Background: The government of South Africa rolled out free anti-retroviral treatment in 2004 but many people living with HIV still present late for treatment while others choose to die rather than accessing this free treatment. This qualitative study was done at Potchefstroom Provincial Hospital Wellness Clinic to establish why many people living with HIV in Potchefstroom present late for treatment. Aim: To establish why people living with HIV/AIDS in Potchefstroom delay in accessing antiretroviral therapy. Objectives: 1.To conduct interviews with selected patients, in order to understand why they delayed accessing antiretroviral treatment. 2. To assess the demographics of patients who delayed in accessing antiretroviral treatment. Methods: This is a qualitative study carried out at the Wellness clinic of the Potchefstroom provincial hospital in the North West province of South Africa. Eight adult participants (3 females and 5 males) were interviewed individually in English, in one-on-one free attitude interviews and the conversations were audio-taped by the researcher. All the respondents were from the nearby black township of Ikageng. The respondents were selected after meeting the inclusion criteria of the study. The researcher asked the respondents to freely describe the reasons why they started antiretroviral treatment late. In addition, a semi-structured open ended questionnaire was also used by the researcher to prompt responses. Interviews went on until saturation point was reached. The audio-taped interviews were transcribed verbatim and the responses were analyzed. Responses from the different participants which bore similarity were assigned a similar color code. By using the cut and paste method, all responses bearing the same color code were pasted on one page resulting into the themes. Results: Four broad themes emerged as the reasons responsible for the late accessing of ART by the respondents. These themes were: 1. Stigma and discrimination, 2. Ignorance and lack of perceived risk of infection, 3. Denial, and 4. Health care system constraints. Conclusions: This small study though not exhaustive by any means, has highlighted some of the reasons why people living with HIV present late for help. The study was done using participants from only one peri-urban population. It is therefore not easy to generalize the results to the whole of South Africa, a country with a lot of social and economical diversities among its people. A bigger study over a wider geographical area might reveal different findings.

Research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, in partial fulfilment of the requirements for the degree MASTER OF MEDICINE (MMED.) (PAEDIATRICS AND CHILD HEALTH). Department of Paediatrics and Child Health Johannesburg, South Africa, 2012 / Cardiovascular disease is a common complication of advanced HIV disease in both paediatric and adult patient groups and may present with left ventricular (LV) dysfunction. Introduction of Highly Active Antiretroviral Therapy (HAART) has improved outcomes in patients presenting with LV dysfunction. However, mitochondrial toxicity, a complication of HAART, may present with myocardial dysfunction.

M.P.H., Faculty of Health Sciences, University of the Witwatersrand, 2011 / Background Few results are available concerning long-term clinical outcomes in ART treatment programs. The objective of this study was to describe clinical and laboratory outcomes for adult patients commenced on ART in Selebi Phikwe, Botswana from June 2004 to June 2005 within one year of commencement of ART. Methods Cross-sectional descriptive study of clinical and laboratory outcomes for 904 adult patients initiated on ART in Selebi Phikwe, Botswana, from June 2004 to June 2005. Data from ART services statistics was analyzed using descriptive statistical methods. Results Most patients had low a basal CD4 cellular count with a median count of 25 cells, which rose to 147 after 12 months of treatment. Of the 84 (9%) deaths, 75 (89%) had a basal CD4 count of less than 10 cells and 48 (57%) died within three months of commencing of ART Conclusion Good clinical and laboratory outcomes for patients on ART in resource limited are achievable. Mortality commonly occurs among patients with low CD4 counts and within three months of commencement of therapy.

M.Sc.(Med.), Epidemiology and Biostatistics, Faculty of Health Sciences, University of the Witwatersrand, 2011 / Background The therapeutic goal of HAART is sustained immune recovery and viral suppression. However some patients still have poor CD4 count responses despite achieving viral suppression. Such discordance immune response has been associated with poor clinical outcomes. We describe the prevalence of discordant immune response during the first 6-months of HAART and determine risk factors associated with this discordance at two large public sector clinics in South Africa. Methods We analysed data from 6 460 HIV-infected adults initiated onto first-line HAART at Goba and Phola Park clinics, in Johannesburg, South Africa between November 2008 and December 2009. Multivariable logistic regression models were used to estimate adjusted odds ratios (AOR) for associations between discordant immune response and clinical and demographic factors. Models were adjusted for WHO clinical stage, baseline CD4 count, education level and HAART regimen. Results At initiation of HAART, most patients were female 592(64.6%) and 803(87.6%) were initiated on 3TC-d4T-EFV/NVP. The mean CD4 count was 155 cells/mm3 (±118.4 sd), mean age was 38.5 years (±8.7 sd) and most patients had haemoglobin >11g/dL (n=645, 71.2%). By 6-months after initiation of HAART, 24% (n=220) of patients had a discordant immune response, 7% (n=67) discordant virologic 5 response and 21% (n=1359) had been lost to follow-up. In multivariable analysis, higher baseline CD4 cell count (CD4≥200cells/mm3): AOR=3.02; 95%CI 2.08-4.38; p<0.001) and moderate anemia (8-9.4 g/dL) at baseline (AOR=2.30; 95%CI 1.25-4.59; p=0.007) were the strongest predictive factors for development of discordant immune response. Conclusions We found a significant proportion of patients with discordant immune response 6-months after initiating HAART. Simple algorithms utilizing baseline characteristics can be developed for use in clinics in order to identify those patients at risk of development of discordant immune responses. Intensive monitoring of individuals at risk may improve clinical outcomes.

