published_or_final_version / abstract / Medical Sciences / Master / Master of Medical Sciences

Predictors of response of AIDS-associated Kaposi-Sarcoma to standard chemotherapy Overview: Kaposi Sarcoma is the most common HIV-associated cancer. Its etiology and pathogenesis is not fully understood. Little is known about what predicts prognosis, survival and therapeutic response in HIV-KS. In South Africa given the high seroprevalence rates of HIV-l and human herpes virus 8 (HHV 8), Kaposi's sarcoma is a significant problem. The majority of patients have been treated solely with palliation due to the poor outcome associated with a diagnosis of HIV-KS, more so in the absence of highly active antiretroviral therapy (HAART). Since the national ARV rollout programme and the availability and accessibility of HAART to all patients with a diagnosis of HIV-KS, a new strategy has to be established to enable adequate patient selection for chemotherapy. There have been a few published studies addressing the predictors of response to chemotherapy in the first world. However, this is the first study of these factors in HIV-l infected African patients with Kaposi's sarcoma. Aim: To identify and assess the potential value of several parameters predictive of outcome, survival and therapeutic response in HIV- infected patients with KS. Clinical, hematological, biochemical, immunological and virological variables were evaluated. Methods: We collected data from 25 patients with AIDS-KS who were enrolled in a phase III randomized controlled trial comparing HAART alone with the combination of HAART and chemotherapy. All patients were from the combination therapy arm. The following variables were evaluated as predictors of prognosis and therapeutic response: age, gender, ethnic origin, Haemoglobin (Hb), white blood cells (WBCs), lymphocytes, neutrophils, platelets, S.albumin, ALP, GGT, CD4 count, HIV viral load. These variables were assessed in patients at baseline and month 6 of therapy. Patients were staged into good risk and poor risk according to the AIDS clinical trial group (ACTG) criteria. The outcomes assessed were response to treatment and mortality. Results: A total of 25 patients participated to the study. Of these 16(64%) were males and 9(36%) were females, with male: female ratio of 2.7:1. Median age was 34 years (24-47); all patients were of Black African origin. Of the 21 patients, 15 (71.4%) were of good prognosis and 6(28.6%) were of poor prognosis. At baseline the median values of the different variables were as follows: Hb 10.9 g/dl, WBCs 5.95x109/L, lymphocytes 1.7 x109/L, neutrophils 3 x10 9 /L, platelets 272 x10 9 /L, S.albumin 30 gil, total protein 88 gil, ALP 64 U/L, and GTT 21 U/L, CD4 count was 255 cells/mm 3 , HIV-RNA viral load was 42000( 4.610gs). At month 6, 22 patients remained alive, their median values were: Hb 12.2 g/dl, WBCs 4.65 x109/L, lymphocytes 1.5 x109/L, neutrophils 3 x10 9 /L, platelets 301 x109/L, S.albumin 36.5 gil, total protein 84.5 gil, ALP 78.5 U/L, GTT 44.5 U/L, CD4 count 288 cells/mm3 , HIV-RNA viral load was 50500( 4.6910gs). The baseline median CD4 and HIV-RNA viral load counts for the 3 patients who died before month 6 were 47 cells/mm3 and 31000(4.610gs); respectively. Response to therapy was evaluated in 21(84%) patients as 4(16%) patients were missing, of the 21 patients 3 (14.3%) had complete response and 18(85.7%) had partial response. With respect to sex 2(14.3%) males had complete response and 12(85.7%) had partial response, 1(14.3%) female had complete response and 6 (85.7%) had partial response. Non-parametric statistics were used because of the small sample size and the skewness of the data. Variables were described using medians and ranges, and compared between two independent groups using Mann-Whitney tests. Baseline and month 6 comparisons were done using Wilcoxon signed ranks tests. Receiver Operating Characteristic (ROC) curves were used to analyze cut points to optimize sensitivity and specificity of a quantitative variable for a dichotomous outcome. Discussion In the univariate analysis age and sex didn't influence prognosis and therapeutic response, the influence of ethnic origin couldn't be assessed as all patients were of the same ethnic origin. Baseline WBCs (P= 0.004) and lymphocytes (P=0.026) were significantly associated with complete response. Higher values of GGT (p=O.OOl); ALP (P=0.006) were associated with more deaths. Baseline CD4 count and HIV viral load were not of predictive value, lthough change CD4 (P=002) and VL (p=.OOO) over time was significant and most likely attributed to response to therapy. 90.9 % of patients reached undetectable HIV-l Viral loads at month 6. CONCLUSION: Neither CD4 count nor HIV viral load at baseline predicted prognosis or survival; however there was a borderline significance of CD4 (P=0.058) towards a better survival. / Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2006.

