PhD (Microbiology) / Department of Microbiology / Introduction Human Immunodeficiency Virus (HIV-1) continues to be a global public health concern, even though Antiretroviral drugs (ARV), especially Highly Active Antiretroviral Therapy (HAART) has significantly reduced morbidity and mortality due to AIDS globally in developed and developing countries. However, there is still a great need to explore every avenue for new therapeutic interventions due to the limitations and side effects of HAART. Potential major breakthroughs for future therapeutic development were the discoveries more than 10 years ago of the role of HIV-1 co-receptors and anti-viral activities of host restriction factors such as APOBEC3G protein, which is a member of the DNA cytosine deaminase family. Entry of HIV in to the host cell is through the attachment of the viral envelope glycoprotein to the CD4 receptor, and subsequent interaction, mainly with either CCR5 or CXCR4 co-receptors. Inhibitors, such as Maraviroc, which binds to CCR5 inhibiting entry of CCR5 utilizing viruses (R5 viruses), is currently reserved for salvage therapy in many countries including South Africa. In the course of HIV infection, CXCR4 utilizing viruses (X4 viruses) may emerge and outgrow R5 viruses, and potentially limit the effectiveness of Maraviroc. Several host cell APOBEC3 genes (A3D, A3F, A3G and A3H) have been shown to restrict HIV, and the HIV viral infectivity factor (Vif) protein serves to antagonize the action of APOBEC3 proteins, promoting viral replication. The CCR5 co-receptor and the HIV Env V3 loop have also been documented as playing roles in HIV-1 disease progression. The interplay between host and viral genes still needs widespread attention, given that disease outcomes of HIV depend on many factors, including host cell genetics. Since the discovery of these genes and their role in HIV replication, many studies have been conducted that show their association with viral polymorphism. The polymorphisms found in host cell genes can have significant effects on viral replication, transmission and fitness and can also contribute to the overall diversity in HIV-1 populations. It is hypothesized that there are significant polymorphisms in HIV-1 and cellular genes that may differ among different populations. Population-based studies have tried to establish a relationship between host factors such as APOBEC3 and CCR5 polymorphism and the rate of disease progression, but most studies have focused on Caucasian populations. In vi contrast, little information is available for the effects of variation in these genes in African populations such as South Africa, where the HIV epidemic has expanded at an alarming rate. Although several population studies have focused on African Americans, these do not give us a complete picture of the potential variation in Africans, though the studies can be a good guide on which to base additional studies. A more comprehensive analysis involving different African populations will likely provide a better understanding of the mechanisms underlying host-pathogen interactions, especially in view of the fact that African Americans are primarily infected with HIV subtype B, which is rarely seen in Africa. Methodology This study characterized the genetic variability of the APOBEC3 D, F, G and H genes as well as the HIV-1 vif, in an ethnically diverse HIV-1 infected South African cohort using Next Generation Sequencing (NGS). In addition, polymorphism in CCR5 was analyzed in conjunction with an analysis of the V3 loop sequences in HIV-1 from this cohort. Genomic DNA was extracted from peripheral blood mononuclear cells (PBMCs) of 192 HIV-1 infected drug-experienced individuals who presented for routine care at the HIV/AIDS Prevention Group Wellness Clinic (HAPG) in Bela-Bela, Donald Fraser Hope Clinic (DFHC) in Vhufhuli and in local clinics in the Vhembe district of Limpopo Province, South Africa. Next generation sequencing custom based (Tn5 tagmentation and amplicon based) protocols to prepare libraries for host and HIV-1 genes were developed and validated with commercially available library preparation kits. The Tn5 tagmentation methods were used for longer DNA fragments and the custom amplicon based methods were used mainly for the shorter DNA fragments. To determine the variability of the APOBEC3 and CCR5 host genes, gene-specific primers were designed to amplify complete 12.16 kb A3D, 13.31 kb A3F, 10.74 kb A3G, 6.8 kb A3H and 1.3 kb CCR5 genes targeting the regions containing the exons. Libraries for the resulting amplicons were prepared using Tn5 transposase tagmentation methods and sequenced on an NGS Illumina MiSeq platforms generating millions of reads with good read coverage for variant calling. Single nucleotide polymorphisms (SNPs) and indels were determined, verified in dbSNPs and compared to SNPs in other populations reported in the 1000 Genome Phase III and HapMap. A Chi-square goodness-of-fit was used to verify if whether observed genotype frequencies were in agreement with the Hardy-Weinberg Equilibrium. Haplotypes and Linkage disequilibrium were inferred to determine SNP association. vii The HIV-1 vif and env V3 loop genes were also sequenced to determine their degree of variability of these genes and to infer co-receptor usage in the South African population. Gene-specific primers were designed to amplify the 579 bp Vif region and 440 bp containing the 105 bp V3 loop. Sequencing libraries from the resulting amplicons were prepared using either the Tn5 transposase or custom-based library preparation methods and sequenced