3. Electronic Theses and Dissertations (ETDs)

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Ageing with HIV: Psychological and Functional Wellbeing and its biopsychosocial determinants at the Kenyan coast
(University of the Witwatersrand, Johannesburg, 2024) Mwangala, Patrick Nzivo; Abubakar, Amina
Background: Kenya, and sub-Saharan Africa (SSA) in general, are experiencing rapid demographic transitions, including the ageing of the HIV population. Intuitively, this has created a subgroup of vulnerable older adults living with HIV (OALWH) requiring an urgent response in research, policy, and programming to mitigate their complex and transitioning needs. Existing evidence on HIV and ageing, largely from European cohort studies, demonstrates that OALWH are vulnerable to ill health, especially psychological morbidities (e.g. mental and cognitive impairments), geriatric syndromes (e.g. frailty) and multimorbidity. For the last decade, the SSA region has witnessed noteworthy progress in ageing and health, e.g. the establishment of health and ageing cohorts in South Africa. Yet, current evidence on mental, cognitive, and geriatric syndromes among OALWH is inadequate from the region partly because of heterogeneous findings, few well-designed studies, and significant methodological limitations, e.g. small sample sizes, lack of comparison groups and few adapted/validated measurement tools. In Kenya, HIV and ageing is an emergent subject, and little is known about the burden and determinants of these impairments. To address some of these research gaps, this PhD thesis sets out to: (a) Understand the health challenges faced by OALWH and the coping strategies they use to confront these challenges on the Kenyan coast, (b) Document the burden and associated factors of common mental disorders (CMDs) and frailty among OALWH compared to their HIV-uninfected peers on the Kenyan coast, (c) Examine the acceptability, reliability, and validity of a local (Swahili) measure of cognitive function, the Oxford Cognitive Screen Plus (OCSPlus), among older adults and provide a preliminary understanding of their cognitive performance (by HIV status) and associated factors. v Methodology: We used a mixed methods research design to answer our research questions, employing both qualitative and quantitative approaches. The qualitative phase of the study recruited 34 OALWH receiving routine HIV care and treatment, together with their healthcare providers (n=11) and primary caregivers (n=11). Qualitative data were drawn from semi-structured in-depth interviews that were audio-recorded, transcribed verbatim, and analyzed using the framework approach. Data management was done in Nvivo software. The quantitative phase, a cross-sectional survey, involved 440 older adults aged ≥50 years (58% OALWH). Locally adapted and/or validated tools were used to assess CMDs, frailty and cognitive function. All quantitative analyses were conducted using STATA software. Proportions were used to estimate the prevalence of CMDs and frailty among OALWH and their HIV-uninfected peers. Logistic regression was used to examine the factors associated with CMDs and frailty. Different psychometric tests were used to assess the reliability and validity of the OCSPlus tool. Test-retest reliability was evaluated using intra-class correlations. We computed Pearson correlation coefficients to assess convergent validity between OCSPlus and conventional cognitive tests. Multiple linear regressions were used to examine correlates of cognitive function. Results: Our findings from the qualitative phase showed that OALWH face multiple mental health challenges (e.g. symptoms of depression, anxiety, cognitive complaints) and physical health challenges (e.g. hypertension, diabetes, ulcers, somatic symptoms, and functional impairments), which were often complicated by a host of psychosocial challenges including food insecurity, ageism, HIV-related stigma, loneliness, and financial difficulties. Many of the perceived risk factors for these challenges were observed to overlap across the three health domains. Five major themes emerged from analyzing participants’ narratives on coping strategies, including self-care, positive religiosity, social connectedness, generativity and identity and mastery. Our findings also revealed maladaptive coping strategies, including self-isolation, over-reliance on over-the-counter medication, delayed healthcare seeking and skipping meals and medications. In the cross-sectional dataset, we found no significant differences in the vi prevalence of mild depressive symptoms (24% vs 18%) and anxiety symptoms (12% vs 7%) among OALWH compared to their uninfected peers, respectively. However, the prevalence of frailty was significantly higher among OALWH (24%) than their uninfected peers (13%). After adjusting for biopsychosocial factors, HIV seropositivity was not independently associated with CMDs or frailty. In multivariable analyses, the factors associated with increased odds of CMDs and frailty included HIV-related stigma, ageism, loneliness, functional impairment, sleeping difficulties, increasing household HIV burden, chronic fatigue, increasing medication burden, advanced age (>70 years), higher