3. Electronic Theses and Dissertations (ETDs) - All submissions
Permanent URI for this communityhttps://wiredspace.wits.ac.za/handle/10539/45
Browse
10 results
Search Results
Item Defining the role of FC effector function in natural HIV-1 infection(2018)Human immunodeficiency virus type 1 (HIV-1) infects 2 million individuals annually, highlighting the need for an effective vaccine. While broadly neutralizing antibodies (bNAbs), naturally elicited in some HIV-infected individuals, can prevent infection in animal models these have not yet been stimulated by vaccination. RV144, the only HIV vaccine to show any efficacy, implicated the antibody Fc region in protection through functions such as antibody dependent cellular cytotoxicity (ADCC), cellular phagocytosis (ADCP) and complement deposition (ADCD). Consequently, we aimed to characterize Fc effector functions in the context of a bNAb response to inform vaccine design and improve antibodies for passive immunization. This thesis describes the development of a novel assay to measure antibody dependent cellular trogocytosis (ADCT) in HIV infection for the first time. ADCT results in rapid cell death of target cells through the removal of membrane fragments, which is distinct from ADCP. Individuals that developed bNAbs showed higher levels of ADCT and further investigation using assays measuring ADCP, ADCC and ADCD revealed they developed a diversified and potent Fc response early in infection that clearly separated them from other HIV-infected individuals. This profile correlated with good germinal center activity and increased subclass diversity, demonstrating a common mechanistic link between the regulation of the Fc and Fab mediated activities. An individual with bNAbs, CAP256, who also developed potent Fc effector function was found to have persistently high levels of IgG3 which is the most polyfunctional IgG subclass. Monoclonal antibodies isolated from this donor revealed natural usage of a novel IgG3 allele that showed both improved Fc effector function and neutralization compared to IgG1 versions. Hinge switch variants revealed that the increased IgG3 hinge length was responsible for improved neutralization. Our data describe common immune determinants associated with both Fab and Fc function as well as a new Fc effector function, ADCT. This highlights how cooperation between the variable and constant regions, facilitated by the hinge region, could be exploited to enhance the functionality of antiviral antibodies for passive immunity. Overall, these studies provide further clarity on the role of Fc effector functions in HIV infection.Item Validation of self reported measures of adherence to ART and factors associated with adherence in Jinja, Uganda(2016) Made, FelixBackground: Good adherence to ART prolongs survival and improves quality of life in people living with HIV/AIDS. Adherence is commonly assessed using self-reported measures, but these tend to over-estimate adherence. Viral load testing is the gold standard for measuring ART adherence but it is unaffordable in resource limited settings. Therefore, the aims of this small sub-study were to validate self-reported measures of adherence and to find factors associated with adherence to ART in Jinja, Uganda. Methods: This study was a secondary analysis of data collected from a cluster randomized equivalence trial which was carried out to compare facility based ART care versus home based care. In the main study, 1453 participants aged 18 and above were enrolled. A total of 1276 men and women qualified for this sub-study. Receiver operating characteristic (ROC) was computed to see how well two self-reported measures of adherence predicted virological failure. The two self-reported measures were firstly a visual analogue score (VAS) where participants rated the number of doses that they had taken in the past month on a scale from 0 (meaning no ART taken) to 100 (meaning that all required doses had been taken) and secondly an adherence score based on the number of pills missed in the three days before the visit. Logistic regression models were fitted with survey estimator to find factors associated with virological failure. Tobit models were fitted to find factors associated with self-reported adherence measures, since these were restricted to the range of 0-100% and censored. We then compared associated factors among the three different outcome measures. Results: There were 914 women and 362 men in this study. Home based care had larger number of patients (754) than facility based care (522). The median age of the patients was 38 years (IQR 32.0-44.0). Most of the participants were either married (518) or single (456). The majority of the trial participants had primary school