Thesis (MPH.) -- University of Limpopo, 2015 / Purpose / Aim: To find out determinants affecting adherence to antiretroviral therapy in patients receiving free treatment from the wellness clinic at Bela Bela District Hospital in Limpopo province of South Africa. Objectives: To identify the determinants which affect the adherence to ART treatment among patients living with HIV and AIDS and to determine which of these determinants are significant predictors of adherence among HIV and AIDS patients. Methodology: a descriptive retrospective, quantitative research. Sampling: A population of 800 patients existing in the recording book was retrieved from the patients’ records at the wellness clinic. Out of 800 a sample of 260 was derived using a simple size calculator tool. Analysis: data were analysed by SPSS Windows Version 21.0. Descriptive statistics means and frequencies were calculated. Chi-Square tests were done in order to test the association between variables (such as age groups, gender, weight groups, regimens and WHO stages). Logistic regression was run to assess the effect of different determinants on the adherence to ART (e.g. viral load affected the adherence contrary to age, gender and others). Results: Female (65%) was more compliant to their male counterpart (35%). Most of the patients (47.3%) in the study belonged to the age group 21 to 35 years and only (2.7%) in the age group less or equal to 20 years. Most patients were categorised into WHO stage I (31.2%). Only 9.2% of the patients were categorised into WHO Stage IV. Most of the patients in group 2 (41.3%) had a weight between 40kgs and 54kgs and group 1 (4.2%) with patients whose weight was less than 40kgs. One of the patients has no record on weight. The majority of patients (44.2%) had CD4 count, less or equal to 100. Only 2.7% had CD4 count 300 and more. After 6 months of treatment, 37% of patients had CD4 count from 300 and above; 9.7% of the patients had CD4 countless than 200. For 136 (52.3%) of the patients in the sample the information on CD4 count at 6 xi months was missing. The majority of patients (72.7%) in the sample had low viral load and only (27.3%) of the patients had high viral load. Majority of patients (48.5%) were on New 1a Regimen instead of Regimen 1a (30.8%) because of the side effects the latter has on them. Some patients (11.2%) were on Regimen 1b, followed by patients (8.1%) on Regimen New 1b. The remaining patients were on Regimen 1c, Reg 2 and Truvada (1.6%). Findings: The majority of patients were young females; in the age-group of 21-35 years. This is reproductive age with many challenges: earlier exposed to infection, more vulnerable than males, stigmatisation, rape, fear of isolation. Majority of patients were in the WHO stage 1 and 2. The WHO stage does not depend on the level of CD4 count. It is important to consider the weight of the patient before to initiate the treatment. More than the half patients had a CD4 count required to start with ART. After 6 months they were more adherent. Most of them were on regimen Reg (New 1a) because of less side effects. The findings showed also different types of associations with some variables were significant determinants such as CD4 count had significant associations with gender, viral load, regimen, WHO staging, the p-value was lesser than 0.05. Conclusion: The results showed that viral load was the only determinant affecting adherence in the current study. The number of males in this study population was lower than females from the age group of less than 20 and age group of 21 to 35, and females than males in age group 36 to 50 and 51 or more. The lower infectivity of males is linked to the state of denial and not testing for HIV. The lower number in females can be due to their positive trends to the ART in their old age. The reasons for the low number need to be investigated. Awareness campaigns should be intentioned towards males. There should be publicity about the equality of both male and female genders.

Includes bibliographical references / Over the past decade, antiretroviral therapy (ART) programmes have rapidly expanded in resource-limited settings. Access to ART has been accelerated through a public health approach to reduce morbidity and mortality, thereby transforming HIV from a humanitarian crisis to a chronic disease. However, the benefits of ART to patients and communities are dependent on patients being retained in care. This thesis investigates loss to follow-up (LTFU) after ART initiation, in the context of scale-up and limited resources and evaluates models of ART delivery to improve retention. After a brief introduction that offers orientation to the key issues and concepts in the field, Chapter 2 provides a comprehensive literature review discussing the public health concerns related to LTFU in ART programmes, as well as the methodological concerns encountered in studying LTFU. Six results chapters (Chapters 3-8) are presented using complementary cohort data from two collaborative datasets (one from programmes in resource-limited settings and one including only South African cohorts) and from a single ART programme at a community health centre. How to define LTFU is the focus of Chapter 3, demonstrating that definitions can have an appreciable impact on estimates of LTFU. In Chapter 4, temporal factors related to the expansion of ART programmes are investigated, with evidence that the risk of patient LTFU increases with each successive calendar year of ART initiation, and that the rate of programme expansion has a stronger association with the risk of LTFU than absolute programme size. Analyses in Chapter 5 suggest that patients initiating ART at higher CD4 cell counts, above 300 cells/μl, may have an increased risk of LTFU compared to patients initiating ART with lower CD4 cell counts. Taken together, these findings underscore the notion that LTFU is a burgeoning threat to the long-term successes of ART programmes in South Africa and other resource-limited settings. Chapters 6-8 report on the implementation and outcomes from innovative models of ART delivery for stable ART patients. Patient outcomes from (i) a nurse-managed ART service and then (ii) community-based 'Adherence Clubs' highlight that comparable and, in some cases, favourable patient outcomes may be achieved when ART delivery is decentralised. This thesis concludes that LTFU is a significant challenge faced by ART programmes. In the context of ambitious targets and evidence of the potential benefits of ART for individuals and communities, concurrent changes to the health system are necessary to support retention in care. The successes of ART programmes in treating a chronic condition in resource-limited settings can be built upon by expanding community-based ART provision and potentially integrating management of other adulthood illnesses.

