Magister Public Health - MPH / Despite the known benefits of adolescents knowing their HIV status, parents and caregivers (PCG) often delay the disclosure of their children’s HIV status to them due to the fear of stigma and discrimination, the belief that the child thinks they will die, and the lack of disclosure skills. This delay can affect the children’s adherence to treatment, physical health, mental health and can enable unknowing transmission. The Mini Flipster Disclosure Method (MFDM) was developed to assist healthcare workers (HCWs) in supporting the disclosure of an adolescent’s HIV status by their parent or caregiver. This involves a process of educating the child or adolescent about HIV and how it can be successfully managed before informing them that they have HIV. The current study described the experiences of HIV-positive adolescents of the MFDM and those of their caregivers and HCWs in Mpumalanga.

The era of the integrase strand transfer inhibitors (INSTIs) for the treatment of human immunodeficiency virus (HIV) infection began with raltegravir in 2007. Since that time, several other INSTIs have been introduced including elvitegravir, dolutegravir, and, most recently, bictegravir, that have shown great utility as part of antiretroviral regimens in both treatment-naive and treatment-experienced patients. At present, antiretroviral guidelines fully endorse the INSTI class as part of all first-line treatment regimens. After 10 years of experience with INSTIs, newer agents are on the horizon such as cabotegravir and MK-2048 for potential use as either HIV pre-exposure prophylaxis or maintenance therapy. This review provides a brief overview of the INSTI class including agents currently available and those still in development, reviews available data from both completed and ongoing clinical trials, and outlines simplification strategies using INSTIs.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, in partial fulfillment for the degree Masters of Medicine in Paediatrics (MMed) Johannesburg 2012 / Introduction: Highly active antiretroviral treatment (HAART) programs in heavily HIV-TB burdened countries may reduce the risk of TB in children directly by improving the immune system of HIV-infected children; and indirectly by reducing the force of transmission from the adult population. The incidence of childhood TB is a sentinel measure of the control of infectious adult TB cases in the community. Objective: We evaluated the impact that scaling-up of the HAART program in Soweto had on the incidence of hospitalization for culture-confirmed TB in children. Methods: The study was undertaken in Soweto, where the prevalence of HIV was 4-5% in children between 2005 and 2009. The estimated HAART coverage increased from 43% in 2005 to 84% by 2009 in children with HIV/AIDS. Hospitalized cases of culture-confirmed TB in children 3 months to 14 years of age were identified through laboratory and clinical electronic databases. Results: Overall, the incidence (per 100 000) of hospitalization for culture-confirmed TB declined by 58% (95%CI 49.3-65.2) from 2005 (71.4) compared to 2008-9 (30.0); p<0.0001. This included a 67% (95%CI 58.5-74.8) reduction in incidence among HIV-infected children from 2005 (1 601) compared to 2008-9 (517; p<0.0001). v In addition, a 33% reduction was observed in HIV-uninfected children (incidence 19.3 vs 12.9; p=0.016). Fifty-six percent of TB episodes, across all study periods, occurred in HIV-infected children who were mainly (76%) severely immunocompromised. Conclusions: Up-scaling of the HAART program in South Africa has been associated with decline in the incidence of culture-confirmed TB, more so in HIV-infected than HIV-uninfected children. Severely immunocompromised HIV-infected children, however, need to be identified and targeted with HAART and other strategies to further reduce the burden of TB in this group.

