Indiana University-Purdue University Indianapolis (IUPUI) / More than 20 million people have died of AIDS since the early eighties, while nearly 34 millions are currently infected with the HIV. Anti-retroviral therapy (ART) directed at key viral enzymes has changed AIDS from uniformly fatal to a manageable chronic disease. However, ART-associated drug resistance and toxicity have posed a great challenge for long-term management of the disease and have called for development of new therapeutics. In this study, we focused on the viral factor Nef and the host factor Sam68. Nef is a major pathogenic viral determinant for HIV-1, and no therapeutics have been targeted to this factor. Sam68 is indispensible for HIV-1 propagation. We revealed that Sam68 variants were very potent in preventing Nef expression. We found that these effects were associated with their ability to form a macromolecular structure called stress granules (SG). In addition, we demonstrated that these variants bound to nef mRNA in a sequence-specific manner. Furthermore, we showed that these variants co-localized with nef mRNA in SG. Importantly, we validated these findings in the context of HIV-1 infection of its natural target cells and found significant loss of Nef function in these cells. Taken together, these results demonstrate that SG induction and nef mRNA sequestration account for translational suppression of Nef expression and offer a new strategy for development of anti-HIV therapeutics. Sam68 is implicated in a variety of other important cellular processes. Our findings that Sam68 variants were able to induce SG formation prompted us to investigate whether wild-type Sam68 was also recruited to SG. We found that Sam68 was increasingly recruited into SG under oxidative stress, and that its specific domains were involved. However, Sam68 knockdown had no effects on SG assembly, suggesting that Sam68 is not a constitutive component of SG assembly. Lastly, we demonstrated that Sam68 complexed with TIA-1, an essential SG component. Taken together, these results provide direct evidence for the first time that Sam68 is recruited into SG through complexing with TIA-1, and suggest that SG recruitment of Sam68 and ensuing changes in Sam68 physiological functions are part of the host response to external stressful conditions.

This study sought to explore the views of healthcare workers regarding paediatric anti-retroviral therapy (ART) adherence in Nigeria. An exploratory descriptive qualitative research design was used to identify and describe healthcare workers’ views in Kano and Lagos, Nigeria. Three focus group discussions were held. The transcribed data was analysed using the framework approach of data analysis. Healthcare providers perceived poverty, illiteracy, stigma and discrimination, inappropriate care approaches, and parental dynamics as factors influencing ART adherence. Recommendations for enhancing paediatric ART adherence levels in Nigeria included: mainstreaming adherence counselling in paediatric ART and adopting a comprehensive family centred care approach were identified as measures for improving paediatric ART adherence. Other measures included free ART services, quality improvement in paediatric ART services, parental empowerment and stigma and discrimination reduction programmes. / Health Studies / M.A. (Public Health)

The objective of this study was to assess levels of HAART adherence and factors affecting it. An observational, analytic, cross-sectional and quantitative study using IMB model was conducted on a randomly selected 349 HIV/AIDS patients on a HAART regimen. Data collection was done by interviewing respondents using a structured questionnaire. Both descriptive and inferential statistics used in the study. Only 80.2% of the total sample population reported a HAART adherence rate of more than or equal to 95% in this study. The findings highlight the need for on-going educational, informational and other interventions to address the knowledge, motivation and adherence behavioural skills of patients in order to improve the current levels of HAART adherence behaviour. The study also suggested the need for research into objective measures of adherence as well as longitudinal studies on adherence behaviour because strict adherence to treatment is a long-term process and not a one-time activity. / Health Studies / M.A. (Public health)

Health Studies / (M.P.H. (Health Studies))

