Faculty of Health Sciences (ETDs)

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Prevalence and factors of HIV associated Oral Kaposi Sarcoma at Wits Oral Health Centre, Johannesburg
(University of the Witwatersrand, Johannesburg, 2024-07) Chetty, Hasita; Padayachee, Sankeshan; Mafojane, Tumane
Introduction: 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. 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.
HIV infection, antiretroviral therapy and the haemostasis of pregnancy
(University of the Witwatersrand, Johannesburg, 2023-07) Schapkaitz, Elise; Libhaber, Elena; Jacobson, Barry; Büller, Harry
The human immunodeficiency virus (HIV) epidemic affects an estimated 30% of pregnant women living in South Africa. Increasing evidence suggests that women living with HIV are at a heightened risk for venous thrombo-embolism (VTE), which is a significant contributor to maternal mortality. In addition to a higher prevalence of obstetric and venous risk factors, this increased risk of VTE has been attributed to the effects of HIV and/or its treatment. HIV is characterized by immune activation and inflammation, which promote endothelial dysfunction and activation of coagulation. This is more pronounced with untreated HIV, yet this pro-inflammatory and pro-thrombotic balance may persist with long-term suppressive antiretroviral therapy (ART). However, the extent to which ongoing inflammation disrupts maternal haemostasis and predisposes pregnant women living with HIV to its prothrombotic consequences, is currently unknown. The aims of the work presented in this thesis in women living with HIV with access to ART were firstly to identify antepartum and postpartum risk factors for VTE; secondly to assess procoagulant changes in maternal haemostasis; and thirdly to determine risks of thrombosis and bleeding associated with thromboprophylaxis for VTE prevention. An epidemiological case-control study was performed in 128 cases with pregnancy related VTE and 640 matched controls. This study found at least a two-fold increased risk for VTE among pregnant and postpartum women living with HIV. In addition, antepartum risk factors, that may explain the disproportion of VTE risk in HIV, included medical co-morbidities and chronic hypertension, while postpartum risk factors included a personal history of VTE, medical co-morbidities, systemic infection, prolonged hospital admission and postpartum haemorrhage. Opportunistic infections, ART and the degree of immunosuppression were not associated with VTE risk. A sub-study followed and investigated antiphospholipid antibodies (aPL) in 215 women with thrombosis and/or obstetric complications. In this study, 15 (13.2%) of the women with HIV were positive at baseline for one of the five criteria aPL. The prevalence of aPL was not significantly increased among women with HIV, as compared to HIV negative women. Furthermore, the aPL profiles were not significantly different between the two groups. Lupus anticoagulant (LAC) positivity, on a single occasion, was associated with thrombosis (p < 0.003). Subsequently two prospective cross-sectional studies were conducted which assessed endothelial activation as well as fibrinolysis, coagulation and platelet activation in pregnant women with HIV, in each trimester. The studies included three groups: HIV negative, HIV with virological suppression (< 50 copies/mL) and HIV with viral load (VL) of >50 copies/mL. Endothelial activation was evaluated by measuring von Willebrand factor (VWF) antigen, VWF propeptide, multimer patterns and ADAMTS-13 antigen, activity, and antibody levels. The results showed an increase in the ratio of VWF propeptide to VWF antigen in the first, second and third trimester, in the HIV virologically suppressed group (1.7 ± 0.7, 1.7 ± 0.4, 1.6 ± 0.5) and the HIV group with VL > 50 copies/mL (1.9 ± 0.9, 1.7 ± 0.9, 1.6 ± 1.1) compared to the HIV negative group (1.4 ± 0.6, 1.3 ± 0.4, 1.2 ± 0.3, p < 0.05). Virological suppression was not associated with a significant reduction in this ratio, in each trimester. In addition, increased high molecular weight multimers were observed in the HIV groups, despite only a mild reduction in ADAMTS-13 activity compared to the HIV negative group (p < 0.001). Thereafter, fibrinolytic activity was evaluated by measuring d-dimer and plasminogen activator inhibitor-1 (PAI-1). Coagulation activity was determined by measuring thrombin-antithrombin (TAT) complex concentrations, and platelet factor-4 and platelet indices, namely mean platelet volume (MPV) and platelet distribution width as a measure of platelet activation. The results showed increased log d-dimer levels in the first, second and third trimester, in the HIV virologically suppressed group (-1.2 ± 0.5, -0.9 ± 0.4, -0.5 ± 0.3) and the HIV group with VL > 50 copies/mL (- 1.1 ± 0.4, -0.7 ± 0.4, -0.5 ± 0.5) compared to the HIV negative group (-1.4 ± 0.2, -1.1 ± 0.3, -0.8 ± 0.3, p < 0.05). Additionally, log PAI-1 levels were increased in the first, second, and third trimester, in the HIV virologically suppressed group (1.0 ± 0.4, 1.3 ± 0.4, 1.5 ± 0.4) and the HIV with VL > 50 copies/mL (0.8 ± 0.5, 1.2 ± 0.4, 1.5 ± 0.3) compared to the HIV negative group (0.4 ± 0.5, 0.8 ± 0.3, 1.3 ± 0.3, p < 0.05). Virological suppression was not associated with a significant reduction in first and third trimester d-dimer and PAI-1 levels. Thrombin-antithrombin complex levels were not increased, in the HIV virologically suppressed group as compared to the HIV negative group, beyond the first trimester. With regard to platelet parameters, only log MPV measured in the third trimester was decreased in in the HIV virologically suppressed group (2.3 ± 0.1) and the HIV group with VL > 50 copies/mL (2.3 ± 0.1) compared to the HIV negative group (2.5 ± 0.2) (p < 0.001). The last study was a longitudinal study of 129 pregnant women at intermediate or high risk of VTE, who received thromboprophylaxis. Venous thrombo-embolism occurred antepartum in 1.4%, 95% confidence interval (CI) 0.04-7.7 of intermediate and 3.4%, 95% CI 0.4-11.7 of high risk pregnancies. Major, clinically relevant non-major and minor bleeding events occurred in 7.1%, 95% CI 2.4-15.9 of intermediate and 8.5%, 95% CI 2.8-18.7 of high risk pregnancies. Owing to the small number of events, this study could not assess for HIV as a predictor of thrombosis and bleeding. Thus, in conclusion, the findings described in the studies in this thesis contribute to our knowledge in pregnant women living with HIV in the following ways. Firstly, HIV emerged as a significant antepartum and postpartum risk factor for VTE. Traditional obstetric and venous risk factors were also linked to the risk of thrombosis and could be useful for identifying women with HIV, who may benefit from postpartum and/or antepartum thromboprophylaxis. Secondly, this thesis identified heightened markers of endothelial activation and impaired fibrinolysis. Markers such as the ratio of VWF propeptide to VWF antigen, d-dimer and PAI-1 may provide a biological mechanism for the increased risk of pregnancy-related VTE in in HIV. Finally, this thesis provided rates of thrombosis and bleeding in women who received thromboprophylaxis in pregnancy and the postpartum period which can be used to advise women with HIV of the associated risks.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission dynamics and social contact patterns
(University of the Witwatersrand, Johannesburg, 2023-03) Kleynhans, Jacoba Wilhelmina; Cohen, Cheryl; Tempia, Stefano
Background: Understanding the community burden and transmission dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can assist to make informed decisions for prevention policies. Methods: From August through October 2018, before the SARS-CoV-2 pandemic, we performed a cross-sectional contact survey nested in a prospective household cohort in an urban (Jouberton, North West Province) and a rural community (Agincourt, Mpumalanga Province) in South Africa to measure contact rates in 535 study participants. Participants were interviewed to collect details on all contact events (within and outside of the household). During the SARS-CoV-2 pandemic we enrolled 1211 individuals from 232 randomly selected households in the same urban and rural community, and followed the cohort prospectively for 16 months (July 2020 through November 2021), collecting blood every two months to test for SARS-CoV-2 antibodies. Using these longitudinal SARS-CoV-2 seroprevalence estimates and comparing these with reported laboratory-confirmed cases, hospitalizations and deaths, we investigated the community burden and severity of SARS-CoV-2. We also performed a case-ascertained household transmission study