This research focuses on the psychosocial factors that affect adherence to highly active antiretroviral therapy (HAART) amongst HIV/AIDS patients at Kalafong Hospital. Even though the development of such regimens has helped turn HIV infection in the United States into a relatively manageable, though still serious chronic disease, compliance remains one of the major challenges in managing medication for those patients living with HIV/AIDS. This is particularly relevant given the high adherence rate (95%) required to obtain a successful long-lasting effect. In South Africa non-compliance to HAART is an under-explored phenomenon. Consequently, an understanding of factors influencing compliance is still incomplete. A qualitative study that investigates non-adherence to medication in HIV/AIDS patients was undertaken at Kalafong Hospital. This study aimed to understand patients’ psychosocial difficulties resulting in non-adherence. The study was approached in terms of the health belief model (HBM), which addresses individual characteristics pertaining to change, the transtheoretical change model (TTM) and the motivational interviewing model (MI), which address both individual and social contexts pertaining to change. The findings are designed for use by healthcare professionals as a proactive compliance enhancement tool. Participants were recruited through referrals by the medical staff to the researcher. The criteria included that participants had relapsed due to non-compliance with drug therapy. Participants that were currently experiencing difficulties with adherence were also included in the study. Males and females aged between 20 and 40 were included in the study. Fifteen participants between the ages of 20 and 40 participated in the study (13 females and two males). The data were collected by means of semi-structured interviews and follow-up unstructured questions. The interviews were audio recorded and field notes were taken. Data were analysed qualitatively. Sixteen themes emerged and were further classified into two categories: individual and social context. The themes were then compared and integrated with the literature. The study concludes that psychosocial factors such as support from family, friends and healthcare workers was found to be of utmost importance in encouraging adherence. Medication can only prolong a patient’s life if the psychosocial context in which the patient is embedded is considered in the treatment plan. / Dissertation (MA)--University of Pretoria, 2008. / Psychology / unrestricted

With the worldwide increase in numbers of individuals infected with the human-immune deficiency virus (HIV) and acquired immune deficiency syndrome (AIDS), the need for more information became essential. The devastating influences and fatal outcome of this disease is inevitable. These individuals are confronted with mortality and various disabling conditions. One of these disabling conditions is the possible development of a hearing loss. Loss of hearing sensitivity related to HIV/AIDS is only one of numerous effects the virus may have on humans and their quality of life. Therefore increased awareness of HIV/AIDS and the influences of this disease is inevitable for the modern audiologist. The precise nature and the extent of the influence that HIV/AIDS and antiretroviral therapy (ART) has on the hearing ability of a person are unknown to date. Even though a relationship between hearing loss, HIV/AIDS and the administration of relevant medication is expected, no clear explanation is available to provide the public or clinicians with the necessary information on assessments, interventions and aural rehabilitation techniques. Without being able to identify the specific cause, symptoms and place of lesion of the hearing loss, it will be difficult to ensure appropriate monitoring and treatment. Information regarding the influences of HIV/AIDS and ART on hearing sensitivity had to be established to ensure appropriate intervention and rehabilitation options. The first part of this research project reviews the evidence available regarding the possible influences of HIV/AIDS on hearing. Throughout the research a cross-sectional design with quantitative and qualitative approaches were followed comprising of a structured interview, basic and specialized audiometric battery to obtain the necessary case history, as well as results for these different audiological tests that were conducted. The specialised tests included immittance measurements, distortion-product otoacoustic emission (DPOAE) and auditory brainstem response (ABR). The results of this study were discussed in terms of the three sub aims in accordance with the different audiological tests that were conducted. The results indicated that those participants with ART exposure had a significantly higher incidence of hearing loss. The pure tone averages were mainly found within normal limits but decreased with the progression of the final stages of HIV/AIDS. The high and low frequencies of the audiogram were often affected with loss of hearing sensitivity suggesting the presence of a high and low frequency slope. The final three stages of HIV/AIDS had a significantly higher incidence of bilateral hearing loss. ART exposure were associated with more severe degrees of hearing loss. The DPOAE and ABR indicated that cochlear and retro-cochlear damage existed often among these participants. Only 20% participants had abnormal tympanograms suggestive of conductive pathology. The results revealed that the type of pathology varied across the stages of HIV/AIDS. The conclusions and implications of this study are discussed. Recommendations incorporate the development of HIV/AIDS awareness campaigns that includes audiological information on the possible influences, where to refer or where to seek assistance; issues regarding the improvement of the modern audiologists’ knowledge in terms of the management of the audiological needs of individuals with HIV/AIDS and the application of these results in the industrial setting to utilize when they consider granting compensation claims. / Dissertation (MCommunication Pathology)--University of Pretoria, 2008. / Speech-Language Pathology and Audiology / unrestricted