waist/hip ratio, visiting traditional healers, history of combination antiretroviral therapy (cART) regimen change/interruption, and prolonged illness following HIV diagnosis. In contrast, factors associated with reduced odds of CMDs and frailty included easier access to an HIV clinic, residing in larger households, higher household income, having a social network of friends, and being physically active. Most of these factors were corroborated in the qualitative phase of the study. In our last objective, the OCSPlus measure was found to be acceptable, reliable, and valid. Concerning cognitive performance, OALWH presented with significantly lower mean scores on language and executive function compared to their uninfected peers; however, they (OALWH) performed significantly better on memory. Several factors ranging from behavioural and lifestyle, sociodemographic, medical or treatment factors and psychosocial factors were significantly associated with cognitive performance (using OCSPlus). Discussion: Due to effective antiretroviral therapy (ART), people living with HIV are ageing, and this is witnessed across the world wherever ART is readily available. While this represents the success of HIV care and treatment, those ageing with HIV confront numerous health challenges, some of which are unique to this population, as observed in this study. Older adults living with HIV on the Kenyan coast are vulnerable to mental, cognitive, and functional health challenges, which appear to be complicated by several psychosocial challenges. Despite the observed health challenges, OALWH are able to integrate several positive strategies to promote or address their mental health and well- being. The findings of this study are timely in addressing some of the existing gaps in vii understanding the mental, cognitive, and functional health of OALWH in the country and set the stage for further research and the development of relevant interventions and healthcare strategies to improve the care of these adults. OALWH need to be recognized as an unique subpopulation requiring targeted health and social services, given the unique health challenges observed in this study. Relatedly, there is a need to build the capacity of healthcare providers, for instance, in the screening and management of CMDs and frailty, at least for the OALWH at risk of poor health outcomes, e.g., those facing multiple psychosocial challenges and deteriorating HIV treatment indicators. The majority of healthcare providers interviewed in the qualitative phase lamented their lack of skills and capacity to screen and manage CMDs and cognitive impairments. Additional support may include helping OALWH and their caregivers to mobilize social support and referrals, where possible, to relevant institutions and increase access to basic needs and services. The Kenya HIV prevention and treatment guidelines also need to be updated to highlight the unique needs of OALWH, e.g. multimorbidity. Different models of care have been recommended for the care of OALWH, including comprehensive geriatric assessment and integration of chronic care services into routine HIV care services. Formative work can be conducted to assess the possibility of introducing these models into care. Future work needs to ascertain the cause-and-effect association of the reported correlates and carry out formative work on the feasibility of multicomponent psychological and physical interventions to address identified health problems, e.g. psychosocial challenges, CMDs and frailty.
The association between poor sleep quality and cardiometabolic risk in HIV+ individuals and the general population living in a rural area of South Africa
(University of the Witwatersrand, Johannesburg, 2024) Reddy, Tracy; Scheuermaier, Karine; Karstaedt, Alan
Studies show that both poor sleep quality and HIV infection independently increase cardiometabolic risk (CMR). Additionally, poor sleep quality is common with HIV infection. Our study investigated whether HIV infection interacts with poor sleep quality to affect CMR in people living with HIV (PLWH) in a rural area of South Africa. We recruited 200 HIV+ participants and 200 controls from Qwa Qwa in Free State in South Africa and assessed their CMR, sleep quality, daytime sleepiness, risk of obstructive sleep apnoea and degree of depressive symptoms. Sleep quality (p = 0.15), daytime sleepiness (p = 0.31) and the cardiometabolic risk score (MetScore) (p = 0.93) were similar between HIV+ and control participants. Fewer HIV+ participants had a high risk of sleep apnoea (p = 0.019) but more HIV+ participants had symptoms of clinical depression (p = 0.0007). Poorer sleep quality in the HIV+ participants was associated with pain (p = 0.0006), more severe depressive symptoms (p<0.0001) and longer HIV duration (p = 0.011). However, HIV infection was not associated with a higher MetScore (p = 0.18) once age, sex and sleep and depression markers were adjusted for. Additionally, HIV infection increased the risk of hypertension (p = 0.016). HIV status did not interact with sleep quality (p = 0.32) to affect CMR. Our findings indicate that healthcare facilities should consider monitoring CMR factors in HIV+ individuals.
