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.

Thesis (M Med.(Obstetrics & Gynecology))--University of Limpopo,2009. / OBJECTIVE: The objectives of the study were: 1) To determine the pattern of toxicity/side-effects among women using Highly Active Antiretroviral Therapy (HAART) in the perinatal period in comparison with women who were treated with intra- partum prophylaxis of nevirapine at the time of delivery. 2) To evaluate the effects of either approach of therapy on maternal and fetal outcomes. METHODOLOGY: STUDY DESIGN The department of Obstetrics and Gynaecology has begun to administer HAART to pregnant women identified for ARV programme. These women were counseled and recruited prospectively for the study. The study involved comparison of pregnancy outcomes between women identified for HAART and those who were HIV infected but who only required intra-partum prophylaxis in labour to prevent mother-to-child transmission of HIV with nevirapine.

Thesis (M Med Pharmacy)--University of Limpopo, 2011 / Most pharmaceutical agents can result in side effects and toxicities that in some instances may be life threatening, especially if there is delay in their recognition. For various reasons it is therefore imperative to study adverse events associated with antiretroviral agents (ARVs). The aim of this study was to study the adverse events in adult HIV-infected patients receiving antiretroviral therapy at a public health treatment site, and to quantify the frequency of adverse events in different population subgroups. A retrospective cohort study was conducted in a sample of 99 patients (i.e. 70% females and 30% males) from a public health clinic providing antiretroviral drugs to more than 1500 patients. The reported adverse events were neurological disorders (33%), rash (17%), gastrointestinal toxicity (16%), lactic acidosis (14%), hepatitis (7%), lipodystrophy (7%), pancreatitis (5%), IRIS (3%), anaemia (1%), and gynaecomastia (1%). Based on the analysis of the presented data in this report, age, weight, gender, and pCD4 count are not the predictors for the development of lactic acidosis, pancreatitis, and peripheral neuropathy. The duration of treatment was found to be the predictor for the development of lactic acidosis, pancreatitis, and peripheral neuropathy in this study sample. More frequent and closer monitoring of the reported adverse events will be necessary for patients treated longer on ART. Information bias is possible as case data for all reported adverse effects were collected retrospectively from hand-written patient records which were not consistent and standardised.

Thesis (MPH))--University of Limpopo (Medunsa Campus), 2011. / Botswana was the first country in Africa to aim to give antiretroviral treatment to all its HIV positive deserving citizens in 2001. This brought about a significant improvement in survival and quality of life of HIV infected patients as well as a dramatic decrease in the incidence of opportunistic infections. However, although many reports about metabolic abnormalities and abnormal body fat distribution among people on ART have been published elsewhere, little is known about this in Botswana. The purpose of this study was to investigate the prevalence and factors associated with development of metabolic syndrome among people with HIV on ART at the IDCC Clinic at Princess Marina Hospital, Gaborone, Botswana. Methods This was a cross-sectional study based on patient interviews and review of records. A structured questionnaire and a data collection form were used to collect data on demographic, socioeconomic, lifestyle, clinical and laboratory data. Metabolic Syndrome was defined using the International Diabetes Federation (IDF) criteria. Patients who consented to participate were interviewed and their records were reviewed to collate data. Only patients that had been on treatment from January to December 2010 were included. Results A total of 190 subjects participated in the study, 141 (74.2%) females and 49 (25.8%) males. The age of the participants ranged from 24 to 71 with a median age of 40.5 years (IQR: 35 – 49). The overall prevalence of metabolic syndrome in this study was 11%. Metabolic syndrome was associated with traditional risk factors such as hypertension and high triglycerides; but with some unique features such as age, current employment and current NRTI use were also identified. In the bivariate analysis to identify the determinants of metabolic syndrome, the odds for developing MS were higher among participants who were married, employed, on a salary and used ART regimens containing NRTIs. High cholesterol, fasting blood glucose and triglycerides were also associated with the development of metabolic syndrome. There was a significant association with age as people over 45 years were significantly shown to have metabolic syndrome than the younger ones. The median age of participants who had metabolic syndrome was higher at 45 years (IQR: 39 – 53 years) that those without metabolic syndrome at 40 years (IQR: 34 – 48). Married participants were 13 times more likely to develop MS than their unmarried counterparts [OR (95%CI)]: 13 (1.91 - 88.35), p=0.009]. Participants who were employed and had a salary as their source of income were 27.54 times more likely to develop MS although the difference was not statistically significant. The type of regimen affected the prevalence of metabolic syndrome; in fact Up to 17 of the 21 participants with metabolic syndrome used a combination of drugs with NRTIs and NNRTIs as well as PI in 8 cases. So the use of a protease inhibitor based ART regimen increased the odds of developing MS by 51.57 times [OR (95%CI)]: 51.57 (1.55 – 1709.64), p=0.027]; while in case of NRTIs the odds were 78.53 times more for the likelihood to develop MS [OR (95%CI)]: 78.53 (1.10 – 5565.50), p=0.044]. Although there was no significant association between the duration of ART and the development of metabolic syndrome; the median duration of ART among participants with metabolic syndrome was higher at 68 months (IQR: 51 – 80) compared to those without metabolic syndrome at 56 months (IQR: 40 – 68). With regard to sex, 16.3% of the male participants had metabolic syndrome compared to 9.2% among the females; but the difference was not statistically significant. Conclusion In conclusion, the prevalence of metabolic syndrome was low, affecting only 11% of the study participants. The factors associated with the occurrence of the syndrome were the male sex, the long duration on treatment, being married, employed, and over 45 years old. The most significant factors were being on NRTIs and PIs containing regimens. These findings suggest that patients on antiretroviral treatment with the above characteristics should be monitored regularly for metabolic syndrome.