Background Potential causes of poor antiretroviral therapy (ART) treatment outcomes can be patient or health system related. Data on the effect of health system on ART outcomes is scarce. Objective: To compare treatment outcomes of HIV positive adults (≥18 years) initiating ART in either private or public HIV clinics in Johannesburg, South Africa. Methods: A retrospective cohort analysis was conducted on HIV positive, ART naïve adults initiating ART at a public (Themba Lethu Clinic) or private HIV clinic in Johannesburg between 01 January 2005 and 31 December 2011. Treatment outcomes included mortality, loss to follow up (LTFU; defined as >90 days since last scheduled visit date), failure to suppress viral load (>400copies/ml) at 6 and 12 months and absolute change in CD4 count from baseline until 6 and or 12 months after ART initiation. Survival analysis was performed using Kaplan Meir curves. Multivariate Cox proportional hazards models were used to assess predictors of mortality and LTFU. Generalized estimation equations were used to determine predictors of failure to suppress viral load while absolute change in CD4 count was analysed using the Wilcoxon rank sum test. Results: A total of 11690 patients initiated ART at the public clinic compared to 574 at the private clinic. Patients were similar in terms of age, gender and baseline viral load. Private clinic patients were less likely to die [aHR=0.39;95% CI 0.14-1.06] or to be retained on ART [aHR=1.59;95% CI 0.94-2.70], although both estimates lacked statistical significance. Public clinic patients presented with advanced HIV [WHO stage 3 or 4, p<0.001] compared to the private clinic. However, private clinic patients were 63% more likely to have a detectable viral load at 12 months of follow up [RR=1.63;95% CI 1.15-2.32]. There were no differences in the absolute CD4 changes between the private and public clinic at 6 months (median 99 IQR 43-78 vs. 103 IQR 52- 168; p=0.584) respectively. Conclusion: This study demonstrates that health systems have an influence on ART outcomes. The private sector is commended for early initiation of treatment and the availability of a variety of ARV drugs. However there is need for standardization of prescribing practices and care. Better virological responses amongst public patients can be attributed to better adherence to treatment and reduced LTFU rates compared to the private sector. Public-private partnerships are thus encouraged to address shortcomings of either sector.

M.P.H.,Faculty of Health Sciences, University of the Witwatersrand, 2011 / Introduction: Although the number of patients receiving ART is expanding nothing is really known about their adherence behaviours. Better outcomes with ART will not be achieved unless patients adhere to their treatments. It is also important to know and understand the factors that play a role in non-adherence so that the relevant interventions can be designed and implemented. Aim: The study aimed to determine adherence to ART in the clinic. By describing patient perceptions of their care, health care worker perception of challenges that they face in the clinic the study was aimed to determine the factors associated with non-adherence in the clinic as well. Materials and methods: A cross-sectional study of patients and health care workers at the Lerato clinic in Germiston Hospital. Adherence was accessed using pharmacy refill records and self-report. Both patients and health care workers were interviewed using questionnaires. The patient questionnaire had both closed and open-ended questions. Health care worker questionnaire accessed health care worker perceptions of the care that was given to patients. Triangulation produced a mixture of information that enabled not only cross- validation of the data, but minimised bias. Results: Ninety seven percent (97%) of the patients reported that they never missed their doses of medication. The adherence rate reported by pharmacy refill was 81% and the patients interviewed (n=67) had a mean age of 38.7 years and a median of ART use of 18 months. Both health care workers and patients were faced with challenges that impacted negatively on adherence. HCW’s faced workload, burnout, irregular debriefing, space constraints as well as irregular training while patients received the after effects of HCW challenges. These included among others waiting long in congested areas. Patients had financial constrains and hunger that were increased as a result of being on ART. Conclusion: Drug shortages, service availability and treatment costs did not affecting adherence to ART in the clinic. Strategies to maximise adherence in this situation should focus on meeting the needs of health care workers and patients. Special attention should be paid to addressing health care workers such as training, debriefing, the appointment system, defaulter system as well as fear of disclosure and discrimination.

