Clinic In Cape Town Research Articles

Knowledge and perceptions of blood donors of the Western Cape Blood Services, South Africa, toward vaginal sample donation for biobanking

IntroductionDepletion of Lactobacillus species and an overgrowth of anaerobes in the vaginal tract bacterial vaginosis (BV)], is associated with non-optimal reproductive health outcomes, and increased susceptibility to sexually transmitted infections (STIs). BV is currently treated with antibiotics, although these provide suboptimal cure levels and high recurrence rates. Vaginal microbiota transplantation (VMT), the transfer of vaginal fluid from healthy donors with an optimal vaginal microbiota to a recipient with BV, has been proposed as an alternative treatment strategy.MethodsHere, we investigated knowledge and perceptions of blood donors to the concept of an optimal vaginal microbiome and VMT via the Western Cape Blood Service (WCBS) clinics in Cape Town, South Africa, by a self-administered questionnaire.Results & discussionAnalysis of responses from 106 eligible women showed that 86% (91/106) would consider donating samples. Responses significantly associated with willingness to donate vaginal samples included: (1) belief that helping others outweighs the inconvenience of donating vaginal sample (p = 1.093e−05) and (2) prior knowledge of the concept of a healthy vaginal microbiome (p = 0.001). Most potential donors (59/91; 65%) were willing to receive a VMT themselves if needed. Participants who were unwilling to donate vaginal samples (15/106; 14%) indicated that vaginal sample collection would be unpleasant and/or embarrassing. The benefits of a collaboration with WCBS for this project include the naturally altruistic nature of blood donors, the constant in-flow of donors to WCBS clinics, and the infrastructure and logistical aspects in place. Data from this observational study highlight factors affecting the willingness of blood donors to become vaginal sample donors.

Health System Factors Influencing the Integration of Pre-Exposure Prophylaxis into Antenatal and Postnatal Clinic Services in Cape Town, South Africa.

Oral pre-exposure prophylaxis (PrEP) is an effective and safe option to prevent HIV acquisition and vertical HIV transmission in pregnant and breastfeeding women. Understanding health system factors influencing the integration of PrEP into care for pregnant and breastfeeding women is key to increasing access. We explored managers' and health care workers' (HCWs) experiences with integrating PrEP into antenatal care and postnatal care services in primary health care clinics in Cape Town, South Africa. This exploratory qualitative study used codebook thematic analysis, where HCWs were purposively, heterogeneously sampled from an implementation science study. Semistructured individual interviews were conducted with 9 managerial-level staff, and 3 focus group discussions were conducted with HCWs (nurses, midwives, and HIV counselors) providing PrEP (6-7 HCWs per group) between November 2022 and January 2023 (N=28). Interview guides covered health system facilitators, barriers, and recommendations. The Health Systems Dynamics framework guided data analysis and presentation of results. PrEP integration into antenatal care services was described as acceptable and feasible; however, changes to HIV testing policy and indicators in breastfeeding women are needed to integrate PrEP into postnatal clinics, together with identification of mother and baby as a dyad in visits. Results showed that supportive policies facilitated wider, simplified PrEP provision. The availability and accessibility of prescribing nurses and lay HIV counselors, PrEP (both within facilities and in communities), and information about PrEP for implementers and pregnant and breastfeeding women will be pivotal to facilitating integration. Facilitators for PrEP integration include task-shifting PrEP education and identification of women for PrEP initiation to HIV counselors, changes to national guidelines defining who can prescribe PrEP, revision and integration of PrEP training for HCWs, community-level interventions for PrEP demand creation and stigma reduction, and provision of differentiated PrEP delivery options.

Exploring the effects of mental health on bonding and caregiving among pregnant and postpartum persons with likely depression and/or PTSD in South Africa: A qualitative analysis.

Perinatal mental health disorders place a particularly high public health burden on South Africa (SA) via negative health outcomes for the birthing parent and adverse health outcomes for infants (e.g., low birth weight, preterm deliveries, malnourishment) as well as emotional and behavioral problems in children. Depression, posttraumatic stress disorder (PTSD), and other mental health disorders may also compromise engagement in HIV prevention behaviors during the perinatal period, when HIV acquisition risk increases. This is particularly important in SA, where almost a quarter of women between ages 15 to 49 have HIV. There is little research exploring the anticipated impacts mental health symptoms have on one's ability to emotionally connect or caregive after delivery; this critical information will enable providers to support women and their mental health during the transition from pregnancy to postpartum. HIV-negative pregnant persons were recruited from an antenatal clinic in Cape Town as a part of a larger study investigating mental health barriers to pre-exposure prophylaxis (PrEP) uptake during pregnancy. Participants qualified for an in-depth interview based on elevated symptoms of depression and/or PTSD. The interviews explored the likely impact of their mental health symptoms on their baby's wellbeing, their ability to bond with their baby, and their ability to meet their baby's needs. Following the principles of thematic analysis, we identified three main themes that described these relationships: (1) a strong perceived connection between maternal mental health and baby's wellbeing; (2) perceived strains on bonding with the baby; and (3) negative impact of mental health on likelihood of completing parenting tasks. This study will inform future mental health programming to prepare pregnant persons with mental health symptoms for a successful postpartum period with respect to bonding and caring for their infant.

