Cervical cancer is the third most commonly diagnosed cancer globally and it has also been identified as one of three AIDS defining malignancies. Highly active antiretroviral therapy (HAART) is a combination of three or more antiretroviral drugs which are classified as nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs). HAART has been shown to play a significant role in reducing the incidence of some AIDS defining malignancies, although its effect on cervical cancer is still unclear. It is hypothesized that HAART might reduce cancer risk by interacting with different signalling molecules and pathways that are involved in cancer in order to induce cell death and thus inhibit cell proliferation. The broader aim of this study was to understand the relationship between cervical cancer and HAART. This was achieved by studying the expression of key signalling molecules in cancer; MUC1 and NFkB (P65) and morphological features using scanning electron microscopy following 24 hour treatment of a cervical cancer cell line, HCS-2 with drugs which are commonly used as part of HAART; Emtricitabine (FTC), Tenofovir disoproxil fumarate (TDF), Efavirenz (EFV), Atripla combination (ATP) and Kaletra combination (LPV/r) at their clinical plasma concentrations. Quantitative real time polymerase chain reaction (qPCR) was used in order to study the gene expression of MUC1 and P65 and the data was analysed using the 2-ΔΔCT method to calculate fold change. The statistical analysis was conducted using JMP 11 software. MUC1 and P65 gene expression was reduced following drug treatment. Protein expression was studied by means of Immunofluorescence and MUC1 and P65 protein expression was reduced following drug treatment. Scanning electron microscopy revealed characteristic features of apoptotic cell death such as loss of cell contacts, reduced density and size of microvilli, increase in surface blebbing and budding and degradation of apoptotic bodies following treatment with all the drugs. In conclusion, the drugs used in this study

There have been great strides in increasing access to antiretroviral treatment for HIV-positive people in South Africa. However it has been observed that men are not accessing treatment to the same extent as women. In Soweto only 30% of the people accessing treatment are men, where the expected rate would be around 45%. Whilst there have been some studies observing treatment uptake, they do not explain the behavioural component.

Thesis (M.Med.(Psychiatry))--University of the Witwatersrand, Faculty of Health Sciences, 2014. / The Luthando Neuropsychiatric HIV clinic was set up at Chris Hani Baragwanath Academic Hospital as an anti-retroviral roll out centre, specifically designed to provide anti-retroviral therapy to HIV positive patients with a psychiatric illness. Adherence to HIV treatment is essential for virological suppression, and non-adherence is a key factor in treatment failure. Research has suggested that psychiatric illness may negatively influence adherence to ART. Importantly, negative perceptions with regards to adherence may affect the decision to initiate ART in psychiatric patients. Attendance at clinic appointments is the first step in adherence, and has been found to be one of the most important predictors of medication adherence. Attendance at first clinic appointment is easily measurable in a limited resource setting, such as South Africa. The aim of this study was to examine the rate of attendance at the first clinic appointment post discharge from psychiatric hospitalization in HIV positive psychiatric patients initiated on ART as in-patients, and to determine which factors, if any may be related to clinic attendance. This study was a retrospective record review, conducted at Chris Hani Baragwanath Academic Hospital, at the Luthando clinic. Patients that were initiated on ART as psychiatric in-patients, 18 years to 65 years of age from 1st July 2009 to 31st December 2010 and then discharged for follow up as out-patients at Luthando clinic were included in the sample. The primary outcome was attendance at the clinic post discharge from hospital. Socioeconomic and clinical data were also recorded and analysed, comparing attendant and non-attendant P a g e | vi groups. The rate of attendance was 79.59%. There were a number of similarities between the attendant and non-attendant patients in terms of demographic and clinical data. The only significant difference between the attendant and non-attendant groups was disclosure of HIV status, and significantly fewer non-attendant patients had disclosed their HIV status to their treatment supporter (p = .01). Further research needs to quantify the significance of in-patient vs. out-patient initiation of ART, as well as to investigate the impact of a psychiatric diagnosis on attendance at ART clinics. Non-disclosure of HIV status needs to be further investigated and addressed in HIV treatment facilities in order to improve attendance.