Worldwide, an estimated 34 million people were living with HIV, but only 47% of the people in low- and middle-income countries eligible for antiretroviral therapy (ART) were receiving treatment at the end of 2010. The aim of this study was to investigate factors associated ART initiation as well as to determine ART uptake by age-group, gender and clinic catchment in a typical rural sub-Saharan African setting. Methods: Data from the Africa Centre 2010 population-based HIV surveillance (including C4 count measurement) was linked to the HIV treatment and care programme database. Those successfully initiating treatment (n=482) were then compared against those eligible for treatment but had not yet been initiated (n=117). The variables for analysis included gender, age, education level, employment status, number of individuals in the household, household asset index, distance of homestead from the nearest clinic, number of prior pregnancies and live births a woman ever had as well as the baseline CD4 count (at ART initiation and 2010 measurement for those not yet initiated). ART uptake by age-group, gender and across six clinic catchments was calculated using the population-based HIV surveillance from 2011 through linkage to the HIV treatment and care programme database. Results: Of the 1 308 HIV infected individuals who had CD4 count results, 599 were eligible for therapy based on a CD4 count criteria of <200 cells/mm3. Of these 80.5% (482/599) had initiated ART as of 31 October 2011. In the adjusted logistic regression model, males were 71% (OR = 0.29, p<0.001) less likely to have initiated therapy compared to females. Those in the 30 - 44 year age-group were 84% more likely to initiate therapy (OR =1.84, p=0.039) compared to those in the 15 - 29 year age-group. Individuals who had secondary and higher levels of education and those who lived far away (≥4 kilometres) from the nearest clinic were less likely to initiate ART (OR = 0.29, p = 0.001 and OR = 0.67, p = 0.337) compared to those with primary and lower levels of education and those who lived within 2 kilometres of the clinic respectively. Employed individuals were about twice as likely to initiate ART (OR 1.99, p = 0.017) compared to the unemployed. Overall the ART uptake across the study area among all HIV positive individuals was 32.5%. ART uptake and median CD4 count at initiation by clinic catchment ranged from 31.0% to 43.2% and 132 to 153 cells/mm3 respectively across the six clinic catchments. Conclusion: Although the overall rate of ART initiation was high, certain population groups were not covered well. Interventions that target younger people, males and unemployed individuals can help in reaching as many treatment eligible individuals as possible.

Master of Science in Epidemiology in the field of Epidemiology and Biostatistics June, 2017 / Background Hepatitis B and ART have been established to cause liver damage. We compared the changes in the levels of Alanine amino Transferase (ALT) in HBV/HIV co-infected and HIV infected women on ART to determine liver disease among women on ART in Lilongwe Malawi using Data from the BAN study. Methods We conducted a secondary data analysis from The BAN study to investigate the changes in the levels of ALT among HIV/HBV co-infected and HIV mono-infected women who were randomised into the maternal ART arm. In brief The BAN study assessed the benefit of nutritional supplementation given to women during breastfeeding, the benefit and safety of antiretroviral medications given either to infants or to their mothers to prevent HIV transmission during breastfeeding and the feasibility of exclusive breastfeeding followed by early, rapid breastfeeding cessation. ALT was monitored up to 48 weeks with an average of 12 follow-ups per individual. Continuous variables i.e. Age, ALT and CD4 count were compared between HIV/HBV co-infected women and HIV mono-infected women using the Wilcoxon rank sum test. Multiple regression analyses were performed using longitudinal data Generalised Linear mixed models to evaluate the relationship between ALT and HIV/HBV co-infection, among HIV-infected women, controlling for ART regimen, CD4 count and visit. All individuals were included in the analysis regardless of the different numbers of follow-up visits. To show the change of ALT levels longitudinal line graphs were used. Predictions of ALT levels per visit were also plotted using margin plots. Results The study subjects comprised of 544 women of whom 5.6% were HIV/HBV co-infected. The age range of the study population was 16-45 years. Median age at enrolment was 26(IQR: 22-29). The median ALT enzyme level of HIV/HBV co-infected individuals was slightly higher at baseline (13 UI/L (10-16) vs 14 UI/L (11-18, p=0.10) and at the last follow-up (17UI/L (14-22) vs 19 UI/L (16-26, p=0.04) compared to HIV mono-infected counterparts. HIV/HBV co-infection women were 3.28 times (1.43-9.03 p= 0.01) more likely to have abnormal ALT, compared to their mono-HIV infected counterparts. Individuals that were initiated on Nelfinavar as first line ART were 3.22 times (1.85-5.59 p=0.001) more likely to have elevated ALT compared to those that were initiated on LPV/r based regimen. Moderately immune suppressed women (CD4 count of between 200 to 500 cells/dl) were 0.38 times less likely to have elevated ALT(0.15-1.00) while women who were severely immune suppressed had 3.51 times more likely to have abnormal ALT . Overall there was an increase in the level of ALT per each subsequent visit. Conclusion Individuals co-infected with HIV/HBV generally had higher levels of ALT compared to HIV mono-Infected individuals and this increased over time. The current study suggests that monitoring of ALT in patients co-infected with HIV/ HBV on ART should be performed regularly, and the caution should be taken when prescribing first line ART. / MT2017

