Stepped care to optimize pre-exposure prophylaxis (PrEP) effectiveness in pregnant and postpartum women (SCOPE-PP) in South Africa: a randomized control trial

Background HIV incidence among pregnant and postpartum women remains high in South Africa. Pre-exposure prophylaxis (PrEP) use remains suboptimal in this population, particularly during the postpartum period when women’s engagement with routine clinic visits outside PrEP decreases. Key barriers to sustained PrEP use include the need for ongoing contact with the health facility and suboptimal counseling around effective PrEP use. Methods Stepped Care to Optimize PrEP Effectiveness in Pregnant and Postpartum women (SCOPE-PP), is a two-stepped unblinded, individually randomized controlled trial (RCT) that aims to optimize peripartum and postpartum PrEP use by providing a stepped package of evidence-based interventions. We will enroll 650 pregnant women (> 25 weeks pregnant) who access PrEP at a busy antenatal clinic in Cape Town at the time of recruitment and follow them for 15 months. We will enroll and individually randomize pregnant women > 16 years who are not living with HIV who are either on PrEP or interested in starting PrEP during pregnancy. In step 1, we will evaluate the impact of enhanced adherence counselling and biofeedback (using urine tenofovir tests for biofeedback) and rapid PrEP collection (to reduce time required) on PrEP use in early peripartum compared to standard of care (SOC) (n = 325 per arm). The primary outcome is PrEP persistence per urine tenofovir levels and dried blood spots of tenofovir diphosphate (TFV-DP) after 6-months. The second step will enroll and individually randomize participants from Step 1 who discontinue taking PrEP or have poor persistence in Step 1 but want to continue PrEP. Step 2 will test the impact of enhanced counseling and biofeedback plus rapid PrEP collection compared to community PrEP delivery with HIV self-testing on PrEP use (n = up to 325 postpartum women). The primary outcome is PrEP continuation and persistence 6-months following second randomization (~ 9-months postpartum). Finally, we will estimate the cost effectiveness of SCOPE-PP vs. SOC per primary outcomes and disability-adjusted life-years (DALYs) averted in both Step 1 and 2 using micro-costing with trial- and model-based economic evaluation. Discussion This study will provide novel insights into optimal strategies for delivering PrEP to peripartum and postpartum women in this high-incidence setting. Trial registration NCT05322629 : Date of registration: April 12, 2022

Personal NO2 and volatile organic compounds exposure levels are associated with markers of cardiovascular risk in women in the Cape Town region of South Africa

CITATION: Everson, F., et al. 2019. Personal NO2 and volatile organic compounds exposure levels are associated with markers of cardiovascular risk in women in the Cape Town region of South Africa. International Journal of Environmental Research and Public Health, 16(13):2284, doi:10.3390/ijerph16132284.The original publication is available at http://www.mdpi.comENGLISH ABSTRACT: Exposure to ambient NO2 and benzene, toluene ethyl-benzene and m+p- and o-xylenes (BTEX) is associated with adverse cardiovascular effects, but limited information is available on the effects of personal exposure to these compounds in South African populations. This 6-month follow-up study aims to determine 7-day personal ambient NO2 and BTEX exposure levels via compact passive diffusion samplers in female participants from Cape Town, and investigate whether exposure levels are associated with cardiovascular risk markers. Overall, the measured air pollutant exposure levels were lower compared to international standards. NO2 was positively associated with systolic and diastolic blood pressure (SBP and DBP), and inversely associated with the central retinal venular equivalent (CRVE) and mean baseline brachial artery diameter. o-xylene was associated with DBP and benzene was strongly associated with carotid intima media thickness (cIMT). Our findings showed that personal air pollution exposure, even at relatively low levels, was associated with several markers of cardiovascular risk in women residing in the Cape Town region.https://www.mdpi.com/1660-4601/16/13/2284Publisher's versio