Thesis (M.Sc. in Epidemiology)--University of the Witwatersrand, Faculty of Health Sciences, 2014. / Introduction: The prevalence of the Human Immunodeficiency Virus (HIV) in South Africa was 17.8% among 15 to 49 year olds in 2010. Antiretroviral therapy (ART) has thus played a crucial role in mitigating the impact of the HIV epidemic. Themba Lethu Clinic is one of the largest single clinics providing ART in South Africa. One of the challenges of ART provision is ensuring adherence to taking the medication. To date there has been no clear consensus on the ideal way to measure adherence in resource limited settings (RLS). Viral load is perhaps the best and most reliable indicator of poor adherence but is expensive and not easily accessible or available in many RLS. Surrogate markers such as mean cell volume (MCV), CD4 cell count, self-reported adherence and missed visits have been shown to be useful to measure adherence but their reliability remains unclear. The aim of the study was to identify other markers that can be used to measure adherence using viral load as the gold standard. Materials and methods: The study was a retrospective analysis of HIV-positive ART-naïve adults (≥ 18 years) initiating standard first-line ART at the Themba Lethu Clinic in Johannesburg, South Africa between April 2004 and January 2012. The association between the last self-reported adherence, change in MCV calculated from baseline to 6 months, change in CD4 count calculated from baseline to 6 months (≥ or < the expected increase of 50 cells/mm3 at 6 months) and missed visits (defined as a scheduled appointment that had been missed by ≥ 7 days but not by more than 3 months) and poor adherence (defined as a viral load ≥ 400copies/ml after 6 months on ART) was tested using Poisson regression models with robust error variance to estimate incidence rate ratio (IRR) and 95% confidence interval (CI). The IRR was used to approximate the relative risk (RR) of poor adherence. Interacting variables were stratified by each other, to create a new variable. The diagnostic accuracy of each identified marker of adherence was also tested using sensitivity, specificity, positive predictive values and negative predictive values. Results: 7160 patients were eligible for the study and of these 63.2% were female. The median age was 36.7 years. The median CD4 count was 101 cells/mm3 at baseline and 18.9% of the patients had poor adherence at 6 months. Variables associated with poor adherence at 6 months were change in CD4 count stratified by change in MCV at 6 months (change in CD4 count ≥ expected and change in MCV ≥ 14.5fL; adjusted relative risk (aRR) 1, change in CD4 count ≥ expected and change in MCV < 14.5fL; aRR 3.11 95% CI 2.41 – 4.02, change in CD4 < expected and change in MCV ≥ 14.5fL; aRR 1.23 95% CI 0.76 – 2.00 and change in CD4 count < expected and change in MCV < 14.5fL; aRR 6.98 95% CI 5.35 – 9.09), CD4 count at baseline (> 200 cells/mm3; aRR 1, 101 – 200 cells/mm3; aRR 1.05 95% CI 0.80 – 1.38, 51 – 100 cells/mm3; aRR 1.08 95% CI 0.80 – 1.47 and ≤ 50cells/mm3; aRR 1.34 95% CI 1.02 – 1.76) , WHO stage at baseline (stage I; aRR 1, stage II; aRR 1.16 95% CI 0.90 – 1.48, stage III; aRR 1.27 95% CI 1.04 – 1.55 and stage IV; aRR 1.44 95% CI 1.12 – 1.84) and MCV at baseline (< 80fL; aRR 1, 80 – 100fL; aRR 1.33 95% CI 1.01 – 1.75 and > 100fL aRR 0.98 95% CI 0.62 – 1.55). Sensitivity and specificity of the change in CD4 stratified by change in MCV at 6 months to predict poor adherence were 86.5% and 37.3% respectively for all eligible patients. For patients on AZT-based regimens the variables associated with poor adherence at 6 months were change in CD4 count at 6 months (≥ expected; aRR 1 and < expected; aRR 7.66 95% CI 0.98 – 59.91) and pregnancy during the first 6 months on ART (Never pregnant; aRR 1 and pregnant during follow up; aRR 9.11 95% CI 2.17 – 38.25). Sensitivity and specificity of the change in CD4 count at 6 months to predict poor adherence were 64.7% and 75.2% respectively for all eligible patients on AZT-based regimens. Sensitivity and specificity of pregnancy during the first 6 months on ART to predict poor adherence were 20% and 97.6% respectively for all eligible patients on AZT-based regimens. Discussion: Change in CD4 count stratified by change in MCV at 6 months was an expected marker of adherence as CD4 count is expected to rise in adherent patients on ART and since most patients (62.9%) were on d4T or AZT-based regimens. Pregnancy during the first 6 months on ART appeared as a marker of adherence for patients on AZT-based regimens before multiple imputation possibly due to missing data hence results for this variable should be interpreted with caution. Contrary to previous studies, self-reported adherence was not associated with poor adherence at 6 months before multiple imputation. This could have been due to the fact that that > 50% of patients had missing data for this variable. The variable is also vulnerable to recall and reporting bias so even after multiple imputation, the area under the receiver operating characteristic (ROC) curve remained < 0.55. The number of missed medical visits and regimen change were also markers of adherence in a few of the models after multiple imputation and require further investigation. In conclusion, the markers of adherence to ART are change in CD4 count stratified by change in MCV at 6 months and pregnancy during the first 6 months on ART for patients on AZT-based regimens. These could help health workers identify poor adherence in the absence of viral load testing and target patients for adherence interventions to prevent virological failure.

