Antiretroviral therapy and HIV-associated cardiovascular disease: a prospective cardiac biomarker and CMR tissue characterization study.

AIMS: Biochemical markers are fundamental in cardiac evaluation, and various novel assays have recently been discovered. We prospectively evaluated the hearts of newly diagnosed people living with human immunodeficiency virus (PLWH) using cardiac biomarkers, compared them with human immunodeficiency virus (HIV)-uninfected controls, and correlated our prospective findings with cardiovascular magnetic resonance imaging (CMR). METHODS AND RESULTS: Newly diagnosed, antiretroviral therapy (ART)-naïve PLWH were recruited along with HIV-uninfected, age-matched, and sex-matched controls. All participants underwent measurement of high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), soluble ST2 (sST2), and galectin-3, as well as a CMR study with multiparametric mapping. The HIV group started ART and was re-evaluated 9 months later. The cardiac biomarkers and their correlation with CMR parameters were evaluated in and between groups. Compared with controls (n = 22), hs-cTnT (4.0 vs. 5.1 ng/L; P = 0.004), NT-proBNP (23.2 vs. 40.8 ng/L; P = 0.02), and galectin-3 (6.8 vs. 9.0 ng/mL; P = 0.002) were all significantly higher in the ART-naïve group (n = 73). After 9 months of ART, hs-cTnT (5.1 vs. 4.3 ng/L; P = 0.02) and NT-proBNP (40.8 vs. 28.5 ng/L; P = 0.03) both decreased significantly and a trend of decrease was seen in sST2 (16.5 vs. 14.8 ng/L; P = 0.08). Galectin-3 did not demonstrate decrease over time (9.0 vs. 8.8 ng/mL; P = 0.6). The cardiac biomarkers that showed the best correlation with CMR measurements native T1, T2, and extracellular volume were NT-proBNP (rs ≥ 0.4, P < 0.001) and galectin-3 (rs ≥ 0.3, P < 0.01). CONCLUSIONS: Our cardiac biomarker data support the presence of subclinical myocardial injury, remodelling, and fibrosis at HIV diagnosis, and ART had a positive influence on these blood markers. It remains unclear if the underlying pathological processes were fully addressed by ART. The ability of cardiac biomarkers to detect and track tissue abnormalities diagnosed with CMR showed promise. With additional research, this could lead to improvements in screening and monitoring myocardial abnormalities, even in CMR-limited settings.

Ten-year predictors of major adverse cardiovascular events in patients without angina.

BACKGROUND: Longstanding cardiovascular risk factors cause major adverse cardiovascular events (MACE). Major adverse cardiovascular events prediction may improve outcomes. The aim was to evaluate the ten-year predictors of MACE in patients without angina. METHODS: Patients referred to Inkosi Albert Luthuli Hospital, Durban, South Africa, without typical angina from 2002 to 2008 were collected and followed up for MACE from 2009 to 2019. Survival time was calculated in months. Independent variables were tested with Cox proportional hazard models to predict MACE morbidity and MACE mortality. RESULTS: There were 525 patients; 401 (76.0%) were Indian, 167 (31.8%) had diabetes at baseline. At 10-year follow up 157/525 (29.9%) experienced MACE morbidity, of whom, 82/525 (15.6%) had MACE mortality. There were 368/525 (70.1%) patients censored, of whom 195/525 (37.1%) were lost to follow up. For MACE morbidity, mean and longest observation times were 102.2 and 201 months, respectively. Predictors for MACE morbidity were age (hazard ratio [HR] = 1.025), diabetes (HR = 1.436), Duke Risk category (HR = 1.562) and Ischaemic burden category (HR = 1.531). For MACE mortality, mean and longest observation times were 107.9 and 204 months, respectively. Predictors for MACE mortality were age (HR = 1.044), Duke Risk category (HR = 1.983), echocardiography risk category (HR = 2.537) and Ischaemic burden category (HR = 1.780). CONCLUSION: Among patients without typical angina, early ischaemia on noninvasive tests indicated microvascular disease and hyperglycaemia, predicting long-term MACE morbidity and MACE mortality.Contribution: Diabetes was a predictor for MACE morbidity but not for MACE mortality; patients lost to follow-up were possibly diabetic patients with MACE mortality at district hospitals. Early screening for ischaemia and hyperglycaemia control may improve outcomes.