Background. An inherent challenge in HIV prevention studies is making sure that trial participants understand the information. This study explored trial participants’ perceptions and comprehension of the informed consent process in a pre-exposure HIV prevention study. Method. Face-to-face in-depth interviews, using a study guide, were held with twenty interviewees purposively selected from ex-participants of an HIV prevention study. Audio-recorded data were transcribed, translated, coded using NVivo 8, and analysed according to themes. Results. The participants were all women between the ages of 18 and 40. Participants felt that key information had been given during the informed consent process. Most felt that the process of obtaining informed consent was rushed with some participants citing a need for more time to make a decision regarding participation. Some participants felt pressured to sign consent forms. Some found it difficult to ask questions and mixed feelings existed on male partner involvement in the decision-making process. Conclusions: Participants experienced the consent process as rushed and most only fully comprehended study concepts with time. Their concerns necessitate the reassessment of informed consent processes in a developing world setting. / Thesis (M.Soc.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2012.

This study investigated selected Christian denominations in the Durban Functional Region's response to HIV/AIDS and the extent of their involvement within the issues of HIV/AIDS. The study also explored how the churches viewed the development of holistic services and hence their involvement with social workers. Seven of the so-called mainline Christian churches participated in the study. Interviews were conducted with the head of each denomination and one other member of clergy from each of the seven denominations. The study was exploratory in nature. Data was collected using semi-structured interviews with the participants being selected utilising purposive and availability sampling. The literature review comprised theological reflection on what the church's role should be as well as literature exploring the necessity for holistic services in the ambit of HIV/AIDS. Some of the findings of this research included the lack of knowledge clergy have around HIV/AIDS, the lack of knowledge some clergy have about their denominational policies regarding HIV/AIDS, and the limited response of some congregations to the pandemic. There is also a sense of negativism amongst some clergy about HIV/AIDS. There is no hope of the promise the Christian faith gives. The recommendations that stemmed from this research are the training of clergy in HIV/AIDS, training of clergy regarding their denomination's policies and offering practical advice on how a church can respond, the need for the dissemination of this information to all role-players so that a holistic service can become a reality, and finally that more extensive research is done into the church and HIV/AIDS. / Thesis (M.A.)-University of Natal, Durban, 2003.

HIV/AIDS remains one of the most pressing challenges facing South African society. South Africa has the highest number of people living with HIV as well as the highest number of people on HIV treatment globally, yet only 37% of persons eligible for treatment have access to treatment. The advent of HAART ushered in a new era in the treatment of HIV infection. HIV infection was no longer a life threatening terminal illness, HIV/AIDS became a chronic manageable disease. The full clinical benefit of HAART can only be achieved with near perfect adherence i.e. > 95%. This means taking the medication exactly as prescribed; on time, no missed doses, every day, lifelong. No other chronic medication requires such stringent adherence rates for optimal therapeutic benefit, which may mean the choice between life and death. Achieving near perfect adherence poses a serious challenge to health service providers and persons on treatment as typical adherence rates for medication prescribed over long periods are in the 50 – 75 % range. Persons on HAART live with the additional burden of drug resistance and limited treatment options if near perfect adherence rates are not achieved. The purpose of this qualitative study was to explore the factors that influence adherence to HAART. These factors may be related to the person, the health care team and system, the treatment regimen, the social and economic environment or to the effects of HIV disease. Factors may either negatively or positively influence a person’s ability to adhere optimally to their prescribed treatment. A small sample of thirteen participants were purposefully selected for this study. Data was collected using in-depth interviews which were tape recorded and transcribed for thematic analysis. The value of this study is that it may assist health care providers, persons on treatment and the health care system to better comprehend the challenges of lifelong optimal adherence to HAART. / Thesis (M.A.)-University of KwaZulu-Natal, Durban, 2011.