A Research Report Submitted to the School of Public Health, University of the Witwatersrand, Johannesburg, in Partial Fulfilment of the Requirements for the Degree of Master of Science in Medicine in the Field of Epidemiology and Biostatistics: March 25, 2013 / Background: More than 33 million people are estimated to be living with HIV worldwide. Sub-Saharan Africa bears a disproportionate share of the global HIV burden. An estimated 15 million people living with HIV in low and middle income countries were in need of (HAART) in December 2009. HAART services require advanced laboratory technologies to monitor disease progression and therapeutic response, which are scarce in developing countries. Several simple and widely available markers have been proposed for use in low income countries including total lymphocyte count (TLC), haemoglobin and body mass index. Methodology: This study is a secondary data analysis of prospectively collected cohort data from HIV positive adults. The study measured the effect of exposure variables of haemoglobin (Hb) and body mass index (BMI). All cause mortality was the outcome of interest. Crude estimates of mortality were made with Kaplan-Meier mortality curves. Cox proportional hazards models were used to estimate adjusted hazard ratios. Exposure status was considered at initiation period. Outcomes were measured from two weeks post initiation of treatment to a maximum of two years of follow-up period. A composite score was developed to estimate the overall risk of mortality. Results: A total of 11,884 patients who satisfied the inclusion criteria were included in the analysis. A total of 1,305 deaths were observed during the follow-up period, representing 10.2% of the cohort at baseline. Most of the deaths were observed during the first four months of follow-up period. Patients with moderated to severe anaemia experienced 2.6 (HR = 2.6, 95% CI 1.8 - 3.6) times greater hazard of mortality adjusted for possible confounders. Patients with very iv low BMI experienced twice (HR=2.0, 95% CI 1.6, -2.5) greater hazard of mortality adjusted for a list of predictors. Race, age at initiation, employment status, smoking, alcohol consumption, baseline TB and baseline WHO stage did not show significant effect in the multivariate cox regression model. A composite score was developed to estimate the overall risk of mortality in patients based on measurements of baseline BMI and haemoglobin. Cox regression model adjusted for CD4 cell count shows high risk patients experienced 4.7 (HR = 4.7, 95% CI 2.9 – 7.6) times greater hazard of mortality compared to patients in the low risk group. Patients in the medium risk group experienced 3.4 (HR = 2.6, 95% CI 2.6 – 4.4) times greater hazard of mortality as opposed to patients in the low risk group. Conclusion: Haemoglobin and body mass index provide excellent prognostic information independent of CD4 cell count in HIV positive patients newly initiated on HAART. They can be used to reliably predict mortality. Combining measurements of haemoglobin and BMI through composite scoring improves their predictive ability. They can have good clinical application in rural and remote facilities to screen patients for clinical and diagnostic services.

The high prevalence of HIV has been a major cause for concern in Lesotho and the clinical course has witnessed some service lapses, complications and deaths. The researcher was therefore motivated to conduct this study with the aim to assess care and outcomes offered to HIV patients at St. Joseph’s Hospital. The objectives were to describe patient socio-demographic and clinical characteristics at initiation of antiretroviral therapy, to describe clinical parameters of haemoglobin, AST, CD4 count levels as outcome proxy of care and to analyze the rate and predictors of patient retention and lost to follow-up. Methods A retrospective cohort study of 1060 patients initiated on ART at the Thusong ART Clinic in St. Joseph’s Hospital, Roma between August 2005 and July 2008 was conducted. Relevant documentation was captured from the patients’ clinical records hard copy files onto the Therapy-Edge (TE) database tool used. Patient confidentiality was respected The dataset was closed on 31st October 2012. Data were analyzed using STATA version 11. Results The total number of patients enrolled during the study period of August 2005 – July 2008 was 1060. The findings on the patients studied showed that 99.5% were Sotho with the majority of 70.2% being female. Patients in the age group of 16-35 years were 22.2%, in the age groups of 36-55 years and >55 years were 58.3% and 19.5% respectively. Median age was 43 years. Employed persons were 24.3%, students were 2.3%, unemployed persons were 44.8% and 28.6% were of unknown employment status. On WHO classification, 18.1% was WHO Stage I, 34.6% was Stage II, 43.4% was Stage III and 3% was Stage IV. Median weight at enrollment was 55.6kg. Baseline CD4 count < 50 cells/mm3 was 13.3%, count of 50 – 199 cells/mm3 was 43.2%, CD4 count ≥ 200 cells was 38.7%. Patients with Hb <10g/dl were 17.3%. On patient retention over a period of about 6 years, 57% of the patients were still alive and in care, 11.3% had been transferred out to the health centers and clinics, 29.5% were lost to follow up. It is noteworthy that only 2.2% were recorded as dead. Conclusion The study showed that more than half of the HIV patients on ART were female, thus suggesting better access to care and health seeking behaviour. Clinical parameters of haemoglobin, AST, CD4 cell counts used to monitor progress over follow-up period showed results comparable with other similar studies. Baseline CD4 count, WHO stage, age, gender and employment status were agreeable with studies in other settings to predict those lost to follow-up (LFTU). The low percentage of documented deaths suggests that some deaths may have been included in LTFU. Better documentation, staff training and retention, decentralization of care and proper follow-up measures are steps in the right direction for better ART monitoring and outcomes.