Assessment of the in vitro phenotypic drug susceptibility of HIV-1 subtype C drug-resistant variants to Doravirine (DOR)
(University of the Witwatersrand, Johannesburg, 2024) Reddy, Nikita; Basson, Adriaan
The high prevalence of antiretroviral drug resistance warrants approval of novel antiretroviral drugs that are effective against drug resistant-variants. Doravirine (DOR) is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) with an improved safety profile, requires only a single daily dose, and has shown activity against prevalent NNRTI drug resistance mutations. To understand the impact of NNRTI drug resistance mutations on DOR in South Africa, in which HIV-1 subtype C is prevalent, this study assessed the in vitro phenotypic drug susceptibility of DOR against prevalent HIV-1 subtype C drug-resistant variants. Replication-defective HIV-like pseudoviruses (PSV) containing the most prevalent NNRTI drug resistance mutation combinations (n=20), as well as the single mutations (n=15) they contain, were generated and screened in a single-cycle in vitro phenotypic assay for susceptibility to DOR. An initial screen of DOR against wild-type PSVs showed no significant differences in Islatravir (ISL) potency among subtypes B and C. Furthermore, the combination of DOR with ISL showed a significant synergistic inhibition of a wild-type HIV-1 subtype C PSV. High-level DOR resistance was observed with the V106M and Y188L single mutants, while the remaining single mutants remained susceptible or showed a low level of resistance to DOR. Combinations of mutations that included V106M, Y188L, and P225H showed a high level of resistance to DOR. Given the lower prevalence of the latter mutations in treatment-naïve and -experienced patients in South Africa, DOR would likely be an effective treatment option. However, genotypic drug resistance testing may be advised prior to initiation of DOR-containing regimens for NNRTI-experienced individuals.
Cardiovascular toxicity of combined administration of ethanol and combination antiretroviral therapy in HIV naïve diabetic Sprague Dawley male rats
(University of the Witwatersrand, Johannesburg, 2024) Zwane, Mcebo Treasure; Mbajiorgu, Ejikeme; Johnson, Jaclyn
Atripla, a combination antiretroviral drug (cART) was the first once daily antiretroviral treatment to be approved by FDA in 2008. Since then, Atripla has been the first line of treatment in HIV/AIDS management, and one of widely used medications, with 76% of people living with HIV on medication. The incidence of diabetes in Africa has increased, owing to decreased mobility and increasing urbanization in the continent. Excessive alcohol consumption on the continent, especially in South Africa is common across all age groups, with ethanol (alcohol) often taken concomitantly with antiretroviral drugs. This results in co-presence of cART and alcohol in a diabetic condition. Adult male Sprague-Dawley rats divided into 8 groups were used: untreated (negative control), diabetic (diabetes, diabetes + alcohol, diabetes + Atripla, and diabetes + Alcohol + Atripla), and treated (alcohol alone, alcohol and Atripla, and Atripla alone). Harvested hearts’ morphology was investigated (surface area and weight) before being processed and histological investigations were carried out (H&E for structural differences, Pentachrome for collagen and muscle profile, and Verhoeff Van Gieson for collagen and elastic fiber profiling). Fasting glucose levels were measured and recorded throughout the study. Enzyme-linked immunosorbent assays for troponin I&T (myocardial degeneration), MDA, and GPx (oxidative stress) were performed. Additionally, immunohistochemistry for expression of eNOS (as a marker for endothelial homeostasis) and c- reactive protein CRP (as a marker for inflammation) were performed. The fasting glucose was significantly increased in diabetes + Alcohol + Atripla group (DBALCARV) throughout the study period (p=0.001), and morphological examination revealed a decrease in body weight (p=0.001) and total surface area of the heart (p=0.01). The coronary 5 artery had a significant decrease in tunica media thickness (p=0.02), while the aorta was increased (p=0.001). The collagen in the coronary arteries was significantly increased when examined with Pentachrome special stain (p=0.032). The collagen was also significantly increased in both ventricle (p=0.015) and atrium (p=0.013). Qualitative analysis of c-reactive protein and endothelial nitric oxide synthase immunohistochemistry showed a reduction in localization of both antibodies. In conclusion, combination of cART, diabetes, and alcohol resulted in changes in cardiac and vascular morphology, fasting glucose, body weight, oxidative stress, myocardial degradation markers, and collagen expression.