education (n=713) and very few achieved tertiary education. A large number of participants had CD4 cell counts of less than 50 cells/mm3 (n=351), and very few of the patients in the trial had CD4 counts greater than 200 cells/mm3. The median CD4 count of the study participants was 116 cells / mm3 (IQR 43.0-167.0). A very large number of the patients were either in WHO clinical stage II or III (Stage II: n= 595; Stage III: n=577). A total of n=1079 (84.56%) and n=197 (13.44%) participants had no virological failure and failure respectively. The ROC methods showed that the iv self-reported adherence measures estimated virological failure with a sensitivity that ranged between 35-65%. Female patients had lower odds of experiencing virological failure (odds ratio: 0.7; 95% CI: 0.485, 0.968; p=0.033). The odds of virological failure decreased with each one year increase in age (OR: 0.95; 95% CI: 0.928, 0.979; p=0.001). Participants who found adherence reminders very useful were less likely to experience virological failure (P=0.001). Conclusion: This study show that self-reported measures are not good predictors of ART adherence since approximately only a half of the Jinja participants with virological failure were predicted by such measures. None of the factors associated with virological failure was also associated with both of the self-reported adherence measures. Viral load testing should be encouraged in place of self-reported adherence measures to ART. In addition, alternative methods of measuring adherence such as electronic medication monitoring, pharmacy refills and drug level detection should be investigated.Item HIV and TB care and treatment: patient utilization and provider perspectives in rural KwaZulu-Natal(2017) Chimbindi, Natsayi ZanileThe epidemics of tuberculosis (TB) and Human Immunodeficiency Virus (HIV) in sub-Saharan Africa are closely related and particularly persistent, proving a considerable burden for healthcare provision, and complicating utilization of care. Concern has been expressed about patients’ experience at healthcare facilities as this may impact on drug adherence, treatment success and willingness to return for regular monitoring and drug pick-up. This is particularly relevant for HIV programmes, with HIV now a chronic disease, with daily treatment necessary for life; TB treatment is limited in duration, to six months although can be as long as two years in case of multiple drug resistant TB. Utilization of healthcare services is an important determinant of health outcomes generally, with public health relevance, particularly for HIV and TB services in areas of high prevalence. The main aim of universal health coverage is to make healthcare accessible without barriers based on affordability, availability or acceptability of services. Various factors have been shown to hinder or enable patient utilization of healthcare services, such as organization of services, costs of transport to and from clinics, time loss at clinics receiving care, staff attitudes, waiting times and cleanliness of facilities. Objectives This study aimed to determine and quantify factors associated with healthcare utilization in patients utilizing HIV care (including those not yet initiated on antiretroviral treatment (ART) - pre-ART) or TB treatments in a rural sub-district of Hlabisa in KwaZulu-Natal and to understand healthcare providers’ perspectives regarding patient care and provision of quality care. The study used data from patient exit interviews, and additionally findings from interviews with healthcare providers in the local HIV treatment and care programme, structured around the responses from the patient-exit interviews. The study had three specific objectives: 1) to establish and quantify factors associated with healthcare utilization, with utilization decomposed to availability, affordability and acceptability of healthcare services, for patients in HIV or TB treatment and care; 2) to quantify ability-to-pay for healthcare and identify associated factors for patients in pre-ART care, or on ART or TB treatment; 3) to understand the healthcare providers’ perspectives regarding patient care and provision of quality HIV care. Methods In 2009 patient-exit interviews were conducted in six primary healthcare (phc) clinics in rural South Africa with 300 patients receiving ART and 300 patients receiving TB treatment; patients were randomly selected using a two-stage cluster random sampling approach with primary sampling units (phc) selected with probability-proportional-to-size. In 2010 an additional 200 HIV-infected patients in pre-ART care from the same clinics were interviewed. Patient-exit interviews were conducted in a private room outside the facility and all data were analysed