of symptomatic SARS-CoV-2 index cases living with HIV (LWH) and not LWH (NLWH) in two urban communities (Jouberton, North West Province and Soweto, Gauteng Province) from October 2020 through September 2021. We enrolled 131 SARS-CoV-2 index cases at primary healthcare clinics. The index cases and their 457 household contacts were followed up for six weeks with thrice weekly visits to collect nasal swabs for SARS-CoV-2 testing on reverse transcription real-time polymerase chain reaction (rRT-PCR), irrespective of symptoms. We assessed household cumulative infection risk (HCIR), duration of virus detection and the interval between index and contact symptom onset (serial interval). By collecting high-resolution household contact patterns in these households using wearable sensors, we assessed the association between contact patterns and SARS-CoV-2 household transmission. Results: During the contact survey, we observed an overall contact rate of 14 (95% confidence interval (CI), 13-15) contacts per day, with higher contact rates in children aged 14-18 years (22, 95%CI 8-35) compared to children <7 years (15, 95%CI 12-17). We found higher contact rates in the rural site (21, 95%CI 14-28) compared to the urban site (12, 95%CI 11-13). When comparing the household cohort seroprevalence estimates to district SARS-CoV-2 laboratory-confirmed infections, we saw that only 5% of SARS-CoV-2 infections were reported to surveillance. Three percent of infections resulted in hospitalization and 0.7% in death. People LWH were not more likely to be seropositive for SARS-CoV-2 (odds ratio [OR] 1.0, 95%CI 0.7–1.5), although the sample size for people LWH was small (159/1131 LWH). During the case-ascertained household transmission study for SARS-CoV-2, we estimated a HCIR of 59% (220/373) in susceptible household members, with similar rates in households with an index LWH and NLWH (60% LWH vs 58% NLWH). We observed a higher risk of transmission from index cases aged 35–59 years (adjusted OR [aOR] 3.4, 95%CI 1.5–7.8) and ≥60 years (aOR 3.1, 95% CI 1.0–10.1) compared with those aged 18–34 years, and index cases with a high SARS-CoV-2 viral load (using cycle threshold values (Ct) <25 as a proxy, aOR 5.3, 95%CI 1.6–17.6). HCIR was also higher in contacts aged 13–17 years (aOR 7.1, 95%CI 1.5–33.9) and 18–34 years (aOR 4.4, 95% CI 1.0–18.4) compared with <5 years. Through the deployment of wearable sensors, we were able to measure high-resolution within-household contact patterns in the same households. We did not find an association between duration (aOR 1.0 95%CI 1.0-1.0) and frequency (aOR 1.0 95%CI 1.0-1.0) of close-proximity contact with SARS CoV-2 index cases and household members and transmission. Conclusion: We found high contact rates in school-going children, and higher contact rates in the rural community compared to the urban community. These contact rates add to the limited literature on measured contact patterns in South Africa. The burden of SARS-CoV-2 is underestimated in national surveillance, highlighting the importance of serological surveys to determine the true burden. Under-ascertainment of cases can hinder containment efforts through isolation and contact tracing. Based on seroprevalence estimates in our study, people LWH did not have higher SARS-CoV-2 community attack rates. In the household transmission study, we observed a high HCIR in households with symptomatic index cases, and that index cases LWH did not infect more household members compared to people NLWH. We found a correlation between age and SARS-CoV-2 transmission and acquisition, as well as between age and contact rates. Although we did not observe an association between household contact patterns and SARS-CoV-2 transmission, we generated SARS-CoV-2 transmission parameters and community and household contact data that can be used to parametrize infectious disease models for both SARS-CoV-2 and other pathogens to assist with forecasting and intervention assessments. The availability of robust data is important in the face of a pandemic where intervention strategies have to be adapted continuously.
Avascular necrosis (AVN) of the hip in patients operated in the Orthopaedic Arthroplasty Unit at Chris Hani Baragwanath Academic Hospital
(University of the Witwatersrand, Johannesburg, 2023-08) Mwoyofiri, Jephta; Magobotha, S.K.; Frey, C.; Jingo, M.