Introduction: Improvements in early detection of human immunodeficiency virus (HIV), linkage to treatment, and availability of antiretroviral therapy (ART) have contributed to increasing life expectancy for people living with HIV (PLHIV) in South Africa. These improvements have resulted in the decline of HIV cause-specific mortalities. In addition to existing tuberculosis burden in PLHIV, cases of chronic non-communicable diseases (NCDs) are increasing in the general population. Considering the ageing population of PLHIV in South Africa, it is important to understand their health needs, as well as identify potential drivers of comorbidities that may provide avenues for future interventions. This study aimed at exploring HIV and comorbidity profiles in a virtual cohort of a population of healthcare clients accessing care in public facilities in Khayelitsha, Cape Town. Methods: Routinely collected data for healthcare clients accessing care in public facilities in 2016/17 were obtained from the Western Cape Provincial Health Data Centre, and analysed to describe ascertained comorbidities, comparing the profiles of PLHIV and HIV-negative individuals. The risks of comorbidity occurrence in PLHIV, in the context of other comorbidities and HIV metrics such as ART duration, viral load and CD4 cell counts, including the contribution of comorbidities to unsuppressed viral load levels in PLHIV were explored. Findings: The findings show that accessing HIV care may lead to earlier ascertainment of common chronic NCDs – hypertension, diabetes, chronic kidney disease (CKD), cervical cancer in PLHIV, compared to HIV-negative clients. Analysis of routine health data suggests that ascertainment of comorbidities differs for healthcare clients due to sub-population differences including age, sex, HIV status and reasons for accessing care. Routine laboratory testing results for renal function reflect distinct healthcare experiences by age for healthcare clients with and without HIV. Analysis of routine data shows that presence of an existing comorbidity may contribute to the incidence of other comorbidities and unsuppressed viral load levels in PLHIV. Conclusion: From real life routine health data, this study has explored comorbidities profiles of PLHIV and HIV-negative clients and observed that routine health data could provide a better understanding of disease profiles, healthcare access and requirements for both PLHIV and HIV-negative clients.

No description available.

Magister Public Health - MPH / Background: Human Immune Deficiency Virus (HIV) is a public health challenge worldwide. Antiretroviral therapies (ART) are medications that treat HIV virus infection by suppressing the virus and stopping progression of HIV disease, and that improve quality of life. People initiated on ART need to adhere to their treatment for the rest of their lives. In 2016, there were 7,1 million people (age 15-49) in South Africa living with HIV, representing 19 % of the global HIV burden, with 56% of the adults on ART. Life expectancy of South Africans for both males and females improved between 2009 and 2011 because of ART treatment. People lost to follow up while on ART compromise their own health and the long term positive benefits of the ART regimen, and hence there is a growing emphasis to improve the retention of people who are already on treatment. Aim: This study was conducted examining HIV positive South African Clothing and Textile Workers Union (SACTWU) members who are currently on ART treatment and had previously been lost to follow up (LTFU) from ART care. The study aimed to explore factors associated with LTFU of clients on ART treatment and care among the South African Clothing and Textile Union members living with HIV and attending the SACTWU Worker Health Program Clinic.