Magister Public Health - MPH / Despite the known benefits of adolescents knowing their HIV status, parents and caregivers (PCG) often delay the disclosure of their children’s HIV status to them due to the fear of stigma and discrimination, the belief that the child thinks they will die, and the lack of disclosure skills. This delay can affect the children’s adherence to treatment, physical health, mental health and can enable unknowing transmission. The Mini Flipster Disclosure Method (MFDM) was developed to assist healthcare workers (HCWs) in supporting the disclosure of an adolescent’s HIV status by their parent or caregiver. This involves a process of educating the child or adolescent about HIV and how it can be successfully managed before informing them that they have HIV. The current study described the experiences of HIV-positive adolescents of the MFDM and those of their caregivers and HCWs in Mpumalanga.

This study sought to appreciate the influence of antiretroviral medications on the daily lives of children in Botswana. The aim of the study was to explore and gain in-depth understanding of the influence that antiretroviral medications have on the children’s lives. The study focused on children receiving services from the Bamalete Lutheran Hospital in Ramotswa, Botswana. It is important to give children an opportunity to have their voices heard as not doing so might present missed opportunities for the various care and support services providers. The study was qualitative as it sought to come closer to the individual children and get their own personal perspective of the influence of medication on their lives. The phenomenological strategy was applied to derive the description from each participant. Although the study was mainly applied as hoping to add a dimension of the meaning of antiretroviral medication from the children’s perspective which would facilitate improvements on service delivery; it can also be seen to contribute toward the body of knowledge as there are limited literature resources in this area. The sampling method used in this study was purposive in order to ensure a variety of responses and an enriched understanding of how the participants perceived the influence of these medications. A few broad areas of discussion were developed to facilitate the one-to-one unstructured interview. The conclusion from this study is that children do have stories to share in terms of how they perceive the influence of antiretroviral medications in their lives. These stories need to be explored and understood to facilitate better targeted care and support services for them. The stories from the sixteen children interviewed in this study are herein reported as well as the conclusions and recommendations that followed them. The general theme from listening to the stories of the children is that children understand that they have to take the medications and that it helps to improve their health. / Dissertation (MSW)--University of Pretoria, 2010. / Social Work and Criminology / unrestricted

The era of the integrase strand transfer inhibitors (INSTIs) for the treatment of human immunodeficiency virus (HIV) infection began with raltegravir in 2007. Since that time, several other INSTIs have been introduced including elvitegravir, dolutegravir, and, most recently, bictegravir, that have shown great utility as part of antiretroviral regimens in both treatment-naive and treatment-experienced patients. At present, antiretroviral guidelines fully endorse the INSTI class as part of all first-line treatment regimens. After 10 years of experience with INSTIs, newer agents are on the horizon such as cabotegravir and MK-2048 for potential use as either HIV pre-exposure prophylaxis or maintenance therapy. This review provides a brief overview of the INSTI class including agents currently available and those still in development, reviews available data from both completed and ongoing clinical trials, and outlines simplification strategies using INSTIs.

