Exploring the validity of routine individuated service data for antenatal HIV surveillance in the Western Cape.

Background: In the Western Cape, South Africa, public-sector individual-level routine data are consolidated from multiple sources through the Provincial Health Data Centre (PHDC). This enables the description of temporal changes in population-wide antenatal HIV seroprevalence. We evaluated the validity of these data compared to aggregated program data and population-wide sentinel antenatal HIV seroprevalence surveys for the Western Cape province. Methods: We conducted a retrospective cohort analysis of all pregnancies identified in the PHDC from January 2011 to December 2020. Evidence of antenatal and HIV care from electronic platforms were linked using a unique patient identifier. HIV prevalence estimates were triangulated and compared with available survey estimates and aggregated programmatic data from registers as recorded in the District Health Information System. Provincial, district-level and age-group HIV prevalence estimates were compared between data systems using correlation coefficients, absolute differences and trend analysis. Results: Of the 977800 pregnancies ascertained, PHDC HIV prevalence estimates from 2011-2013 were widely disparate from aggregate and survey data (due to incomplete electronic data), whereas from 2014 onwards, estimates were within the 95% confidence interval of survey estimates, and closely correlated to aggregate data estimates (r = 0.8; p = 0.01), with an average prevalence difference of 0.4%. PHDC data show a slow but steady increase in provincial HIV prevalence from 16.7% in 2015 to 18.6% in 2020. The highest HIV prevalence was in the Cape Metro district (20.3%) Prevalence estimates by age group were comparable between sentinel surveys and PHDC from 2015 onwards, with prevalence estimates stable over time among younger age-groups (15-24 years) but increased among older age-groups (> 34 years). Conclusions: This study compares sentinel seroprevalence surveys with both register-based aggregate data and consolidated individuated administrative data. We show that in this setting linked individuated data may be reliably used for HIV surveillance and provide more granular estimates with greater efficiency than seroprevalence surveys and register-based aggregate data.

Can routine antenatal data be used to assess HIV antiretroviral therapy coverage among pregnant women? Evaluating the validity of different data sources in the Western Cape, South Africa.

BACKGROUND: Accurate measurement of antenatal antiretroviral treatment (ART) coverage in pregnancy is imperative in tracking progress towards elimination of vertical HIV transmission. In the Western Cape, South Africa, public-sector individual-level routine data are consolidated from multiple sources, enabling the description of temporal changes in population-wide antenatal antiretroviral coverage. We evaluated the validity of different methods for measuring ART coverage among pregnant women. METHODS: We compared self-reported ART data from a 2014 antenatal survey with laboratory assay data from a sub-sample within the survey population. Thereafter, we conducted a retrospective cohort analysis of all pregnancies consolidated in the Provincial Health Data Centre (PHDC) from January 2011 to December 2020. Evidence of antenatal and HIV care from electronic platforms were linked using a unique patient identifier. ART coverage estimates were triangulated with available antenatal survey estimates, aggregated programmatic data from registers recorded in the District Health Information System (DHIS) and Thembisa modelling estimates. RESULTS: Self-reported ART in the 2014 sentinel antenatal survey (n = 1434) had high sensitivity (83.5%), specificity (94.5%) and agreement (k = 0.8) with the gold standard of laboratory analysis of ART. Based on linked routine data, ART coverage by the time of delivery in mothers of live births increased from 67.4% in 2011 to 94.7% by 2019. This pattern of increasing antenatal ART coverage was also seen in the DHIS data, and estimated by the Thembisa model, but was less consistent in the antenatal survey data. CONCLUSION: This study is the first in a high-burden HIV setting to compare sentinel ART surveillance data with consolidated individuated administrative data. Although self-report in survey conditions showed high validity, more recent data sources based on self-report and medical records may be uncertain with increasing ART coverage over time. Linked individuated data may offer a promising option for ART coverage estimation with greater granularity and efficiency.

Factors associated with vertical transmission of HIV in the Western Cape, South Africa: a retrospective cohort analysis.

INTRODUCTION: Monitoring mother-infant pairs with HIV exposure is needed to assess the effectiveness of vertical transmission (VT) prevention programmes and progress towards VT elimination. METHODS: We used routinely collected data on infants with HIV exposure, born May 2018-April 2021 in the Western Cape, South Africa, with follow-up through mid-2022. We assessed the proportion of infants diagnosed with HIV at birth (≤7 days), 10 weeks (>1 to 14 weeks) and >14 weeks as proxies for intrauterine, intrapartum/early breastfeeding and late breastfeeding transmission, respectively. We used mixed-effects Poisson regression to assess factors associated with VT in mothers known with HIV by delivery. RESULTS: We included 50,461 infants born to mothers known with HIV by delivery. HIV was diagnosed in 894 (1.8%) infants. Among mothers, 51% started antiretroviral treatment (ART) before and 27% during pregnancy; 17% restarted during pregnancy after ≥6 months interruption; and 6% had no recorded ART during pregnancy. Most pregnancy ART regimens included non-nucleoside reverse transcriptase inhibitors (83%). Of mothers with available results (90% with viral load [VL]; 70% with CD4), VL nearest delivery was <100 copies/ml in 78% and CD4 count ≥350 cells/µl in 62%. HIV-PCR results were available for 86%, 67% and 48% of eligible infants at birth, 10 weeks and >14 weeks. Among these infants, 0.9%, 0.4% and 1.5% were diagnosed positive at birth, 10 weeks and >14 weeks, respectively. Among infants diagnosed with HIV, 43%, 16% and 41% were diagnosed at these respective time periods. Among mothers with VL<100, 100-999, 1000-99,000 and ≥100,000 copies/ml nearest delivery, infant HIV diagnosis incidence was 0.4%, 2.3%, 6.6% and 18.4%, respectively. Increased VT was strongly associated with recent elevated maternal VL with a seven-fold increased rate with even modestly elevated VL (100-999 vs. <100 copies/ml). VT was also associated with unknown/low maternal CD4, maternal age <20 years, no antenatal ART, later maternal ART start/restart in pregnancy and ART gaps. CONCLUSIONS: Despite high maternal ART coverage and routine postnatal prophylaxis, ongoing VT remains a concern. Timing of infant HIV diagnoses suggests intrapartum and/or breastfeeding transmission in nearly 60%. Interventions to ensure retention on ART and sustained maternal viral suppression are needed to reduce VT.

