PhD, Faculty of Health Sciences, University of the Witwatersrand / The aim of the study was to explore the practice of antiretroviral (ARV) therapy services, specifically regarding the patients’ issues and experiences, as well as the experiences of the health care providers rendering these services. Qualitative research methods were used, including a metasynthesis of qualitative research articles on human immunodeficiency virus (HIV) positive patients on ARV therapy, and phenomenological methods of inquiry. The study objectives were to conduct a metasynthesis of qualitative research on HIV-positive people on ARV therapy; to investigate the experiences of HIV-positive people who are on ARV therapy; to identify the constraints faced by HIV-positive people receiving ARV therapy; and to explore adherence to ARV therapy. The study was conducted in eThekwini district in KwaZulu Natal (KZN) province. The district was chosen considering the number of clinics rolling out ARV therapy. Three institutions initiating ARV therapy participated in the study; one urban, one semi-urban and one rural clinic, to ensure representation of each type. Participants were recruited from two initiating hospitals and one Community Health Centre providing ARV therapy. The metasynthesis revealed a shared set of four themes viz.: 1. Acceptance of, and coping with, HIV positive status 2. Social support and disclosure 3. Experiences and beliefs about HIV medication and health care 4. Provider relationships and health system factors Qualitative analyses of interviews with clients indicated their experiences and concerns, and were summarized in these themes: 1. Life before and after knowing HIV status 2. Initiating and continuing ARV therapy 3. Adherence to, and side effects of, the ARV therapy treatment 4. Social support for people on ARV treatment vi 5. Positive outcomes of being on ARV treatment 6. Improving access to ARV treatment services Analyses of in-depth interviews with health care providers specified their experiences, and were categorized into three themes viz.: 1. Establishing and maintaining a good client-provider relationship 2. Facilitators of and adherence to ARV treatment 3. Barriers to access to treatment

Background: Antiretroviral drug resistance is steadily growing in populations of HIV treatment-naive individuals due to person-to-person transmission. However, Iowa-specific data for transmitted antiretroviral drug resistance-associated mutations prevalence has not been previously reported. We postulate that the prevalence of drug resistance in Iowa does not differ significantly between HIV risk groups. Methods: Data were collected from electronic medical records and an HIV Program database between 2006 and 2011. Information included age, gender, risk exposure group, viral load, CD4 count, CD4%, and other HIV risk factors and behaviors. Results: Transmitted drug resistance mutations (TDRM) were not associated with many risk factors, but rapid plasma reagin (RPR) screening for syphilis was significant (p=0.02) and used as a proxy for highest level of sexual risk behavior. RPR was used with minor NRTI and NNRTI along with intravenous drug use in logistic regression to model the likelihood of acquiring TDRM. Conclusion: Some question the practicality of implementing genotypic ARV resistance testing guidelines because of uncertainty about the prevalence of ARV drug resistance among treatment-naïve patients but harboring resistance mutations puts patients at high risk of failing effective, first-line therapies. Hence, genotypic resistance testing at HIV diagnoses can not only improve disease management but also assist in surveillance.

Background: Adherence to antiretroviral (ARV) medications in excess of 90-95% is necessary for optimal response to suppress HIV replication and to maintain and/or restore immune function. A number of interventions have been shown to improve ARV adherence, but no research has been conducted which evaluates proactive monitoring of pharmacy refill adherence and subsequent intervention when inadequate adherence is identified. Purpose: The purpose of this project was to compare treatment response, pharmacy refill adherence and self-reported medication adherence between two groups of patients: those participating in an AIDS Drug Assistance Program (ADAP) and those participating in a Medicaid-funded medication access program. The ADAP served as a structured adherence intervention (SAI) based on procedural and administrative processes required by the state-managed program Additionally, covariates that can impact adherence were studied including utilization of adherence services and interventions and factors related to HIV disease, antiretroviral agents and sociodemographic factors. Method: This retrospective comparative study examined secondary data to assess 424 patients who received clinical and pharmacy services at one treatment site in 2005. Analysis: Logistic regression was performed to test the effects of the SAI on treatment response (CD4 and HIV RNA response), self-reported adherence, and pharmacy refill adherence while controlling for the covariates. Results: Patients participating in the SAI demonstrated higher levels of both self-reported and pharmacy refill adherence compared to patients receiving usual care. Although patients participating in the SAI program demonstrated better virologic (HIV RNA) responses to HAART compared to patients receiving usual care, immunologic (CD4 lymphocyte) responses to HAART were not significantly different compared to subjects in the usual care program. Conclusion/Discussion: This study provides information on the effects of a structured programmatic intervention on medication adherence and response to treatment and will be used to inform policy decision making at the local and State level.