Cardiac scoring systems, coronary artery disease and major adverse cardiovascular events: A scoping review.

BACKGROUND: In 2019, the World Health Organization (WHO) declared coronary artery disease (CAD) as the leading cause of death globally for the last 20 years. Early screening and detection (primary prevention) and intervention (secondary prevention) are necessary to curb CAD and major adverse cardiovascular event (MACE) prevalence. A scoping review to assess the current literature on using cardiac scoring systems to predict CAD and MACE was performed. METHODS: The research question 'What is the literature on using cardiac scoring systems to predict CAD and MACE?' was addressed. The updated Arksey and O'Malley and the Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews methodologies were used. The search terms 'coronary artery disease' and 'cardiac scoring systems' and 'major adverse cardiovascular events' were used in the Boolean search on PubMed, ScienceDirect, MedLine and Cochrane Library. RESULTS: The final list consisted of 19 published English results after the year 2000. There were six results without participants (four clinical guidelines, one review article and one ongoing clinical trial). Scoring systems were cardiovascular risk estimation systems focusing on the primary prevention of CAD; MACE was discussed but not scored. There were 13 robust results published from completed multinational clinical trials with participants. These results focused on a scoring system for the secondary prevention of CAD and MACE. CONCLUSION: Scoring systems remain an objective method for primary and secondary prevention of CAD and MACE.Contribution: Scoring systems may be helpful with clinical uncertainty or to standardise patient results for comparison in research.

Erythrocytapheresis in Children and Young Adults with Hemoglobinopathies and Iron Overload in Need of Iron Chelation Therapy.

Limited data regarding erythrocytapheresis in children, adolescents, and young adults have been published. The aim of this study was to evaluate erythrocytapheresis, either as a standalone therapy or in combination with iron chelation therapy, in children and young adults with hemoglobinopathies in whom current iron chelation therapy is not sufficient in decreasing the iron overload during management. We retrospectively analysed erythrocytapheresis in 19 patients with hemoglobinopathies in need of iron chelation therapy diagnosed with sickle cell disease (SCD) or ß-thalassemia major. Patients were divided into (1) a case cohort who received erythrocytapheresis alone or in combination with iron chelation therapy and (2) a control cohort who received oral iron chelation therapy alone. Serum ferritin and haemoglobin levels were compared at five different time points over a one-year period. In the erythrocytapheresis cohort, there was a significant decrease in serum ferritin (p < 0.001). In the iron chelation therapy alone cohort, there was no significant decrease in serum ferritin over time (p = 0.156). Comparing the evolution of median serum ferritin between therapy with erythrocytapheresis and iron chelation therapy showed a statistically significant difference (p = 0.008). Patients with ß-thalassemia major receiving erythrocytapheresis showed a greater reduction in serum ferritin compared to patients without (p = 0.036). A difference could not be shown between the erythrocytapheresis and iron chelation single therapies (p = 0.100). This study showed an overall significant reduction in serum ferritin in patients with hemoglobinopathies treated with erythrocytapheresis in addition to iron chelation. A clinical, although not statistical, trend of higher haemoglobin levels was maintained. Erythrocytapheresis in paediatric patients with ß-thalassemia major was as effective in decreasing ferritin levels as in previously reported studies with SCD. Erythrocytapheresis is a promising therapy for treating and preventing transfusion-related iron overload.

Reliability and validity of the Shona version of the Exercise Benefits and Barriers Scale in Zimbabwean adult people living with HIV/AIDS.