Background: Avascular necrosis (AVN) of the femoral head is a progressive structural damage of the head of the femur because of interruption of blood supply to the subchondral bone resulting in the collapse of the head of the femur and secondary arthritis. Moreover, this chronic debilitating disease of the hip causes an immense contribution to the need for total hip arthroplasty (THA) and is common in young persons between the third and fifth decades of life. The aim of the study was to describe the causes of osteonecrosis of the femoral head (ONFH) in patients operated at Chris Hani Baragwanath Academic Hospital (CHBAH) Arthroplasty unit from 2017 to 2022. Methods: A retrospective review of all patients operated between the above-mentioned period, was conducted through collecting the patients’ demographic data, risk factors and treatment given. Results: The study had 285 participants with AVN from a total of 838 patients who had hip surgery. There were 149 (52%) females and 136 (48%) males. The mean age was 51.7 years with a SD 11.4 years. Majority of the patients were in the age group: 50 ‒ 59 years. The main risk factor of AVN was human immunodeficiency virus (HIV) with 117 (41%) patients. Those on highly active anti-retroviral therapy (HAART) were 115 (98%) patients. The median cluster of differentiation 4 (CD4) count was 584 (IQR 470 ‒ 711) and the viral load was undetected in 29 of the 32 (91%) patients with recorded viral load results. Ficat/Arlet stage 4 had 199 (70%) patients and all our patients had total hip replacement. Conclusion: ONFH contributes significantly to the burden of total joint arthroplasty in young patients. As our study has shown, there are several risk factors such as HIV, alcohol use and steroids being among the commonest. Our study draws attention to the significant burden that HIV has on hip pathology. HIV was the commonest cause of AVN at our local health institution and may be in the Sub-Saharan region. However, in our study we could not isolate HAART as a cause of AVN due to inadequate patient records. Majority of patients usually present with advanced stages of ONFH requiring a femoral head sacrificing operation due to late referral and long waiting list before surgery.
Risk factors for caries and periodontal diseases: a comparative4 study among HIV-positive and HIV-negative adults in nyarugenge5 district, Rwanda
(University of the Witwatersrand, Johannesburg, 2024) Murererehe, Julienne
Dental caries and periodontal diseases are among HIV-positive persons' most frequent oral conditions. These common oral diseases contribute to the impairment of general health and well- being. Dental and periodontal problems among HIV-positive individuals are more severe and difficult to manage than dental and periodontal problems among HIV-negative people. Thus, risk factors for caries and periodontal diseases must be controlled for comprehensive oral health and the general well-being of HIV-positive patients. The burden of oral diseases is reported to be high in Rwanda. Nearly 65% of the oral health survey participants had experienced dental caries and above 54% had untreated cavities. In addition, dental calculus was found among 60% of participants. More than 34% had oral debris. Surprisingly, more than 70% of this population has never visited dentists or dental facilities. This evidence gives impetus to undertake more focused investigations on oral diseases in Rwanda, particularly among HIV-positive people. Therefore, this study sought to assess the risk factors for caries and periodontal diseases among HIV-positive and negative adults in Nyarugenge District, Rwanda Methods This research used a mixed-method approach (qualitative embedded design). For the quantitative part, a comparative cross-sectional study was conducted among 200 HIV-positive and 200 HIV- negative adults aged ≥18 years. Consecutive and purposive sampling method was used to select participants for quantitative and qualitative parts of the study respectively. Caries was assessed using the Decayed (D), Missing (M), and Filled Teeth (F) index (DMFT). Periodontal disease was assessed using the Plaque Index (PI), Community Periodontal Index of Treatment Need (CPITN), and Clinical Attachment Loss (CAL). Oral health Related Quality of Life (OHRQoL) was assessed using the oral health impact profile short version (OHIP-14). Descriptive statistics, Chi-square test, t-test, Cronbach alpha, and multiple logistic regression were applied to analyse quantitative data using Stata version 15. For the qualitative data collection, in-depth interviews (IDIs) were conducted among 10 HIV-positive and 11 HIV-negative adults with caries and periodontal diseases using a semi-structured interview guide. Thematic content analysis using an inductive approach was applied for data analysis of IDIs. NVivo software version 11 was used to code and organize the data. Results A higher proportion (50.5%) of HIV-positive adults had experienced caries (DMFT>0) compared to HIV-negative counterparts (40.5%) and the difference was statisticaly significant (p=0.045). The prevalence of D was higher (23.5%) among HIV-positive compared