Cardiovascular risk and endothelial function in people living with HIV/AIDS: design of the multi-site, longitudinal EndoAfrica study in the Western Cape Province of South Africa

CITATION: Strijdom, H., et al. 2017. Cardiovascular risk and endothelial function in people living with HIV/AIDS: design of the multi-site, longitudinal EndoAfrica study in the Western Cape Province of South Africa. BMC Infectious Diseases, 17:41, doi:10.1186/s12879-016-2158-y.The original publication is available at http://bmcinfectdis.biomedcentral.comBackground: There is growing evidence of an interaction between HIV-infection, anti-retroviral therapy (ART) and cardiovascular diseases (CVD). Epidemiological studies in Europe and North America have been observing a shift towards an increased incidence of coronary heart disease and acute myocardial infarctions in HIV-infected populations compared to the general population even after adjusting for traditional cardiovascular risk factors. Despite South Africa (and sub-Saharan Africa, SSA) being regarded as the epicentre of the global HIV epidemic, very little is known about the prevalence of cardiovascular risk factors and precursors of vascular disease in HIV-infected populations in this region. The knowledge gap is further widened by the paucity of data from prospective studies. We present the rationale, objectives and key methodological features of the EndoAfrica study, which aims to determine whether HIVinfection and ART are associated with altered cardiovascular risk and changes in vascular endothelial structure and function in adults living in the Western Cape Province of South Africa. Methods: In this longitudinal study, comprehensive cardiovascular assessments of HIV-negative and HIV-positive (with and without ART) study participants are performed by clinical and biochemical screening for traditional cardiovascular risk factors and biomarkers of CVD. Vascular and endothelial function is determined by brachial artery flow-mediated dilatation (FMD), carotid-intima-thickness (IMT) measurements and quantitative retinal blood vessel analyses, complemented by vascular endothelial biomarker assays. Finally, we aim to statistically determine whether HIVinfection and/or ART are associated with increased cardiovascular risk and vascular endothelial dysfunction, and determine whether there is progression/regression in these endpoints 18 months after the baseline assessments. Discussion: The EndoAfrica study provides a unique opportunity to recruit a cohort of HIV-infected patients and HIVnegative controls who will be comprehensively and longitudinally assessed for cardiovascular risk and disease profile with vascular endothelial function as a potentially important intermediate cardiovascular phenotype. To our knowledge, it is the first time that such a systematic study has been established in the context of SSA and South Africa.http://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-016-2158-yPublisher's versio

Evaluating the use of oral pre-exposure prophylaxis among pregnant and postpartum adolescent girls and young women in Cape Town, South Africa