Introduction: Despite the widely known benefits of physical activity (PA), only 25% of people living with HIV (PLHIV) meet the WHO-recommended minimum PA levels. Consequently, it is essential to understand PA barriers and facilitators using objective measures. Although the Exercise Benefits and Barriers Scale (EBBS) is extensively used, its psychometric evidence is fragmented and has not been previously validated in PLHIV. This study aimed to translate and validate the EBBS Shona version in Zimbabwean PLHIV. Methods: A cross-sectional study was used to recruit 567 PLHIV from four (4/9) randomly selected polyclinics (primary healthcare facilities) in urban Harare, Zimbabwe. We recruited adult patients (aged ≥18 years) with a confirmed diagnosis of HIV. Participants had to be willing to provide informed consent, not acutely unwell, and proficient in the Shona language. We used a forward-backwards translation method to translate the EBBS from English to Shona, a native Zimbabwean language. After cross-cultural adaptation, we pretested the draft version in 10 PLHIV to assess the face validity, understandability and cultural appropriateness using semi-structured interviews. Thereafter, the EBBS was administered to 567 consecutively-selected PLHIV. Factor analyses were performed for construct validity evaluation. Results: Most participants were female (72.5%) and reached secondary/high school (78.8%), with a mean age of 39.9 (SD 12.1) years. The EBBS-Shona version yielded a four-factor solution consisting of three benefits factors and one barrier factor against the originally postulated six-factor structure. The EBBS-Shona yielded α = 0.85 and intraclass correlation coefficient = 0.86, demonstrating excellent reliability. Increased perception of exercise benefits was positively correlated with increased reports of physical activity, higher health-related quality of life and lower psychiatric morbidity; evidence for construct validity. Discussion: This study demonstrates the validity and reliability of the EBBS-Shona version in Zimbabwean PLHIV. The EBBS-Shona version can be used for research and clinical purposes to glean data to inform the development, implementation, and evaluation of bespoke PA interventions for PLHIV.

The pre-surgical factors that determine the decision to proceed to resection in children diagnosed with high-risk neuroblastoma in a resource limited setting.

Surgical control has prognostic value in neuroblastoma (NB). Advanced NB is common at diagnosis in South Africa. We investigated the pre-surgery factors that influenced decisions to perform surgical resections. We included 204 patients with high-risk NB from a national retrospective study, who completed induction chemotherapy between 2000 and 2016.The median age was 32.4 months (IQR 15.1 - 53.5 months). Primary tumor resection was achieved in 76.9% of patients between 0-18 months of age, 51.8% between 18-60 months and 51.7% older than 60 months (p < 0.001). Only 43.2% of patients with distant metastatic disease had surgery done (p < 0.001). LDH was >750 U/L in 46.8% and ferritin >120 g/dL in 53.1% of those who had surgery (p = 0.005). The majority (80.4%), who had achieved post-induction metastatic complete remission (mCR), were operated, while 28.7% without mCR had surgery (p < 0.001). The long-term overall survival in patients with mCR and primary tumor resection was 36.5% compared to those with mCR without primary tumor resection (25.4%) and without mCR (≤3.0%)(p < 0.001). Age (p < 0.001), stage (p < 0.001), mCR (p < 0.001) and treatment setting (p < 0.001) were of prognostic significance. The tumor site and MYCN-amplification did not significantly predict resection rates. Post-induction mCR and stage were associated with surgical resection and five-year OS (p < 0.001) on multivariate analysis.Patients with high-risk NB who achieved mCR and had primary tumor resections are curable in limited resourced settings. Stage and post-induction mCR were significant variables that led to surgery. These variables should be included as indications in the management of metastatic NB in resource limited settings.

High-risk neuroblastoma that achieved post-induction chemotherapy metastatic remission and have undergone resection, is curable, even in limited resource settings.Achieving metastatic complete remission was the only factor that significantly predicated if surgery was done.The age at diagnosis, stage and hospitals with expertise in neuroblastoma surgery were of prognostic significance in South Africa.If a patient with high-risk neuroblastoma achieves metastatic complete remission in a resource limited setting, it should be an indication for resection of the primary tumor.

Risk factors of poor developmental outcome in children with tuberculous meningitis.

