the t-test, for all continuous independent variables, to test for association. The estimate used was a 95% confidence interval, and a p-value of < 0.05 was considered significant. Results: The study showed that 52.6% of individuals were in clinical stage I at baseline. Viral suppression (viral load < 50 copies/ml) at 6 months was 64% (n = 648), 72% (n =193) at 60 months and 94% (n = 16) at 132 months. Fifty-nine percent had consistent viral suppression for a period of at least 6 months. Consistent viral suppression (viral load < 50 copies/ml on at least one consecutive occasion without any intervening viral load > 50 copies/ml) for at least 54 months was only 14%, while 2.3% had a delay in switching from a failing regimen. The mean CD4 count at baseline was 227 cells/μL, and 538 cells/μL at 60 months. The mean CD4 cell count increase from baseline to 6 months was 190 cells/μL. The immuno-virologic discordance was 27%. Patients with higher baseline CD4 count and females were significantly (p = 0.001 and 0.031 respectively) more likely to achieve viral suppression at 6 months. Those below 45 years and females were v significantly (p = 0.011 and 0.043 respectively) more likely to achieve adequate CD4 count increase at 6 months. Conclusions: The proportion of individuals with viral suppression in the District increased from 6 months onwards, and is fairly adequate. However, sustainability of viral suppression, once attained, is low. Adequate immunologic response, however, seems high. Males and age group above 45 years appear to have poorer responses to HAART.

MEd (Educational Management) / Department of Educational Management / See the attached abstract below

See the attached abstract below

MPH / Department of Public Health / Background: The provision of antiretroviral treatment for people living with HIV/AIDS has encountered many challenges associated with poor adherence in South African and other countries in Africa as a whole including globally. Taking ARVs Properly has shown to reduce viral load to a level where the virus becomes undetectable and these results in an increase of CD4 count cells. These decreases chances of oppotunistic infections but it requires a proper adherence and compliance to treatment which seems to be difficult to most patients on ART. Purpose: The study investigated factors contributing to clients defaulting antiretroviral treatment. Methodology: A qualitative explorative cross-sectional study design was conducted at Matoks in Capricon District, in the months of May, June and July 2017. A purposive sampling method was used to select 19 respondents whom where willing to voluntrily participate in the study from a population of People Living With HIV/AIDS (PLWHV). An indepth face to face interview was used to collect data, guided by a central question and probing. It was then analyzed by the use of eight steps of Tesch. Results: The findings revealed that women were more defaulters than men. Shortages of antiretroviral treatment and most clients were unable to collect ART on time due to lack of transport to the clinic and the long distance from their perspective homes to the clinic. Socio economic conditions and indegenious health beliefs were some of factors identified. Recommendations: extensive health education and promotion should be intensified to reach all community members of Matoks and PLWHA in terms of HIV/AIDS care and consistent taking of treatment that clients who live far away from the clinic will be able to collect the ARV treatment nearer to their place of residents. / NRF

MPH / Department of Public Health / Human Immune Deficiency Virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS) place a significant burden on the caregivers for people living with HIV/AIDS (PLWHA). Caring for PLWHA is usually carried out by community members who are recruited from the same community as the PLWHA. These community members are trained to provide services as volunteer caregivers. The caregivers face various challenges in the process of giving care to PLWHA, often inadequately assisted by relatives, friends, neighbours, private individuals, grassroots traditional and political leaders. This results in caregivers being overwhelmed by their responsibilities, making their coping process even more difficult. The aim of this study was to explore the challenges experienced by community home-based caregivers (CHBCGs) caring for people living with HIV/AIDS at Tsianda Village, in Makhado Municipality, South Africa. This study adopted a qualitative explorative design. The population for this study were all CHBCGs caring for PLWHA. Non probability purposive sampling was used to select the community home-based caregivers working at Tsianda Community Home-based care organisation. In-depth interviews, using a semi-structured interview guide, was conducted by the researcher and a voice recorder were used to record data from participants. Data saturation was reached at the 11th participant. This is when the participants were no longer giving new information. The data collected from the study were analysed thematically. The following themes emerged from data analysis: Challenges for community home-based caregivers, perceived support for community home-based caregivers, coping strategies for community home-based caregivers. Measures to ensure trustworthiness and the code of ethics to protect the rights of the participants was applied and observed. The findings of the study revealed that community home-based caregivers experience various challenges which have a negative impact on their personal life, as well as their physical and psychological wellbeing. Community home-based care also uses different strategies to cope with these challenges. It was concluded that the community home-based caregivers are experiencing serious shortages of personal protective equipment, which makes them work with the fear of being infected with the diseases. It is recommended that the DOH should take it into consideration to provide the CHBCG’s organization with enough personal protective equipment for their safety and working without fear of being infected with deadly viruses. / NRF