BackgroundAdolescent girls and young women (AGYW) in South Africa are at a higher risk of acquiring HIV. Despite the increasing availability of daily oral pre-exposure prophylaxis (PrEP) for HIV prevention, knowledge on PrEP use during pregnancy and postpartum periods at antenatal care (ANC) facilities remains inadequate.MethodsData from HIV-uninfected pregnant women in Cape Town, South Africa, were used in this study. These women aged 16–24 years were enrolled in the PrEP in pregnancy and postpartum (PrEP-PP) cohort study during their first ANC visit. Using the PrEP cascade framework, the outcomes of the study were PrEP initiation (prescribed tenofovir disoproxil fumarate and emtricitabine at baseline), continuation (returned for prescription), and persistence [quantifiable tenofovir diphosphate (TFV-DP) in dried blood samples]. The two primary exposures of this study were risk perception for HIV and baseline HIV risk score (0–5), which comprised condomless sex, more than one sexual partner, partner living with HIV or with unknown serostatus, laboratory-confirmed sexually transmitted infections (STIs), and hazardous alcohol use before pregnancy (Alcohol Use Disorders Identification Test for Consumption score ≥ 3). Logistic regression was used to examine the association between HIV risk and PrEP, adjusting for a priori confounders.ResultsA total of 486 pregnant women were included in the study, of which 16% were “adolescents” (aged 16–18 years) and 84% were “young women” (aged 19–24 years). The adolescents initiated ANC later than the young women [median = 28 weeks (20–34) vs. 23 weeks (16–34), p = 0.04]. Approximately 41% of the AGYW were diagnosed with sexually transmitted infection at baseline. Overall, 83% of the AGYW initiated PrEP use during their first ANC. The percentage of PrEP continuation was 63% at 1 month, 54% at 3 months, and 39% at 6 months. Approximately 27% consistently continued PrEP use through 6 months, while 6% stopped and restarted on PrEP use at 6 months. With a higher risk score of HIV (≥2 vs. ≤1), the AGYW showed higher odds of PrEP continuation [adjusted odds ratio: 1.85 (95% CI: 1.12–3.03)] through 6 months, adjusting for potential confounders. Undergoing the postpartum period (vs. pregnant) and having lower sexual risk factors were found to be the barriers to PrEP continuation. TFV-DP concentration levels were detected among 49% of the AGYW, and 6% of these women had daily adherence to PrEP at 3 months.ConclusionsAGYW were found to have high oral PrEP initiation, but just over one-third of these women continued PrEP use through 6 months. Pregnant AGYW who had a higher risk of acquiring HIV (due to condomless sex, frequent sex, and STIs) were more likely to continue on PrEP use through the postpartum period. Pregnant and postpartum AGYW require counseling and other types of support, such as community delivery and peer support to improve their effective PrEP use through the postpartum period.Clinical Trial NumberClinicalTrials.gov, NCT03826199

Depressive symptoms and cardiometabolic health in urban black Africans : the SABPA study