HIV-associated lipodystrophy (HIVLD) syndrome is a condition comprising abnormalities in distribution of body fat and metabolism of lipids and glucose that arises in HIV-infected patients on long-term antiretroviral therapy. This thesis describes clinical research into aspects of the natural history and treatment of HIVLD, as well as molecular research into its pathogenesis centred on subcutaneous adipose tissue. Results demonstrate HIVLD to be a treatment-induced syndrome characterised by initial gains in body fat followed by selective, progressive loss of limb fat. Exposure to thymidineanalogue nucleoside reverse transcriptase inhibitors (tNRTI) induces lipoatrophy through mitochondrial dysfunction of which inhibition of mitochondrial RNA expression, rather than mitochondrial DNA depletion, is an early feature. Mitochondrial dysfunction is associated with decreases in expression of peroxisome proliferatoractivated receptor gamma (PPAR??), an adipocyte transcription factor, which helps explain how tNRTI exposure leads to the loss of adipocyte function. Once established, lipoatrophy is characterised by mitochondrial DNA depletion, although this depletion occurs throughout the mitochondrial genome, suggesting an underlying cause other than inhibition of DNA polymerase gamma. HIVLD is a difficult syndrome to treat. Lipoatrophy is resistant to treatment with rosiglitazone, an agonist of PPAR??, which is ineffective in the setting of ongoing tNRTI therapy and mitochondrial dysfunction. Dyslipidaemia is also difficult to treat as use of pravastatin in the setting of ongoing exposure to protease inhibitors results in only modest declines in fasting cholesterol concentrations. Gains in central fat, such as that seen in patients with buffalo hump, are associated with insulin resistance and diabetes, but only occur in a relatively small percentage of treated patients, suggesting a role for genetic factors in its development. Use of strategies such as avoidance of tNRTI in firstline ART, genetic screening to identify those at risk of toxicities and targeted selection of interventions in subgroups of affected patients, may help prevent this syndrome occurring and better treat those patients in which it has already occurred.

Amendments appended. / Bibliography: leaves 140-165. / xi, 165 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Microbiology and Immunology, 2005

Thesis (MCur. (Faculty of Health Sciences))--University of Pretoria, 2006. / Summary in English. Includes bibliographical references.

Background: Aboriginals are overrepresented in Canada’s HIV epidemic and are more likely to be infected with HIV through injection drug use (IDU) than non-Aboriginals. However, little research has investigated the outcomes of combination antiretroviral therapy (cART) among Aboriginal HIV-patients or compared outcomes between Aboriginal and non-Aboriginal HIV-patients. Objectives: The primary objectives of this research were to 1) compare all-cause and HIV-related mortality rates between Aboriginal and non-Aboriginal HIV-patients after they start cART, 2) determine if Aboriginal patients were less likely to achieve virological suppression and more likely to experience subsequent treatment failure after starting cART; 3) describe and compare the health-related quality of life (HRQL) of Aboriginal and non-Aboriginal HIV-patients; and 4) describe the life stability of Aboriginal and IDU HIV-patients treated with cART and explore associations between life stability, clinical status, and HRQL. Methods: This research was conducted in northern Alberta, Canada using a clinical database, vital statistics data, and data collected through interview and a self-administered HRQL questionnaire. Data analyses included multivariable Cox proportional hazards models and multiple linear and logistic regression models. Results: After starting cART, Aboriginals suffer higher rates of all-cause and HIV-related mortality than non-Aboriginals. Furthermore, Aboriginals are less likely to achieve virological suppression after starting cART and, among those who achieve suppression, Aboriginals experience higher rates of virological failure ≥1 year after suppression. Aboriginal IDUs, Aboriginal non-IDUs, and non-Aboriginal IDUs reported similarly worse physical HRQL compared to non-Aboriginals non-IDUs. Among Aboriginals and IDUs, factors significantly associated with poor clinical status were unemployment, lower income, not completing high school, homelessness, and perceiving that one’s current life was not much better compared to before starting cART. Similarly, factors significantly associated with lower HRQL in this group were unemployment, perceiving that one’s current health or one’s current life was not much better compared to before starting cART, and having a current CD4 cell count ≤350 cells/μL. Conclusions: Overall, after starting cART, Aboriginal HIV-patients suffer worse outcomes than non-Aboriginal HIV-patients. Future research should investigate adherence among Aboriginals and IDUs treated with cART and explore their treatment experiences to develop interventions to improve the prognosis of these vulnerable populations.