The health care industry in Nigeria is increasingly grappling with challenges of meeting end users’ requirements and expectations for quality antiretroviral therapy (ART) service provision. This study sought to explore and describe the quality of antiretroviral therapy in public health facilities in Nigeria and the perceptions of the end users. A descriptive qualitative research design was used in the study in order to generate ideas from end users for improving quality of ART service provision, and prompt additional research activities. Unstructured focus group discussions were conducted with end users (n=64) in 6 locations across the 6 geopolitical zones of Nigeria. Data was analysed using the framework approach because it reflects the original accounts and observations of the end users and the Weft QDA version 1.0.1 software to validate the results. Findings revealed that end users were satisfied with uninterrupted antiretroviral drug supplies, courtesy treatment, volunteerism of support group members and quality counselling services. End users expect public health facilities to accept diagnostic results from collaborating facilities, implement continuous quality improvement (CQI), maintain clean and adequate health infrastructure, reduce end user waiting time, reduce stigma, comprehensively assess end users during each clinic visit and ensure uninterrupted ART services. They also expect effective collaboration between healthcare providers and support group members, to enhance the quality of life of people living with HIV (PLHIV). End users identified the following as quality gaps in ART service provision: weak health facility leadership, non-attractive ART service infrastructure, frequently interrupted laboratory services, demotivated and inadequate health care workers, long waiting time, interrupted medicine supplies and inadequate procedure for complaints management. In conclusion, the following recommendations were proffered: deploy and train additional health care workers, integrate ART into regular health services, improve supply chain management of health commodities, and reduce end user overload in clinics. Finally, a best practice guideline for the provision of end user focused ART service provision was developed. / Health Studies / D.Litt. et Phil. (Health Studies)

Submitted in fulfillment of the requirements for the Degree of Master of Technology: Biomedical Technology, Durban University of Technology, 2012. / Antiretroviral therapy (ART) was introduced because it has shown to reverse the Acquired Immunodeficiency syndrome (AIDS), by reducing the HIV replication, allowing the regeneration of the patient’s immune system. ART is given to patients for the rest of their lives as part of HIV clinical care, but the use of ART has shown evidence of metabolic side effects which range from manageable to life threatening complications. Aims and objectives of the study The aim of the study was to investigate whether patients on ART developed metabolic side effects such as pancreatitis, dyslipidaemia and hepatotoxicity. These metabolic side effects were determined by laboratory testing of blood levels of specific biomarkers at stipulated intervals. Any significant change in the blood levels of these specific biomarkers was identified. Methodology : The study included 92 patients who were already selected for the ART programme which is in accordance to the South African National Antiretroviral Therapy Guidelines of 2003 Laboratory blood analysis was conducted. The repeated measures analysis of variance (ANOVA) was used to compare changes in biomarkers over time. The severity of each side effect was assessed by grading each biomarker laboratory result through the use of an established toxicity grading table. Results : It was found that the biomarker blood levels were not significantly altered within 12 months of ART, however, there was a gradual increase of most biomarker values, indicating that abnormalities may be detected after a longer period of treatment. Conclusion : Within 12 months of treatment, life-threatening toxicities were not detected. It may be speculated that if ART is monitored correctly, life-threatening toxicities may be avoided in many patients.

Assignment (MA)--University of Stellenbosch, 2005. / ENGLISH ABSTRACT: Adherence to medical regimes and the difficulties associated with patient adherence are well documented. Furthermore, non-adherence with prescribed medication is ubiquitous. Regarding HIV, strict adherence to combination highly active antiretroviral therapy regimes is a prerequisite for immunological reconstitution. Certain factors have been identified as predicting non-adherence. However, the role of personality variables on adherence has been neglected, specifically with regards to personality pathology. Moreover, there is a high rate of comorbidity between HIV and Axis II disorders, including BPD. Despite controversy, the DSM-IV-TR identifies nine fundamental criteria required for the diagnosis of BPD to be made. These criteria are considered separately in an attempt to elucidate their potential role on non-adherence. Clinically, it is likely that the criteria interact to create a gestalt effect, further complicating adherence. / AFRIKAANSE OPSOMMING: Patient voldoening ter mediese aanbevele en die probleme geassosier daarmee is goed gedokumenteer. En verder is dit allerdags dat patlente nie met hul voorgeskrewe medikasie voldoen nie. In verband met MIV, streng voldoening tot HAART is a voorvereiste vir immunologiese hersamestelling. Sekere faktore is geidentifiseer wat voldoening en die teenoorgestelde daarvan voorspel. Alhoewel, die rei van persoonlikheid veranderlikes op voldoening is nie in ag geneem nie, spesifiek in verband met persoonlikheid patologie. Bowenal, is daar n hoe frekwensie van komorbiditeit tussen MIV en As II steurings, insluitend BPO. Ten spyte van kontroversie, die OSM-IV-TR identifiseer nege fundementele kriteria, waarvan vyf teenwoordig moet wees vir n diagnose van BPO. Hierdie kriteria word individueel bespreek in n poging om hulle impak op patiente voldoening te illustreer. Klinies is dit heel moontlik dat daar interaksie is tussen die kriteria wat n gestalt effek sal skep, wat voldoening weer verder sal kompliseer.