Comparatively, HIV like most viruses is very minute, unadorned organism which cannot reproduce unaided. It remains the most deadly disease which has ever hit the planet since the last three decades. The spread of HIV has been very explosive and mercilessly on human population. It has tainted over 60 million people, with almost half of the human population suffering from AIDS related illnesses and death finally. Recent theoretical and computational breakthroughs in delay differential equations declare that, delay differential equations are proficient in yielding rich and plausible dynamics with reasonable parametric estimates. This paper seeks to unveil the niche of delay differential equation in harmonizing low HIV viral haul and thereby articulating the adopted model, to delve into structured treatment interruptions. Therefore, an ordinary differential equation is schemed to consist of three components such as untainted CD4+ T-cells, tainted CD4+ T-cells (HIV) and CTL. A discrete time delay is ushered to the formulated model in order to account for vital components, such as intracellular delay and HIV latency which were missing in previous works, but have been advocated for future research. It was divested that when the reproductive number was less than unity, the disease free equilibrium of the model was asymptotically stable. Hence the adopted model with or without the delay component articulates less production of virions, as per the decline rate. Therefore CD4+ T-cells in the blood remains constant at 𝛿1/𝛿3, hence declining the virions level in the blood. As per the adopted model, the best STI practice is intimated for compliance. / Mathematical Sciences / Ph.D. (Applied Mathematics)

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

Thesis (M.Med. (Radiation Oncology)) -- University of Limpopo, 2020 / Introduction Invasive cervical cancer (ICC) constitutes almost 50% of all cancer conditions diagnosed and treated at the Polokwane/Mankweng Hospital Complex (PMHC). HIV infection is also a very common condition. There is no consensus on the relationship between the two clinical conditions among patients treated at PMHC. There is a need to describe the simultaneous occurrence of the two clinical conditions among these patients to define a rational approach to these conditions’ clinical management. Methodology This was a retrospective review of medical records of patients diagnosed with ICC who were treated at PMHC in Limpopo Province, South Africa in 2013. Results Three hundred and twenty-nine medical records were reviewed in this study; 64% of the patients were HIV-negative, and only 35% were HIV-positive. Thirty-five percent of the patients were younger than 50 years of age, followed by those aged 50–59 years (23%). Among women in the age group 30–59 years, the most common ICC stages were IIB and IIIB. In women older than 60 years, stages IIB, IIIA, IIIB and IVA were the most common. In the HIV-positive women, 18% had a CD4 cell count of less than 200/μL, compared to 2% in the HIV-negative women (p <0.05). Among the HIV-negative women, stages IIIB (49.8%) and IIB (24.6%) were the most common, where as among those who were HIV-positive, stages IIIB (55.6%) and IIB (22.6%) dominated. Conclusion This retrospective study did not find any relationship between HIV infection and ICC in patients treated at PMHC. However, it indicated that a significant proportion of HIV-positive women with ICC had lower CD4 cell counts compared to those of HIV-negative women. KEY CONCEPTS: Invasive cervical cancer, Human immunodeficiency virus, Stage, Prevalence, CD4 cell count, Age, Polokwane/Makweng Hospital Complex