Diagnostic accuracy of Truenat MTB Plus, Truenat MTB Ultima and Xpert MTB/RIF Ultra for the diagnosis of pulmonary TB in an HIV-endemic setting.

Truenat MTB Plus (MTB Plus) and MTB Ultima (Ultima) are World Health Organization-endorsed low-complexity tuberculosis (TB) tests, however, performance data are scarce. Adults (≥18 years; n=498) self-presenting with symptoms to primary care clinics in Cape Town, South Africa (19/02/2016-22/02/2023) provided sputa. We evaluated the accuracy of MTB Plus and Ultima, with Xpert MTB/RIF Ultra (Ultra) as a comparator, vs. a single culture (TB reference standard) or MTBDRplus on an isolate (rifampicin susceptibility reference standard). The proportion of MTB Plus and Ultima unsuccessful results was 20% (95% confidence interval 17, 23) and 14 (11, 16), respectively, with ≥half resolving upon retesting the same eluate. In a three-way analysis, MTB Plus, Ultima and Ultra had sensitivities of 84% (78, 88), 90% (85, 93), and 92% (87, 95), and specificities of 95% (92, 97), 85% (80, 88) and 95% (92, 97) for TB. The proportion of unsuccessful results for MTB-RIF Dx done the same day as DNA extraction was 9% (3, 16; MTB Plus-positives) and 18% (10, 26; Ultima-positives) [if after day-of-extraction, these were 27% (18, 35) and 44% (35, 51)]. Same-day rifampicin susceptibility testing was often unsuccessful in samples with "very low" load [73% (58, 89) MTB Plus, 75% (65, 86) Ultima] but had 100% (40, 100) sensitivity and 99% (96, 100) specificity (for both MTB Plus- or Ultima-positive DNA). Lot variation in unsuccessful and false-positive results was observed. Ultima showed comparable sensitivity to Ultra but specificity, lot variation, and, like MTB-RIF Dx, unsuccessful result rates were suboptimal. European & Developing Countries Clinical Trials Partnership, and South African Medical Research Council.

Integration of HIV pre-exposure prophylaxis (PrEP) services for pregnant and breastfeeding women in eight primary care clinics: results of an implementation science study

BackgroundAlthough HIV vertical transmission has declined significantly in sub-Saharan Africa, incident HIV infection in pregnant and postpartum women is estimated to account for over one-third of HIV vertical transmission. Oral pre-exposure prophylaxis (PrEP) for pregnant and breastfeeding women (PBFW) is included in South African PrEP guidelines since 2021; however, integration of PrEP services within ante- and postnatal care remains limited.MethodsBetween March 2022 and September 2023, we evaluated the integration of PrEP for PBFW in eight antenatal clinics in Cape Town, South Africa, following training and mentorship of providers. We applied an adapted Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework to evaluate the integration of PrEP services for pregnant and breastfeeding women. Before the study, PrEP was not routinely offered. We implemented a staff didactic/practice-based training and mentorship on PrEP provision targeting PBFW. We evaluated the following: (1) Reach as the proportion of women initiating PrEP among women counselled and tested for HIV, (2) effectiveness as PrEP continuation up to 3 months by pregnant vs. breastfeeding women, (3) adoption of PrEP integration via pre- and post-training assessments and ongoing mentorship assessments, (4) implementation through clinic trends of PrEP offer over time, and (5) maintenance: continued PrEP offer 3 months following the intervention.ResultsIn 8 facilities providing ante- and postnatal care, we trained 224 healthcare providers (127 nurses and 37 counsellors). Of those, we mentored 60 nurses, midwives, and HIV counsellors working with pregnant and breastfeeding women, with 80% of nurse/midwives and 65% of counsellors scoring ≥ 80% on the final mentoring assessment. Overall, 12% of HIV-negative pregnant women started PrEP, and 41% of those continued PrEP up to 3 months. Among HIV-negative breastfeeding women, 14% initiated PrEP, and 25% continued PrEP up to 3 months. All eight facilities continued providing PrEP 3 months post intervention.ConclusionsIn these high HIV prevalence clinics, the proportion of pregnant and breastfeeding women initiating and continuing PrEP rapidly increased but was limited among breastfeeding women. Staff training, mentorship, and PrEP integration were well-adopted by nurses and counsellors, and services continued following the intervention. Barriers included limited HIV testing of breastfeeding mothers and need for additional PrEP-trained nurses.

Inflammatory markers in pregnancy are associated with postpartum weight in South African women living with HIV on antiretroviral therapy.