to HIV-negative adults (13.6%) (p=0.011). The Mean (SD) DMFT score among HIV-positive and HIV-negative participants were 2.28 (3.68) and 1.29 (2.21) respectively (p=0.001). The predictors of caries in HIV-positive persons were being female (OR= 2.33; 95%CI= 1.14-4.75), frequent dental visits (OR= 4.50; 95% CI=1.46-13.86) and detectable RNA viral load (OR= 4.50; 95% CI=1.46-13.86). Among HIV-negative participants, the middle age range (36-45 years) [OR= 6.61; 95%CI=2.14- 20.37], and frequent dental visits were significantly associated with caries (OR=3.42; 95%CI: 1.337-8.760). For periodontal status, having dental calculus was the most prevalent item of the CPITN found among HIV-positive 168 (84%) and 182 (92%) HIV-negative individuals. The mean (SD) score for CAL was higher in HIV-positive persons 1.23 (0.95) compared to HIV-negative counterparties 0.99 (0.75). The difference was statistically significant (p=0.003). Being a male was a predictor of having dental plaque and a need for periodontal treatment for both HIV-positive (PI OR: 2.90 (95%CI=1.26-6.66)); (CPITN OR: 3.33 (95%CI=1.14-9.70)) and HIV-negative respondents (PI OR:3.28 (95%CI=1.48-7.28)); (CPITN: OR: 7.78 (95%CI=1.04-58.07)). A higher percentage of HIV-positive individuals had poorer OHRQL than HIV-negative counterparties in all items of OHIP-14 except for OHIP3 (found it uncomfortable to eat any foods because of problems with teeth or mouth) and OHIP-14 items (being totally unable to function because of problems with teeth or mouth). The findings revealed significant results regarding OHIP1 “trouble pronouncing any word” with a prevalence of 11(2.5%) and 9(2.25%) in HIV-positive and HIV-negative participants, respectively. Also, HIV-positive persons had higher percentage 11(2.75%) for the OHIP 13 item “life not satisfying due to teeth and mouth problems” than HIV-negative counterparties 8(2%) and the difference was statistically significant p≤0.05. Moreover, dental caries was significantly associated with poor OHRQoL among HIV-positive and HIV-negative participants for all 14 items of OHIP-14 tool. There was no association between periodontal disease and OHRQoL in both HIV-positive and HIV-negative adults. Two broad domains and five themes emerged from the interviews. The first broad domain was “perceptions on causes of oral diseases” with 2 themes (individuals and external themes). The second broad domain was “perceptions on oral diseases effect” with 3 themes (physical or functional effect, psychological effect and social effect themes). Conclusion and recommendations This research showed a higher prevalence of caries and CAL among HIV-positive adults than HIV- negative counterparts. Also, the mean (SD) PI value was significantly higher in HIV-positive adults compared to the mean PI value in HIV-negative individuals. The reported higher prevalence of caries in HIV-positive persons was associated with being female, detectable viral load, and frequent dental visits. Periodontal disease was associated with older age, being male in HIV-positive and HIV-negative participants. Moreover, HIV-positive adults reported poorer OHRQoL than HIV-negative counterparties. Furthermore, qualitative results revealed individual and external levels factors of oral disease and emphasized the physical/ functional, psychological and social effects of oral diseases on quality of life. Therefore, there is a need for effective oral health interventions specific to HIV-positive persons in Rwanda. The interventions should also raise awareness of the risk of common oral diseases (such as dental caries, and periodontal disease) and provide preventive oral health services among the Rwandan population, especially HIV-positive individuals. There is a need for a collaborative effort to establish programmes for regular and timely screening and management of periodontal disease and dental caries among the general population and specifically, HIV-positive individuals in Rwanda. To ensure timely oral health care among HIV- positive Rwandans, this study provides baseline data to aid policymakers and stakeholders to integrate oral health care services within HIV treatment programmes in R
A laboratory based retrospective study of plasma cell myeloma in the public sector of South Africa from 2017 to 2019
(University of the Witwatersrand, Johannesburg, 2024) Wilding, Bradley Thomas; George, Jaya