on either an Illumina MiSeq or a MiniSeq platform generating millions of reads with good read coverage for variant calling. Phylogenetic analysis was done to determine the relatedness of the sequences. Major and minor variants were determined for HIV-1 and env V3 loop quasispecies was analysed for co-receptor usage; in an effort to draw inferences for the subsequent utility of Maraviroc as salvage therapy in South Africa. Results and Discussion Next generation library preparation; Tn5 tagmentation based and custom amplicon based protocols to sequence host and HIV genes were successfully developed and used to sequence and characterize variability in host cell APOBEC3D, F, G H, CCR5 and the HIV-1 vif gene and the V3 loop region of the env gene. The HIV-1 env V3 loop sequences generated (and quasispecies analyzed) were used to infer co-receptor usage in treatment-experienced individuals; in an effort to draw inferences for the subsequent utility of Maraviroc as salvage therapy in South Africa. Quality V3 loop sequences were obtained from 72 patients, with 5 years (range: 0-16) median duration on treatment. Subtypes A1, B and C viruses were identified at frequencies of 4% (3/72), 4% (3/72) and 92% (66/72) respectively. Fifty four percent (39/72) of patients were predicted to exclusively harbor R5 viral quasispecies; and 21% (15/72) to exclusively harbor X4 viral quasispecies. Twenty five percent of patients (18/72) were predicted to harbor a dual/mixture of R5X4 quasispecies. Of these 18 patients, about 28% (5/18) were predicted to harbor the R5+X4, a mixture with a majority R5 and minority X4 viruses, while about 72% (13/18) were predicted to harbor the R5X4+ a mixture with a majority X4 and minority R5 viruses. The proportion of all patients who harboured X4 viruses either exclusively or dual/mixture was 46% (33/72). Thirty-five percent (23/66) of the patients who were of HIV-1 subtype C were predicted to harbor X4 viruses (χ2=3.58; p=0.058), and 57% of these (13/23) were predicted to harbor X4 viruses exclusively. CD4+ cell count less than 350 cell/μl was associated with the presence of X4 viruses (χ2=4.99; p=0.008). The effectiveness of Maraviroc as a component in salvage therapy may be compromised for a significant number of chronically infected patients harboring CXCR4 utilizing viii viruses in the study cohort. Although from the current study a subset of patients harboring CCR5 utilizing viruses may benefit from Maraviroc, characterizing and identifying if variation in CCR5 are located at Maraviroc binding sites was of importance to investigate. The following variants; P35P, S75S, Y89Y, A335V and Y339F and their varying frequencies were detected in the CCR5 gene. The A335V variant was detected at a higher frequency of 17.4% (29/167). The G265S variant is reported for the first time in this study at 0.6% (1/167) frequency. The SNPs detected were in strong LD (D’= 1, R2 = 0.0) with minor deviation from the Hardy-Weinberg Equilibrium. These variants were not located at the binding motif of Maraviroc. The variants A335V and Y339F were detected at a higher frequency in this study than previously reported in South Africa. Variability in APOBEC3 host cell genes was also characterized in our study cohort. The following APOBEC3 variants compared to the GRCh37 consensus sequence were detected: R97C, R248K and T316T in A3D; R48P, A78V, A108S, S118S, R143R, I87L, Q87L, V231I, E245E, S229S, Y307C and S327S in A3F; S60S, H186R, R256H, Q275E and G363R in A3G and N15Δ, G105R, K140E, K121D, E178D in A3H. Minor allele frequency variants (MAF<5%); L221L, T238I, C224Y and C320Y in A3D; I87L, P97L and S229S in A3F; R256H, A109A, F119F and L371L in A3G, which are frequent in the European population, were also detected. In addition, novel R6K, L221R and T238I variants in A3D and I117I in A3F were detected. Most of the SNPs were in strong LD with minor deviation from the Hardy-Weinberg Equilibrium. Four, six, four, and three haplotypes were identified for A3D, A3F, A3G, and A3H respectively. In general, polymorphism in A3D, 3F, 3G and 3H were higher in our South African cohort than previously reported among other African, European and Asian populations. The APOBEC3 antagonist HIV-1 vif gene was also sequenced to determine the level of diversity in a South African population and also correlated with APOBEC3 variation. Functional Vif without frameshift mutation was observed in all samples except in 4 samples. The functional domain and motifs, such as Zn binding motifs, proline-rich domain, human casein kinase, and the N and C-terminal CBF interaction site were highly conserved. APOBEC binding motifs and the nuclear localization signal were less conserved in the South African HIV-1 Vif. APOBEC3 H variation strongly correlates with Vif variation. All the Vif sequences were subtype C, except one sample, which was identified as an A1/C recombinant. The vif gene in a South African population was under purifying selection, with the dS= 0.2581 and dN= 0.0684 and the dN/dS value = 0.265. There is a high genetic diversity in the South African vif gene, which may ix influence the neutralization and restriction of APOBEC genes. Conclusions In conclusion, the protocols developed in this study can be applied to amplify and sequence any host and HIV-1 genes of interest allowing much deeper and more sensitive profiling of host gene and HIV-1 genetic diversity. Our findings show that a highly significant number of chronically HIV-1 subtype C infected patients in Maraviroc-free treatment harbor CXCR4 utilizing viruses. The data is useful in the