Postpartum weight (PPW) contributes to long-term obesity, a growing concern in persons with HIV (PWH). We investigated whether inflammatory markers in pregnancy may be involved in postpartum (PP) obesity in PWH. A total of 57 pregnant PWH enrolled at ≤14 weeks gestation (T1) in Gugulethu antenatal care clinic in Cape Town and followed through 48 weeks PP were included. Plasma soluble (s) CD14, sCD163, leptin, tumour necrosis factor receptor 1 (TNFR-1), resistin, adiponectin, and interleukin-6 (IL-6) were assayed in duplicate using the Luminex platform. We considered each inflammatory marker at T1 (n=57) and T3 (29-36 weeks gestation, n=31) as a separate exposure of interest. Linear mixed effects models were fit to examine whether each exposure was associated with average PPW and PPW trajectories; linear regression was used for associations with PPW change between T1 and 48 weeks. Median age was 32 years (IQR, 29-35), 98% were multigravida, and 49% had a BMI≥30 kg/m2. Higher T1 sCD14 levels were associated with higher average weight through 48 weeks PP (ß = 0.002, p=0.04), and T3 sCD14 with higher PPW gain (ß = 0.007, p=0.04). Leptin (ß = 0.414, p<0.01), TNFR-1 (ß = 11.048, p<0.01) and resistin (ß = 0.714, p=0.01) at T3 were associated with higher average PPW, and IL-6 (ß = 2.266, p=0.02) with PPW gain. These findings suggest that low-grade inflammation in pregnancy may play a role in postpartum obesity, pointing to potential mechanisms with implications for long-term cardiometabolic health in PWH.

Field study to determine the reliability of HIV viral load results shows minimal impact of delayed testing in South Africa.

Understanding factors that impact HIV viral load (VL) accuracy in resource-limited settings is key to quality improvement. We evaluated whether testing delay and specimen storage between 25 °C and 30 °C before testing affected results. Between November 2019 and June 2023, 249 individuals on antiretroviral therapy, or with newly diagnosed HIV, were recruited from clinics in Cape Town and Gqeberha, South Africa, and three plasma preparation tubes were collected. One tube was tested within 24 h, while the others were stored uncentrifuged at ambient temperatures before testing. Centrifugation and testing of matched samples were performed on Day 4 and Day 7 after collection. Time delay and ambient storage had minimal impact in specimens with a Day 1 VL of > 100 copies/mL. When grouped by Day 1 VL range, 96% - 100% of specimens at Day 4 and 93% - 100% at Day 7 had VLs within 0.5 log copies/mL of the first result. The greatest variability at Days 4 and 7 was observed when the Day 1 VL was < 100 copies/mL. However, there was no trend of increasing difference over time. Of Day 1 specimens with undetectable VL, or VL < 50 copies/mL, 80% had concordant results at Day 4 and 78% at Day 7. These results show that VL is stable in plasma preparation tubes for 7 days when stored at room temperature. There is significant variability in specimens with low VL, but variability is not affected by testing delay. Ideal HIV VL testing conditions are frequently unachievable in resource-limited settings. Data are needed on whether this impacts on the validity of test results. Our results provide reassurance that storage at ambient temperature for up to 7 days before testing does not substantially affect the VL result.

Evaluation of Noninvasive Tools for Predicting Esophageal Varices in Patients With Cirrhosis at Tygerberg Hospital, Cape Town.

Background: In patients with cirrhosis, esophageal variceal hemorrhage (EVH) is a devastating consequence of portal hypertension (PH). Upper endoscopy is considered the gold standard for the detection and diagnosis of esophageal varices (EVs), despite being invasive and costly. This study was aimed at identifying and evaluating the diagnostic accuracy of noninvasive tools in predicting EVs in patients with compensated cirrhosis. Methods: This cross-sectional study included 50 patients with compensated cirrhosis at the Tygerberg Hospital Gastroenterology Clinic in Cape Town between November 2022 and May 2023. We collected clinical, anthropometric, and laboratory data from patients' physical and electronic charts. All patients underwent an abdominal ultrasound, vibration-controlled transient elastography (VCTE) to assess liver and splenic stiffness, and upper endoscopy. In this comparative study, we evaluated the diagnostic accuracy of different noninvasive tools in detecting EVs in patients with compensated cirrhosis. Results: Of the 50 patients included in the study, 30 (60%) were female and 20 (40%) were male. The patients' age ranged from 18 to 83, with a mean age of 46.6 years. Cirrhosis was mainly due to alcohol use (n = 11, 22%), hepatitis B virus (HBV) infection (n = 11, 22%), and autoimmune hepatitis (n = 10, 20%). The patients included in the study were divided into two subgroups: with (n = 34, 68%) or without (n = 16, 32%) EVs. Statistically significant differences were detected between groups in platelet count (PC), liver stiffness measurement (LSM), spleen stiffness measurement (SSM), portal vein diameter (PVD), bipolar spleen diameter (SBD), aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4), platelet/bipolar spleen diameter ratio (PSR), liver stiffness-spleen size-platelet ratio (LSPS), liver stiffness-spleen stiffness-platelet ratio score (LS3PS), and spleen stiffness-spleen size-platelet ratio score (SSPS) (p < 0.001). The highest diagnostic precision was observed with SSM (96%), SSPS (96%), LS3PS (94%), LSPS (94%), PSR (94%), and PC (92%). SBD (88%), LSM (86%), APRI (82%), and FIB-4 (82%) had the lowest diagnostic accuracy. Conclusion: SSM and SSPS have the highest diagnostic accuracy for predicting the presence of EVs in patients with compensated cirrhosis. LSPS, LS3PS, and PSR come second at 94%. We recommend SSM and SSPS in institutions with transient elastography equipped with the software necessary to measure splenic stiffness. We introduce and propose LS3PS as a novel composite score for predicting the presence of EVs in patients with compensated cirrhosis. Large-sample-size studies are needed to validate these prediction scores and to allow direct comparison with Baveno VII. These prediction tools can help clinicians avoid unnecessary endoscopic procedures in patients with compensated cirrhosis, especially in developing countries with limited resources such as South Africa.