Thesis (MPH))--University of Limpopo (Medunsa Campus), 2010. / Introduction: HIV-positive parents taking antiretroviral therapy are faced with the difficult decision of whether and what details to share about their HIV status with their children. They need to decide if, when, and how they will disclose their illness to their children. Many reasons have been identified which influence parents’ decision to disclose their HIV status to their children. Aim and objectives: The aim of the study was to explore parental decision and experiences of disclosing or not disclosing their HIV status to children and to explore strategies used by non-disclosed parents to conceal their HIV status from their children. Methodology: Using a qualitative approach, six focus group discussions were conducted with a sample of disclosed and non- disclosed biological parents of children aged between 7-18 years. Participants were recruited from a wellness clinic at the Dr George Mukhari where they routinely collect antiretrovirals. A total of 44 parents (13 biological fathers and 31 mothers) were recruited and participated in two focus groups with disclosed parents, three with non disclosed parents and a pilot focus group interview with disclosed and non disclosed parents. Findings: Disclosure to children was difficult and occurred within a context influenced by death, dying and discrimination. Despite parents being on ARVs, fear of death and dying continues to influence disclosure to children. HIV related practices like taking ARVs and child feeding practices predisposes parents to stigma and discrimination and was major reason for non-disclosure to children, family and neighbours. Whereas previously, prior to the availability of ARVs, parents disclosed to prepare children to face parental death, now disclosure occurs for children to support parents in adherence and when they are sick. The need for support is not surprising given that for parents who disclosed immediately, disclosure was prompted by ill health. The primary reason parents delayed disclosure is because they do not know how to tell the child. One other concern was that disclosure will makes children responsible for caring for parents. By delaying disclosure parents were protecting their children mostly from being hurt, from social rejection and discrimination and from fear of mother’s death. Conclusion: Regardless of whether parents had disclosed or not disclosed the decision to disclose was difficult and emotional for parents, and is influenced by various factors. Due to stigma and discrimination disclosure in most families is often treated as a secret; parents do everything possible to protect their HIV status. Common strategies used to protect their HIV status include hiding antiretrovirals, removing labels from ARV bottles, use of different packages for ARVs, taking medication privately and substituting TB for HIV. Parents believed that by delaying disclosure they were protecting their children from consequences of disclosure. Most children reacted positively to disclosure and were protective and supportive to parents, while some non disclosed children became suspicious of parental status. Recommendations: There is need for the development of health service practices that would protect HIV positive people taking ARVs from stigma and discrimination. Most HIV positive parents currently on ARVs have seronegative and seropositive children. They therefore need to develop strategies to discuss managing HIV illness especially with their seropositive children who also need to have their diagnosis disclosed. It is imperative that disclosure guidelines are developed to guide parents in disclosing HIV to children. Key words: Parental, disclosure, non disclosure, HIV positive, children, qualitative research.