Philosophiae Doctor - PhD / The continued success of antiretroviral programmes in the treatment of HIV is dependent on access to a cost-effective HIV drug resistance test (HIV-DRT). HIVDRT involves sequencing a fragment of the HIV genome and characterising the presence/absence of mutations that confer resistance to one or more drugs. HIV-DRT using conventional DNA sequencing is prohibitively expensive (~US$150 per patient) for routine use in resource-limited settings such as many African countries. While the advent of ultra deep pyrosequencing (UDPS) approaches have considerably reduced (3-5 fold reduction) the cost of generating the sequence data, there has been an even more significant increase in the volume of data generated and the complexity involved in its analysis. In order to address this issue we have developed Seq2Res, a computational pipeline for HIV drug resistance test from UDPS genotypic data. We have developed QTrim, software that undertakes high throughput quality trimming of UDPS sequencing data to ensure that subsequently analyzed data is of high quality. The comparison of QTrim to other widely used tools showed that it is equivalent to the next best method at trimming good quality data but outperforms all methods at trimming poor quality data. Further, we have developed, and evaluated, a computational approach for the analysis of UDPS sequence data generated using the novel Primer ID that enables the generation of a consensus sequence from all sequence reads originating from the same viral template, thus reducing the presence of PCR and sequencing induced errors in the dataset as well as reducing. We see that while the Primer ID approach does undoubtedly reduce the prevalence of PCR and sequencing induced errors, it artificially reduces the diversity of the subsequently analysed data due to the large volume of data that is discarded as a result of there being an insufficient number of sequences for consensus sequence generation. We validated the sensitivity of the Seq2Res pipeline using two real biological datasets from the Stanford HIV Database and five simulated datasets The Seq2Res results correlated fully with that of the Stanford database as well as identifying a drug resistance mutations (DRM) that had been incorrectly interpreted by the Stanford approach. Further, the analysis of the simulated datasets showed that Seq2Res is capable of accurately identifying DRMs at all prevalence levels down to at least 1% of the sequence data generated from a viral population. Finally, we applied Seq2Res to UDPS resistance data generated from as many as 641 individuals as part of the CIPRA-SA study to evaluate the effectiveness of UDPS HIV drug resistance genotyping in resource limited settings with a high burden of HIV infections. We find that, despite the FLX coverage being almost three times as much as that of the Junior platform, resistance genotyping results are directly comparable between both of the approaches at a range of prevalence levels to as low as 1%. Further, we find no significant difference between UDPS sequencing and the "gold standard" Sanger based approach, thus indicating that pooling as many as 48 patient's data and sequencing using the Roche/454 Junior platform is a viable approach for HIV drug resistance genotyping. Further, we explored the presence of resistant minor variants in individual's viral populations and find that the identification of minor resistant variants in individuals exposed to nevirapine through PMTCT correlates with the time since exposure. We conclude that HIV resistance genotyping is now a viable prospect for resource limited setting with a high burden of HIV infections and that UDPS approaches are at least as sensitive as the currently used Sanger-based sequencing approaches. Further, the development of Seq2Res has provided a sensitive, easy to use and scalable technology that facilitates the routine use of UDPS for HIV drug resistance genotyping.

From the early 1990s, rates of HIV infection increased dramatically in South Africa and by the early 2000s, AIDS emerged as the main cause of death for adult South Africans. During the first half of the 2000s, the South African government’s response to this crisis was inadequate, marked by denial and delays in implementing prevention and treatment, resulting in thousands of preventable deaths. Yet, apart from the challenges posed by the predominantly urban-based Treatment Action Campaign (TAC), the absence of a social response to this crisis is notable, especially in rural settings. This scenario forms the broad backdrop to this ethnographic study that draws on participant observation and interviews undertaken over a three-year period (2002-2005) in KwaBomba village previously in the Gazankulu Homeland, now located in the Bushbuckridge municipality of the South African lowveld. An ethnographic perspective provides an intimate vantage point from which to view peoples’ experiences of the AIDS epidemic and their responses in context. This perspective draws attention to gaps in public health and biomedical understandings of the epidemic and suggests alternatives to these understandings. In Bushbuckridge, mortality and morbidity due to AIDS became visible in the late 1990s and early 2000s. Households were incapable of dealing with the burden of illness and death while the health services were often unwilling and ill-prepared. HIV prevention campaigns based on individual behaviour change were not well suited to a context in which HIV spread through sexual networks. Despite widespread awareness of the threat of AIDS, the disease was subjected to public censorship and AIDS suffering was concealed. Public discourses of AIDS were hidden within gossip and rumour and articulated as witchcraft suspicions and accusations. Although these discourses appear to deny and suppress the reality of AIDS, I suggest that they are active attempts to deal with the AIDS crisis: gossip and rumour allocate blame and construct a local epidemiology through which the epidemic can be surveilled; interpreting AIDS as witchcraft creates the possibility of avenging untimely death. These discursive forms are critical in informing individual and social responses to the AIDS epidemic. While the absence of public acknowledgement of AIDS as a cause of illness and death suggests denial and fatalism and appears to limit public action, subaltern discourses create shared secrets to manage the AIDS epidemic at the local level. Furthermore, these discourses may constitute a form of resistance against biomedical models of causality. Ethnographic enquiry at the local level offers a nuanced understanding of social responses to the AIDS epidemic. By examining forms of expression that lie outside the domain of public health, the thesis reveals how these constitute significant forms of social action in response to the epidemic. / Thesis (PhD)--University of Pretoria, 2012. / Anthropology and Archaeology / unrestricted