using STATA 11. In 2012, a qualitative study was carried out with healthcare providers in eight (of 17) randomly selected phc clinics; 25 ART healthcare providers were engaged in discussion structured around patient-exit interviews feedback to assess possible challenges/facilitators ART healthcare providers face when providing care. Discussions took place in the consultation rooms when no clinical sessions were ongoing and these were recorded and transcribed; and data were managed using Nvivo 10. Thematic content analysis was conducted using both inductive and deductive approaches and clinic or healthcare provider identifiers were removed and replaced with pseudonyms. Summary statistics describe patient characteristics by patient group and key availability, acceptability and affordability factors associated with utilization of healthcare services; separate univariate and multivariable regression models were run to assess associations between patient characteristics and these key availability, acceptability and affordability factors. Patient socio-demographic characteristics (sex, age, education, employment and marital status) were controlled for and adjusted for clustering at facility-level. Factor analysis was performed to investigate underlying patient satisfaction factors. Results Socio-demographic characteristics of the patients More women than men were seen in the primary care clinic, especially among pre-ART patients (79%), followed by 62% HIV and 53% utilized TB care, with an age-sex profile comparable to previous studies in the area. Pre-ART patients were significantly younger than ART and TB patients, with a median age of 32 years for pre-ART patients, 39 years for ART patients and 37 years for TB patients. Unemployment at household level was high, up to 86% of ART patients’ head of households were unemployed and only 9% of TB patients were employed.Item Clinical and microbiological characterisation of invasive enteric pathogens in a South African population: the interaction with HIV(2017) Keddy, Karen HelenaIntroduction Human immunodeficiency virus (HIV) has been associated with invasive enteric infections in HIV-infected patients, since it was first described in the 1980s. In South Africa, HIV remains an important health challenge, despite the introduction of antiretroviral therapy (ART) in 2003. In association with this, is an ongoing problem of invasive enteric infections, including those due to Shigella and Salmonella, including Salmonella enterica serovar Typhi (Salmonella Typhi). There are few South African data available as to the incidence of invasive disease due to these pathogens and how these data may contrast with the presentation and outcome in HIV-uninfected patients. The associated risk factors for mortality due to invasive enteric pathogens and whether there has been a response with ART as an intervention also needs further elucidation. Aims This work was undertaken to better describe the burden of invasive enteric infections (Shigella, nontyphoidal Salmonella and Salmonella Typhi) in association with HIV, define risk factors for mortality and establish whether the introduction of ART has impacted on disease burdens due to these pathogens. Methods Laboratory-based surveillance for enteric pathogens was initiated in 2003. Basic demographic details (age and gender) were collected on all patients where possible. In 25 hospital sites in all nine provinces, additional clinical information was collected by trained surveillance officers, including HIV status, data reflecting severity of illness, other immune suppressive conditions, antimicrobial and antiretroviral usage and outcome (survival versus death). Laboratories were requested to transport all isolates to the Centre for Enteric Diseases (CED) at the National Institute for Communicable Diseases of the National Health Laboratory Service (NHLS) in Johannesburg for further characterisation, including serotyping, antimicrobial susceptibility testing and molecular typing where relevant (whether isolates could respectively be classified as Salmonella Typhimurium ST313 and Salmonella Typhi H58). Additional cases were sought through audits of the Central Data Warehouse (CDW) of the NHLS. Annual incidence rates were calculated according to published estimates of population by age group by the Actuarial Society of South Africa for the Department of Statistics of the South African government. Analyses were specifically directed at invasive shigellosis, Salmonella meningitis, typhoid fever in South Africa and nontyphoidal salmonellosis in Gauteng Province, South Africa. Data were recorded in an Access database and analysed using chisquared test to establish differences between HIV-infected and uninfected individuals and