Comparing a point-of-care urine tenofovir lateral flow assay to self-reported adherence and their associations with viral load suppression among adults on antiretroviral therapy.

Point-of-care (POC) lateral flow assays (LFA) to detect tenofovir (TFV) in urine have been developed to measure short-term ART adherence. Limited data exist from people living with HIV in routine care. Adults on TFV-containing regimens, having a routine viral load (VL) at an HIV clinic in Cape Town, South Africa were enrolled in a cross-sectional study. Patients recalled missed ART doses in the past three and 7 days and urine was tested using a POC TFV LFA. VL on the day was abstracted from medical records. Among 314 participants, 293 (93%) had VL <1000 copies/mL, 20 (6%) had no TFV detected and 24 (8%) reported ≥1 missed dose in the past 3 days. Agreement between VL ≥1000 and undetectable TFV was higher compared to 3-day recall of ≥1 missed dose (Kappa 0.504 vs. 0.163, p = 0.015). The AUC to detect VL ≥1000 was 0.747 (95% CI 0.637-0.856) for undetectable TFV. This was statistically significantly better than for 7-day recall (0.571 95% CI 0.476-0.666, p = 0.040) but not for 3-day recall (0.587 95% CI 0.492-0.681, p = 0.071) of ≥1 missed dose. In this largely virally suppressed cohort, TFV in urine had better agreement with VL than self-reported adherence and was a better predictor of viraemia on two of three self-report measures. Used in combination with VL, the POC urine TFV LFA could flag patients with viraemia in the presence of ART. Further research is needed to understand the potential application in different populations on ART, including pregnant women.

Dementia subtypes, cognitive decline and survival among older adults attending a memory clinic in Cape Town, South Africa: a retrospective study

BackgroundThere are no published longitudinal studies from Africa of people with dementia seen in memory clinics. The aim of this study was to determine the proportions of the different dementia subtypes, rates of cognitive decline, and predictors of survival in patients diagnosed with dementia and seen in a memory clinic.MethodsData were collected retrospectively from clinic records of patients aged ≥ 60 seen in the memory clinic at Groote Schuur Hospital, Cape Town, South Africa over a 10-year period. Diagnostic and Statistical Manual of Mental Disorders (DSM–5) criteria were used to identify patients with Major Neurocognitive Disorders (dementia). Additional diagnostic criteria were used to determine the specific subtypes of dementia. Linear regression analysis was used to determine crude rates of cognitive decline, expressed as mini-mental state examination (MMSE) points lost per year. Changes in MMSE scores were derived using mixed effects modelling to curvilinear models of cognitive change, with time as the dependent variable. Multivariable cox survival analysis was used to determine factors at baseline that predicted mortality.ResultsOf the 165 patients who met inclusion criteria, 117(70.9%) had Major Neurocognitive Disorder due to Alzheimer’s disease (AD), 24(14.6%) Vascular Neurocognitive Disorder (VND), 6(3.6%) Dementia with Lewy Bodies (DLB), 5(3%) Parkinson disease-associated dementia (PDD), 3(1.8%) fronto-temporal dementia, 4(2.4%) mixed dementia and 6(3.6%) other types of dementia. The average annual decline in MMSE points was 2.2(DLB/PDD), 2.1(AD) and 1.3(VND). Cognitive scores at baseline were significantly lower in patients with 8 compared to 13 years of education and in those with VND compared with AD. Factors associated with shorter survival included age at onset greater than 65 (HR = 1.82, 95% C.I. 1.11, 2.99, p = 0.017), lower baseline MMSE (HR = 1.05, 95% C.I. 1.01, 1.10, p = 0.029), Charlson’s comorbidity scores of 3 to 4 (HR = 1.88, 95% C.I. 1.14, 3.10, p = 0.014), scores of 5 or more (HR = 1.97, 95% C.I. 1.16, 3.34, p = 0.012) and DLB/PDD (HR = 3.07, 95% C.I. 1.50, 6.29, p = 0.002). Being female (HR = 0.59, 95% C.I.0.36, 0.95, p = 0.029) was associated with longer survival.ConclusionsKnowledge of dementia subtypes, the rate and factors affecting cognitive decline and survival outcomes will help inform decisions about patient selection for potential future therapies and for planning dementia services in resource-poor settings.