The study emanates from the need to identify the biopsychosocial factors that influence patients’ adherence to antiretroviral therapy (ART) within the South African context The specific goal of the study was to explore these in order to make recommendations to enhance service delivery. Applied research was conducted, with its primary task being to stimulate thought and action concerning the challenges faced by patients who are on ART. In order to gather comprehensive data, the researcher engaged in a combination of the qualitative and quantitative approaches. For the qualitative case study the researcher made use of semi-structured interviews, utilizing the non-probability sampling method, aiming to understand and interpret the meaning that the multidisciplinary team accorded to matters of antiretroviral treatment. For the quantitative part of the study the probability random sampling method was made use of for the quantitative descriptive survey. Questionnaires were employed to collect data from 201 patients already on antiretroviral medication. The conclusions, which were drawn from the research findings, identified challenges to adherence to ART: the study confirmed that since the advent of combination antiretroviral therapy (HAART), HIV/AIDS has been transformed into a manageable and chronic condition, and has undoubtedly extended and improved the quality of life for people living with HIV/AIDS. However, it also confirmed that ART, is a complex intervention, which is accompanied by severe biopsychosocial implications, requiring near-perfect adherence in order to prevent the development of resistance. The impact that the various psychosocial needs of millions of HIV/AIDS people living on ART will have on current social structures and services, will tax the available professional social services, particularly the social work profession. The social correlation of HIV/AIDS and poverty is endorsed by the findings, confirming that the high level of unemployment, coupled with families who are headed by women and who receive little support, lead to almost total dependency on social security. The findings further indicate a specific relationship between socio-economic circumstances and the ability to adhere to ART. Empowering HIV/AIDS patients, to be able to adhere to ART, is therefore indicated, as is the further need for a regulator of HIV/AIDS support services, in order to protect and promote high standards of service delivery, especially counselling. / Thesis (DPhil)--University of Pretoria, 2007. / Social Work and Criminology / DPhil / unrestricted