univariate and multivariate analysis to compare risk factors for mortality. Data in the number of patients accessing ART were derived through audits of the CDW, by using the numbers of patients on whom viral loads were done annually as a proxy. Results Between 2003 and 2013, a total of 10111 invasive enteric isolates were received by CED. For patients for whom sex was recorded, 3283/6244 (52.6%) of patients presenting with invasive enteric infections were male; invasive disease was predominantly observed in children less than five years of age (1605/6131; 26.2%) and those who were aged between 25 and 54 years (3186/6131; 52.0%), with the exception of typhoid fever where the major burden was in patients aged 5 to 14 years (302/855; 35.3%). KH Keddy 81-11384 PhD iv More HIV-infected adult women were observed with invasive shigellosis (P=0.002) and with typhoid fever compared with adult men (P=0.009). Adults aged ≥ 15 years were more likely to die than children aged < 15 years (invasive shigellosis, odds ratio [OR]=3.2, 95% confidence interval [CI]=1.6 – 6.6, P=0.001; Salmonella meningitis, OR=3.7, 95% CI=1.7 – 8.1, P=0.001; typhoid fever, OR=3.7, 95% CI=1.1 – 14.9, P=0.03; invasive nontyphoidal salmonellosis, OR=2.0, 95% CI=1.6 – 2.5, P<0.001). HIV-infected patients had a significantly higher risk of mortality compared with HIVuninfected patients (invasive shigellosis, OR=4.1, 95% CI=1.5 – 11.8, P=0.008; Salmonella meningitis OR=5.3, 95% CI=1.4-20.0, P=0.013; typhoid fever, OR=11.3, 95% CI=3.0 – 42.4, P<0.001; invasive nontyphoidal salmonellosis OR=2.5, 95% CI=1.7 – 3.5, P<0.001). In all patients, severity of illness was the most significant factor contributing to mortality (invasive shigellosis, OR=22.9, 95% CI=2.7 – 194.2, P=0.004; Salmonella meningitis OR=21.6, 95% CI=3.5 – 133.3, P=0.01; typhoid fever, OR=10.8, 95% CI=2.9 – 39.5, P<0.001; invasive nontyphoidal salmonellosis OR=5.4, 95% CI=3.6 – 8.1, P<0.001). Between 2003 and 2013, ART was significantly associated with decreasing incidence rates of invasive nontyphoidal salmonellosis in adults aged 25 - 49 years (R=-0.92; P<0.001), but not in children (R=-0.50; P=0.14). Conclusion Decreasing incidence rates of invasive nontyphoidal salmonellosis and shigellosis suggest that ART is having an impact on opportunistic enteric disease in HIV. Further work is necessary however, to fully understand the associations between age, sex and invasive enteric pathogens. Specifically, this work would include typhoid fever, Shigella transmission from child to adult carer, development of invasive enteric infections in HIV-exposed children and whether the decreasing incidence rates can be sustained. Moving forward, an understanding of invasive enteric infections in the HIV-uninfected patient may assist in targeting severity of illness as a risk factor for mortality.Item Nurse initiated and managed anti-retroviral treatment: An ethical and legal analysis in South Africa.(2014-03-28) Ford, PelisaThis research investigated the ethical and legal issues that impact on the urgent implementation of Nurse Initiated and Managed Anti-Retroviral Treatment (NIMART) in South Africa, which is part of the task-shifting strategy recommended by the World Health Organization (WHO) to deal with the human resource shortage that has negatively impacted access to Anti-Retroviral Treatment (ART) in developing countries (WHO;2006). The objectives were to review and analyse the existing legal framework and provisions for NIMART in South Africa; and to identify ethical issues and implications of NIMART within the current legal framework. It analysed the legal issues that impact on the implementation of NIMART within the public health service in South Africa, as well as the ethical basis and implications of NIMART on the practice of nurses in the scale-up of Anti-Retroviral Treatment in Primary Health Care (PHC). A comparative analysis was done with case studies of task-shifting in other developing countries and evidence-based recommendations for an enabling and long-term sustainable ethico-legal approach to task-shifting were established. The research concluded that despite the existing legal framework for NIMART in South Africa being firmly founded in the Constitution and further enabled by health policy, challenges exist in implementation of certain critical aspects of the enabling legislation relating to nurse training and accreditation required for full authorization to practice NIMART and that these technical challenges if not attended to could threaten the long-term sustainability of NIMART.Item Sexually transmitted infection (STI) and HIV / AIDS related knowledge, attitudes, perceptions and behaviour among San learners in a combined school in Platfontein, Northern