consideration of whether to include entry antagonists such as Maraviroc in alternative forms of treatment for patients failing second line treatment regimen in the study setting. The determination of co-receptor usage prior to initiation of therapy consisting of Maraviroc is suggested. Variation in the CCR5 coding region were observed at higher frequencies compare to other studies conducted in South African populations at different locations. This data may suggest that different populations in South Africa have different SNP frequencies. All the polymorphisms identified in the study were not located at the Maraviroc binding motif, therefore the subset of patient infected by R5 viruses may benefit from this drug. We have shown that significant APOBEC3 variation exists among an ethnically diverse population of South Africa by providing extensive data for 4 different A3 genes that are known to restrict HIV infection, but have only been sparsely studied in African populations. This study provides a baseline for future studies that would functionally characterize SNPs identified in this population, in order to understand the role of novel and/or low frequency variants observed. Ex vivo and in vivo studies will increase our understanding of how these variants might have cumulatively impacted the epidemic in Northern South Africa. This study also shows that there is a high level of HIV-1 Vif diversity in the study area. This diversity may impact the expression and packaging of Vif proteins, and the infectivity of HIV. In addition, a significant correlation was observed between HIV-1 Vif variation and APOBEC3 H haplotypes. / 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

PhD (Public Health) / Department of Public Health / Background: South Africa continues to struggle with the high prevalence of Human Immunedeficiency Virus and Acquired Immune deficiency Syndrome. Young people of the university going age are the most affected by this disease. The higher education sector, particularly teachers, are well placed to mitigate this pandemic through teaching and learning. Despite the fact, that a lot has been written on the need to integrate HIV/AIDS content into curricula very few institutions of higher learning are heeding the call mainly due to lack of guidance on how to integrate HIV/AIDS content. Aim:The aim of the study was to develop a framework that facilitate integration of HIV/AIDS content into university curricula. Methods: This cross-sectional study employed quantitative methodology and was conducted in two phases : Data was collected using different methods such as cross sectional surveys, content analysis and systematic reviews. For cross sectional surveys the target population included teachers and students and they were selected using systematic and purposive sampling respectively. The study setting was University of Venda. Data were analysed using SPSS, version 23. Multiple logistic regression and chi-square tests (χ2) were employed to determine the associations. Results: The thesis comprises five interdependent studies. Study one: A systematic review of peer-reviewed journals and grey literature of HIV/AIDS programmes in higher education was conducted. It was found that HIV/AIDS content was integrated mainly into existing , compulsory, undergraduate modules, health sciences disciplines focused on basic facts about HIV/AIDS. The HIV/AIDS content was taught using classroom based teaching strategies. Study two: A quantitative content analysis, to gauge the extent of HIV/AIDS integration into the curricula in various departments at Univen was conducted. The results of this study suggest that HIV/AIDS content was limited as only 68 modules/courses out of 1979 had HIV/AIDS content in different disciplines across all eight schools at the university. Study three: A survey was conducted to assess the knowledge, attitudes and practices of students towards learning about HIV/AIDS content among 340 students . The study found out that majority of the students possessed high knowledge about HIV/AIDS, though they had misconceptions about HIV transmission routes. Further they supported the introduction of formal teaching and learning about HIV/AIDS in their disciplines and very few students were taught about HIV/AIDS in their studies. Study four: A survey was conducted to assess knowledge, attitudes and practices of teachers towards teaching and learning of HIV/AIDS content in the curriculum among 240 teachers . The results showed that the majority of teachers were knowledgeable about HIV/AIDS , had positive attitudes towards the teaching and learning of HIV/AIDS content in the curriculum and very few taught about HIV/AIDS. Study five: Data from the study findings, literature and analysis of the curriculum were integrated within Information ,Motivation and Behaviour Model to develop the proposed framework for integrating HIV/AIDS content. Conclusion: The purpose of the study was to develop a framework that facilitates the integration of HIV/AIDS content into the undergraduate curriculum. The proposed framework in this study may assist HEIs, faculties and teachers to integrate HIV/AIDS content formally into their curriculum and ensure that various academic departments can integrate HIV/AIDS-related issues into the undergraduate curricula. The framework outlines HIV/AIDS competencies for different levels of study in various disciplines and its adoption may assist HEIs in producing graduates who can survive and work in a world ravaged by HIV/AIDS. In order to implement the proposed framework for integration of HIV/AIDS content into undergraduate curricula, recommendations were made. / NRF