Background Plasma cell myeloma is a haematological malignancy characterized by clonal proliferation of plasma cells. This malignancy is frequently associated with the production of a monoclonal protein in either serum and / or urine, referred to as an M protein, which is used as a screening test for patients. Patients are then further investigated to assess if they meet the International Myeloma Working Group (IMWG) diagnostic criteria for plasma cell myeloma. There is limited literature describing plasma cell myeloma in South Africa, particularly in people living with HIV. Objective The primary objective of this study was to describe plasma cell myeloma in patients diagnosed in the public sector of South Africa over a three-year period. The secondary objective was to compare demographic features (age, sex) and diagnostic criteria, between the myeloma patients living with HIV and the HIV negative myeloma patients. Methods A retrospective analysis was performed on data from 4518 patients who had a positive immunofixation on serum and / or urine from public sector hospitals, between 2017 and 2019. A total of 718 of the 4518 patients met the laboratory criteria for plasma cell myeloma and were included in the analysis. Demographics (age, sex) and laboratory investigations used in the diagnostic criteria for plasma cell myeloma were analysed and statistically compared across the different HIV status of patients. Results Plasma cell myeloma patients presented at a mean age of 59.46 years with a female to male ratio of 1.2:1. In the patients that met the diagnostic criteria the most common end-organ damage present was anaemia in 77.16% patients and the most common biomarker of malignancy was a bone marrow trephine biopsy plasma cell percentage t60% in 55.71% patients. IgG isotype was the most common paraprotein detected on serum immunofixation in 58.5% of the patients. Kappa was the most common Bence-Jones protein detected in 27.16% of patients which was 1.76 times more common than lambda Bence-Jones protein. People living with HIV were younger 55.11 (±9.79) as compared to their HIV negative counterparts (p value 0.010). No other statistically significant difference was noted when comparing HIV status groups Conclusion In conclusion, this study described the demographics, laboratory investigations and diagnostic features of plasma cell myeloma patients diagnosed in the South African public sector from 2017 to 2019. We found that people living with HIV were diagnosed at younger age when compared to their HIV negative counterparts
The relationship between the combined effects of life-course trauma and HIV on cognition in rural South African adults: A secondary data analysis
(University of the Witwatersrand, Johannesburg, 2024) Kupa, Nkgodi Obed; Matsena-zingoni, Zvifadzo; Mall, Sumaya
Background: Lifecourse traumatic events (TE) refers to both childhood and adult trauma. Childhood TE refers to a spectrum and domains of adverse experiences occurring before the age of 18. Global and South African-based research suggests that life-course TE are associated with both physical and mental disorders including HIV and poor cognition (also referred to as neurocognitive impairment (NCI)). While data suggests that life-course TE, HIV and NCI are highly prevalent in South Africa and risk of NCI has been researched, little is known of the combined effect of life-course TE and HIV on NCI in adulthood. To fill the gap in the literature, I analysed data from the Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa (HAALSI), from rural Bushbuckridge (Mpumalanga province). Study Aim To examine the combined (interaction) effect of TE and HIV infection on the cognition of older adults in South Africa. Methods: I analysed (secondary) data from the HAALSI study. The main exposures analysed were: life-course TE and HIV-positive status. A pre-analysis phase consisted of several exploratory steps to define the exposure and outcome: First TE data which had been measured by the English Longitudinal Study of Aging (ELSA) life history questionnaire were examined. The main exposure variable was coded 1 if one experiences a TE and 0 otherwise from seven potential TE. NCI, the main outcome variable was defined based on measuring cognitive domains: orientation and memory. A score≥1.5 standard deviations (SD) below the mean of the baseline cognitive function distribution on the cognitive assessment (managing to know the date, day, month and president) will mean no NCI while a score below the means some degree of NCI). The main outcome variable was cognition measured by the Oxford Cognitive Screener (OCS-plus). Based on the validation of Tablet-Based OCS-plus in HAALSI, OCS-Plus included nine brief tests measuring cognitive ability in nine different domains, including language, memory (intentional and incidental), and executive functioning (task switching-alternating jobs between tasks), attention (auditory), and praxis (doing things). A stand-alone application called OCS- Plus was developed using Matlab and Psychophysics Toolbox for Windows Surface Pro tablets. Further preparatory steps for the analysis included: the exposure variables (HIV status and composite trauma-defined as the presence of at least one trauma item-) were created as follows: 1. HIV status was categorized into HIV positive and negative and coded 1 and 0 respectively. 2. Composite trauma was coded 1 if ever experienced any of the seven trauma items and 0 if none were experienced. Four groups of participants were created by exposure status. These were: 1. HIV positive and also experienced TE. 2. HIV negative but experienced TE. 3. HIV positive but TE negative. 