BACKGROUND: Neurodevelopmental delay is a significant long-term complication of childhood tuberculous meningitis (TBM). The objective of this study was to assess risk factors for neurodevelopmental delay in children with TBM. METHODS: We conducted a retrospective cohort study of children diagnosed with TBM at Tygerberg Hospital, Cape Town, South Africa, over a 30-year period between 1985 and 2015. We assessed the relationship between demographic, clinical, laboratory and neuro-imaging characteristics, and cognitive impairment at the conclusion of anti-tuberculous treatment. Poor outcome was defined as moderate-to severe cognitive impairment. RESULTS: A total of 327 TBM patients were included, 71 (21.7%) suffered a poor outcome. Multivariate analysis revealed that decreased level of consciousness (adjusted OR (aOR): 4.68; 95%CI: 2.43-13.88; p = 0.005), brainstem dysfunction (aOR: 3.20; 95%CI: 1.70-6.00; p < 0.001), and radiological infarction (aOR: 3.47; 95%CI: 1.87-6.45; p < 0.001) were associated with a poor developmental outcome. Left hemispherical (single and multiple) stroke and bilateral stroke were associated with poor developmental outcomes. CONCLUSION: Certain neurological signs as well as radiological infarct characteristics are important predictors of poor developmental outcome. Anticipation of the likely level of cognitive impairment at diagnosis allows more accurate prognostication and prompt institution of supportive and rehabilitative measures, after the acute illness.

Depression, Anxiety, and Their Association to Health-Related Quality of Life in Men Commencing Prostate Cancer Treatment at Tertiary Hospitals in Cape Town, South Africa.

BACKGROUND: Comorbid depression and anxiety in men with localised prostate cancer (CaP) largely go undiagnosed and untreated and their effects on health-related quality of life (HRQOL) in men with CaP should not be underestimated. We examined the prevalence of depression and anxiety and its association with HRQOL in men about to commence treatment for CaP and the differences between treatment groups, radical prostatectomy (RP) and radiation therapy (RT). METHOD: One hundred and seven participants from a longitudinal prospective observational study assessing depression, anxiety and HRQOL in men with localised CaP (DAHCaP), were used in this cross-sectional analysis. Data were collected shortly before participants were scheduled to receive their treatment. The Centre for Epidemiologic Studies Depression Scale (CES-D), the State Trait Anxiety Inventory (STAI), the Memorial Anxiety Scale for Prostate Cancer (MAX-PC), the European Organisation for Research and Treatment in Cancer Quality of Life questionnaire (EORTC QLQ-C30) and (EORTC QLQ-PR25) were used in this analysis. RESULTS: Symptoms of depression pre-treatment were noted in 39.3%, state anxiety 28%, trait anxiety 31.4% and prostate cancer anxiety in 12.1% of participants. Statistically significant correlations (P ≤ .05) with the CES-D and a cluster of symptoms on the EORTC QLQ-C30 domains for Global Health (rs = -.35), fatigue (rs = .38), pain (rs = .32), dyspnoea (rs = .28), insomnia (rs = .30) and finance (rs = .26) and EORTC QLQ-PR25 domains for urinary symptoms (rs = .43), bowel (rs = .43) and hormone replacement therapy (HRT) (rs = .41) were observed.Statistically significant correlations were also noted between the STAI-S and EORTC QLQ-C30 and EORTC QLQ-PR25. No statistically significant difference was noted between treatments. CONCLUSION: More men were depressed than anxious with significant associations with HRQOL prior to commencement of treatment. CaP treatments should focus not only on the prevailing indisposition but include a psychooncological and HRQOL assessment at pre-treatment in high-risk individuals.

Prevalence and Characteristics of HIV-Associated Stroke in a Tertiary Hospital Setting in South Africa.

BACKGROUND AND OBJECTIVES: Antiretroviral treatment (ART) era HIV-associated stroke data from sub-Saharan Africa are limited. We determined the prevalence of HIV in patients presenting with acute symptomatic stroke and compared risk factors, clinical characteristics, and brain imaging with age-matched stroke patients without HIV. METHODS: We conducted a retrospective study of adults presenting with any type of stroke to Tygerberg Hospital in a 12-month period. Patients living with HIV (PLWH) and HIV-uninfected (HIV-) patients were matched based on age group (1:2 ratio). Patients were identified by keyword search, while HIV status was ascertained from laboratory data. Clinical and imaging data were extracted from medical records. RESULTS: Among 884 patients presenting with acute strokes, the minimum prevalence of HIV infection was 9.3% (95% CI: 7.4%-11.2%), with 496 patients (56.1%) with negative HIV status and 306 patients with unknown HIV status (34.6%). The mean age at presentation in PLWH was 46 (±11) years compared with 55 (±14) years in HIV- patients (p < 0.001). Smoking was less prevalent in PLWH with an adjusted relative risk ratio of RR = 0.58 (95% CI: 0.39-0.86). Concurrent infection was more prevalent in PLWH (25.6% vs 4.9%, p ≤ 0.001) with an adjusted relative risk ratio of RR = 2.07 (95% CI: 1.49-2.84), largely in patients with a CD4 count <200 cells/µL. PLWH with higher CD4 counts (≥200 cells/µL, 51.3%) had more traditional risk factors and less concurrent infection. Among PLWH, 68.3% were on ART, and 39.3% of them had been started or restarted on ART within the past 6 months. Basal ganglia infarcts (35.6% vs 18.3%, p = 0.014) and multiple vascular territory involvement (25.4% vs 7.7%, p = 0.002) were more common in PLWH. Clinical presentation, ischemic stroke type, and in-hospital outcomes did not differ between the groups. DISCUSSION: Stroke patients with HIV were younger, had less traditional cardiovascular risk factors, and more concurrent infections than patients without HIV, especially those with a lower CD4 count. Recent ART initiation or reinitiation rates were high. Significant differences in CT brain imaging findings were seen. Understanding the multifactorial mechanisms underlying increased stroke risk, including associated infections and potential ART-associated immune reconstitution, is crucial and needs further study.