PhD (Physiology), North-West University, Potchefstroom Campus, 2014Motivation - Depression is a mental disorder that has been associated with cardiovascular morbidity and mortality in the Western world. Cardio-metabolic mechanisms have been implicated as possible intermediating factors in the relationship between depressive symptoms and cardiovascular disease; however this has not yet been determined in black Africans (hereafter referred to as Africans). Aim - The overarching aim of this study was to investigate the relationship between depressive symptoms and cardio-metabolic risk. We therefore aimed to assess cardio-metabolic function, neuroendocrine responses, inflammatory and haemostatic markers in Africans with depressive symptoms compared to those without symptoms of depression. Methodology - Manuscripts presented in Chapter 2, 3 and 4 utilised data from the cross-sectional, target population multi-disciplinary “Sympathetic activity and Ambulatory Blood Pressure in Africans' (SABPA) study. The participants comprised of 200 African teachers from the Dr Kenneth Kaunda District in North-West province, South Africa. As cardiovascular disease is compromised by a positive HIV status, 19 participants were excluded from further statistical analysis. Stratification was based on the Patient Health Questionnaire 9-item (PHQ-9), which has been validated in a sub-Saharan African setting. PHQ-9 scores > 10 were used to classify participants as having signs of depressive symptoms. Subjects were further stratified by gender (Manuscript 1 and 3) and cortisol responses (Manuscript 2). Cardio-metabolic health measures included 24-hour blood pressure, metabolic syndrome markers, neuroendocrine markers [cortisol and 3-methoxy-4-hydroxy-phenylglycol (MHPG)], left ventricular hypertrophy (LVH), inflammatory and haemostatic markers (fibrinogen, C-reactive protein, plasminogen activator inhibitor-1 and D-dimer). Resting 12-lead ECG Cornell Product-Left ventricular hypertrophy (CP-LVH) was measured as a marker of target end-organ damage and cardiovascular dysfunction (Manuscript 1 and 2). Means and prevalence were computed through t-test and Chi-square analysis respectively. Significant differences of mean cardio-metabolic measures between depressive symptom status groups were also determined by analysis of covariance (adjusted for traditional cardiovascular risk factors and additional factors as specific per manuscript). Multivariate analysis was used to demonstrate associations between left ventricular hypertrophy (LVH) and cardio-metabolic markers in Africans with depressive symptoms (Manuscript 1 and 2) and a logistic regression analysis were performed to examine the association between depressive symptoms and inflammatory/haemostatic factors (Manuscript 3). All subjects who participated gave informed consent, the study was approved by the Ethics Committee of North-West University (NWU-0003607S6), in accordance with the principles outlined by the World Medical Association Declaration of Helsinki of 1975 (revised 2008). Results and conclusions of the individual manuscripts - The aim of the study was to investigate the associations between depressive symptoms and cardio-metabolic function including cardiovascular dysfunction. Markers of cardio-metabolic function assessed were 24 hour blood pressure measurements, metabolic syndrome markers, neuroendocrine markers [cortisol and 3-methoxy-4-hydroxy-phenylglycol (MHPG)], inflammatory and haemostatic variables (fibrinogen, C-reactive protein, plasminogen activator inhibitor-1 and D-dimer). Manuscript 1, focused on LVH as a marker of cardiovascular dysfunction and metabolic syndrome components as markers of cardio-metabolic function. The aim of the study was to assess the associations between LVH and metabolic syndrome (MetS) risk markers in participants with and without depressive symptoms. Results revealed that in African men with depressive symptoms the most significant determinants of LVH were systolic blood pressure (SBP) and the percentage glycosylated haemoglobin (HbA1c). While in African women (with depressive symptoms), this association was determined by low high-density lipoprotein (HDL-cholesterol). The study concluded that in black African men, independent of depressive symptoms, cardiometabolic factors (namely SBP and HbA1c) may be the driving significant factors in the development of cardiovascular diseases. Furthermore, the data showed that depressive symptoms in African women were associated with a measure of target end organ damage, and that this association was driven by a metabolic factor. Manuscript 2, the aim of this manuscript was to examine the relationship between depressive symptoms, neuroendocrine responses [with cortisol and 3-methoxy-phenylglycol (MHPG) as markers] and cardiovascular risk, i.e. LVH. The results revealed that Africans with depressive symptoms demonstrated blunted cortisol and MHPG levels in response to acute mental stress, in comparison to those without symptoms of depression. Additionally, these low cortisol and blunted MHPG responses were associated with LVH in this ethnic group. The conclusion for this manuscript was that, blunted neuroendocrine responses linked depressive symptoms and ECG left ventricular hypertrophy in Africans. When coupled to their hypertensive status, these vasoconstrictive responses (cortisol and MHPG) may underpin the increased long-term depression and vascular disease risk in urban Africans. Manuscript 3, the aim of this manuscript was to investigate the relationship between depressive symptoms and inflammatory/haemostatic markers in a cohort of urban-dwelling black African men and women. Our data demonstrated hyper coagulation vulnerability in African men with depressive symptoms. The African men with signs of depression displayed higher plasminogen activator inhibitor (PAI-1) levels and marginally elevated D-dimer levels. It was concluded that hyper coagulation may partially be the mediating factor between depressive symptoms and cardiovascular risk in African men; a situation that may be exacerbated by hyper kinetic blood pressure. In conclusion, through the assessment of cardio-metabolic function and neuroendocrine responses, it seems that Africans with depressive symptoms are at great risk for cardiovascular related morbidity and mortality, this was particularly evident in the African men (Manuscript 1 and 3). Additionally, it appears that blunted neuroendocrine responses and hyper-coagulation could be seen as possible cardiovascular risk markers in Africans with depressive symptoms.Doctora

Cardiovascular function and psychological distress in urbanised black South Africans : the SABPA study