Background: Due to its continuous exposure to food antigens and microbes, the gastrointestinal tract (GIT) is in a constant state of low level immune activation and contains an abundance of activated CCR5+CD4+ T lymphocytes, the primary target HIV-1. As a result, the GIT is a site of intense viral replication and severe CD4+ T cell depletion, a process that begins during primary HIV-1 infection and continues at a reduced rate during chronic infection in association with increased production of pro-inflammatory cytokines, a breakdown in the epithelial barrier, microbial translocation, systemic immune activation and the continued recruitment and infection of new target cells. AntiRetroviral Therapy (ART) is only partially effective in reversing these pathogenic changes. Despite the importance of the GIT in HIV-1 pathogenesis, and as a reservoir of persistent virus during ART, little is known about the diversity of HIV-1 in the GIT, or how different tissues in the GIT respond to ART. Objectives: Primary objectives of this thesis were to: 1) characterize the diversity of HIV-1 RNA variants in different parts of the GIT; 2) determine whether there is compartmentalized evolution of HIV-1 RNA variants in the GIT and whether these variants are likely to have different biological properties; 3) investigate the impact of ART on immune restoration in the GIT. Methods: A prospective study of the duodenum, jejunum, ileum and colon of African AIDS patients with chronic diarrhea and/or weight loss, sampled before and during 6 months of ART. RNA extracted from gut biopsies was reverse transcribed and PCR amplified. Env and gag PCR fragments were cloned, sequenced and subjected to extensive phylogenetic analysis; pol PCR fragments were analyzed for drug resistance. CD4+, CD8+ and CD38+CD8+ T cells levels in biopsies collected at baseline (duodenum, jejunum, ileum and colon) and after 3 (duodenum) and 6 (duodenum and colon) months of ART were quantified by flow cytometry and immunohistochemistry, plasma and tissue VL by the Nuclisens assay. Results: Viral diversity varied in different regions of the GIT with env HIV-1 RNA variants being significantly more diverse than gag variants. Gag HIV-1 RNA variants were widely dispersed among all tissue compartments. Some env variants formed tight monophyletic clusters of closely related viral quasispecies, especially in the colon, a finding that is suggestive of compartmentalized viral replication and adaptive evolution. CD4+ T cell and VL levels were significantly lower, while CD8+ including activated CD38+CD8+ T cell levels were higher in the duodenum and jejunum versus the colon. After 6 months of ART, a significant but incomplete recovery of CD4+ T cells was observed in the colon but not in the duodenum. Failed restoration of CD4+ T cells in the duodenum was associated with non-specific enteritis and CD8+ T cell activation. Conclusions: These results advance our understanding of the GIT as a host-pathogen interface by providing new insights into the diversity, evolution and dissemination of HIV-1 variants in the GIT. Strategies aimed at decreasing immune activation, especially in the small intestine, may be highly beneficial in enhancing the therapeutic efficacy of ART. / Thesis (PhD)--University of Pretoria, 2014. / lk2014 / Immunology / PhD / Unrestricted

MSc (Microbiology) / Department of Microbiology / Background: Human Herpes Virus-8 (HHV-8) and Human Immunodeficiency Virus (HIV) are endemic in sub-Saharan Africa. However, the prevalence of HHV-8 in HIV-infected individuals in sub-Saharan Africa has not been fully described and characterized. Objectives: The objective of this study was to determine the seroprevalence and genetic subtypes of HHV-8 in an HIV-infected population in Cameroon. Methodology: KSHV/HHV-8 Enzyme-linked Immunosorbent Assay (ELISA) kit (Advanced Biotechnologies Inc., USA) was used to detect IgG antibodies in the plasma of 406 HIV-infected outpatients of the Mutengene Baptist Health Centre, Cameroon. To detect the viral presence, a 233 bp fragment of the ORF 26 gene of HHV-8 was targeted by polymerase chain reaction (PCR) in total DNA purified from patients’ whole blood. A 453 bp of the K1 gene was amplified by nested PCR, sequenced and phylogenetically analysed to infer subtypes. The online tool, Synonymous Non-synonymous Analysis Program (SNAP), was used to determine the rate of synonymous and nonsynonymous mutations in the K1 gene. The genetic variability among the derived K1 nucleotide sequences was determined by mean genetic distance analysis. Results: Of the 406 participants, an HHV-8 seroprevalence of 79.1% was obtained. There was a statistically significant association of seroprevalence with age (p= 0.00), CD4+ cell count (p= 0.02), marital status (p= 0.02) and ownership of a transistor radio set (p= 0.00). Seventy samples (23.3%) were successfully amplified for ORF 26 gene confirming the presence of replicating virus. K1 sequences were obtained for 14 of the 20 (70%) K1 amplified DNAs. The mean genetic diversity of K1 sequences ranges from 0.0%-22.3%. Phylogenetic analysis revealed two infecting viral subtypes in the study cohort: subtype A5 (57.1%), and subtype B (35.7%). Greater positive selection and genetic diversity were observed in A5 subtype compared to B subtype of K1. Interestingly, one sample (BM 547) clustered with an unclassifiable sequence from South Africa. Conclusions and recommendation: This study revealed the endemicity of HHV-8 infection in the studied population, with subtypes A5 and B as the most important epidemiological genetic variants. In addition, targeting the ORF 26 region by PCR could be an approach to detect replicating virus in individuals. Further studies should investigate the association between HHV-8 infection and KS development in the study area which is endemic for HIV. This study contributes data to the HIV/HHV-8 co-infection landscape in the study area and in Africa at large.