Abstract Human Immunodeficiency Virus (HIV), a chronic medical condition characterized by cycles of wellness and illness, has the potential to decrease the physical activity levels and functional independence of infected individuals. Although antiretroviral therapy has been credited with improving and maintaining the immune status of infected patients by increasing cluster of differention 4 (CD4) count and suppressing viral load, the short- and long-term side effects of antiretroviral medication and the possible negative impact of these side effects on physical well-being have not yet been fully investigated. Therefore, I assessed the relationship between CD4 count, habitual physical activity levels and functional independence in a group of HIV positive South African adults either taking or not taking antiretroviral medication. I also compared the aerobic capacity, muscle strength and physical activity levels (activity counts) of age-matched black HIV negative females and HIV positive females who were taking antiretroviral medication. For the first part of the study, a Lifestyle and Physical Activity Questionnaire was completed by 186 black* male and female HIV positive outpatients who were recruited from a Johannesburg based antiretroviral roll out site. Of these patients, 121 were on first line antiretroviral treatment (median time of seven months), and 65 patients were not taking any medication. The questionnaire, as well as recording HIV history and current CD4 count, assessed each patient’s ability to independently perform one or more tasks of daily living as well as his/her monthly occupational, household and recreational physical activity levels. From the subjects’ responses, a total metabolic equivalent (MET) score for one month was calculated. The second part of the study assessed the full blood counts, aerobic capacity (submaximal bicycle ergometer test), lower limb strength (isokinetic dynamometry), hand grip strength (hand dynamometer) and seven day physical activity counts (actigraphy) of ten HIV positive black females recruited from the same Johannesburg antiretroviral roll out site. All of these patients had been taking first line antiretroviral treatment for a median time period of seven months. Ten HIV negative age-matched black females acted as their controls. From the questionnaire, significant correlations were observed between CD4 count and length of time on antiretroviral medication (P < 0.0001; r = 0.45), and between CD4 count and total monthly physical activity level (P = 0.0067; r = 0.20). Patients who considered themselves functionally independent had a significantly higher CD4 count that those patients who required help from others (P = 0.0031). The second part of the study revealed no significant difference in aerobic capacity, lower limb muscle strength (peak torque), handgrip strength and seven day physical activity counts between the female HIV positive patients and HIV negative controls. My results show that the use of antiretroviral medication (median time of seven months) increases CD4 count which translates into an increased habitual physical activity level and greater sense of functional independence. I have also shown that HIV positive females who are taking antiretroviral medication have an aerobic capacity, leg strength, handgrip strength and physical activity count which is not statistically different to their HIV negative counterparts. In this sample, the side effects associated with the administration of antiretroviral medication did not negatively impact on physical well-being. However, more research needs to be conducted on the possible physical activity limiting side effects of longer term antiretroviral medication administration, which may limit habitual physical activity levels. * Footnote: Race does not refer to any biological attributes but rather to the compulsory classification of people into the Population Registration Act. Although the act has been amended, these categories are still powerful and commonly used by the South African Government and statistical services.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, in partial fulfillment for the degree Masters of Medicine in Paediatrics (MMed) Johannesburg 2012 / Introduction: Highly active antiretroviral treatment (HAART) programs in heavily HIV-TB burdened countries may reduce the risk of TB in children directly by improving the immune system of HIV-infected children; and indirectly by reducing the force of transmission from the adult population. The incidence of childhood TB is a sentinel measure of the control of infectious adult TB cases in the community. Objective: We evaluated the impact that scaling-up of the HAART program in Soweto had on the incidence of hospitalization for culture-confirmed TB in children. Methods: The study was undertaken in Soweto, where the prevalence of HIV was 4-5% in children between 2005 and 2009. The estimated HAART coverage increased from 43% in 2005 to 84% by 2009 in children with HIV/AIDS. Hospitalized cases of culture-confirmed TB in children 3 months to 14 years of age were identified through laboratory and clinical electronic databases. Results: Overall, the incidence (per 100 000) of hospitalization for culture-confirmed TB declined by 58% (95%CI 49.3-65.2) from 2005 (71.4) compared to 2008-9 (30.0); p<0.0001. This included a 67% (95%CI 58.5-74.8) reduction in incidence among HIV-infected children from 2005 (1 601) compared to 2008-9 (517; p<0.0001). v In addition, a 33% reduction was observed in HIV-uninfected children (incidence 19.3 vs 12.9; p=0.016). Fifty-six percent of TB episodes, across all study periods, occurred in HIV-infected children who were mainly (76%) severely immunocompromised. Conclusions: Up-scaling of the HAART program in South Africa has been associated with decline in the incidence of culture-confirmed TB, more so in HIV-infected than HIV-uninfected children. Severely immunocompromised HIV-infected children, however, need to be identified and targeted with HAART and other strategies to further reduce the burden of TB in this group.