Cape(2014-02-05) Fredericks, Mercedes BerylPrevention of Human immunodeficiency virus (HIV) in South Africa includes early detection and treatment of sexually transmitted infections (STIs), as well as health promotion activities. The latter include health education programmes and the promotion of screening activities such as voluntary counselling and testing (VCT). The South African government recognises the need for creating equity for access to health care services. The 1997 White Paper for the Transformation of the Health System, stipulates one of the aims of health Policy in the new South Africa as ‘promoting equity by developing a single, unified health system’. This commitment is inclusive of the Platfontein community which comprises the two largest San-groups in South Africa: the !Xun and the Khwe who were settled on the Platfontein farm at the end of 2004. There are 3500 !Xun and 1100 Khwe currently living in the Platfontein community. A health facility, compliant with the principles of Primary Health Care (PHC), was built on the farm to render services to the Khwe and !Xun communities who were not recognised as a distinct cultural group during the Apartheid era in South Africa. For the young people in the community it was the first time they could access the formal schooling and health system in South Africa. The objective of this study was to assess the perceptions, attitudes, behaviour and knowledge levels among the school-going youth of the Platfontein community, about STIs, HIV/AIDS and the health care services that are available to them.Item Clinical outcome of HIV patients who commence antiretroviral therapy at different CD4 levels(2011) Mothapo, Khutjo PeterBackground: The decision of when to start treatment in an HIV-infected individual has always been problematic as far as CD4 count is concerned. Aims: To determine the clinical outcome of patients who commence HAART at different CD4 cell count levels. Method: Retrospective analysis of records of a cohort of patients who are received ART at workplace wellness clinics in three mines in Limpopo province from January 2003 to December 2009. Patients were divided into three groups based on their baseline, group A (CD4 <100), group B (CD4 101-200) and group C (CD4 201-250) Each patient’s data was analyzed one year after his/her commencement. Results: The percentage of patients who died in group A (16%) differs significantly from the percentage of patients who died in group B (4%) (Fisher exact test p= 0.038) and also differ significantly from the percentage of patients who died in group C (0%) (Fisher exact test p= 0.011). The percentages of patients who developed TB in the three groups are 8%, 8% and 2.9% respectively. When compared statistically, these percentages do not differ significantly (Fisher exact test p=0.059).The percentages of patients with severe bacterial pneumonia in the three groups (2%, 2% and 0% respectively) do not differ significantly (Fisher exact test p=0,276).The percentage of hospital admissions for patients in group A (18%) differ significantly from the percentage in group B (6%) and the percentage in group C (6%) (Fisher exact test p= 0.05). The percentage of patients with weight loss of more than 10% of baseline value in group A (24%) differ significantly from the percentage in group B (4%) (Fisher exact test p= 0.003) and also differ significantly to from the percentage in group C (0%) (Fisher exact test p= 0.001). The percentage of patients with undetectable viral load in group B (89%) is significantly different from the percentage in group A (69%) (Fisher exact test p= 0.03) and is also significantly different from the percentage in group C (61%) (Fisher exact test p= 0.008).The change in mean CD4 cell count was found to be statistically significant within each group (paired t test, p<0.0001), but the mean changes between the three groups (132,141 and 172) respectively, do not differ significantly (ANOVA test). Conclusion: Patients with baseline CD4 cell count of less than 100 have a poor clinical outcome when compared to patients with baseline CD4 cell count of more than 100. Efforts must be made to identify patients early before CD4 cell count fall to below 100 and preferably initiate HAART when CD4 cell count is above 200.Item Knowledge of HIV/AIDS, related attitudes and participation in risky sexual behaviour among first and fourth year female students at the University of Botswana.