The association between substance use and HIV in two Sub-Saharan African countries, 2014 - 2016
(University of the Witwatersrand, Johannesburg, 2024) Jack, Samantha Louise; Mall, Sumaya
Background People Living With HIV/AIDS (PLWHA) are recognized to have an increased risk of substance abuse - alcohol heavy episodic drinking (HED), tobacco smoking, and illicit drugs. Substance use amongst PLWHA is associated with poorer antiretroviral treatment (ART) adherence, increased risk of cancers, and worse morbidity and mortality. Substance use is also associated with an increased risk of HIV infection amongst those who are HIV negative. The majority of this research is focused outside of the African continent and in high-income countries; thus, this study aims to contribute towards research in low-middle income African countries such as South Africa and Kenya. Aim This study aims to investigate the association between HIV and substance use in South Africa and Kenya, and the possible associated covariates. Methods The study population for this secondary data analysis included n=7919 men and women participants drawn between the ages of 40 and 60 recruited between August 2013 and August 2016. The Mann-Whitney test was used for continuous variables and all other categorical variables were analysed using a chi squared test or Fisher’s exact test. Predictive factors for the logistic regression models were informed by the literature review and conceptually modelled using a Direct Acyclic Graph. An overall logistic regression model was run which included both countries, and then separate logistic regression models were run for Kenya and South Africa. Results The prevalence of substance use in the overall sample was 54.30%. In Kenya it was 51.33% and in South Africa (SA) 55.60%. The prevalence of HIV in the overall sample was 20.94%. In Kenya HIV prevalence was 13.66%, and in SA 23.35%. PLWHA had a 1.22 greater odds of substance use than those who were HIV negative in the overall sample (p=0.012, 95%CI 1.04 - 1.43). In Kenya, PLWHA had a 1.49 higher odds of substance use (p=0.013, 95%CI 1.09 - 2.03). In SA, there was no significant association found between HIV status and substance use. In the Kenyan logistic model HIV status, sex, marital status and employment status were found to be associated with substance use. Full-time employment and marriage presented as protective factors against substance use in Kenya. In the SA logistic model age, sex, marital status and employment status were associated with substance use. Marriage was also a protective factor for the SA model. Self-employment and informal employment increased the odds of substance use by more than two-fold in the SA model (aOR=2.27, p<0.001, 95%CI 1.63-3.16; aOR= 1.50, p=0.0008, 95%CI 1.19-1.91 respectively). The factor with the largest odds for substance use across all three models was being male, with increased odds of 15.5 in the overall model (p<0.0001, 95%CI 13.4-17.9), 11.6 in Kenya (p<0.0001, 95%CI 8.65-15.5) and 17.7 in South Africa (p<0.0001, 95%CI 14.9-21.1). Conclusion Treatment of substance use disorders should become a staple in integrated routine ART care as the prevalence of substance use in PLWHA in this study and across the literature is high, especially in men The implementation of the substance use treatment should be tailored to the unique gendered and socioeconomic factors that are present in each country.