Thesis (M.Sc. in Epidemiology)--University of the Witwatersrand, Faculty of Health Sciences, 2014. / Introduction: The prevalence of the Human Immunodeficiency Virus (HIV) in South Africa was 17.8% among 15 to 49 year olds in 2010. Antiretroviral therapy (ART) has thus played a crucial role in mitigating the impact of the HIV epidemic. Themba Lethu Clinic is one of the largest single clinics providing ART in South Africa. One of the challenges of ART provision is ensuring adherence to taking the medication. To date there has been no clear consensus on the ideal way to measure adherence in resource limited settings (RLS). Viral load is perhaps the best and most reliable indicator of poor adherence but is expensive and not easily accessible or available in many RLS. Surrogate markers such as mean cell volume (MCV), CD4 cell count, self-reported adherence and missed visits have been shown to be useful to measure adherence but their reliability remains unclear. The aim of the study was to identify other markers that can be used to measure adherence using viral load as the gold standard. Materials and methods: The study was a retrospective analysis of HIV-positive ART-naïve adults (≥ 18 years) initiating standard first-line ART at the Themba Lethu Clinic in Johannesburg, South Africa between April 2004 and January 2012. The association between the last self-reported adherence, change in MCV calculated from baseline to 6 months, change in CD4 count calculated from baseline to 6 months (≥ or < the expected increase of 50 cells/mm3 at 6 months) and missed visits (defined as a scheduled appointment that had been missed by ≥ 7 days but not by more than 3 months) and poor adherence (defined as a viral load ≥ 400copies/ml after 6 months on ART) was tested using Poisson regression models with robust error variance to estimate incidence rate ratio (IRR) and 95% confidence interval (CI). The IRR was used to approximate the relative risk (RR) of poor adherence. Interacting variables were stratified by each other, to create a new variable. The diagnostic accuracy of each identified marker of adherence was also tested using sensitivity, specificity, positive predictive values and negative predictive values. Results: 7160 patients were eligible for the study and of these 63.2% were female. The median age was 36.7 years. The median CD4 count was 101 cells/mm3 at baseline and 18.9% of the patients had poor adherence at 6 months. Variables associated with poor adherence at 6 months were change in CD4 count stratified by change in MCV at 6 months (change in CD4 count ≥ expected and change in MCV ≥ 14.5fL; adjusted relative risk (aRR) 1, change in CD4 count ≥ expected and change in MCV < 14.5fL; aRR 3.11 95% CI 2.41 – 4.02, change in CD4 < expected and change in MCV ≥ 14.5fL; aRR 1.23 95% CI 0.76 – 2.00 and change in CD4 count < expected and change in MCV < 14.5fL; aRR 6.98 95% CI 5.35 – 9.09), CD4 count at baseline (> 200 cells/mm3; aRR 1, 101 – 200 cells/mm3; aRR 1.05 95% CI 0.80 – 1.38, 51 – 100 cells/mm3; aRR 1.08 95% CI 0.80 – 1.47 and ≤ 50cells/mm3; aRR 1.34 95% CI 1.02 – 1.76) , WHO stage at baseline (stage I; aRR 1, stage II; aRR 1.16 95% CI 0.90 – 1.48, stage III; aRR 1.27 95% CI 1.04 – 1.55 and stage IV; aRR 1.44 95% CI 1.12 – 1.84) and MCV at baseline (< 80fL; aRR 1, 80 – 100fL; aRR 1.33 95% CI 1.01 – 1.75 and > 100fL aRR 0.98 95% CI 0.62 – 1.55). Sensitivity and specificity of the change in CD4 stratified by change in MCV at 6 months to predict poor adherence were 86.5% and 37.3% respectively for all eligible patients. For patients on AZT-based regimens the variables associated with poor adherence at 6 months were change in CD4 count at 6 months (≥ expected; aRR 1 and < expected; aRR 7.66 95% CI 0.98 – 59.91) and pregnancy during the first 6 months on ART (Never pregnant; aRR 1 and pregnant during follow up; aRR 9.11 95% CI 2.17 – 38.25). Sensitivity and specificity of the change in CD4 count at 6 months to predict poor adherence were 64.7% and 75.2% respectively for all eligible patients on AZT-based regimens. Sensitivity and specificity of pregnancy during the first 6 months on ART to predict poor adherence were 20% and 97.6% respectively for all eligible patients on AZT-based regimens. Discussion: Change in CD4 count stratified by change in MCV at 6 months was an expected marker of adherence as CD4 count is expected to rise in adherent patients on ART and since most patients (62.9%) were on d4T or AZT-based regimens. Pregnancy during the first 6 months on ART appeared as a marker of adherence for patients on AZT-based regimens before multiple imputation possibly due to missing data hence results for this variable should be interpreted with caution. Contrary to previous studies, self-reported adherence was not associated with poor adherence at 6 months before multiple imputation. This could have been due to the fact that that > 50% of patients had missing data for this variable. The variable is also vulnerable to recall and reporting bias so even after multiple imputation, the area under the receiver operating characteristic (ROC) curve remained < 0.55. The number of missed medical visits and regimen change were also markers of adherence in a few of the models after multiple imputation and require further investigation. In conclusion, the markers of adherence to ART are change in CD4 count stratified by change in MCV at 6 months and pregnancy during the first 6 months on ART for patients on AZT-based regimens. These could help health workers identify poor adherence in the absence of viral load testing and target patients for adherence interventions to prevent virological failure.