Thesis (M.Sc. (Physiology))--North-West University, Potchefstroom Campus, 2009.Motivation: Cardiovascular disease (CVD) is one of the leading causes of death worldwide, with the greatest mortality rates occurring in low and middle income countries. The increase in the prevalence of risk factors such as hypertension, obesity and diabetes in Sub-Saharan Africa has led in an increase of the prevalence of CVD. It remains largely unclear whether psychological distress and more specifically the perception of own health and / depression may contribute to this observed increase in the prevalence of CVD in this population group. To our knowledge investigations exploring these aspects have not been done in the African context, thus the association between depression as an outcome of psychological distress and cardiovascular dysfunction in Africans is a new frontier that requires further exploration in the population group. Objective: The aim of this study was to investigate the association between psychological distress and cardiovascular function in urbanized black South Africans which included a target population of 200 Africans, men (n=101) and women (n=99). The participants were stratified into a hypertensive (HT) and normotensive (NT) group. Methodology: The manuscript presented in chapter 2 made use of the data obtained from the SABPA (Sympathetic activity and Ambulatory Blood Pressure in Africans) project. A group of 200 black Africans from governmental institutions of the North West Province of South Africa were recruited. All procedures conducted were approved by the North-West University Ethics Committee and written informed consent was given by all the participants prior to the study. Anthropometric measurements were taken with the assistance of registered biokinetisists. Resting cardiovascular variables such as heart rate (HR), arterial compliance (Cw), total peripheral resistance (TPR) and the mean arterial pressure (MAP) were obtained with the use of a Finometer device. The 24 hours ambulatory blood pressure (BP) (AMBP) measurements were obtained with a Cardiotens apparatus. The resting ECG NORAV PL-1200 data determined left ventricular hypertrophy (L VH) by making use of the Cornell product (RaVL+ SV3) *QRS. Psychological distress questionnaire assessed the perception of health (General Health Questionnaire; GHQ-28) and depression severity (Patient Health Questionnaire; PHQ-9). Participants were stratified into hypertensive and normotensive groups based on the European Society of Hypertension (ESH) 2007 guidelines using the 24hr AMBP as a norm. Results were adjusted for confounders (age, body mass index, smoking, alcohol consumption and physical activity). One way Analysis of Covariance (ANCOVA) was done to determine significant differences between age, body mass index, lifestyle factors cardiovascular variables and psychological parameters. For more detailed description of the subjects, study design and analytical procedures used in this study the reader is referred to the Methods section in Chapter 2. Results and Conclusion: The hypertensive (HT) men and women were more obese (p<0.01) with a larger waist circumference (WC) (p=0.05) and a lower compliance (p</=0.05) compared to their normotensive (NT) counterparts. Only the HT men revealed a higher Cornell product value (p=0.06) compared to NT counterparts. In HT men, somatisation was positively associated with blood pressure (SBP & DBP), while in HT women it was associated with heart rate (HR). Major depression was associated with a left ventricular hypertrophy in HT men and MAP in HT women. Logistic regression analysis followed to predict the strongest contributor to HT in Africans. It was indicated that depressed women are 1.13 times more likely to develop hypertension than men. In conclusion, these results suggest a possible association between depression as an outcome of psychological distress and cardiovascular dysfunction in urbanised Africans. Depression has also been identified as a contributor to HT in African women.Master

Blunted neuro-endocrine responses linking depressive symptoms and ECG left ventricular hypertrophy in black Africans: the SABPA study

Objective: Chronic psychosocial stress as experienced in an urban environment plays an important role in the aetiology of depression-related cardiovascular risk. It is uncertain whether acute mental stress responses aggravate this risk. Therefore, we aimed to explore the associations between depressive symptoms, neuroendocrine acute mental stress responses and cardiovascular risk, that is ECG-left ventricular hypertrophy (ECG-LVH), in a black South African cohort. Materials and methods: The substudy sample consisted of 179 black African men and women from the Sympathetic Activity and Ambulatory Blood Pressure in Africans study. Depressive symptoms were evaluated using the nine-item Patient Health Questionnaire and the participants were stratified into black Africans with depressive symptoms and without. Cortisol and 3-methoxy-phenylglycol (MHPG) responses were analysed during rest and exposure to the Stroop mental stressor. Cortisol median split responses were determined and stratified sex groups accordingly into above (>1.5 ng/ml) and below (≤1.5 ng/ml) responders. Blood pressure and ECG-LVH data were obtained from 24-h ambulatory monitoring and 12-lead ECG. Results: The Africans with depressive symptoms demonstrated mean hypertensive status, blunted cortisol and MHPG acute mental stress responses (P≤0.05). In Africans with depressive symptoms and low cortisol stress responses, blunted MHPG acute mental stress responses were associated with ECG-LVH in Africans [adjusted R 2=0.20; β=0.92 (95% confidence interval 0.74, 1.10); P≤0.02]. Conclusion: Blunted neuroendocrine responses were linked to depressive symptoms and ECG-LVH in black Africans. When coupled to their hypertensive status, these vasoconstrictive agent responses may underpin the increased long-term depression and vascular disease risk in urban Africans