Master of Public Health - MPH / It is well documented that mortality rates have decreased and the survival of HIV and AIDS patients has been prolonged since the introduction of highly active antiretroviral therapy (HAART) in 1996. Although HAART has dramatically improved the prognosis of HIV disease, some HIV patients on HAART still die of HIV related illnesses. It is important to understand what these factors are in order to mitigate the impact on these factors on patient survival and achieve better outcome for these patients. The aim of this study was to determine risk factors for long term survival of patients on HAART in Uganda. Data for 2,244 out of 30,000 clients receiving care and treatment at TASO Entebbe was retrospectively analyzed. TASO Entebbe is a non-governmental HIV clinic that provides care and treatment to HIV positive clients. Long term survival in this case was defined as survival for more than 5 years after initiation on HAART. Logistic regression and survival analysis were conducted. Female clients had a 12% lower risk of death compared to the male clients (AHR=0.88 [CI: 0.443- 0.936]). Clients that had pulmonary TB had 1.3 times higher risk of death compared to clients that did not have pulmonary TB (AHR=1.33 [CI: 1.162-2.733]). Clients initiated at CD4 cell counts less than 250 cells/μl had almost 7 times higher adjusted odds of death compared to those initiated at CD4 cell counts greater than 500 cells/μl (AOR= 6.95 [CI: 2.882-16.744]) and clients initiated at CD4 cell counts between 250 cells/μl and 500 cells/μl almost 3 times higher adjusted odds of death compared to clients initiated at CD4 cell counts greater than 500 cells/μl (AOR 2.56 [CI: 1.004-6.520]). It is recommended that an aggressive HIV testing strategy be put in place to facilitate early identification of HIV positive patients. Early identification would enable early initiation into HAART well before the CD4 cell counts fall below 500 cells/μl. The observed higher risk of mortality amongst men suggests interventions to promote early HIV testing and treatment initiation amongst men. The observed high risk of mortality for patients with pulmonary TB, calls for aggressive TB case finding and treatment of positive in order to reduce the HIV/TB related mortality.

>Magister Scientiae - MSc / Adverse effects are a significant factor that determine how long patients will tolerate a given antiretroviral drug regimen. They also influence treatment options, and play an important role in the much needed adherence to treatment by patients on Highly Active Antiretroviral Therapy (HAART). This study is aimed at understanding adverse effects experienced by patients on the first line antiretroviral therapy at Keetmanshoop Hospital in Namibia. Methods : A retrospective quantitative method was used to review records of patients on first line antiretroviral treatment who started treatment between November 1st 2007 and December 1st, 2008 and followed up until they reached 36 – 48 months on treatment. Records of 94 patients were found eligible to be included in the study. Data was analysed using Stata 12 data analysis software. Results : The most reported adverse effect was musculoskeletal disorders (25%) whereas headache (16%) was the least reported. Low haemoglobin (78%) was the most common recorded hematologic adverse effect whereas low red cell distribution width and low mean platelet volume were the least recorded adverse effects (0%). A Male patient was more likely to experience a low haemoglobin levels compared to a female patient (adjusted OR: 3.29, 95% CI: 1.3 – 8.3). A male patient was found to be 64% times less likely to experience a higher mean cell haemoglobin compared to a female patient (adjusted OR. 0.31, 95% CI: 0.11 – 0.87). A patient on nevirapine was more likely to experience an elevated creatinine level compared to a patient on efavirenz (adjusted OR; 36.0, 95%CI: 2.02 – 62.5). At baseline, a patient who had prior exposure to ART had an 81 times (adjusted OR: 81.4, 95%CI: 5.3 – 119, p-value=0.00) increased odds of experiencing a high mean cell volume (MCV) compared to a patient with no ART exposure. A patient with a higher CD4 count was also less likely to experience a low hemoglobin compared to a patient with low CD4 count (adjusted OR; 0.31, 95% CI: 0.12 – 0.77). The author recommends further studies with higher sample size to confirm whether higher creatinine levels are more prevalent in patients on nevirapine compared to patients on efavirenz; this will have clinical implications especially in patients with impaired renal system. Antiretroviral treatment increases chances of developing macrocytosis anaemia; clinical implication of this condition may need to be investigated.