Thesis (MA)--University of Stellenbosch, 2011. / ENGLISH ABSTRACT: The topic of antiretroviral adherence remains a subject of continued importance, as it is associated with positive health outcomes amongst patients attending public healthcare facilities. Available literature on adherence behaviour mainly focuses on the psychological and behavioural barriers, while overlooking the multitude of structural barriers within the patient’s environment affecting the patient’s adherence to antiretroviral treatment and care. The present study provides a unique perspective on adherence behaviour amongst persons living with HIV and receiving antiretroviral treatment, as it identifies important structural barriers to clinical attendance and pill-taking. The sample for this study were selected from patients attending an infectious diseases clinic at a major peri-urban secondary hospital and receiving antiretroviral therapy, nurses and doctors providing health services to patients, and patient advocates providing psychosocial support to patients under the auspices of a local non-governmental organisation. The participants included in this study were selected by means of convenience sampling to participate either in semi structured interviews or focus group discussions. Participants were assured of the confidentiality of the process and their anonymity in both cases. Both semi structured interviews and focus groups were digitally recorded and transcribed after which transcriptions were entered into Atlas.ti for textual analysis. Transcriptions were thematically analysed according to the perceptions of various participants. The main themes that emerged from the present study included individual barriers, poverty-related barriers, institutionrelated barriers, and social and community-related barriers. The results of the present study were triangulated by considering the concurrences and discrepancies between the patients, clinicians and patient advocates on the main, and subthemes. These themes were then discussed according to Bronfenbrenner’s (1972) Ecological Systems Theory, which divided the main themes identified according to the different systems operating within the patient’s environment, i.e. the micro-, exo-, and macrosystem. The microsystem included both individual psychological and behavioural barriers and poverty-related barriers. Institutional barriers were considered within the exosystem of the patient’s ecological environment. And the social and community-related barriers were considered within the macrosystem of the patient’s ecological environment. The significance of this study lies in the identification of adherence behaviour as the product of the patient’s environment through the examination of triangulated data. Future research may include effective ways in which patients can be assisted in developing the necessary skills to cope with their environment and to enhance social support. The development of strategies to support newly-enrolled patients also still needs investigation. / AFRIKAANSE OPSOMMING: Volgehoue antiretrovirale behandeling bly ‘n onderwerp van voortdurende belang omdat dit geassosieer word met positiewe gesondheidsuitkomste onder pasiënte wat van openbare gesondheidsfasiliteite gebruik maak. Beskikbare literatuur oor volhoudings gedrag fokus grootliks op sielkundige en gedragshindernisse, terwyl veelvuldige strukturelehindernisse binne die pasiënt se omgewing steeds misgekyk word. Dié studie bied ‘n unieke perspektief op volhoudingsgedrag onder MIV-positiewe pasiënte wat tans antiretrovirale terapie ontvang, aangesien dit belangrike strukturele hindernisse tot kliniek bywoning en die neem van medikasie identifiseer. Dié steekproef sluit pasiënte in wat tans antiretrovirale terapie by ‘n aansteeklike siektes-kliniek by ‘n peri-stedelike sekondêre hospitaal ontvang. Dit sluit ook dokters en verpleegsters in wat gesondheidsdienste aan dié pasiënte verskaf, en pasiënt- advokate wat psigo-sosiale ondersteuning aan pasiënte verskaf onder die vaandel van ‘n plaaslike nieregerings organisasie. Dié deelnemers is deur middel van gerieflikheidssteekproef geselekteer om aan semi-gestruktureerde onderhoude of fokusgroepbesprekings deel te neem. Deelnemers van albei groepe is van hul anonimiteit en die vertroulikheid van die proses verseker. Beide die semi-gestruktureerde onderhoude en die fokusgroepbesprekings is digitaal opgeneem en transkripsies is daarvan gemaak, waarna die transkripsies in Atlas.ti gelaai is vir tekstuele analise. Transkripsies is tematies geanaliseer volgens die persepsies van die verskeie deelnemers. Die hooftemas wat na vore gekom het, sluit in individuele hindernisse, armoedeverwante hindernisse, institusieverwante hindernisse asook sosiale en gemeenskapsverwante hindernisse. Resultate van dié studie is getrianguleer deur die verskille en ooreenkomste te vind tussen pasiënte, klinici en pasiënt-advokate oor die hoof- en subtemas. Die hooftemas is toe volgens Bronfenbrenner (1972) se Ekologiese Sistemeteorie verdeel in die verskillende sisteme teenwoording in die pasiënt se omgewing, naamlik die mikro-, ekso-, en makrosisteem. Die mikrosisteem het individuele sielkundige en gedragshindernisse asook die armoedeverwante hindernisse ingesluit. Institusieverwante hindernisse is binne die eksosisteem van die pasiënt se ekologiese omgewing beskou en sosiale en gemeenskapsverwante hindernisse is beskou binne die makrosisteem van die pasiënt se ekologiese omgewing. Die belang van dié studie lê in die identifisering van volhoudingsgedrag as produk van die pasiënt se omgewing, soos beskou deur die Ekologiese Sistemeteorie. Toekomstige navorsing kan fokus op effektiewe maniere waarop pasiënte bygestaan kan word om die nodige vaardighede te ontwikkel om hul omgewing beter te kan hanteer en beskikbare sosiale ondersteuning te kan verbeter. Die ontwikkeling van strategieë om nuwe pasiënte by te staan, benodig ook verdere navorsing.