Factors associated with late HAART initiation: A retrospective study of adults living with HIV in Gauteng Province, South Africa, 2016 to 2022
(University of the Witwatersrand, Johannesburg, 2024) Govender, Logashnee; Kufa-Chakezha, Tendesayi
The nationwide implementation of antiretroviral therapy (HAART) in South Africa (SA) has been in effect since 2005. Despite the improved access to HAART, there is a persistent trend of delayed presentation for Human Immunodeficiency Virus (HIV) care, resulting in increased premature mortality. Between 2010-2011 and 2014-2015, Gauteng Province (GP) reported the highest number of patients entering HIV care with CD4 cell counts of < 200 cells/mm³, this being the benchmark for Advanced HIV Disease (AHD). This study therefore aimed to establish the prevalence of AHD in HAART naïve adults entering the HIV HAART programme between March 2016 and March 2022. The intention was to identify the factors associated with AHD at entry into HIV care and to assess the evolution of AHD before, during and after the COVID-19 vaccination era. The secondary data analysis entailed utilizing archived specimen data from the National Health Laboratory Service Corporate Data Warehouse (NHLS CDW). Logistic regression analysis was used to determine the associations between various factors and AHD, and time series analysis to visualise the trend of AHD over time. The multivariable logistic regression model was applied to determine factors associated with AHD and trend analysis was used to investigate the impact of COVID-19 on proportion of AHD patients starting ART. Among the 859 152 individuals included in the analysis, the median age was 39 years [IQR 32-46], 64.8% were females, and 79.2% entered the HIV care programme from clinics. There was a consistent decrease in the proportion of patients entering care over time, from 19.4% in 2017 to 11.4% in 2021. The prevalence of AHD in patients initiating HAART for the first time in Gauteng Province ranged between 24% and 27% from March 2016 to March 2022. The COVID-19 pre-vaccination period showed an increase in median CD4 counts in some districts, while others remained stable or decreased slightly. Compared to 18–24-year age group, patients in the 35 to 49 age group had a higher odds (OR =1.57, [95% CI: 1.542-1.60], p value < 0.001) of presenting with AHD at HAART initiation. Compared to females, male patients had higher odds of AHD at HAART initiation (OR=2.06, [95% CI: 2.04-2.08], p value <0.001). Patients presenting for HAART initiation in the West Rand District had a higher odds of AHD (OR =1.11, [95% CI: 1.08-1.13], p value < 0.001) compared to Johannesburg Metro. Patients presenting to clinic facilities for HAART initiation had lower odds (OR =0.61, [95% CI: 0.60- 0.62], p value < 0.001) of AHD than those at hospitals. v Limitations included missing and incorrect data, which resulted in data having to be excluded. Despite the nation-wide availability of HAART, the prevalence of AHD in Gauteng Province remained high, indicating the presence of barriers hindering access to readily available HIV treatment. Further research is required to identify the barriers experienced by patients with AHD in accessing HAART across all districts, with a focus on men. HAART programmes for men need to be prioritised to encourage them to test and treat for HIV timeously. The results highlight the significant effects that pandemics and unexpected adverse events can have on people living with HIV.
Prevalence and factors of HIV associated Oral Kaposi Sarcoma at Wits Oral Health Centre, Johannesburg
(University of the Witwatersrand, Johannesburg, 2024) Chetty, Hasita; Padayachee, Sankeshan; Mafojane, Tumane
HIV associated Oral Kaposi Sarcoma (OKS) is a neoplasm predominantly occurring in immunocompromised patients. Therefore, it is often observed in an HIV positive and AIDS population (Moore & Chang, 2003). KS is caused by the Kaposi Sarcoma Herpes Virus (KSHV) or Human Herpes Virus-8 (HHV8) (Naidoo et al, 2016). The risk of acquiring KS increases in the presence of HIV infection and immunosuppression (Kamulegeya & Kalyanyama, 2008). HIV-KS can occur at any stage of HIV infection but has been more prevalent at the stage of AIDS or severe immune impairment (Khammissa et al., 2012). Both HHV8 infection and HIV/AIDS are highly prevalent in Africa (Kamulegaya and Kalyanyama, 2008). There is a lack of current evidence documenting the relationship between HIV/AIDS and OKS since the implementation of ART, therefore this study intends to augment the existing literature. This study aimed to determine the prevalence and factors of HIV associated OKS, on histopathologically diagnosed patients attending the WITS Oral Health Centre, Johannesburg, between 2008 and 2018. This period predates and postdates the roll out of ART in the South African public health sector in 2012 and speaks to the relationship between ART and the occurrence of HIV associated OKS. Materials and Method: This is a cross-sectional study using records from the Wits Oral Health Centre (WOHC) and National Health Laboratory Service (NHLS). The study period is 10 years from January 2008 to December 2018. Prevalence of OKS was calculated based on patients with a positive histopathological diagnosis of OKS within the study period from the NHLS database. Ethical Considerations: Permission was requested from the Academic Affairs and Research Management System (AARMS) National Health Laboratory Service (NHLS) and WOHC to access patient files. Records of patients with a positive OKS histopathological diagnosis were noted. They were allocated a study number and patient number on a data sheet. The corresponding patients’ files were accessed from WOHC to attain further information (as per the data sheet). Patient confidentiality was be maintained as no names were recorded and files were allocated a number for cross-referencing between NHLS and WOHC data. 11 Ethics clearance was attained from the Wits Human Research Ethics Committee to carry out this study. Results: The prevalence of OKS that was found in this population (137679 patients seen at WOHC) was 0.017432%(n=24). There were more females that presented with OKS than males. The mean age of presentation was 39.11 years of age (SD 12.459). There was a significant relationship between high viral loads and a low CD4 count. The palate was the site most frequently biopsied in diagnosed OKS cases. Conclusion: The prevalence of OKS over the study period was very low. The mean age of OKS presentation was 39.21 years of age. More females presented with HIV associated OKS than males and the palate was the site, from which most biopsy samples were taken in OKS diagnoses. There is a significant relationship between high viral loads and low CD4 cell counts. This study is suggestive that a possible reason for the low number of OKS cases could be administration of ART by state institutions in South Africa, this can be further investigated to establish the effect of ART on OKS.
