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.

MSc Physiotherapy, Faculty of Health Sciences, University of the Witwatersrand, 2009 / HIV is having devastating effects on Africa as a whole and more specifically on Sub-Saharan Africa. Children are vulnerable to the disease and in most cases being hit the hardest. Parenting at the best of times involves some form of stress, and caring for a chronically ill child increases the parenting stress levels. Antiretroviral treatment has a positive effect on children with HIV, however it is not well understood what effect antiretroviral treatment has on the parenting stress levels of the caregivers of children with HIV. The aim of the study was to establish whether caregivers of children diagnosed with HIV show a change in stress levels after commencement of anti-retroviral treatment for their children. The objectives of the study were: to determine if any of the subsections of the PSI-SF were affected by the commencement of antiretroviral treatment in the children; to determine if a correlation existed between the CD4 count of the child and the parenting stress level of the caregiver and to determine whether the age of the child impacted on the scores of the PSI-SF. The demographic data of the participants were also analysed. This study involved secondary analysis of existing data for the study "A longitudinal study of neurodevelopmental delay in HIV positive children" conducted by Joanne Potterton utilising a longitudinal pre-post test study design where participants were compared to their own baseline scores. The Parenting Stress Index Short Form (PSI-SF) was used to establish the parenting stress levels within its three different subsections. The PSI-SF was completed by the caregivers at visit one, two and three. These visits were to the Harriet Shezi Clinic at Chris Hani Baragwanath Hospital, Soweto, Johannesburg. The children were antiretroviral naïve at visit one, and at visit two which was six months later, they commenced antiretroviral treatment with a six months follow-up which was visit three. iv Forty-five participants were included in the study. The paired ‘t’ test showed a significant change (‘p’ = 0.02) in the subsections Parent Child Dysfunctional Interaction and Difficult Child(change in mean -3.31 and -2.78 respectively), while the subsection of Parenting Distress had no significant change between visit one and visit two (change in mean -2.09). The change in mean between visit two and three was -1.84 for the Parental Distress subsection, 0.6 for the Parenting Child Dysfunctional Interaction subsection and 0.8 for the Difficult Child subsection. The paired ‘t’ test was applied to visit one and three and the subsection Parenting Distress showed the greatest positive change of 'p' = 0.00 with a change in mean of -3.93. There was no correlation between the CD4 count of the child and the PSI of the caregiver at any of the visits (r=-0.2, 0.11,0.3, p=0.15, 0.5, 0.06 respectively). There was no correlation between the age of the child and the parenting stress of the caregiver at any of the visits (r=0.13,0.08,0.5 p=0.39,0.6 and 0.1 respectively). The stress levels of the caregivers decreased over the study period however there was no significant decrease with the commencement of antiretroviral treatment.

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.

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.