PhD (Health Sciences) / Department of Advanced Nursing Science / The HIV/AIDS is a global epidemic which affects all people, regardless of their religion, race, age, ethnicity or geographic location. The church of Africa, which hosts the largest numbers of infected and affected people, is also challenged to be involved in the response against HIV/AIDS epidemic. Church leaders are experiencing difficulties in fulfilling their role in HIV/AIDS interventions of which they have not received training. The complexity of HIV/AIDS demands a training programme that does not simply deal with symptoms, but it must address the complexities behind and in front of the spread, and earnestly seek effective ways of controlling the spread, as well as various strategies of caring for the infected and those affected with HIV and AIDS. The purpose of this study was to develop an adapted HIV/AIDS training programme for church leaders in the Limpopo Province of South Africa. A convergent parallel mixed methods design was used; quantitative and qualitative data were collected during the same phase of the research process. The population comprised of church leaders from Christian churches in the Limpopo province. A non-probability purposive sampling was used for qualitative approach, while quota sampling was used for quantitative approach. Questionnaires were used to collect quantitative data, while in-depth interviews were used to collect qualitative data in this study. Data analysis was done separately and the two sets of results were merged into an overall interpretation of the study that informed the development of an adapted HIV/AIDS training programme. The findings of the study revealed that church leaders were not trained on how they can be involved in the response against HIV/AIDS epidemic in the Limpopo province. The current training programme did not clarify church leaders’ role towards the HIV/AIDS epidemic. The curriculum development process structure by Meyer and Van Niekerk (2008), and elements outlined by Dickoff, James and Wiedenbach (1968), were adapted to develop the training programme. A developed training programme was then validated by HIV/AIDS trainers and experts in programme development. Relevant recommendations were made to encourage churches to work effectively in addressing the HIV/AIDS epidemic in the Limpopo Province. / NRF

MSc (Microbiology) / Department of Microbiology / Background: Antiretroviral treatment (ART) has grown to be one of the most effective tool in the fight to control HIV/AIDS morbidity and mortality worldwide. However, due to the emergence of drug resistant HIV, ART efficacy can be jeopardized. Drug resistant HIV strain has a potential of becoming a major public threat, as its limit treatment options on people living with HIV. With several findings worldwide reporting drug resistant HIV to be currently being transmitted to ART-naïve persons, measures have been taken to genotype drug resistant HIV prior to treatment initiation. However, in resource limited countries such measures are not executed especially in public sectors due to the costs associated with the required assays for genotyping. Objective: The objectives of the study was to establish a deep sequencing protocol (Next Generation Sequencing-NGS) using an Illumina MiniSeq Platform and subsequently apply it to genotype HIV in chronically infected drug naïve persons for resistance mutations and viral genotypes Methods: HIV positive Individuals without any exposure to ART (Treatment-naive) were recruited. Partial pol fragment (complete protease and ~1104bp reverse transcriptase) were amplified and purified. Libraries were prepared using Nextera XT library preparation kit, fragmented, tagmented, pooled and denatured then sequenced with Illumina MiniSeq instrument. Consensus sequences were derived, aligned and phylogenetically analysed. The Stanford HIV Drug Resistance Algorithm was used to infer the presence of drug resistant mutants, at the viral minority and majority population levels. Results and discussion: An NGS protocol to generate nucleotide sequences for drug resistance inference was established. No major drug resistance mutations were detected against protease, reverse transcriptase inhibitors in the study subjects investigated. Nevertheless, V179D change was observed in one patient (8.3%). V179D has been shown to impact a low-level resistance to NNRTI. On the other hand, several secondary and unusual mutations at known drug sites were detected even at minority threshold level of <20%. Conclusion: No major drug resistance mutations was detected in the drug naïve study population. This finding suggests that there is no risk of treatment failure to the investigated subjects, however it is important to assess the potential phenotypic v | P a g e significance of the identified secondary resistance mutations in the context of HIV-1 subtype C. The established NGS protocol should be applied in subsequent HIV drug resistance studies. / NRF