A wellness intervention to address weight gain in people living with HIV

Abstract Background Dolutegravir-based antiretrovirals are the cornerstone of HIV treatment in LMICs but has shown to be associated with excessive (≥10%) weight gain. Increased body mass index combined with fat redistribution poses increased risk for diabetes, hypertension, and cardiovascular disease. The South African Diabetes Prevention Program (SA-DPP) is a lifestyle intervention program, including nutrition education, physical activity, and other risky behaviors and has been adapted to poorly resourced communities in Cape Town. We aimed to adapt the SA-DPP intervention for people living with HIV (PLWH) and assess its acceptability and feasibility. Methods PLWH and health staff were drawn from three primary health clinics in Cape Town (n = 35). Purposive sampling was used. Five focus groups (FG) with PLWH; two individual interviews (II) with PLWH; five interviews with health staff, including two II with medical doctors; two with a pair of nurses each and a group of three lay counsellors and three II with experts on diet and exercise lifestyle (n = 6). The FG and interviews explored two parts 1) PLWH experience of HIV treatment, their lifestyle issues, the education and support received from clinics and 2) review, evaluation and perspectives on the current SA-DPP intervention and tools. FG and interviews were transcribed and thematically analyzed. Results The SA-DPP curriculum was positively reviewed by PLWH and health staff. This included acceptability of the content and structure of the material. The content was deemed thorough and detailed in relation to nutrition and exercise. “The physical active part here, is something that I need in my life, this is something that I need in my health, the improve your sleep and the stress”. Practical in its approach, gave options within reach, in terms of availability and cost. Conclusions The intervention content was deemed accessible and covered all important areas. Experts thought it a resource PLWH could use over time and across illnesses. Key messages • This study provides insight into the challenges faced by PLWH in trying to live a healthier lifestyle. • The result of this study will translate into a healthy lifestyle intervention that can easily be adopted in the current primary health care set up for PLWH.

Tenofovir diphosphate in dried blood spots and HIV-1 resistance in South Africa

BackgroundSuboptimal antiretroviral (ART) adherence can lead to virologic failure with consequent HIV-1 resistance. Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is a powerful biomarker of cumulative adherence, predictive of future viremia. It has been associated with resistance in Persons With HIV (PWH) in South Africa and the US. We explored the relationship of TFV-DP concentrations with antiretroviral drug resistance at the time of treatment failure in SA.MethodsAdult PWH from health clinics in Cape Town, South Africa on efavirenz-based first-line ART containing tenofovir disoproxil fumarate (TDF) with an undetectable (< 50 copies/mL) HIV-1 viral load (VL) were prospectively enrolled in an observational cohort for 12 months. Monthly study visits included blood collection for HIV-1 VL and DBS for TFV-DP. The first confirmed viral breakthrough (VB) > 400 copies/mL triggered HIV-1 genotyping at the subsequent visit. An electronic adherence (EA) device monitored ART adherence in real-time, estimated as a percent for the 30-days prior to VB. Wilcoxon rank sum test was used to compare median [IQR] TFV-DP by genotype outcome.ResultsOf 250 individuals, (n = 195, 78% women), 21 experienced VB, with a median of 5 [4;7] months on study, and a median EA of 33.3 [13.3;53.3]%. Demographic characteristics between those with and without VB were similar. Median VL at VB was 4.0 [3.2;4.5] log copies/mL. TFV-DP concentrations trended down towards the VB visit. Median TFV-DP concentrations were significantly higher in those HIV-1 genotype did not amplify due to being virally suppressed at the subsequent visit (n = 10; 380 [227–661] fmol/punch, p = 0.035; EA 45 [24.9; 59.2]%); than in those who were successfully genotyped with evidence of drug resistance (n = 5, 241 [150–247] fmol/punch, EA 20 [6.7;36.7]%) and in individuals who did not have resistance (n = 3, 39.9 [16.6; 93.9] fmol/punch; EA 33.3 [16–38]%). Three genotype collections were not done. Only non-nucleoside reverse transcriptase inhibitor-associated mutations were identified on resistance testing. (K103N, E138K, Y118H).ConclusionTFV-DP in DBS showed a step-wise inverse relationship with VB and drug resistance, with evidence of low cumulative ART adherence in PWH who developed antiretroviral resistance. Monitoring TFV-DP concentrations could be a valuable tool for predicting future VB and future resistance.