Magister Public Health - MPH / Background: The hallmark of HIV infection is immunosuppression which predisposes to unusual infections and malignancies generally known as opportunistic diseases (ODs). Globally, ODs are the major cause of morbidity and mortality in people living with HIV (PLHIV). Since the advent of Highly Active Antiretroviral Therapy (HAART), a significant decline in AIDS progression and ODs has been observed globally. However, most of the evidence suggesting sustained decline in AIDS progression and ODs has come from high-income settings with relatively less burden of ODs in the pre-HAART era. The findings of studies in high-income settings may not be generalizable to resource-limited settings. Lack of information regarding the burden of ODs in HAART-experienced populations in Nigeria and the risk factors for their occurrence has made it difficult to fully assess the sustained efficacy of HAART in the country. The aim of this study was to investigate the prevalence of and risk factors for HIV-related opportunistic diseases amongst HAART patients at the Federal Medical Centre (FMC) in Owerri, Nigeria. Study design and setting: A quantitative, cross-sectional descriptive and analytical study was conducted with 354 adult HIV-infected patients 15 years and above, who were on HAART for a minimum of 12 weeks at the HIV clinic of the FMC, Owerri, South-east Nigeria. Patients currently manifesting an OD whose onset ante-dated the commencement of HAART were excluded. The participants were recruited by simple random sampling. Data collection: Using a structured questionnaire, data was collected by clinicians through interviews, physical and laboratory examinations for patients that provided informed consent and met the study criteria. The questionnaire captured patient’s socio-demographic information and other relevant clinical/laboratory data. Data Analysis: The data was analysed using Epi info version 3.5.1 and Open Epi Version 2.2.1. Descriptive statistics for HIV-related ODs were carried out using percentages and frequencies tables for categorical variables and means (SD) or medians (IQR) for numerical variables. In univariate analysis, the Chi-square test was used to determine significance of association between OD and socio-demographic and clinical variables while the Student "t"-test was used to compare group means. Logistic regression model (multivariate analysis) was used to determine the independent risk factors for the occurrence of ODs using parameters that had a p-value of <0.25 on univariate analysis. All reported p-values <0.05 were considered statistically significant. Results: The mean age of the participants was 41.1 ± 10.0 years; and females were in the majority (65.8%). Over 40% of them were rural dwellers, 50.4% belonged to the lower socioeconomic class, and 55% had a monthly household income less than 20,000 Naira. Fifty percent (50%) of them had advanced immunosuppression at first presentation. The median duration of HAART (3 years) paralleled the median duration of HIV diagnosis (3.4 years) and HAART adherence rate was 78%. The overall prevalence of ODs was found to be 22.4%. Among the 76 patients diagnosed with ODs, the leading conditions were candidiasis (38.2%), TB (34.2%), dermatitis (25%), chronic diarrhoea (6.6%) and sepsis (6.6%). The independent risk factors for the occurrence of ODs were household income less than 20,000 Naira (Adjusted odds ratio [AOR] = 2.4, 95% CI 1.1-5.1), HIV duration of less than 3 years (AOR= 2.1, 95% CI 1.1- 4.2), advanced WHO clinical stage at baseline (AOR= 8.1, 95% CI 4.0-16.4), baseline haemoglobin less than 10 g/dl (AOR= 2.9, 95% CI 1.3-56.1), current CD4 cell count less than 200 cells/μl (AOR= 3.0, 95% CI 1.14-6.2), and HAART non-adherence (AOR= 5.4, 95% CI 2.6-11.2). Past history of TB was found to be a strong predictor of TB (AOR= 5.3, 95% CI 1.4-20.2). Conclusions: Opportunistic diseases are common in patients receiving HAART in Nigeria and candidiasis and TB remain the leading conditions. Late presentation and HAART non-adherence are among the strongest risk factors for ODs in patients receiving HAART. Others include duration of HIV diagnosis less than 3 years, presence of anaemia at the time of first presentation and having a low CD4 cell count while on HAART. Beyond these clinical risk factors, poverty increases the risk of developing an OD during HAART and may emerge a strong determinant of HIV-related ODs in developing countries. Recommendations: A high index of suspicion for ODs remains necessary in HAART patients. Health education on HIV screening and early presentation should be intensified. PLHIV who are anaemic before commencement of HAART, those with low CD4 cell count despite HAART use, and low-income earners should become target groups for a more aggressive evaluation for ODs. Prophylaxis for TB and fungal infections in the absence of active disease should be widely implemented in developing countries. HAART adherence should be intensified.