4. HIV negative and trauma negative. Descriptive statistics were calculated for both exposures and outcomes as well as relevant sociodemographic variables. Both unadjusted and adjusted logistic regression techniques were employed to examine the combined effect of life course TE and HIV on NCI in older adults. The adjusted logistic regression models were done: 1) handling HIV and composite trauma separately and 2) considering the interaction term of HIV and composite trauma. Variables such as education, employment status, age, nationality, gender, hypertension, stroke, HIV status, marital status and composite trauma were considered confounders and adjusted accordingly. Results: Of the 5,059 study participants recruited and residing in the Agincourt study area in Bushbuckridge, 65% of the study participants had experienced at least 1 TE, and the most common trauma experienced were “ever experiencing severe financial hardship which was experienced by 58.74% of the participants, 39.73% whom “ever experienced a natural disaster” and 23.30% “ever experienced a death of a relative or friend” and the prevalence of NCI was 7% ( n=352).. The median age of participants was 64 (IQR: 55-74) years; 53.07% of the study participants were females; 44.42% had no formal education, and 72.63% of the study participants were not working. In the multiple logistic regression model with the interaction term, the odds of having NCI decreased by 64% (AOR=0.36; 95%CI: 0.25-0.52) and 59% (AOR=0.41; 95%CI: 0.24-0.75) among those who had some primary school (1-7 years) and some secondary school (8+ years), respectively compared to those with no education. The odds of having NCI decreased by 98% (AOR=1.98; 95%CI: 1.05-3.72) among those who were not working compared to those employed. A one-year increase in age was associated with a 5% increase in the odds of having a cognitive impairment (OR=1.05; 95%CI: 1.04-1.07). Those who were married had 37% (OR=0.63, 95%CI: 0.47-0.84) reduced odds of having NCI compared to those who were married. Those without composite trauma had 90% (AOR=0.10; 95%CI: 0.07-0.15) reduced odds of having NCI compared to those who have composite trauma. Those who were HIV positive and had experienced composite trauma had an increased odds of 1.78 (95% CI: 1.04-3.04) of having NCI compared to those who are HIV negative and had not experienced composite trauma. In the interaction model, we found no association between HIV status, stroke, or hypertension and NCI. However, the results of the interactionmodel suggested a significant association between HIV and the composite trauma score on NCI. Conclusions: The results suggest that lifecourse TE and HIV infection influence NCI. The full HAALSI cohort could be employed to examine the effect of TE data collected at baseline and incident NCI at later waves
Risk factors for recurrent tuberculosis among HIV patients who are on anti-retroviral treatment in rural northeast, South Africa
(University of the Witwatersrand, Johannesburg, 2024) Kanzoole, Kingsley; Ibisomi , Latifat; Kabudula, Chodziwadziwa
Background: Tuberculosis (TB) is a major public health concern, and according to the World Health Organization (WHO), is one of the top 10 causes of death worldwide. Recurrent TB is a significant contributor to the overall TB burden worldwide, particularly in areas where TB prevalence is high (4–6), and among HIV infected people. Aim: In this study, we investigated the risk-factors that are associated with the recurrence of TB among HIV infected people in rural northeast, South Africa. Methods: The study employed a retrospective cohort study design and used data from Agincourt health socio-demographic surveillance system spanning from 1st January 2014 to 31st December 2022. Data analysis was conducted using STATA 17 SE as the analytical tool. Cox regression was used to determine risk factors for recurrent TB among HIV patients on ART in rural northeast, South Africa. Results: The study included 4,803 participants with 1,326 (27.6%) males and 3,477 females (72.4%). The participants were predominantly of HIV WHO Stage 1 (84.7%), followed by Stage 2 (7.6%), then Stage 3 (7.0%) and Stage 4 (0.7). The age distribution had 24.8% aged 18-29, 34.5% aged 30-39, 23.1% aged 40-49, 11.0% aged 50-59 and 6.6% aged 60 and above. The study population had a CD4 count median of 229 cells/mm3 with an IQR of 112-390 cells/mm3 and a median duration of previous TB treatment of 31 weeks with an IQR of 16-49 weeks. Out of the 4,803 patients, 396 (8.2%) experienced recurrent TB. This translated to a recurrence rate of 3.0 per 100 person years. The median time to TB recurrence was 1.93 years, with approximately 50% experiencing the recurrence within this period. The significant risk factors associated with recurrent TB were being male (AHR=1.48, CI: 1.11 – 1.96), WHO HIV stage (AHR=2.53, CI: 1.81 – 3.54), baseline CD4 count (AHR=0.98, CI: 0.98 – 0.99), and duration of previous TB treatment (AHR=0.96, CI: 0.93 – 0.98). Conclusion: This study has identified significant risk factors for recurrent TB among HIV patients in rural northeast South Africa. Male patients have a higher risk, necessitating targeted interventions. Advanced HIV stages increase recurrence risk, emphasizing early diagnosis and management. Maintaining higher CD4 counts and continuous monitoring during and after TB treatment are vital to reducing recurrence. These findings inform strategies to improve health outcomes and control recurrent TB among HIV patients receiving ART in the region