Background:- The HIV and AIDS epidemic is a major catastrophe that affects millions of people worldwide. Antiretroviral medication combinations have revolutionised HIV treatment since 1996, transforming the virus from a death sentence to a manageable condition. In order to obtain full therapeutic benefits it is vitally important that patients adhere to their prescribed medication. Being informed about the disease and medication contributes to patient adherence and management. Pharmacists are considered to be the most accessible health professional and can help HIV -infected patients deal with barriers to medication access, manage adverse effects and medication interactions, and adhere to medication regimens by appropriate counselling. The public sector is defined as that part of an economy that is controlled by the state. At the study site, which is a public sector facility, the roll out of antiretroviral medication started in 2006. At the time all patients were counselled by trained counsellors, before seeing a doctor. At the pharmacy the medication was collected with no intense counselling by a pharmacist as the patients would have visited the trained counsellors first. Subsequently it was found that there were many queries regarding HIV and AIDS. It was then decided in October 2007, that the pharmacist support the counselling done by the counsellors in that they should reinforce what was said by the counsellors, together with giving detailed information to patients on their health and medication. This study was therefore undertaken to measure pharmacists' role in the management and adherence of HIV infected patients at this institutional facility. Method: The study was undertaken at a public sector health facility using anonymous structured questionnaires and was divided into 3 phases: Pre-Intervention, Intervention and Post-Intervention phases. After obtaining patient consent the questionnaires were administered during the 1st phase. A month later all patients visiting the pharmacy were counselled intensely on various aspects of HIV and the antiretroviral medication. Thereafter patients who took part in phase 1 were asked to participate in the 2nd phase. After obtaining their consent again, the same questionnaire was administered to them. Quantitative variables were compared between pre and post intervention using paired t-tests or Wilcoxon signed ranks tests. Categorical variables were compared using McNemar's chi square test (Binary) or McNemar-Bowker test for ordinal variables. Results: A response rate of 87.5% was obtained with the majority of the patients being female. Almost 70% of the participants were in the age-range of 21-40 years old. The majority of the participants did not have post school education. Most of the participants (95.4%) did not know that HIV is a virus that causes AIDS in the pre intervention phase, but this decreased to 93.7% in the post intervention phase. The participants knowledge of people who have sexually transmitted diseases are least at risk of getting HIV, healthy food will cure HIV and smoking and drinking alcohol will weaken the HIV virus, increased significantly from the pre-intervention phase to the post intervention phase. Knowledge on the modes of transmission either increased or remained unchanged. Overall the mean knowledge score on the disease itself had increased significantly (SD 6.6%) [p<0.01] after the pharmacists' intervention (pre-intervention was 82.1 %, post-intervention was 86.3%). In both phases, over 40% of all patients stored their medication in the cupboard. The majority of the patients took their medication either with or without food at both phases of the study. After the intervention, the frequency of taking medication with a fatty meal or any time they remember was decreased to 0. A significant improvement was noted in the overall knowledge score with regards to medication taking and storage (p<0.05). Conclusion: Pharmacist intervention had a positive impact on HIV infected patients' HIV and AIDS knowledge on the disease and on the antiretroviral medication use and storage. / Thesis (M.Pharm.)-University of KwaZulu-Natal, Durban, 2011.

There are two dominant approaches to counselling for sexual risk reduction In South Africa. The TASO model which is based on client centred principles, informs much of vCT counsellors' training. More recently, the (ARRM) AIDS Risk Reduction Model which includes a cognitive behavioural component to counselling for sexual risk reduction has been introduced. A sample of vCT counsellors who have been trained using the ARRM were interviewed to develop an understanding of their experiences of using this approach. These participants provide a vCT service to clients in the midlands of the province of KwaZulu-Natal. A central finding was that although counsellors experienced the cognitive behavioural approach as having good potential for effecting sexual behaviour change, numerous barriers were identified to applying the approach within the South African context. Counsellors were also critical of the TASO model as a model for counsell ing for sexual risk reduction. Elements of the cognitive behavioural approach they experienced as useful included its potential for changing cognitions (misconceptions and myths in communities), the collaborative nature of the approach, negotiating strategies for risk reduction, use of a problem solving approach, follow-up and monitoring of behaviour. Barriers identified included contextual constraints such as poverty, gender power differentials and cultural practices. Also identified as a barrier was the dominance of the biomedical approach within the health care system. Despite identifying barriers to the application of this approach, counsellors remained optimistic that cognitive behavioural approaches could be adapted to the life context of their clients and that this could be facilitated through further training and mentoring. / Thesis (M.A.)-University of KwaZulu-Natal, Durban, 2007.

Prevention of HIV following sexual assault is an important aspect of rape care. This includes taking Post Exposure Prophylaxis for 28 days. The present study aimed to provide an in-depth understanding of social and environmental factors that predisposed, promoted and also served as barriers to adherence to post exposure prophylaxis to prevent HIV infection after sexual assault in women in the Eastern Cape Province. The study involved a purposive sample of women who were offered Post Exposure Prophylaxis (PEP) after a sexual assault. Sixteen women were accessed at the Sinawe Referral Centre and participated in the study. Their ages ranged from 16 to 73 years. An interview guide was developed to assist the researcher, and semistructured, in-depth interviews were used to collect data. These women were interviewed at the end of 28 days of taking the prophylactic medication. The data were analyzed inductively using grounded theory. Only three women completed the 28 days of PEP treatment. Participants gave different explanations for why they did not complete the treatment with only four participants returning to the centre for their medication. Some reported having no money for transport; others mentioned deciding to discontinue the medication because of its side-effects. Poor support systems, both within the community and the health services, including the provision of conflicting information also played a role. The study showed that few women were able to complete their PEP medication and knowledge about the service and access to it were the main factors that lead to non-adherence. There is an urgent need for the improvement of PEP services particular in the support to the women during the period of taking the PEP treatment to ensure protection from HIV after a sexual assault. / Thesis (M.A.)-University of KwaZulu-Natal, Durban, 2008.