(2012-02-16) Cavric, GordanaIntroduction Botswana still has the second highest HIV prevalence in the world with little indication of any significant decline. In Botswana, women are disproportionately affected: young women account for more than half (58 %) of the adults living with HIV thus indicating a significant gender disparity in HIV infection. University educated, urban young women aged 19-39 have been identified as group at particularly high risk of HIV infection. Aim This study aimed to assess knowledge and attitudes regarding HIV and AIDS and how such knowledge and attitudes have implications for participation in risky sexual behavior among female University of Botswana students in their first and fourth years of study. Methodology This study was conducted at the University of Botswana (UB) in Gaborone. Data was collected using a selfadministered questionnaire on Knowledge of HIV/AIDS and participation in Risky Sexual Behavior among female students in first and fourth year of studies at University of Botswana. Results The knowledge regarding the “window period” and infectivity during the window period was significantly lower for first year students compared to fourth years. Attitudes towards people with HIV were positive in both groups, while affirmative attitudes towards premarital sex are increasing as the students progress academically. The analyses highlight that the percentage of women who reported having been sexually active the proceeding year was significantly higher among fourth year students (82.6%) than their first year counterparts (56.9 %), (p<0.01), with the number of partners significantly higher among women in their fourth year. Significantly, 3% of first year female students stated that their partners did not want to use a condom while 7 percent of the participants themselves said that that was the case. Amongst fourth year UB female students responding, 4% said that their partners did not want to use a condom, yet 14% participant said that they themselves did not want to use one. Overall, the prevalence of self-reported STI’s was significantly higher among fourth year students when compared with first year students 19 of 155 [12.26% ]vs. 4 of 144 [2.78 %] p<0.01 . Conclusion This study explored the knowledge of HIV/AIDS and participation in risky sexual behavior amongst female students in their first and fourth years at the University of Botswana. The study supported the findings that higher levels of formal education are associated with better knowledge of how to protect oneself from HIV/AIDS transmission. Although many HIV/AIDS prevention campaigns might have contributed to educated women being knowledgeable about how to protect themselves from HIV/AIDS transmission and the importance from abstaining from risky sexual behavior, a small but significant proportion of women still do not use condoms consistentlyItem Burden of respiratory disease among paediatric patients infected with HIV/AIDS(2012-01-19) Da Cunha, Natalia Cristina PicarraHIV is a prominent infection in society and its health implications are seen in the paediatric wards daily. Despite its multi-system effect on the body, it particularly results in many respiratory infections. Effective understanding of the disease profile and management of patients with HIV relies on correct statistics and proper use of resources. Since the introduction of anti-retrovirals in 2004 in South Africa, the impact of HIV/AIDS on respiratory disease needs to be re-evaluated. The purpose of the study is to understand the disease profile of children with HIV/AIDS with regard to the presence of respiratory conditions with which they present, the need for chest physiotherapy and their health status. Of the 125 patients recruited in this study 55% were boys, average age was 20.55 months (SD= 23.64), average length of hospital stay of 2 ½ weeks (mean=18.76, SD=19.19), 80% discharged and 9.6% died. The most common respiratory conditions presented included bacterial pneumonia (66.4%), tuberculosis (48%) and pneumocystis jirovecii pneumonia (23.2%). The least common condition was lymphoid interstitial pneumonitis (4.8%). Two thirds of the children (68.8%) presented with a high burden of disease. Physiotherapy treatment was indicated for 96% of the patients mainly due to excess secretions and poor air entry. About forty percent (40.8%) of children were taking anti-retrovirals with an average length of use of 9.81 months (SD=11.61). Three out of four (75%) mothers were not involved in a PMTCT program. The analysis of immune status revealed a mean CD4 percentage 17.33% (SD=10.96), CD4 absolute 631.36 cell/mm3 (SD=610.36) and viral load 2.6 million copies /ml (SD=9.08 million copies/ml). A higher burden of disease was related to the use of anti-retrovirals, a lower immunity, female patients, longer length of hospital stay and incidences of mortality occuring at later periods of hospital stay. Results of this study highlight the characteristics of respiratory disease burden among children with HIV in a South African setting in a post HAART era.