Both HIV and tuberculosis (TB) have been documented to have detrimental effects on the nutritional status of those infected and nutritional status is a strong predictor of disease progression and survival. Body composition measures can be used as a proxy for nutritional status and takes into account body fat, muscle and water. It constitutes Fat Mass(FM), Fat Free Mass (FFM), Total Body Water (TBW), Extracellular Water (ECW), Intracellular water (ICW), Daily Energy Expenditure (DEE), Basal Metabolic Rate (BMR), phase angle and BMI which can be analysed as separate outcomes. Its use in evaluation of nutritional status has been reported to give more accurate results than the use of weight alone. We compared body composition measures and changes over a 12 month period in patients with HIV alone to patients with HIV and TB.

Dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand , Johannesburg, in fulfillment of the requirements for the degree of Master of Science in Medicine, Johannesburg, 2011 / HIV-associated sensory neuropathy (HIV-SN) is a common complication of HIV infection and its treatment with dideoxynucleoside drugs such as stavudine. Pain is a symptom in about 75% of cases of HIV-SN. The aim of this study was to set up the intraepidermal nerve fibre density (IENFD) quantification technique in a South African Laboratory and then to use this technique to investigate whether the presence of pain in individuals with HIV-associated sensory neuropathy was associated with the dying back of epidermal nerve fibres at the site at which pain was experienced.

The effect of anti-retroviral therapy (ART) rollout can be measured in a number of ways including treatment coverage, behaviour change and the emergence of resistance. However, changes in population mortality are undoubtedly the most important measurable effect. Objectives: To describe trends in child and adult all-cause mortality versus HIV/AIDS related mortality before and after ART rollout; and to identify significant clusters of child and adult all-cause mortality versus HIV/AIDS related mortality in space-time, during pre and post ART rollout eras at Agincourt and Dikgale health and demographic surveillance systems (HDSSs) in South Africa. Design: Mortality data were extracted from both the Agincourt and Dikgale HDSSs for the period 1996–2010. Mortality rates by age group, year and village were calculated assuming a Poisson distribution and using precise person-years as the denominator. The Kulldorff spatial scan statistic was used to test for clusters of age group all-cause and HIV-related mortality both in space and time. Clusters were mapped using Quantum geographic information systems (GIS) software. Results: Both HIV-related and all-cause mortality decreased gradually over the years after the introduction of ART in 2007 for the two HDSS sites. Several statistically significant clusters of higher all-cause and HIV-related mortality were identified both in space and time. In the Agincourt HDSS, specific areas were consistently identified as high risk areas; namely, the east/south-east corner and upper central to west regions, pre ART. In the Dikgale HDSS, no significant clusters were identified using the spatial only analysis but one significant cluster, located towards the north of the Dikgale HDSS site, was identified using the space-time scanning, post ART. In Agincourt, no significant clusters of mortality were detected after the introduction of ART whereas in Dikgale, a significant cluster for all-cause mortality in the under-five age group was detected for the years after the introduction of ART. Conclusion: This work revealed the existence of spatio-temporal clusters of both child and adult mortality at the Agincourt and Dikgale HDSSs and that the introduction of ART had a substantial influence in reducing both HIV-related and all-cause mortality in rural South Africa. There is need though to take into account socio-demographic characteristics so as to determine fundamental risk factors influencing these spatio-temporal HIV-related and all-cause mortality patterns.