Background In 2010, 2.2 million adolescents were living with HIV (Human Immunodeficiency Virus) worldwide. This study aimed to describe the socio-demographic and clinical characteristics of the adolescents (10-19 years old) initiating anti-retroviral treatment (ART) and to investigate characteristics that are associated with virological failure in adolescents on ART. Methods This was an analysis of adolescents initiating ART from June 2004-2010 at the Hlabisa Treatment and Care Programme in KwaZulu-Natal, South Africa. Data was collected from two datasets at Africa Centre for Health and Population Studies. Time to outcomes of death and lost to follow up (LTFU) were quantified using Kaplan-Meier estimates. The outcome was virologic response (< 70copies/ml) after at least 6 months on ART and the associations with an unsuppressed viral load were investigated using multivariable logistic regression. Results 543 adolescents, median age 15 years (IQR 12-18), initiated ART; 67.8% (368) were females. Age at treatment initiation showed a bimodal distribution, with a peak at 11 years and another at 17-19 years; 61 females aged 16-19 years initiated ART whilst pregnant. At baseline, median CD4 count was 152 cells/μl (IQR 72-251), 392 (72.2%) had prior TB and 129 (23.8%) a weight-for-age z-score ≤ -2 (i.e. were under-nourished). Numbers of adolescents starting ART increased from 53 in the years 2004-2006 to 196 in 2010. Overall mortality was 36.5 per 1000 person years (95% CI 27.2 - 48.8); LTFU 98.8 per1000 person years (95% CI 82.8-118). Adjusting for age and gender, LTFU was significantly higher in females initiating in late adolescence (15-19 years) (p<0.001) and 24 (39.3%) of those initiating ART whilst pregnant were LTFU. The first viral load after initiation was taken at a median time of 11.25 months (IQR 7.78-16.20). Of the 364 adolescents with a viral load result after at least 6 months of ART, 119 (32.7%) had an unsuppressed viral load (95% CI 27.9- 37.5). Adolescents who initiated in the year 2010 were found to have less odds of an unsuppressed viral load compared to those who initiated between 2004 and 2006 [adjusted Odds Ratio (aOR) 0.29 (95% CI 0.11-0.79)]. Those who had the first viral load test done after > 30 months of ART had higher odds of an unsuppressed viral load compared to those tested after 6-12 months of ART [ aOR 6.88 (95% CI 1.29-36.66)]. Conclusion Despite the yearly increase in adolescents initiating ART, good virological responses can be obtained through increased ART support to both individuals and health care providers. Timely viral load monitoring identifies those in need of increased adherence support on ART and may result in good virological responses. Recommendations Adolescents on ART are a vulnerable group that requires special attention to improve clinical and virological outcomes. Adolescent friendly ART clinics may be useful in providing this service and mitigate the high attrition rates of those on treatment for HIV. Public health awareness campaigns on HIV and its treatment may have a positive impact on virological response to ART and therefore campaigns targeting adolescents must be intensified. Early virological testing after 6 months on ART to monitor treatment responses helps to identify those with sub-optimal response to ART and reduce the progression to virological failure and drug resistance to anti-retroviral drugs.

Submitted in partial fulfilment of the requirements for the degree of Master of Public Health, in the field of Maternal and Child Health, to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, September 2014 / Introduction: Nevirapine (NVP) is used in combination antiretroviral treatment especially for pregnant HIV infected women. NVP has been shown to be inferior and more toxic than other similar drugs, but continues to be used in developing countries due to cost. Aim: This study aimed to determine the prevalence of NVP toxicity and associated factors among 478 pregnant women from three public health facilities in inner city Johannesburg. Materials and methods: We employed a cross-sectional retrospective record review study design to analyse the records of 478 pregnant women in the above mentioned public health facilities. Variables including demographic (age, weight, gestational age) and clinical (CD4 cell count, WHO HIV clinical stage, prior ART experience) characteristics were extracted and the association between these characteristics and the development of toxicity post NVP exposure was explored. Results: The study found that approximately nine out of ten women (89.5%) were ART naïve at the time of NVP initiation. When compared with ART naïve women, ART experienced women had a slightly higher mean CD4 cell count, however, for both groups of women, mean CD4 cell count was less than 250 cells/mm3. Overall, 85.1% of women had a CD4 cell count less than 250 cells/mm3. More than half (55.3%) of the women were in the third trimester of pregnancy and the majority (82%) classified as WHO HIV clinical stage one. At least one adverse event was reported in 63 (13.2%) women. Mild skin rash was the most prevalent adverse event, occurring in 9.6% of women. Hepatotoxicity occurred in 5.3% of women and severe skin rash occurred in 1.5% of women. Almost 85% of adverse events occurred in women with CD4 cell counts <250 cells/mm3. WHO HIV clinical stage II and IV were significantly associated with the overall development of toxicity (ρ <0.01). Conclusions: Whilst the overall prevalence of mild and severe skin rash in this sample was less than that demonstrated in earlier studies, a higher overall prevalence of hepatotoxicity was found. When compared with ART naïve women, ART experienced women were found to have a higher prevalence of mild skin rash. Hepatotoxicity and severe skin rash only occurred in ART naïve women. In this sample, CD4 cell count ≥250 cells/mm3 was not associated with the development of NVP adverse events. Recommendations: Our findings support the continued use of NVP as part of combination ART regimens in women of African descent. In contrast with previously published data, our study showed a significant association between WHO HIV clinical stage and NVP toxicity, our study also included relatively few women with higher CD4 cell counts. Further research including predominantly healthy HIV infected pregnant African women as well as women with higher CD4 cell counts is required in order to fully explore the association between these variables and the development of NVP post-exposure toxicity.