Thesis (MPH)--University of Limpopo, 2010. / Background: Antiretroviral therapy led to a revolution in care of patients with HIV/AIDS in a developed world. Treatment is not a cure but it also presented with new challenges of side effects, drug resistance and it also dramatically reduces rate of mortality and morbidity and it also improves quality of life to people living with HIV/AIDS, and it also now considered as manageable chronic diseases. Aim: Aim of the study is to establish and describe reasons for treatment and regimen change in a cohort of HIV positive patients on ART enrolled in the pharmaco-epidemiological survey at Tshepang wellness clinic. Objectives: is to determine reasons for treatment and regimen change, types of treatment and regimen change among patients on ART who are enrolled in pharmacoepidemiological survey at Tshepang wellness clinic. Design and Methods: Study is a retrospective cohort study, and sample size of 301 medical records of a cohort of HIV positive patients on ARVs enrolled in a longitudinal pharmaco-epidemiological survey from November 2006-May 2007 reviewed. Data extraction tool used to collect data and software called SPSS 17.0 used to analyze data and relevant themes were extracted to determine distribution of variables. Results: Results of this study indicated that 91 (85%) were males and (87.8%) 191 were females. Age was grouped as teenagers (15-25yrs), young adults (26-49yrs) and adults (50- 70yrs). Results also shows reasons of treatment and regimen change of which majority of patients 134(44.8%) changed due toxicity followed by 16 (5.4%) who changed because of pregnancy, and the other 4(1.3%) changed because of resistance, and the last 2(0.7%) which are regarded as minorities change because of T.B. Conclusion and Recommendations: Results shows that majority of pharmacovigilance patients were initiated Regimen 1 compared to other regimens. Toxicity appear as the main reason of treatment and regimen change on this study as 140(46.4%) reported toxicities (peripheral neuropathy, lactic acidosis, lipodystrophy and lipoatrophy). Implementation of monitoring of adherence needed for prevention of resistance and virological failure.

Thesis (MPH)--University of Limpopo, 2009. / 􀁸Introduction Northern Uganda is experiencing a lull in a 20 year civil war that had led to the massive displacement of people from their homes. Majority of people living in internally displaced people’s camps are now returning to their homes. The HIV scourge in the region has been fanned by the war, exposing the population to a higher prevalence of 8.4 % as compared to the HIV country average of 6.2%. Government in collaboration with other stakeholders is scaling up antiretroviral therapy in this resource limited, post-conflict setting through the decentralized health care delivery system. Factors that could influence long-term retention in such a setting are as yet poorly understood. Methodology This was a methodological retrospective review of 402 patient clinic cards, ART register and pharmacy records at regional referral hospital, district hospital and health centre IV. A quantitative approach was used to determine the retention rates for clients initiated on antiretroviral therapy at the three levels of care after 3, 6, 12, and 24 months. Predictors for loss to follow-up were derived from demographic and clinical characteristics captured in the clinic records. 􀁸Data management Data was summarized using frequency tables and bar graphs. Analysis was done using EPI-INFO and SPSS computer packages. Bivariate analysis was carried out to evaluate the association between the variables and loss to follow-up. 􀁸ResultsOverall 43.5% of patients were lost to follow-up from the ART programs. The district hospital retained most patients (73.1%), the regional referral hospital (53.7%) and health centre IV retained least (36.6%). Majority of patients were lost to follow-up after 3 completed months and least after 24 completed months. Patients accessing ART at the district hospital were five times more likely to remain in care (OR 0.21 95% CI 0.08, 0.50) and those at the regional hospital 2 times more likely (OR 0.48 95% CI 0.22, 1.07) as compared to those at the health centre. Loss to follow-up was 16 times more likely to occur in the bedridden functional status (OR16.3 95% CI2.0, 132.2) and three times more likely in the ambulant patient compared to those able to work. In this study age, sex, occupation, weight, WHO clinical stage and CD4 lymphocyte count were not predictive of retention on the ART program. 􀁸ConclusionProviding an accessible high quality ART service is feasible in the post-conflict region, as illustrated by the level of retention of patients at Kitgum District Hospital, through task shifting, training, and mentoring of lower cadre health workers. The collaboration of community based organizations to enhance the continuum of care at community level significantly improves retention of patient in the programme. There is need to relax the eligibility criteria and adopt strategies that will promote earlier access to VCT services so that appropriate care is initiated to patients before they are too weak.