Introduction: Improvements in early detection of human immunodeficiency virus (HIV), linkage to treatment, and availability of antiretroviral therapy (ART) have contributed to increasing life expectancy for people living with HIV (PLHIV) in South Africa. These improvements have resulted in the decline of HIV cause-specific mortalities. In addition to existing tuberculosis burden in PLHIV, cases of chronic non-communicable diseases (NCDs) are increasing in the general population. Considering the ageing population of PLHIV in South Africa, it is important to understand their health needs, as well as identify potential drivers of comorbidities that may provide avenues for future interventions. This study aimed at exploring HIV and comorbidity profiles in a virtual cohort of a population of healthcare clients accessing care in public facilities in Khayelitsha, Cape Town. Methods: Routinely collected data for healthcare clients accessing care in public facilities in 2016/17 were obtained from the Western Cape Provincial Health Data Centre, and analysed to describe ascertained comorbidities, comparing the profiles of PLHIV and HIV-negative individuals. The risks of comorbidity occurrence in PLHIV, in the context of other comorbidities and HIV metrics such as ART duration, viral load and CD4 cell counts, including the contribution of comorbidities to unsuppressed viral load levels in PLHIV were explored. Findings: The findings show that accessing HIV care may lead to earlier ascertainment of common chronic NCDs – hypertension, diabetes, chronic kidney disease (CKD), cervical cancer in PLHIV, compared to HIV-negative clients. Analysis of routine health data suggests that ascertainment of comorbidities differs for healthcare clients due to sub-population differences including age, sex, HIV status and reasons for accessing care. Routine laboratory testing results for renal function reflect distinct healthcare experiences by age for healthcare clients with and without HIV. Analysis of routine data shows that presence of an existing comorbidity may contribute to the incidence of other comorbidities and unsuppressed viral load levels in PLHIV. Conclusion: From real life routine health data, this study has explored comorbidities profiles of PLHIV and HIV-negative clients and observed that routine health data could provide a better understanding of disease profiles, healthcare access and requirements for both PLHIV and HIV-negative clients.

Cardiovascular diseases (CVDs) are the leading causes of death globally. Recent studies show that CVDs are one of the major causes of morbidity and mortality in people living with HIV/AIDS (PLWHA). HIV symptoms arise as our body tries to fight off the virus but as our immune system weakens as CD4 T cells are targeted. As these T cells diminish in quantity, it leaves the body susceptible to other infections, which is why ARV drug treatment is used. NRTIs are common drug treatments for these viruses as they inhibit the enzyme reverse transcriptase. Unfortunately, these NRTIs are known to cause dilated cardiomyopathy, while protease inhibitors are known to cause increased cardiovascular mortality and heart failure. Treatment of these side effects is crucial since millions of people are on these ARV drug treatments. Therefore, we analyzed RNA sequencing data of neonatal ventricular cardiomyocytes treated with ARV's to determine the regulatory pathway of upregulated/downregulated genes associated with the ARV treatment. It was seen that many of the upregulated genes such as PSEN and PSENEN2 were mitophagy control genes, and most of the downregulated genes were from complexes I-IV of the oxidative phosphorylation chain. Based on the genomic data, we hypothesized that increasing the expression of these downregulated genes could potentially reduce mitochondrial dysfunction and bring back the functionality of the complexes. Research has shown that rapamycin treatment can potentially reduce the effects of mitochondrial dysfunction, and tests were conducted to see how much expression changed. Another indicator of mitochondrial dysfunction is the detection of ROS, and this project aims to see how rapamycin will affect the presence of these ROS.