Fertility preservation among women diagnosed with cancer in South Africa

There is a growing trend worldwide to offer fertility preservation to newly diagnosed cancer patients, but little research exploring the experience of fertility preservation among this population exists. Our aim was to explore fertility preservation among female cancer survivors in South Africa. We conducted interviews with 10 women who received fertility preservation at fertility clinics in Cape Town and Johannesburg, South Africa. Interviews lasted between 38 and 76 min and were audio recorded, transcribed, and then entered into ATLAS.ti. We analysed the interviews using reflexive thematic analysis. Four themes were constructed, namely (1) entering fertility preservation: motivation and risk, (2) an emotional rollercoaster, (3) needing more information, and (4) a costly source of hope. Participants reflected on choosing between cancer treatment and delaying the cancer treatment to accommodate for fertility preservation, with the importance of biological motherhood reported as a key factor. Both the cancer diagnosis and hormones taken as part of treatment resulted in participants feeling highly emotional. Participants expressed a need for more information on fertility preservation. Finally, even though the process was costly, participants reported that it was a worthwhile endeavour as it instilled in them a sense of hope. Our findings indicate that there is a need to increase awareness of fertility preservation in South Africa. Moreover, considering the pressure that patients are under, their emotional states, and their lack of adequate information, it is important for healthcare professionals to pay careful attention to the needs of patients throughout the process and provide patients with referrals to psychological services when needed. Our findings also indicate gaps in the informed consent process between patients and healthcare professionals that must be addressed by the latter.

A "Bundle of Care" to Improve Anticoagulation Control in Patients Receiving Warfarin in Uganda and South Africa: Protocol for an Implementation Study.

The quality of warfarin anticoagulation among Sub-Saharan African patients is suboptimal. This is due to several factors, including a lack of standardized dosing algorithms, difficulty in providing timely international normalized ratio (INR) results, a lack of patient feedback on their experiences with treatment, a lack of education on adherence, and inadequate knowledge and training of health care workers. Low quality of warfarin anticoagulation, expressed as time in therapeutic range (TTR), is associated with higher adverse event rates, including bleeding and thrombosis, and ultimately, increased morbidity and mortality. Processes and interventions that improve this situation are urgently needed. This study aims to evaluate the implementation of the "warfarin bundle," a package of interventions to improve the quality of anticoagulation and thereby clinical outcomes. The primary outcome for this study is TTR over the initial 3 months of warfarin therapy. Patients aged 18 years or older who are newly initiated on warfarin for venous thromboembolism, atrial fibrillation, or valvular heart disease will be enrolled and followed up for 3 months at clinics in Cape Town, South Africa, and Kampala, Uganda, where the warfarin bundle is implemented. A retrospective review of the clinical records of patients on warfarin treatment before implementation (controls) will be used for comparison. This study uses a mixed methods approach of the implementation of patient- and process-centered activities to improve the quality of anticoagulation. Patient-centered activities include the use of clinical dosing algorithms, adherence support, and root cause analysis, whereas process-centered activities include point-of-care INR testing, staff training, and patient education and training. We will assess the impact of these interventions by comparing the TTR and safety outcomes across the 2 groups, as well as the cost-effectiveness and acceptability of the package. We started recruitment in June 2021 and stopped in August 2022, having recruited 167 participants. We obtained ethics approval from the University of Cape Town Faculty of Health Sciences Human Research Ethics Committee, the Provincial Health Research Committees in South Africa, the Joint Clinical Research Centre Institutional Review Board, Kampala, and the University of Liverpool Research Ethics Committee. As of February 2023, data cleaning and formal analysis are underway. We expect to publish the full results by December 2023. We anticipate that the "bundle of care," which includes a clinical algorithm to guide individualized dosing of warfarin, will improve INR control and TTR of patients in Uganda and South Africa. We will use these findings to design a larger, multisite clinical trial across several Sub-Saharan African countries. DERR1-10.2196/46710.

TB preventive therapy preferences among children and adolescents.

BACKGROUND: TB preventive therapy (TPT) is critical for ending TB, yet implementation remains poor. With new global guidelines expanding TPT eligibility and regimens, we aimed to understand TPT preferences among children, adolescents and caregivers.METHODS: We undertook a discrete choice experiment among 131 children, 170 adolescents and 173 caregivers, and conducted 17 in-depth interviews in 25 clinics in Cape Town, South Africa. The design included attributes for location, waiting time, treatment duration, dosing frequency, formulation/size, side effects, packaging and taste. Mixed-effects logistic regression models were used for analysis.RESULTS: Among children and caregivers, the number and size of pills, taste and side effects were important drivers of preferences. Among adolescents and caregivers, clinic waiting times and side effects were significant drivers of preferences. Adolescents expressed concerns about being stigmatised, and preferred services from local clinics to services delivered in the community. Dosing frequency and treatment duration were only significant drivers of choice among adolescents, and only if linked to fewer clinic visits.CONCLUSIONS: Introducing shorter TPT regimens in isolation without consideration of preferences and health services may not have the desired effect on uptake and completion. Developing TPT delivery models and formulations that align with preferences must be prioritised.