A dissertation submitted to the Faculty of Science, University of the Witwatersrand, in fulfilment of the requirement for the degree Master of Science (MSc) in Chemistry. Johannesburg, March 2017. / A series of [Pt(diimine)(Ln-O,S)]Cl complexes, where Ln-O,S represents a series of N,N dialkyl-N’-acylthiourea ligands and diimine represents (1,10-Phenanthroline; 5,6-dimethyl 1,10-phenanthroline or [3,2-d:2’,3’-f]-quinoxaline were successfully synthesised and characterised. A new crystal structure was obtained for N,N-di(2-hydroxy)-N’ benzoylthiourea which revealed an interesting herringbone crystal packing arrangement. The cytotoxicity of the series of complexes was evaluated on H1975 lung cancer cell lines at 50 µM and 5 µM. All the complexes were highly cytotoxic with cell death of 90-98% at 50 µM. However, at 5 µM there were much more variations on cell viability percentages. Although the structure–activity relationship can only be established when the IC50 (the concentration of an inhibitor where the response is reduced by half) values are determined, it is clear that the complexes containing the methyl substituents on the 5 and 6 positions of the phenanthroline moiety were the most cytotoxic with almost 98% cell death at 5 µM. The solubility of the complexes did improve by using N,N-dialkyl-N’-acylthiourea as ancillary ligands, however aqueous solubility remains a major problem. Sulphobutyl-ether-β-cyclodextrin (captisol) and low-molecular-weight surfactant micelles as drug delivery systems were considered in attempt to improve the solubility. DOSY NMR Spectroscopy revealed that there was no inclusion complex formation between the complex and capstiol, although the chemical shift trend suggested that there is at least some interaction. The low-molecular-weight surfactant micelles were considered as an alternative, which showed some promise as a drug delivery system, since the aqueous solubility improved and a colloidal suspension was obtained. / LG2018

Introduction: This study is a secondary data analysis of HIV/AIDS patients on Anti-retroviral Therapy (ART), at Themba Lethu HIV/AIDS clinic, who have had the first break in the continuity of taking their Antiretrovirals (ARVs) of more than 10 days, measured by patient missing the refill appointment for more than 10 days. The clinic started in 2004. HIV/AIDS is high in South Africa with about 400,000 AIDS patients on ARVs. For ARVs to be most effective they must be taken continuously without breaks, and for life. Without this, there is risk of ARVS drug resistance development and consequent failure of the ART program. Some patients may break this continuity and this seems to be a problem in South Africa. Where the patients develops side-effects or is not responding well to treatment, clinicians may also cause a break in the therapy. This study described the first break as when it occurred and for how long it lasted, investigated the factors associated with this break and the association of the first break and the last CD4 count. Materials and methods: 7,930 adults (≥18 years, either gender) on ART and baseline CD4 <250 cells/μl were included in the study. The study group were patients who had first break in continuity of therapy of more than 10 days. The first break was described as when it occurred after months of ART initiation and how long(days) the first break lasted. Patients on Post- Exposure Prophylaxis, single-dose Nevirapine, Prevention-of mother-To-Child- transmission therapy, and those with breaks in therapy of more than 364 days were excluded. Outcome variables was the last CD4 count. Analyses were in STATA 10, at 95% confidence interval. Median and quartile ranges were used to describe participants in the study. T-test, Fishers exact test and chi-square were used to compare groups. Regression was used to determine demographic and clinical factors associated with first break in therapy and also to determine the association of first break in therapy and the last CD4 count. Results: The median duration on ART for the patients was 764 days. 63% of patients had a break in ART. 47.5% of patients had their first break in therapy within the first 2 years of being on the ART program, with the largest proportion within the first 6 months of therapy. Most patient came with advanced disease(CD4 <100cells/μl, WHO clinical staging IV). Women were twice more than men. They tended to come earlier for therapy, took longer to improve and delayed in having the first break compared to men (254 vs. 205 days). Baseline hemoglobin and unemployment were factors associated with when the first break occurred. The median length of first break was 21 (Q1-Q3 7-43) Unemployment and baseline hemoglobin were associated with length of first break. The first break in therapy was associated with the last CD4 count. The longer the patient stayed on ART without the first break, the higher the last CD4 would be. Peripheral neuropathy had a statistically significant positive association with the last CD4 count. However, baseline CD4, Age, baseline BMI, WHO stage IV, baseline hemoglobin and unemployment had a statistically significant but negative association with the last CD4 count. The weakness of using the missing appointment system is that it does not inform clinician whether patients is really taking or not taking ARVs at home. Its strength over the self reported adherence system is that it is free of recall bias. Conclusion: Though Themba Lethu clinic has a follow-up system in place for patients missing refill appointment, up to 63% patient missed their appointment to collect medicine on time and this had a negative effect on the last CD4. There is need to strengthen existing follow-up method besides decentralising the ART services in Johannesburg.