Introduction: The high prevalence of HIV in South Africa was confirmed by Department of Health (2005) which reported an HIV prevalence rate of 40.7 percent amongst antenatal clinic attendees at public facilities in KwaZulu-Natal in 2004. Abstinence is one of the strategies used by many different cultures where young unmarried people are encouraged to abstain from sex until marriage, to prevent young girls from getting pregnant and acquiring sexually transmitted infections (STIs). Aim: The aim of this study was to investigate African rural high school learners' choice of sexual abstinence and to compare abstinent versus non-abstinent African rural high school learners in order to be able to develop tailored educational messages. Abstinence was defined as not having penetrative sex, since this is the accepted definition of abstinence in Zulu culture. Objectives: a) To investigate the prevalence of abstinence from sexual intercourse amongst African rural high school learners, b) To assess demographic, psychosocial, and economic determinants of abstinence from sexual intercourse, c) To make recommendations about abstinence interventions. Method: A descriptive cross-sectional study was carried out in a rural area (Ugu District in southern KwaZulu-Natal). One class of Grade 9 learners, ages 14-20 years, was selected from each often randomly selected rural high schools. An anonymous selfreporting semi-structured questionnaire used the I-Change model to investigate demographic and economic information, attitudes, social influences, self-efficacy and intentions towards sexual abstinence. Chi square and T-tests were used for bivariate analysis and Logistic regression was used to develop a model for abstinence from sexual intercourse. Results: A total of 454 learners participated with a mean age of 16.76 years (SD 1.41) age range 14-20 years. Of the sample 208 (45.8%) were male and 246 (54.2%) female. The majority were Christian (84.6% (n=384)) and of this population, 28.3% (n=127) reported that they had 'ever had sex'. Furthermore, 24.5% (n=91) of learners reported that they were currently sexually active. Fifty six percent (n=252) of learners reported that they abstained from sex. When comparing learners reporting abstinence (n= 252) with those not abstinent (n= 202), abstinent learners were significantly more often females, who had never had sex (p / Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2007.

South Africa has had one of the fastest growing HIV epidemics in the world and almost 30% of women attending public antenatal clinics (ANC) are currently infected with the virus. But as the epidemic is starting to level off and antiretroviral therapy (ART) is becoming increasingly available, few methods exist to determine the impact of ART or other interventions on the epidemic in South Africa. This thesis explores the epidemiology and dynamics of HIV infection and investigates the potential impact of ART. Methods Total and age-specific prevalence data are analysed in time and space and are used to investigate patterns of infection in men and women, urban and rural, and low and high risk populations. Dynamical models are developed to estimate incidence from age-specific prevalence and trends over time and are compared to laboratory-based estimates of recent HIV sero-conversion. Incidence is estimated in different populations in South Africa. A dynamical model is developed to estimate the impact of ART on the future course of the HIV epidemic. Results HIV prevalence varies geographically and by age, sex and race. The average female-tomale HIV prevalence ratio is 1.7 and prevalence peaks at an older age among men than women. The age at which prevalence peaks among women has increased from 23.0 to 26.5 years between 1995 and 2002. Four patterns of infection are identified: among pregnant women attending ANCs, among men and women in the general population, and among migrant workers. HIV incidence among ANC attendees peaked in the mid to late 1990s (at 6.6% per year nationally) with variation between provinces. Current estimates of HIV prevalence and incidence among the general population in South Africa (aged 15-49 year) are 18.8% and 2.4% per year, respectively. Age-specific incidence estimates from dynamical models and laboratory methods are in good agreement provided the window period for the laboratory method is increased. Over the next ten years the provision of ART could avert 1 to 1.5 million deaths depending on whether it is provided when the CD4 cell count falls to 200 or 350 cells/ul. By 2015 about 1.1 million people will be receiving ART but this will have little impact on the incidence of HIV and scaling up of prevention efforts remains urgent. Conclusions The thesis explores some of the determinants and patterns of HIV prevalence and incidence in South Africa in order to find better ways to manage the epidemic of HIV, monitor changes and evaluate progress in control efforts. In order to fight the epidemic we need to mobilize the best possible science in support of those people and communities affected by the epidemic. / Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2007.