Concentrations of Efavirenz, Tenofovir, and Emtricitabine in Obesity: A Cross-Sectional Study.

BACKGROUND: Obesity is increasing worldwide including in people living with HIV (PLWH). Antiretroviral pharmacokinetic data in obesity are limited. OBJECTIVES: To measure antiretroviral drug concentrations in obese and nonobese PLWH treated with the fixed-dose combination of efavirenz-tenofovir-emtricitabine. To determine pharmacokinetic differences across indicators of obesity and their associated immunovirological outcomes. METHODS: We conducted a cross-sectional sample analysis of 2 cohort studies. We measured mid-dose efavirenz, 8-hydroxy-efavirenz, tenofovir, and emtricitabine concentrations. Antiretroviral drug concentrations were analyzed by body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR). RESULTS: We performed a study of 213 participants: General obesity was detected in 20.4% using BMI and abdominal obesity in 53.6% using WC and 62.4% using WHR, respectively. The median concentrations of all antiretroviral drugs were lower among obese participants determined by BMI and WC, with efavirenz showing greater differences than tenofovir or emtricitabine. For BMI, results were most striking for efavirenz (1752.3 vs 2342.9 ng/mL, P = 0.002) with lower concentrations in obese participants. Using WC, efavirenz (1845.8 vs 2571.2 ng/mL, P < 0.001), tenofovir (65.8 vs 73.2 ng/mL, P = 0.036), and emtricitabine (159.5 vs 221.0 ng/mL, P = 0.005) concentrations were lower in obese participants. Eight-hydroxyefavirenz concentrations were similar in nonobese and obese participants for WC. Using WHR, the concentrations of all antiretroviral drugs were lower in the obese population, most strikingly for emtricitabine (173.5 vs 229.0 ng/mL, P = 0.015). There were no immunovirological associations. CONCLUSION: We found lower antiretroviral concentrations in all obese groups, most strikingly in participants with abdominal obesity determined by WC. Lower drug concentrations had no immunovirological associations.

Decisional Conflict is Associated with Treatment Modality and not Disease Knowledge in South African Men with Prostate Cancer: Baseline Results from a Longitudinal Prospective Observational Study.

BACKGROUND: Decisional conflict (DC) is a psychological construct that an individual experiences in making a decision that involves risk, loss, regret, or challenges to one's values. This study assessed DC in a cohort of South African men undergoing curative treatment for localised prostate cancer (LPC). The objectives were to (1) to examine the association between DC and prostate cancer knowledge (PCK), demographics, state anxiety, prostate cancer anxiety and time to treatment and (2) to compare levels of DC between treatment groups [prostatectomy (RP) and external beam radiation (RT)]. METHOD: Data, comprising the Decisional Conflict Scale (DCS), Prostate Cancer Knowledge (PCK), State-Trait Anxiety Inventory (STAI-S), the Memorial Anxiety Scale for Prostate Cancer (MAX-PC) and demographic data from 83 participants of a larger prospective longitudinal observational study examining depression, anxiety and health related quality of life (DAHCaP) were analysed. RESULTS: The mean age of participants was 63 years (RP 61yrs and RT 65yrs; p< 0.001). Most were of mixed ancestry (72.3%). The total DCS scores between the treatment groups (RP 25.00 and RT 18.75; p = 0.037) and two DCS sub-scores-uncertainty (p = 0.033), and support (p = 0.048), were significantly higher in the RP group. A statistically significant negative correlation was observed between state anxiety and time between diagnosis and treatment in the RP group (Spearman's rho = -0.368; p = 0.030). There was no correlation between the DCS score and PCK within each treatment group (Spearman's rho RP = -0.249 and RT = -0.001). CONCLUSION: Decisional conflict was higher in men undergoing RP. Men were more anxious in the RP group regarding the time treatment was received from diagnosis. No correlation was observed between DC and PCK. Pre-surgical management of DC should include shared decision making (SDM) which is cognisant of patients' values facilitated by a customised decision aid.