A Case Series of Cystinuric Stone Formers in Western Cape, South Africa: SLC3A1 or SLC7A9 Mutations and Phenotype

Objective To describe the genetic mutations and phenotype in the first African series of patients with cystinuria. Methods Patients with cystinuria were recruited from a specialist metabolic renal stone clinic in Cape Town, South Africa, for DNA sequencing to detect mutations in SLC3A1 and SLC7A9. Chart reviews and patient interviews were conducted to record demographics, previous medical history, family history, stone-specific history, age at first presentation, cystinuria complications, urine cystine:creatinine ratio, stone analysis, and serum creatinine. Results Nine patients were included: 3 male patients and 6 female patients. The mean age (± SD) of patients was 33.43 ± 19.96 years. The median age (± IQR) at initial diagnosis of cystinuria was 16 ± 18 years, but the age ranged from 2 to 66 years. Three of 9 patients included (33.3%) had chronic kidney disease (CKD); however, none were receiving dialysis. Most patients initially presented with a staghorn calculus (4/9; 44.4%). The mean serum creatinine (± SD) was 84 ± 38 μmol/L. The mean urine cystine (± SD) was 2083 ± 1249 nmoL/mg creatinine. Eight patients had mutations in the SLC3A1 gene; 1 had mutations in both SLC3A1 and SLC7A9. Of the patients with only SLC3A1 mutations, 1 patient was homozygous and the rest were compound heterozygotes (two different mutations identified in the same gene). Four patients had a pathogenic variant in addition to an “uncertain significance” variant in SLC3A1. There were 9 mutations (5 pathogenic and 4 “unknown significance”) in SLC3A1 and 1 mutation in SLC7A9. Two of these were novel mutations. Conclusion This “first in Africa” series of cystinuria patients showed marked heterogeneity in both phenotype and genotype, with a predominance of SLC3A1 mutations. This heterogeneity is similar to that reported in international cohorts.

Fetal Alcohol-Related Postnatal Growth Restriction Is Independent of Infant Feeding Practices and Postnatal Alcohol Exposure in a Prospective South African Birth Cohort

Prenatal alcohol exposure (PAE) causes growth restriction that worsens in the first year of life. However, the roles of postnatal nutrition in fetal alcohol growth restriction and the impact of postnatal alcohol exposure via breastmilk on growth remain unknown. We aimed to compare infant feeding practices during the first 6.5 months of life between heavy drinkers and abstainers/light drinkers, to examine whether these practices play confounding roles in fetal alcohol growth restriction, and to determine the impact of postnatal alcohol exposure via breastmilk on growth. Eighty-seven heavy-drinking pregnant women and 71 abstainers/light drinkers (controls) were recruited prenatally from antenatal clinics in Cape Town, South Africa. Demographic background and alcohol, cigarette, marijuana, and methamphetamine use during pregnancy were assessed pre- and postnatally. Infant feeding practices were assessed at 6.5 months postpartum using the USDA Infant Feeding Questionnaire. Infant weight, length, and head circumference were measured at 2 weeks, 6.5 and 12 months, and 5 years. Neither prenatal nor postnatal alcohol consumption was related to the duration of breastfeeding, exclusive breastfeeding, exclusive formula, or mixed feeding. Complementary feeding practices were remarkably similar between exposure groups. PAE was related to all postnatal anthropometry measures at all age points, independent of infant feeding practices. Postnatal alcohol exposure via breastmilk was unrelated to any anthropometry outcome after control for PAE. In conclusion, fetal alcohol-related postnatal growth restriction was not attributable to differences in postnatal infant feeding practices or postnatal alcohol exposure and is thus likely a direct teratogenic effect of PAE.

The impact of persistent precarity on patients' capacity to manage their treatment burden: A comparative qualitative study between urban and rural patients with multimorbidity in South Africa.