Virological response in children and adolescents switching to dolutegravir based regimens in Johannesburg, South Africa – A Longitudinal Cohort Study
(University of the Witwatersrand, Johannesburg, 2023) Mafora, Tshiamo; Technau, Karl
Introduction: Dolutegravir (DTG) was introduced into South African HIV management guidelines in November 2019, and has since been the mainstay of both adult and paediatric first line antiretroviral treatment (ART) regimens. Following its rapid and widespread introduction we assessed the rate of virological suppression over two years in paediatric patients switching to DTG as part of first line treatment. Methods: We performed a retrospective cohort study at Rahima Moosa Mother and Child Hospital in Johannesburg, South Africa. Children and adolescents already on first line ART who switched to DTG (between November 2019 and November 2021) were included. Baseline characteristics (at DTG switch) included age, weight, gender, viral load (VL), CD4, and pre-switch regimen. Past ART exposure and past viraemic periods (years VL >1000 copies/ml) were assessed and VL suppression rates (< 50 copies/ml) were calculated at 6, 12 and 24 months post-switch. Associations with non-suppression were assessed using uni- and multivariate analysis. Results: Of the 747 participants that were switched to DTG, 724 (97%) qualified for a VL and 697 (96%) of those had at least one VL done after switch. Overall, 83% (450/543) were suppressed at 6 months, 86% (434/504) at 12, 91% (487/534) at 24 months. Overall, at a median of 637 days after switch, 90% (624/697) were suppressed at their last VL. Factors associated with not being suppressed at the last VL included: missing a follow-up visit by more than 90 days post-switch to DTG (OR: 3.2 [CI:1.5-6.8], p=0.003), switching to DTG with a VL of 50-1000 rather than <50 copies/ml (OR 2.0 [CI:1.1-3.9], p=0.042), having the blood test done during July December (OR 2.0 [CI:1.2-3.4], p=0.011), and having had exposure to viraemia ≥1000 copies/ml for more than two years between first ART start and DTG switch (OR: 1.9 [CI: 0.9-3.7], p=0.071). Conclusion: In our population, similar to other studies, VL suppression was effectively maintained in the majority of patients after switching to DTG. The switch did however result in a loss of suppression in some patients and caution is needed in children and adolescents with missed visits and extensive prior viraemia
Clinicopathological spectrum of cutaneous malignancies at the skin tumour clinic, charlotte Maxeke Johannesburg academic hospital in Johannesburg, South Africa: a 5-year retrospective review
(University of the Witwatersrand, Johannesburg, 2023) Gwinji, Tapiwa Munyaradzi; Modi, Deepak
Background Skin cancer is the most common malignancy in South Africa, incidence of which continues to rise. This disease remains a consistent problem in South Africa due to a multifactorial risk complex arising mainly from the high levels of year-round Ultraviolet (UV) exposure, high burden of HIV and late health seeking behaviour leading to poly-etiological skin cancers. Despite the ever-present danger that is cancer, the data and literature surrounding skin cancers among different races and ethnic groups remains inadequate as there are few population-based cancer registries in South Africa and only histologically confirmed cancers are logged into the national cancer registry. Objectives To describe the nature, extent and demographic characteristics of patients with histologically confirmed skin cancer seen at the Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) multidisciplinary skin cancer clinic during the period of January 2015 to December 2019 and to add to the body of literature concerning skin cancers in South Africa. Methods A retrospective chart review identified all patients who were managed for histologically confirmed malignant skin tumours at CMJAH skin tumour clinic. Types, quantity and distribution of common invasive malignancies by population group, age, gender, anatomical site and risk factor were explored. Result A total number of 531 participants with histologically confirmed skin cancers were identified. The most common malignancies were Kaposi’s sarcoma(KS) (53.2%), squamous cell carcinoma (SCC) (27.0%), basal cell carcinoma (BCC) (10.4%), cutaneous melanoma (CM) (7.4%) and mycosis fungoides (MF) (4.2%). SCC and AIDS-associated KS were the most common skin cancer in the white and black population respectively. Conclusion This study provides valuable scientific data on the distribution and patient demographics of skin cancer in the public health system in Johannesburg, South Africa, on which further research can be based. This study highlights the burden of HIV associated skin cancer in this region. There is a need for further research and equitable appropriation of resources and public health awareness efforts towards strengthening UV and HIV-related skin cancer prevention initiatives in SA.

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