Resilience of adolescents living with HIV in the Cape Metropole of the Western Cape.

Resilience shapes the experiences of adolescents living with HIV (ALWH), enabling them to come to terms with their diagnosis, have hope for the future and maintain meaningful relationships. Yet, little is known about contextual factors associated with resilience resources in South Africa. We aimed to describe individual, relational and community resilience resources, and identify contextual factors associated with resilience. We recruited 385 adolescents, aged 13-18, over a period of 5 months from 11 different public health HIV clinics. The Child and Youth Resilience Measure (CYRM-12) was used to measure resilience resources. Data on demographic variables, psychological attributes, and environmental factors such as HIV-related stigma and stressful life events were collected. ALWH lacked resilience in some aspects of the individual, relational and community domains. For every one-unit increase in the HIV-related stigma and stressful life events scores, resilience decreased by 0.29 (p = 0.01) and 0.37 (p = 0.04) units, respectively. Higher levels of resilience were associated with being virally suppressed (Mann-Whitney U, p = 0.028) although this association was no longer present in the regression model. Efforts to improve resilience amongst ALWH should be focused on fostering individual coping skills, interconnectedness, and positive relationships, to mitigate adverse environmental factors.

How much time do doctors spend providing care to each child in the ED? A time and motion study.

BACKGROUND: The total time per patient doctors spend providing care in emergency departments (EDs) has implications for the development of evidence-based ED staffing models. We sought to measure the total time taken by doctors to assess and manage individual paediatric patients presenting to two EDs in the Western Cape, South Africa and to compare these averages to the estimated benchmarks used regionally to calculate ED staffing allocations. METHODS: We conducted a cross-sectional, observational study applying time and motion methodology, using convenience sampling. Data were collected over a 5-week period from 11 December 2015 to 18 January 2016 at Khayelitsha District Hospital Emergency Centre and Tygerberg Hospital Paediatric Emergency and Ambulatory Unit. We assessed total doctor time for each patient stratified by acuity level using the South African Triage Scale. RESULTS: Care was observed for a total of 100 patients. Median age was 21 months (IQR 8-55). Median total doctor time per patient (95% CI) was 31 (22 to 38), 39 (31 to 63), 48 (32 to 63) and 96 (66 to 122) min for triage categories green, yellow, orange and red, respectively. Median timing was significantly higher than the estimated local benchmark for the lowest acuity 'green' triage category (31 min (22 to 38) vs 15 min; p=0.001) and the highest acuity 'red' category (96 min (66 to 122) vs 50 min; p=0.002). CONCLUSION: Doctor time per patient increased with increasing acuity of triage category and exceeded estimated benchmarks for the highest and lowest acuities. The distinctive methodology can easily be extended to other settings and populations.

Pharmacogenetics of the Late-Onset Efavirenz Neurotoxicity Syndrome (LENS).