People living with multimorbidity in low-and middle-income countries (LMICs) experience a high workload trying to meet the demands of self-management. In an unequal society like South Africa, many people face continuous economic uncertainty, which can impact on their capacity to manage their illnesses and lead to poor health outcomes. Using precariousness - the real and perceived impact of uncertainty - as a lens, this paper aims to identify, characterise, and understand the workload and capacity associated with self-management amongst people with multimorbidity living in precarious circumstances in urban and rural South Africa. We conducted qualitative semi-structured interviews with 30 patients with HIV and co-morbidities between February and April 2021. Patients were attending public clinics in Cape Town (Western Cape) and Bulungula (Eastern Cape). Interviews were transcribed and data analysed using qualitative framework analysis. Burden of Treatment Theory (BoTT) and the Cumulative Complexity Model (CuCoM) were used as theoretical lenses through which to conceptualise the data. People with multimorbidity in rural and urban South Africa experienced multi-faceted precariousness, including financial and housing insecurity, dangerous living circumstances and exposure to violence. Women felt unsafe in their communities and sometimes their homes, whilst men struggled with substance use and a lack of social support. Older patients relied on small income grants often shared with others, whilst younger patients struggled to find stable employment and combine self-management with family responsibilities. Precariousness impacted access to health services and information and peoples' ability to buy healthy foods and out-of-pocket medication, thus increasing their treatment burden and reducing their capacity. This study highlights that precariousness reduces the capacity and increases treatment burden for patients with multimorbidity in low-income settings in South Africa. Precariousness is both accumulative and cyclic, as financial insecurity impacts every aspect of peoples' daily lives. Findings emphasise that current models examining treatment burden need to be adapted to accommodate patients' experiences in low-income settings and address cumulative precariousness. Understanding treatment burden and capacity for patients in LMICs is a crucial first step to redesign health systems which aim to improve self-management and offer comprehensive person-centred care.

Comparing Predictive Ability of Two Objective Adherence Measures in a Community-Based Cohort on Antiretroviral Therapy in South Africa: Tenofovir Diphosphate Concentrations and Electronic Adherence Monitors.

Electronic adherence (EA) and tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) are objective measures of antiretroviral therapy (ART) adherence. We characterized the association between these measures in a prospective cohort of persons with HIV (PWH) on ART. Four primary health clinics in Cape Town, South Africa. We enrolled 250 virally suppressed PWH receiving tenofovir-based ART. We collected EA data, monthly viral load, and TFV-DP in DBS for 12 months. We used logistic regression to estimate the adjusted odds ratio (aOR) and 95% confidence intervals (CIs) for future viral breakthrough (VB) (>400 copies/mL) for each adherence measure. Receiver operating characteristics (ROCs) provided the predictive power of these measures. Participants had a median (IQR) age of 34 (27-42); 78% were women. Twenty-one (8%) developed VB. Logistic regression showed that when percent EA and TFV-DP concentrations increased, the odds of VB decreased. This relationship was consistent at the time of VB (aOR of 0.41 [95% CI: 0.25 to 0.66] for TFV-DP and aOR of 0.64 [95% CI: 0.54 to 0.76] for EA) and for up to 2 months before VB. Both adherence measures predicted future VB at both 1 month and 2 months before viral load measurement. We established that 2 objective adherence measures, EA and TFV-DP in DBS, have a positive association with, and are both strongly predictive of, VB in a community-based South African cohort on ART. Future research is needed to determine the feasibility of implementing these adherence measures in resource-limited settings to facilitate adherence interventions.

Psychosocial determinants of pre-exposure prophylaxis use among pregnant adolescent girls and young women in Cape Town, South Africa: A qualitative study.

In South Africa, at least 7.5million people (age ≥15years) are living with Human Immunodeficiency Virus (HIV). In 2020, 220,000 new infections occurred, approximately one-third of which were among cisgender adolescent girls and women (age ≥15years). The perspectives of pregnant adolescent girls and young women (AGYW) as key, targeted end-users of pre-exposure prophylaxis (PrEP) in this setting are not well known. We purposively recruited participants enrolled in an ongoing cohort study at an urban antenatal clinic in Cape Town, South Africa for in-depth interviews between July-September 2020. We restricted our analysis to pregnant AGYW (age: 16-25years) who initiated daily oral PrEP (Tenofovir/Emtricitabine) antenatally and self-reported either high PrEP persistence (≥25days in the past 30days and no missed PrEP collection), or low PrEP persistence and/or discontinuation (missing >5days in the last 30days or missed PrEP collection). The findings were organized thematically, per the adapted Health Behavior Model (2000), using Nvivo-v.1.5. We interviewed 18 AGYW (mean age = 22years), at a mean of 14weeks postpartum. Higher self-esteem and high-quality study provider-client relationships, including empathic psychosocial support, facilitated PrEP continuation. Reported barriers included unstable social structure characteristics (i.e., financial hardship) and individual factors (i.e., unintended pregnancy, parental rejection, and inadequate peer- and [non-cohabiting] partner support). Participants self-perceived a need for PrEP, feeling susceptible to non-consensual, forced sex, or considering partners' (presumed) sexual risk-taking. Limited community awareness regarding PrEP availability and/or perceived complexity in navigating health system access to PrEP, impede continuation. PrEP-focused healthcare access pathways for pregnant and postpartum AGYW need to be simplified. Further research is needed on health system determinants (i.e., structural barriers, provider-client interactions, and related outcomes) of oral PrEP utilization. In 2022, South Africa announced regulatory approval of long-acting PrEP options (i.e., the dapivirine ring for non-pregnant women and injectable cabotegravir, respectively); these may mitigate implementation barriers reported in this study. However, the safety and efficacy of long-acting PrEP (e.g., injectables, implants) among pregnant or breastfeeding women, specifically, remains to be confirmed in this setting.