Variation in Prices of Medicines Used in the Management of HIV, Type 2 Diabetes Mellitus, and Hypertension in South Africa’s Private Sector, 2022
(University of the Witwatersrand, Johannesburg, 2024) Matanyaire, Nyaradzai; Blaauw, Duane
Background: There is significant variation in the price of medicines used to manage chronic diseases in the private health sector in South Africa. Understanding pricing structures can aid in reducing out-of-pocket payments, enhancing access, and improving medicine affordability. This study aimed to investigate the sources of variation in private sector single exit price (SEP) of medicines used in the management of Human Immunodeficiency Virus (HIV), type 2 diabetes mellitus (diabetes), and hypertension. Methods: This was a cross-sectional quantitative study design using private sector price data published on the Medicine Price Registry (MPR) as of July 11, 2022. To quantify the variation in SEP, the mean, median, and range was calculated for each Anatomical Therapeutic Chemical group (ATC) at level two (ATC2) and active ingredient. Decomposition using Shorrocks' method was used to examine the contribution of price sub-components, namely manufacturer fees and logistics fees to medicine price variations. Field’s inequality decomposition was used to understand the contribution of non-pricing-related factors such as origin of manufacturer and generics to medicine pricing variations. Results: Varying patterns were observed across disease classes, with HIV medicines showing the highest variability and overall highest average SEP per unit. Anti-hypertensives showed the least variation in SEP per unit. Variation in manufacturing costs consistently drove price inequalities across the three disease groups, overshadowing logistics fees. Field’s decomposition unveiled significant contributors to price disparities, such as drug class and origin of manufacturer. For example, hypertension medication pricing was affected by the number of available brands, while HIV medicine price variation was mostly influenced by combination formulations. Conclusions: The findings reveal the complex nature of medicine pricing in South Africa, impacted by regulatory policies and market dynamics. Considerable medicine price variation for HIV, diabetes and hypertension medicines was attributable to both pricing and non- pricing related factors. Policies to control prices of medicines should encompass both, including direct price controls, regulatory frameworks, and generic medicine policies. Policies that promote generic substitution can shift demand towards more cost-effective alternatives, contributing to more uniform pricing and increased access.