BACKGROUND: The late-onset efavirenz neurotoxicity syndrome (LENS) presents as ataxia and/or encephalopathy with supratherapeutic efavirenz plasma concentrations (>4 µg/mL). Efavirenz is primarily metabolized by cytochrome P450 2B6 (CYP2B6), with CYP2A6 as an accessory pathway. We hypothesized that participants with LENS would predominantly be CYP2B6 slow metabolizers. The aim of our study was to determine the frequency of CYP2B6 slow metabolizers in participants with LENS. METHODS: Adult HIV-positive participants on efavirenz-based antiretroviral therapy presenting with LENS were prospectively enrolled. Genetic polymorphisms known to be associated with increased efavirenz plasma concentrations in CYP2B6 (rs3745274, rs28399499, rs4803419) and CYP2A6 (rs28399433) were selected and used to determine proportions of slow metabolizers. Pharmacokinetic analyses were performed using liquid chromatography-tandem mass spectrometry. Median (IQR) plasma efavirenz and 8-hydroxyefavirenz were described. RESULTS: Fifteen participants were enrolled. Thirteen (13/15) were Black-African and 13 were female. Median weight was 49.9kg with a median duration on efavirenz of 2.2 years. All 15 participants were successfully genotyped as slow CYP2B6 metabolizers, with 6 participants additionally having CYP2A6 heterozygous genotype. Thirteen were receiving the CYP2A6 enzyme inhibitor isoniazid, and all 15 were genotypic NAT2 slow or intermediate acetylators. Efavirenz plasma concentration was markedly increased at 50.5 (47.0-65.4) µg/mL; 8-hydroxyefavirenz concentration was markedly decreased at 0.10 (0.07-0.15) µg/mL. CONCLUSIONS: Our cohort provides definitive evidence that LENS is associated with the CYP2B6 slow metabolizer genotype, with a median efavirenz plasma concentration >12-fold higher than the defined upper limit of the therapeutic range. Isoniazid and low body weight are important contributors to LENS development.

Reorganisation of primary care services during COVID-19 in the Western Cape, South Africa: Perspectives of primary care nurses.

BACKGROUND: Primary care nurses play a pivotal role in the response to disasters and pandemics. The coronavirus diseases 2019 (COVID-19) pandemic required preventative, diagnostic, and curative measures for persons presenting with symptoms of COVID-19 by healthcare providers, whilst continuing other essential services. We aimed to investigate the reorganisation of primary care services during COVID-19 from the perspectives of primary care nurses in the Western Cape province of South Africa. METHODS: We administered an online survey with closed and open-ended questions to professional nurses enrolled for a Postgraduate Diploma in Primary Care Nursing at Stellenbosch University (2020) and alumni (2017-2019) working in the Western Cape. Eighty-three participants completed the questionnaire. RESULTS: The majority of the participants (74.4%) reported that they were reorganising services using a multitude of initiatives in response to the diverse infrastructure, logistics and services of the various healthcare facilities. Despite this, 48.2% of the participants expressed concerns, which mainly related to possible non-adherence of patients with chronic conditions, the lack of promotive and preventative services, challenges with facility infrastructure, and staff time devoted to triage and screening. More than half of the participants (57.8%) indicated that other services were affected by COVID-19, whilst 44.6% indicated that these services were worse than before. CONCLUSION: Our findings suggest that the very necessary reorganisation of services that took place at the start of the COVID-19 pandemic in South Africa enabled effective management of patients infected with COVID-19. However, the reorganisation of services may have longer-term consequences for primary care services in terms of lack of care for patients with other conditions, as well as preventive and promotive care.

Estimating Vaccine Confidence Levels among Healthcare Staff and Students of a Tertiary Institution in South Africa.

Healthcare workers were the first group scheduled to receive COVID-19 vaccines when they became available in South Africa. Therefore, estimating vaccine confidence levels and intention to receive COVID-19 vaccines among healthcare workers ahead of the national vaccination roll-out was imperative. We conducted an online survey from 4 February to 7 March 2021, to assess vaccine sentiments and COVID-19 vaccine intentions among healthcare staff and students at a tertiary institution in South Africa. We enrolled 1015 participants (74.7% female). Among the participants, 89.5% (confidence interval (CI) 87.2-91.4) were willing to accept a COVID-19 vaccine, 95.4% (CI 93.9-96.6) agreed that vaccines are important for them, 95.4% (CI 93.8-96.6) that vaccines are safe, 97.4% (CI 96.2-98.3) that vaccines are effective, and 96.1% (CI 94.6-97.2) that vaccines are compatible with religion. Log binomial regression revealed statistically significant positive associations between COVID-19 vaccine acceptance and the belief that vaccines are safe (relative risk (RR) 32.2, CI 4.67-221.89), effective (RR 21.4, CI 3.16-145.82), important for children (RR 3.5, CI 1.78-6.99), important for self (RR 18.5, CI 4.78-71.12), or compatible with religion (RR 2.2, CI 1.46-3.78). The vaccine confidence levels of the study respondents were highly positive. Nevertheless, this could be further enhanced by targeted interventions.

