Thesis (MSc. (Physiology)) -- University of Limpopo, 2016 / Relevance: An increase in the number of HIV positive patients receiving HAART raises important concerns about the metabolic impact of these regimens. The treatment effectively reduces viral load and increase CD4+ count; unfortunately it seems to disrupt carbohydrate and lipid metabolic pathways thereby increasing the risk for CDL by placing an already chronically ill HIV population at risk of more chronic diseases. As a developing country, accessibility to safer regimens of HAART is limited thus patients exposed to toxicities from long term exposure to sub-optimal regimens are even at greater risk. The aim of this study was to assess the long term effects of HAART on biochemical parameters and body composition as an indication of carbohydrate and lipid metabolism. Methods: A prospective cohort of 87 patients receiving HAART for 12 months or more was conducted at baseline and follow-up. Venous blood was collected after an overnight fast. An automated enzymatic colorimetric test was used to analyse plasma glucose and serum TC, HDL-C and TG. The LDL-C levels were calculated from TC and HDL-C. Leptin levels were analysed using human leptin radioimmunoassay kit. Insulin was analysed using an automated access ultrasensitive insulin assay. Anthropometric measurements were taken for the determination of body fat distribution and BMI. All statistical analyses were performed using SPSS version 23. Results: Total cholesterol, LDL-C, and waist circumference significantly decreased from baseline to follow-up (p<0.05). Triglycerides and LDL-C levels were significantly affected by durations between 24–47 and 49–72 months respectively. There were no significant changes in the mean levels of leptin observed within the two lines of regime. Mean leptin levels were 11.36±8.52 ng/ml and 9.67±6.42 ng/ml at baseline and follow-up respectively. Furthermore, the duration of HAART significantly affected BMI and WC at 49–72 months. Patients that met the criteria for diagnosis of DM were only found in PI containing regimens at 6.3% and 5.9% baseline and follow-up respectively. In the first line regimen, the prevalence of DM was only found at follow-up. Conclusion: The present study demonstrated that longer duration between months 49–72 has significant negative effects on the glucose and lipid metabolism of HIV positive patients. The study also highlighted that patients on combinations containing PIs and NRTIs such as stavudine and zidovudine are at higher risk of developing metabolic diseases. / University of Limpopo

Department of Advanced Nursing Science / MCur

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

MCur / Department of Advanced Nursing Science / Survival of children with HIV/AIDS has increased considerably with the use of effective antiretroviral therapy. However, the benefits of this therapy are limited by the difficulty of adherence to the treatment. This study sought to explore the role of professional nurses on anti-retroviral therapy adherence among children in Lejweleputswa district: Free State, South Africa. An exploratory descriptive qualitative research design was used to identify and describe role of professional nurses toward anti-retroviral therapy adherence among children. Population for this study included seventeen (17) professional nurses working in four purposively sampled Primary Health Care clinics invited to participate in the study. Four focus group discussions were conducted in which each group had 6 participants. The transcribed data was analysed using the framework approach of data analysis. Professional nurses in Lejweleputswa district report poor knowledge of parents/caregivers of children, perceived poverty, stigma and discrimination, inappropriate care approaches, and parental dynamics as factors influencing poor ART adherence. Recommendations for enhancing children ART adherence levels in Lejweleputswa district included: mainstreaming adherence counselling in children ART and adopting a comprehensive family centered care approach were identified as measures for improving children ART adherence. Other measures included integration of ART services into Primary Health Care (PHC) services, parental empowerment, development of a programme to reduce stigma and discrimination in the community.

MA (Psychology) / Department of Psychology / Background: Given that there is 57.7 million HIV-diagnosed people living in South Africa and the government has established the largest public antiretroviral programme in the whole world but only 53% are adhering. Adherence remains a challenge, due to presence of mental health issues among HIV diagnosed. Aim: The aim of this study was to investigate adherence to antiretroviral therapy and mental health of HIV-diagnosed patients in Vhembe District, Limpopo Province. Methods: This was a mixed method study using a combination of quantitative and qualitative research approaches. In the quantitative approach, triangulation was utilised in the form of a questionnaire and patients records. Simple random sampling was used to select 134, descriptive analysis using SPSS version 25. For the qualitative approach, a phenomenological research designs was considered and convenience sampling was used to select fifteen participants (15). Data was collected using semi-structured interview; responses were analysed using a computer-aided program called, ATLAS ti. Results: The self-report of adherence was 94.8 %, objectively 39.6% of CD4 count <200c/mm3 at baseline and 34.3% CD4 count after six months was found. 16.5% of females and 2% of males defaulted treatment and 14.9% of missed medical appointments 1-6 times. This study also revealed the mental health issues that HIV-diagnosed patients are struggling with after the diagnosis include the stages of grief, stress, depression, anxiety, mistrust, shame, stigma and discrimination. Recommendation: Effective strategies need to be enhanced and tailor made in effort to encourage patients to take ART diligently. The healthcare providers, community members and the government should be made aware of mental health issues. / NRF