The overall goals of this project were to develop microstructurally based constitutive models to characterize the mechanical behavior of arteries and to investigate the effects of HIV proteins and antiretroviral drugs on the microstructure and mechanical behavior. To this end we created several constitutive models in aim 1 using a rule of mixtures approach, investigated the role of viral proteins in aim 2 through the use a transgenic mouse model, and studied the effects of the antiretroviral drug AZT administered to mice in aim 3. It is well known that the local mechanical environment which cells experience mediates growth and remodeling and that subsequent growth and remodeling can change that mechanical environment. This remodeling includes changes in the content and organization of the constituents of arteries (collagen, elastin, and smooth muscle cells). The first aim thus created models that incorporated the content and organization of these constituents using a rule-of-mixtures approach. The models we developed were able to capture the mechanical behavior of the arteries as well as previously developed phenomenological models while providing more physical meaning to the parameters, some which can be measured experimentally for incorporation into future models. Aims 2 and 3 investigated the mechanical and microstructural changes to murine arteries in response to HIV proteins or the drug AZT. While the development of antiretroviral therapy has greatly increased the life expectancy of patients with HIV, a number of other complications and co-morbidities including cardiovascular disease have become apparent. While clinical data has implicated both the virus and the antiretroviral drugs as playing roles, this work addressed the need of investigating these effects in a controlled manner. Specifically we used mouse models and focused on the two subclinical markers of increased intima-media thickness and arterial stiffening. Aim 2 used a transgenic mouse that expressed most of the human HIV proteins. We observed both intima-media thickening and arterial stiffening in alignment with clinical data. Other changes that also support a proatherogenic phenotype included decreased elastin content and changes in cathepsin activity. Aim 3 administered the antiretroviral drug AZT to healthy mice and we also observed the same subclinical markers of atherosclerosis including intima-media thickening and arterial stiffening as well as the other proatherogenic changes of decreased elastin and changes in cathepsin activity. Several other parameters including axial behavior, opening angles, collagen content, and collagen fiber angles were also quantified. These were important to fully characterize the vessel and may also be incorporated in the future into the constitutive models developed in aim1. In conclusion, in aim 1 we developed a microstructurally based constitutive model of arteries that effectively captures the mechanical behavior and includes parameters that have more physical meaning and some of which are experimentally tractable. Aims 2 and 3 both observed several subclinical markers of atherosclerosis in mice that express HIV proteins or were given AZT, providing a good model for future work and suggesting that both the HIV virus and antiretroviral drugs may play roles in the development of atherosclerosis in HIV.

The study of identity based on the presence of disease has traditionally focused on landmark events, such as diagnosis or the introduction of treatment options. These events have been shown to significantly alter so-called “illness identities.” The project was undertaken in Atlanta, GA, which has a relatively high rate of HIV infection and a large number of HIV-related services and support mechanisms. This study contextualizes illness identities within a larger socio-political and economic paradigm, recognizing that individuals use multiple identities to inform their interactions and decisions, specifically those regarding the beginning and continuation of antiretroviral (ARV) treatment. In addition, structural barriers which limit one’s access to ARV treatment are considered within a context of social and economic marginalization and inequitable power relationships within a post-industrial Western society.

AIM The aim was to explore the experiences of HIV-positive individuals before and after gaining access to antiretroviral therapy in Wakiso District, Uganda and how antiretroviral therapy impacts certain aspects of those living with HIV, such as sexual behavior, support systems, faith and personal identity. METHODS Based on secondary data analysis of “Life On Antiretroviral Therapy: People’s Adaptive Coping And Adjustment To Living With HIV As A Chronic Condition In Wakiso District, Uganda” by Steven Russell (2015). The data was reanalysed using the conceptual framework from Bronfenbrenner’s ecological systems model. RESULTS Six main themes will be presented including personal life after HIV diagnosis, acceptance of HIV status, disclosure of identity, changes in sexual behavior, different types of support systems, and increasing faith and strength from God. After receiving antiretroviral therapy, the quality of life seemed to improve for some of the participants. Participants described their experiences living with HIV/AIDS, such changes in personal goals and perception of self, immediate acceptance of positive HIV results, disclosure of identity to certain people, the different types of support offered from each support system they have, abstaining from sex and the use of contraceptives against future transmission. Furthermore, participants have also described an increase of faith and belief in God in order to cope with HIV/AIDS. CONCLUSION People living with HIV in Wakiso District, Uganda have described significant changes in their lives after receiving antiretroviral therapy. These changes affect them both physically and emotionally therefore more research must be done to investigate the influence of antiretroviral therapy on wellbeing.