PhDH / Department of Public Health / Background: Since the introduction of three-tiered systems appointments, there are a large number of missed appointments among Human immunodeficiency virus-positive clients on Antiretroviral. However, no one knows why these clients missed their scheduled times. Missing of appointments predicts poor adherence and is associated with poor clinical outcomes. Objectives: The proposed study aimed at developing a strategy for reducing the missing of appointments among adults on Antiretroviral Therapy in the Limpopo Province, South Africa. The objectives of the study are to determine patients’ behaviour, the socio-environmental and economic factors that contribute to the missing of appointments and develop strategies to enhance compliance with appointments by Human immunodeficiency virus-positive clients on Antiretroviral therapy in the Limpopo Province. Method: A qualitative research design was used to address the study objectives. Non-probability purposive sampling was used to sample health care centres in Limpopo Province, patients, Professional Nurses and Community Health Workers. Individual interview and focus group discussions strengthened the triangulation of data obtained from the participants. Creswell’s model provided details for data analysis and interpretation. Trustworthiness and Ethics: Measures to ensure data quality, such as credibility, dependability, conformability and transferability, were observed. The researcher ensured compliance with ethical standards to protect the rights of the participants. Approval for this study was obtained from the University of Venda Research Ethics Committee and the Limpopo Department of Health Research Ethics. Results: The study revealed various factors that contribute to the missing of appointments by Human immunodeficiency virus positive-clients on Antiretroviral Therapy. Specific socioeconomic, behavioural, environmental and health service-related factors appear to prevent adherence to appointments. These factors include a lack of family support and client engagement, the absence of financial means, and cultural and religious beliefs. Lack of client involvement in planning their care and poor referral of clients to community health workers were ranked high as being the most contributing factors to clients missing their appointments. Strategy development: Phase 2 of this study dealt with the development of the strategy aimed at reducing the missing of appointment by adults on Antiretroviral Therapy based on the findings of the study. The strengths, weaknesses, opportunities and threats matrix was triangulated in Political, Environmental, Social, Technological and Legal analysis to develop this approach to reduce the missing of appointments among adults on Antiretroviral therapy. A transtheoretical framework illustrated how to implement the strategy. Validation of the developed strategy ensured that the system is free of errors and checked the applicability of the strategies utilising a quantitative design. A simple random sampling approach was used to select the population to participate in this study using the questionnaire developed by the researcher. Almost all respondents agreed that the strategy would facilitate reduced missing appointments by adults on Antiretroviral therapy. Recommendations: Clients involvement and engagement throughout the process of a treatment plan is essential to identify some of the barriers that might contribute to poor adherence to appointment by clients on Antiretroviral therapy. Community health workers and nurses should be capacitated with knowledge and skills to identify the clients at risk of defaulting treatment and appointments and provide counselling that will facilitate behaviour modifications. / HWSETA