Cost-effectiveness of the optimal mix of differentiated service delivery models for HIV care and treatment in Zambia: a mathematical modelling study
(University of the Witwatersrand, Johannesburg, 2024) Lekodeba, Nkgomeleng Abel; Nichols, Brooke; Jamieson, Lise
Background: Zambia has scaled up differentiated service delivery (DSD) models for antiretroviral treatment (ART) to provide more client-centric care and increase service delivery efficiency. The current DSD landscape includes multiple models of care based on guidelines, resources, partner inputs, and other factors. We used local data to identify cost-effective combinations of DSD models that will maximize benefits and/or minimize costs to guide future DSD expansion. Methods: We developed a mathematical Excel-based model using retrospective retention and viral suppression data from a national cohort of ART clients (≥15 years) between January 2018-March 2022 stratified by age, sex, setting (urban/rural), and model of ART delivery. Outcomes (viral suppression and retention in care), provider costs, and costs to clients for each model were estimated from the cohort and previously-published data. For different combinations of the nine DSD models in use, we evaluated the incremental cost to the health system per additional ART client virally suppressed on treatment compared to the 2022 base case. To assess uncertainty in our model parameters, we conducted univariate and multivariate deterministic sensitivity analysis on key model input parameters. Results: Of the 125 scenarios evaluated, six were on the cost-effectiveness frontier: 1) six-month dispensing (6MMD)-only; 2) 6MMD and adherence groups (AGs); 3) AGs-only; 4) fast track refills (FTRs) and AGs; 5) FTRs-only; and 6) AGs and home ART delivery. 6MMD-only was cost-saving compared to the base case, increased the proportion of clients retained in care by 1.2% (95% CI, 0.7; 1.8), virally suppressed by 1.6% (95% CI, 1.0;2.6), and decreased costs to clients by 12.0% (95% CI, -10.8; -12.4). The next two scenarios on the cost-effectiveness frontier, 6MMD + AGs and AGs-only, each cost an additional $245 per person virally suppressed, increased the total number of individuals suppressed on treatment by 2.8% (95% CI, 2.2; 3.3) and 4.0% (95% CI, 3.5; 4.0) and increased costs to clients by 20.1% (95% CI, 9.5; 28.1) and 52.3% (95% CI, 29.8; 68.7), respectively. Under the base case, and scenarios on the cost-effectiveness frontier, cost of ART and laboratory tests were the most influential model parameters to the total health system costs and ICER, respectively. Conclusions: Mathematical modelling using existing data can identify cost-effective mixes of DSD models and allocations of clients to these models, while ensuring that all client sub-populations are explicitly considered. In Zambia, providing 6MMD to all eligible clients is likely to be cost-saving, while health outcomes can be improved by allocating clients to selected models based on sub-population.
The Risk Factors for Progression of Chronic Kidney Disease in a Cohort of South African Black Patients
(University of the Witwatersrand, Johannesburg, 2024) Maharaj, Shriyan
Background Increasing prevalence of chronic kidney disease (CKD) is a global health concern. Complex and heterogenous patient factors influence the natural course of CKD. We examined the relationship between predefined risk factors and the rate of progression and outcomes of CKD. Methods Retrospective chart analysis was performed involving a cohort of 265 adult patients who presented at Chris Hani Baragwanath Hospital during 2010 to 2020. Descriptive statistics representing demographic profiles were examined, as well as associations between risk factors and outcomes. Estimated glomerular filtration rate (eGFR) decline was computed based on the recorded annual eGFR measurements. To examine the relationship between risk factors, eGFR change rate, and categorical patient outcomes, regression analysis was performed. Results The mean age of participants was 56.6 (13.8) years; males constituted 144 (54%) of the study group. Major risk factors included hypertension (83%), diabetes (39%), and HIV (35%). Many patients were impacted by multiple concomitant risk factors (61%), with hypertension being a co-morbid diagnosis in >50% of patients with diabetes and HIV. The annual mean eGFR decline rate over four years was 1.63 mL/min/1.73 m2. Decline rate was higher for diabetics: 2.3 ml/min/1.73 m2 (SD 3.8), almost double that of non-diabetics. Baseline-stage CKD 3A progressed more rapidly than CKD 3B. The mean eGFR was 28.0 mL/min/1.73 m2, with an average decline rate over the study period of 26%. Significant predictors of a higher than average rate of eGFR decline over the study duration were diabetes and dyslipidaemia (OR = 6.65 95% CI: 1.2–34.8). Age, HIV, and smoking also contributed to the rate of decline. Hypertension was not a strong prognosticator in the model. Acute kidney injury (AKI) was a frequent complication, noted in 44 (17%). When documented AKI cases with a significant decline in eGFR were excluded, the overall nature of the relationships reported based on the full sample remained unchanged. Conclusions Common modifiable risk factors, when present at initial evaluation, were demonstrated to accelerate CKD progression and have worse outcomes. These patients are most likely to benefit from close monitoring, tighter risk factor control, and earlier planning for renal replacement therapy.

3. Electronic Theses and Dissertations (ETDs)

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