This qualitative exploratory and descriptive study explored and described the experiences of HIV sero-discordant couples post diagnosis at the Perinatal HIV Research Unit in Soweto, Gauteng Province. Data was collected using in-depth interviews with each individual from seven HIV sero-discordant couples. Following thematic analysis, four themes emerged: immediate response to HIV sero-discordant results; challenges in relation to disclosure of HIV sero-status; limited information on HIV sero-discordant; and the impact of HIV sero-discordant on the couples. All these were mainly linked to poor counselling and inadequate support to HIV sero-discordant couples. The findings of this study have both clinical and policy development implications. Recommendations have been put forward for development of contextual relevant HIV Sero-discordant Couple Counselling and support guidelines focusing of enhancing knowledge and skills of health care professionals responsible for counselling and supporting HIV sero-discordant couples. / Health Studies / MA (Public Health)

This study investigated the challenges faced by implementers of VCT campaigns for higher education distance learning students. Qualitative and explorative approaches, using a case study, were employed as the research methodology. It has been concluded that the administrative planning procedures of VCT campaigns were not properly followed, which resulted in the following difficulties: defining the roles and responsibilities of stakeholders, using limited resources, and the inability to reach all the students, in order to get them to actively participate in the campaigns. Lack of coordination of HIV and AIDS activities and the absence of monitoring and evaluation also impacted negatively on the success of VCT campaigns. This study recommends that VCT campaigns have a proper task team constituting of experts in VCT campaign operations, in order to strategically plan and coordinate all the campaigns' activities. The implementers should also monitor and evaluate these activities on a regular basis. / Social Work / M.A. (Social Behaviour Studies in HIV/AIDS)

The earlier optimism generated by the efficacy of antiretroviral drugs in human immuno-deficiency virus (HIV) patients has been dissipated in the face of the enormous chal-lenge of maintaining a nearly perfect adherence indefinitely. This study set to determine the influence of HIV adherence self-efficacy and beliefs about medicines on antiretrovi-ral therapy adherence, with the aim of developing a framework for enhancing antiretrovi-ral therapy (ART) adherence through focused intervention on modifiable factors from study variables that are strongly associated with ART adherence. A descriptive correlational design was used to assess the predictive relationships of HIV adherence Self-Efficacy, Beliefs about Medicines and ART adherence among 232 HIV-infected patients in a large public health facility in Pretoria. Participants' medication be-liefs were assessed using the Beliefs about Medicines Questionnaire, HIV adherence self-efficacy was assessed with HIV adherence self-efficacy scale (HIV-ASES) and ART adherence was assessed using the AIDS Clinical Trial Group questionnaire. Pearson correlation analysis was used to assess bivariate associations among the variables, and multiple regression analysis was used to examine the relationships among the inde-pendent variables and ART adherence. Mean adherence for the 232 participants was 95% (SD=13.2). Correlation analysis re-vealed positive bivariate associations between perceived general harm and overuse of medications, and ART adherence (p<0.05); between specific necessity and concerns about ARVs, and perceived general harm and overuse of medications (p<0.05); be-tween HIV adherence self efficacy and ART non-adherence (p<0.05). Multiple regres-sion analysis showed significance for perceived general harm and overuse of medica-tions on ART adherence (F(1;231)=11,583;p<0,001) with perceived general harmful ef-fects and overuse of medications explaining 4.8% of the variance. There was signifi-cance for HIV adherence self-efficacy on ART non-adherence (F(1;41)=4.440; p<0.041), with HIV-ASES explaining 9,8% of the variance. Based on the results, a framework for enhancing ART adherence was developed. Activities in the framework consist of baseline screening for adherence facilitators and barriers using the beliefs about medicine questionnaire and HIV ASES, this is followed by focused interventions on identified barriers of ART adherence / Health Studies / D.Litt. et Phil. (Health Studies)

M.A. (Social Behaviour Studies in HIV/AIDS) / This study sought to investigate factors that influence adherence to treatment amongst rural people living with HIV and accessing antiretroviral therapy (ART) at Shongwe hospital in Mpumalanga. Both quantitative and qualitative methods were used. From patients’ case files, a sample of twenty-eight respondents was recruited for the completion of questionnaires. A focus group discussion with nine participants was held, followed by qualitative interviews with three key informants. Findings indicated that a complex web of factors unique to each patient’s social context plays a role in determining whether or not patients adhere to their regimens. Obstacles to adherence are poor social support, problems relating to disclosure, unemployment and economic hardship, traditional and religious beliefs, the quality and nature of adherence counselling and treatment side effects. / Sociology