The 12-month period prevalence and cardiac manifestations of HIV in patients with acute coronary syndrome at a tertiary hospital in Cape Town, South Africa: a retrospective cross-sectional study.

BACKGROUND: HIV-positive patients are increasingly being affected by non-communicable diseases such as coronary artery disease (CAD). Data from high-income countries (HICs) indicate that HIV-positive patients have different risk-factor profiles for acute coronary syndrome (ACS) as well as different cardiac manifestations of this syndrome compared to HIV-negative patients. There is limited data from Sub-Saharan Africa (SSA), and particularly from South Africa with the biggest HIV epidemic in the world. The objective of this study was to determine the 12-month period prevalence of HIV in patients with ACS and to compare the risk-factor profile, ACS presentation and management between HIV-positive and HIV-negative adults. METHODS: We included all patients hospitalised with ACS from 01 January to 31 December 2018 in a tertiary hospital, Tygerberg Hospital, in Cape Town, South Africa. The HIV-status of all patients was determined using routine clinical records. We performed multiple conditional logistic regression on HIV-positive and HIV-negative patients (1:3 ratio) to compare the risk factor profile, ACS presentation and management between the groups. RESULTS: Among 889 patients, 30 (3.4%) were HIV-positive (95% confidence interval (CI): 2.3-4.8). HIV-positive patients were younger, more frequently men, and had a lower prevalence of medical comorbidities and a family history of CAD. They were more likely to present with ST-elevation myocardial infarction (STEMI) [odd's ratio (OR) (95% CI): 3.12 (1.2-8.4)], and have single-vessel disease [OR (95% CI): 3.03 (1.2-8.0)]. Angiographic and echocardiographic data, as well as management, did not differ between the groups. Among HIV-positive patients, 17 (65%) were virally suppressed (HIV viral load < 200 copies/mL) with a median CD4+ count of 271 cells/mm3. The majority (20, 67%) of HIV-positive patients were receiving antiretroviral therapy at the time of the ACS. CONCLUSIONS: We found an HIV-prevalence of 3.4% (95% CI 2.3-4.8) in adults with ACS in a high endemic HIV region. HIV-positive patients were younger and more likely to present with STEMIs and single-vessel disease, but had fewer CAD risk factors, suggesting additional mechanisms for the development of ACS.

Advancing collaborations in health research and clinical trials in Sub-Saharan Africa: development and implementation of a biostatistical collaboration module in the Masters in Biostatistics Program at Stellenbosch University.

BACKGROUND: Sub-Saharan Africa continues to carry a high burden of communicable diseases such as TB and HIV and non-communicable diseases such as hypertension and other cardiovascular conditions. Although investment in research has led to advances in improvements in outcomes, a lot still remains to be done to build research capacity in health. Like many other regions in the world, Sub-Saharan Africa suffers from a critical shortage of biostatisticians and clinical trial methodologists. METHODS: Funded through a Fogarty Global Health Training Program grant, the Faculty of Medicine and Health Sciences at Stellenbosch University in South Africa established a new Masters Program in Biostatistics which was launched in January 2017. In this paper, we describe the development of a biostatistical and clinical trials collaboration Module, adapted from a similar course offered in the Health Research Methodology program at McMaster University. DISCUSSION: Guided by three core principles (experiential learning; multi-/inter-disciplinary approach; and formal mentorship), the Module aims to advance biostatistical collaboration skills of the trainees by facilitating learning in how to systematically apply fundamental statistical and trial methodological knowledge in practice while strengthening some soft skills which are necessary for effective collaborations with other healthcare researchers to solve health problems. We also share some preliminary findings from the first four cohorts that took the Module in January-November 2018 to 2021. We expect that this Module can provide an example of how to improve biostatistical and clinical trial collaborations and accelerate research capacity building in low-resource settings. FUNDING SOURCE: Fogarty International Center of the National Institutes of Health.