Thesis ((MSc(Med)(Pharmacy))--University of Limpopo (Medunsa Campus), 2011. / Background: Anecdotal evidence from fixed Voluntary Counselling and Testing (VCT) centres within the public sector indicates, that many patients are lost in the transition from VCT to Human Immunodeficiency Virus (HIV) care and treatment. The actual number of patients who are eligible for antiretroviral ttreatment (ART) after a positive HIV test, but who do not visit the antiretroviral (ARV) clinic to initiate ART, is currently not known. The need to identify the extent of this problem was therefore evident. Objectives: To investigate and describe the procedures and records used at the VCT centres under study. To identify the proportions of patients who fail to proceed through the different steps of the process from VCT to initiation on ART within a period of six months. To make recommendations for interventions aimed at improving the tracking of patients from the VCT entry point to ART initiation. Methods: The study was conducted as an operational research project at Odi and Stanza Bopape VCT centres. The design of the study was descriptive. Data were collected retrospectively and prospectively over a period of four months. Operational procedures and documentation systems at both VCT centres were observed. The records of all patients who tested HIV positive from 1 April 2009 to 30 June 2009 at Odi and Stanza Bopape VCT centres were identified from the VCT registers and selected for the study. Patients who were eligible for ART were identified based on their CD4 count. Eligible patient names were crossreferenced against the SOZO system (electronic patient database) to determine whether they had attended their pre-treatment visits at the ART clinic and whether ARV medicines had been dispensed to them for the first time. Where there was no proof that the patient attended the pre-treatment visits or finally accessed ART at an ARV clinic within six months, the patient was regarded as lost to initiation on ART. Results: The results obtained from the observational phase of the study showed differences in the procedures followed at the two VCT centres. At Odi VCT centre, patients referred for VCT by medical doctors only had an ELISA test and had to return on a different date for the ELISA test results, while patients visiting the VCT centre voluntarily first had a Rapid test and if positive they had an ELISA test on the same day. At Stanza Bopape VCT centre, patients referred by doctors and patients visiting the VCT centre voluntarily had a Rapid test and an ELISA test after a positive Rapid test. The patients at Odi had their CD4 test results interpreted by the nurse at the VCT centre while at Stanza Bopape the results were interpreted by the doctor at the ARV clinic. x iv The study included a cohort of 743 patients who tested HIV positive from April 2009 to June 2009 at Odi and Stanza Bopape VCT centres. Of these patients 344 tested at Odi VCT centre and 399 were tested at Stanza Bopape. The majority of patients at the two VCT centres were female (55% at Odi VCT centre and 59% at Stanza Bopape VCT centre), unemployed and single. At both VCT centres, patients were expected to return for collection of CD4 results within two weeks of the HIV test. At Odi VCT centre, 159 (49.4%; n=322) patients did not return to collect their CD4 results. Of those who returned, only 41.1% (67; n=163) returned within one month. At Stanza Bopape VCT centre 52.8% (210; n=399) patients did not collect their CD4 results. Of the patients who collected their CD4 count results, 51.3% (97; n=189) collected within one month. The Fisher’s exact test revealed no statistically significant difference (P=0.410) between the two VCT centres in terms of patients who returned for their CD4 results collection and those who did not return. More than half of the patients with accessible CD4 counts at Odi presented late for VCT. This was shown by 65.4% (n=275) of patients with CD4 count 200 cells/mm3 during HIV diagnosis. At Stanza Bopape VCT centre 46.6% (n=386) also had CD4 count 200 cells/mm3. The difference in terms of late presentation between the patients from the two clinics was statistically significant (P<0.001; Fisher’s exact test). The ART initiation rate at both VCT centres was found to be low. More than half of the patients eligible for treatment (CD4 200 cells/mm3) at both VCT centres did not initiate ART. This was shown by 59.4% (n=180) of patients at Odi VCT centre and 67.8% (n=180) of patients at Stanza Bopape VCT centre who did not initiate ART. There was no significant difference (P=0.317; Fisher’s exact test) between the two VCT centres in terms of the patients who did not initiate ART. Conclusion: A high percentage of patients who presented for VCT and were eligible for treatment were lost to initiation on ART. The majority of these patients did not return to collect their CD4 results and thus were lost immediately after VCT. These results suggest a need for an urgent intervention that will improve ART uptake. Recommendations: Patients referred by doctors for VCT at Odi VCT centre should have a Rapid test, and if positive they should have an ELISA and CD4 test on the same day to prevent the loss of patients before they even identify their HIV status. The option of a ‘one stop’ VCT and immediate CD4 results, should be further explored due to the unacceptable patient default rates at both VCT centres. A CD4 count machine which x v will provide results immediately on the same day of the test should be utilised. There must be sufficient personnel and equipment to follow-up on patients who do not return for their CD4 results, pre-treatment counselling and ART. The SOZO system should be integrated between the VCT centres and the ARV clinics to improve the flow of patient information between the VCT centre and the ARV clinic. A qualitative study should be conducted to explore reasons for patients not returning to collect their CD4 results. Key words: VCT; loss to initiation; non-uptake; lost in transition; HIV and AIDS