Depression, cardiometabolic function and left ventricular hypertrophy in African men and women: the SABPA study

Depressive symptoms are associated with an increased risk for developing cardiovascular diseases, driven by its link to the metabolic syndrome (MetS). This phenomenon, however, still needs to be investigated in the African population. The aim of this study is to investigate the association between left ventricular hypertrophy (LVH) and MetS risk markers in a determined sample. The researchers stratified Black African men and women into with depressive symptoms (D) or without depressive symptoms (ND) group, based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria score. Fasting MetS, chronic hyperglycemia (HbA1c), ambulatory blood pressure (BP) and Cornell product-LVH (CP-LVH) in ECG measures were obtained. Depressive symptoms were reported in 45.3% of the sample. Independent of depression status, African men and women revealed a pre-diabetic state (glycated hemoglobin >5.7%). CP-LVH was associated with decreased low high-density lipoprotein cholesterol in D African women. In D African men, systolic BP (P = .001) and HbA1c (P = .08) explained 64% and 31% of the variation in LVH, respectively. In conclusion, depressive symptoms in Black African women were associated with a measure of target end organ damage, CP-LVH, and this association was driven by a metabolic factor. In Black African men, independent of depressive symptoms, LVH, was driven by cardiometabolic factors, namely SBP and HbA1c

Depression symptoms facilitated fibrinolytic dysregulation and future coronary artery disease risk in a black male cohort: the sympathetic activity and ambulatory blood pressure in Africans study

Background: Hypercoagulation is associated with coronary artery disease (CAD). Whether depression symptoms dysregulate inflammatory and hemostatic markers in an African cohort is not known; therefore, we assessed the relationship between depressive symptoms and inflammatory and hemostatic markers as potential CAD risk markers in an African sex cohort. Material and Methods: We included 181 black African urban-dwelling teachers (88 men, 93 women; aged 25-60 years) from the Sympathetic Activity and Ambulatory Blood Pressure in Africans Study. The Patient Health Questionnaire was used to assess depressive symptoms. Fasting plasma concentrations of C-reactive protein, fibrinogen, D-dimer, plasminogen activator inhibitor-1 (PAI-1) and 24-hour blood pressure measures were obtained. Results: Moderately severe depression symptom status was similar in the black sex groups. Both sex groups showed a mean hypertensive state and low-grade inflammation (C-reactive protein > 3 mg/L). Levels of PAI-1 were higher in depressed men, whereas D-dimer levels were lower in depressed women when considering concomitant confounders. In black men only, depressive symptoms were associated with levels of PAI-1 (adj. R2 = 0.12; [beta] = .22 [95% confidence interval, .0-.44]; P = .04) and D-dimer (adj. R2 = 0.12; [beta] = .28 [95% confidence interval, .08-.48]; P = .01), independent of confounders. Conclusion: In black men, depression symptoms accompanied by a mean hypertensive status may up-regulate inflammatory and thrombotic processes. Depression symptoms in black men facilitated hypercoagulation or fibrinolytic dysregulation and potentially increased their CAD risk. Early screening of fibrinolytic markers and for the presence of depressive symptoms is recommende