MSc (Microbiology) / Department of Microbiology / Background: Patients on antiretroviral (ART) are expected to be at least 95% adherent to their treatment, as this will increase their chances of achieving treatment success (maximum and durable suppression of HIV-1 viral load); non-adherence may lead to the development of HIV drug resistance, which may lead to virologic failure and treatment failure. Therapeutic drug monitoring (TDM) has been reported to be the most efficient method to assess treatment adherence in HIV individuals, since it quantifies the concentration of ARTs in biological matrices. This is very effective when using a robust technique such as liquid chromatography tandem mass spectrometry (LCMS/MS), which has played a significant role in the evaluation and interpretation of bioavailability, bioequivalence and pharmacokinetic data. Even with patient adherence, various intra-individual factors have an influence on the expression and function of the genes responsible for the transport (MDR1) and metabolism (CYP2B6) of Efavirenz (EFV). This may lead to single nucleotide polymorphisms (SNPs) in these genes, and this may affect the way antiretrovirals (ARVs) are metabolized. The aim of this study was to evaluate the EFV concentration in plasma to assess patient adherence to treatment and correlate this with genomic occurrences in human and viral genes. Hypothesis: The concentration of ARVs in patient plasma can be used to estimate adherence to treatment; while ARVs’ transport and metabolism can affect bioavailability in a patient’s system. Research Question: Can EFV concentration in plasma be used to estimate patient adherence to treatment? Can transport and metabolism of EFV affect their bioavailability in the patient’s system? Objectives: To determine EFV concentration in plasma to assess patient adherence to treatment and correlate this with genomic occurrences in human genes and viral genes. Methodology: Twenty blood samples were collected from HIV positive individuals before treatment initiation (baseline) and between six to twelve months following treatment initiation (follow-up). The concentration of EFV in patient plasma was measured by LC-MS/MS technique. To infer other factors influencing patient pharmacokinetics output, drug resistance and human genetic characteristics were analyzed. A 1.65kb fragment of the HIV-1 Pol gene was amplified and sequenced to determine drug resistant mutations; while 363bp and 289bp of the MDR-1 and CYP2B6 human genes respectively, were also amplified and sequenced to determine polymorphisms in the transport and metabolism genes. Obtained sequences were manually edited and analyzed using Geneious Version 11.1.5 software. The Stanford HIV Drug Resistance database was used for drug resistant mutation (DRMs) analysis and MDR1 and CYP2B6 test sequences were compared with variant reference sequences to detect the presence of any SNPs. Results: The plasma EFV concentration at baseline and follow-up range was as follows: 0 – 1183ng/ml and below limits of quantification (BLQ) to 15,670ng/ml, respectively. At baseline, 0ng/ml is the expected plasma EFV concentration for patients about to commence treatment; however, two out of twenty patients had 769.9 and 1,183ng/ml drug levels in their system. Post treatment, plasma EFV levels in patients are expected to range from 1,000 – 4,000ng/ml, however, of the twenty patients, two had <1,000ng/ml, and three patients had >4,000ng/ml in their plasma. For Pol amplification, 35% (7/20) were positively amplified at baseline and 25% (5/20) were positively amplified from the follow-ups; 100% (20/20) samples were amplified for both CYP2B6 and MDR1 genes. Detection of drug resistance in the baseline Pol sequences revealed the absence of major mutations in both NRTI and NNRTI drug classes. The G516T polymorphism was present in 15% of the study participants while the homozygous GG and heterozygous GT genotype was present in 25% and 40% of the study participants, respectively. Allele determination was impossible in 20% of the samples, due to the poor nature of the sequence. The homozygous TT variant polymorphism at position 3435 was absent in the entire population, however, the CC and CT genotype was present in 15% and 85% of the study participants respectively. Analysis of EFV concentration in close proximity with the human genetic characteristics reveals that the presence of a Single Nucleotide Polymorphism affects the pharmacokinetic output observed. Discussion and Conclusion: Post treatment, 90% of the study participants indicate adherence to treatment, with only 10% of them having lower than expected EFV concentrations, implying they were non-adherent to their treatment. However, because plasma drug concentrations only reflect a patient’s adherence pattern for a few hours to at most two days, the adherence patterns of these individuals cannot be concluded with certainty. Using plasma EFV as a biomarker to evaluate adherence to treatment in HIV seropositive individuals is a feasible technique, however, its application in non-research settings is still a drawback due to the cost of the method. Characterizing patient inter-individual differences should be taken into consideration, especially since any polymorphism in their transporter and metabolizing genes may influence their overall treatment success. / NRF