A thesis submitted in partial fulfilment of tine requirements for the Degree of Master of Technology: Biomedical Technology, Durban University of Technology, 2007. / In 2004, it was reported that KwaZulu-Natal had the greatest number of HIV infected people, approximately 1.8 million people, of whom an estimated 450 000 were in need of antiretroviral drug therapy based on their Cluster of Differentiation 4 (CD4) counts and clinical status. Studies on the success of antiretroviral drugs in improving the quality of life in HIV infected individuals have been extensively performed and published. However, there are no published data on the effect that immune boosters have in improving the quality of life in such persons. Considering the side effects, toxicity, multi-drug regimens and drug resistance problems associated with antiretroviral therapy, alternative or supplementary therapies may play an important role in improving the quality of life in HIV infected people. Such therapy might help in situations where some patients who qualify for antiretroviral treatment are unable to access them because of several reasons such as long waiting lists, travelling costs, unwilling to take antiretroviral drugs, etc. Some patients have reservations in taking antiretroviral drugs. The stigma associated with the disease may be a major factor. The aim of this study was to investigate the change in the immune status of HIV infected patients that were on the Inochi New Medicine immune booster, as well as, to assess the safety and efficacy of this immune booster in improving the patients’ quality of life. / M

Thesis presented in partial fulfilment for the degree of Master of Management (in the field of Public Sector Monitoring and Evaluation) to the Faculty of Commerce, Law, and Management, University of the Witwatersrand 2016 / The purpose of this research was to assess outcomes of the antiretroviral treatment intervention in Mankweng. The antiretroviral treatment intervention was conceived with the aim to reduce HIV transmission through viral load suppression. Literature has shown that viral load is used as a tool to measure the performance of the intervention and studies on viral load outcomes in rural settings of Limpopo are limited. For this reason, the research was focused on viral load suppression with the aim of (1) determining the proportion of adults with viral load suppression among people taking antiretroviral treatment for 12 months, and (2) identifying factors associated with failure to achieve viral load suppression among people on antiretroviral treatment for 12 months. Binomial logistic regression model was used to identify factors associated with failure to suppress viral load. This study used the theory of change to interpret its findings as well as theories of behavioural planning and self-regulation models to understand the logic that underpins the theory of change. The findings revealed that the majority (78%) of adults achieved viral load suppression, and a quarter of the individuals failed to suppress the viral load. There was no significant difference in baseline characteristics between people who achieved viral load suppression and those who did not. In addition, males, with a low CD4 and opportunistic illnesses when in the primary disease stages were more likely to fail to suppress the viral load. Moreover, people who were initiated on a 3-pill containing treatment and do not have social support were also likely to fail to achieve viral load suppression. Although the study showed a trend of likelihood towards failure to achieve viral load suppression, the estimates were not statistically significant. Theoretical arguments from this study suggest that failure to achieve viral load was attributed to poor adherence to treatment. This is supported by the logic that underpins the theory of change, in which the assumption of adherence was possibly violated. However, the results chain framework highlighted that the implementation of the intervention was effective as it led to good outcomes and an effective intervention. Drawing all this together, the study highlights the need for intensified adherence counseling during treatment in order to improve the performance of the intervention. Author: Ramatsobane Johanna Ledwaba, Thesis Title: Outcomes of the antiretroviral treatment intervention in Mankweng, Johannesburg, March 2016 / GR2018