Hypoxia regulate developmental coronary angiogenesis potentially through VEGFR2- and SOX17-mediated signaling.

Background: Coronary vessels in embryonic mouse heart arises from multiple progenitor population including sinus venosus (SV), endocardium, and proepicardium. ELA/APJ signaling is shown to regulate coronary growth from SV pathway within the subepicardium, whereas VEGF-A/VEGF-R2 pathways is implicated to regulate coronary growth from endocardium pathway. Our previous study show hypoxia as a potential signaling cue to stimulate overall coronary growth and expansion within the myocardium. However, the role of hypoxia and its downstream signaling pathways in the regulation of coronary vessel development is not known. In this study, we investigated the role of hypoxia in coronary vessel development and have identified SOX17- and VEGF-R2-mediated signaling as a potential downstream pathway of hypoxia in the regulation of coronary vessel development. Results: We show that hypoxia gain-of-function in the myocardium through upregulation of HIF-1α disrupts the normal pattern of coronary angiogenesis in developing mouse hearts and displays phenotype that is reminiscent of accelerated coronary growth. We show that VEGF-R2 expression is increased in coronary endothelial cells under hypoxia gain-of-function in vivo and in vitro . Furthermore, we show that SOX17 expression is upregulated in developing mouse heart under hypoxia gain-of-function conditions, whereas SOX17 expression is repressed under hypoxia loss-of-function conditions. Furthermore, our results show that SOX17 loss-of-function disrupts normal pattern of coronary growth. Conclusion: Collectively, our data provide strong phenotypic evidence to show that hypoxia might regulate coronary growth in the developing mouse heart potentially through VEGF-R2- and SOX17-mediated downstream signaling pathways.

Relationship between pulse pressure variation and stroke volume variation with changes in cardiac index during hypotension in patients undergoing major spine surgeries in prone position - A prospective observational study.

Background and Aims: Dynamic indices such as pulse pressure variation (PPV) and stroke volume variation (SVV) are better predictors of fluid responsiveness than static indices. There is a strong correlation between PPV and SVV in the prone position when assessed with the fluid challenge. However, this correlation has not been established during intraoperative hypotension. Our study aimed to assess the correlation between PPV and SVV during hypotension in the prone position and its relationship with cardiac index (CI). Material and Methods: Thirty patients aged 18-70 years of ASA class I-III, undergoing spine procedures in the prone position were recruited for this prospective observational study. Hemodynamic variables such as heart rate (HR), mean arterial pressure (MAP), PPV, SVV, and CI were measured at baseline (after induction of anesthesia and positioning in the prone position). This set of variables were collected at the time of hypotension (T-before) and after correction (T-after) with either fluids or vasopressors. HR and MAP are presented as median with inter quartile range and compared by Mann-Whitney U test. Reliability was measured by intraclass correlation coefficients (ICC). Generalized estimating equations were performed to assess the change of CI with changes in PPV and SVV. Results: A statistically significant linear relationship between PPV and SVV was observed. The ICC between change in PPV and SVV during hypotension was 0.9143, and after the intervention was 0.9091 (P < 0.001). Regression of changes in PPV and SVV on changes in CI depicted the reciprocal change in CI which was not statistically significant. Conclusion: PPV is a reliable surrogate of SVV during intraoperative hypotension in the prone position.

Treatment outcomes among adults with HIV/non-communicable disease multimorbidity attending integrated care clubs in Cape Town, South Africa.

BACKGROUND: The growing burden of the HIV and non-communicable disease (NCD) syndemic in Sub- Saharan Africa has necessitated introduction of integrated models of care in order to leverage existing HIV care infrastructure for NCDs. However, there is paucity of literature on treatment outcomes for multimorbid patients attending integrated care. We describe 12-month treatment outcomes among multimorbid patients attending integrated antiretroviral treatment (ART) and NCD clubs in Cape Town, South Africa. METHODS: As part of an integrated clubs (IC) model pilot implemented in 2016 by the local government at two primary health care clinics in Cape Town, we identified all multimorbid patients who were enrolled for IC for at least 12 months by August 2017. Mean adherence percentages (using proxy of medication collection and attendance of club visits) and optimal disease control (defined as the proportion of participants achieving optimal blood pressure, glycosylated haemoglobin control and HIV viral load suppression where appropriate) were calculated at 12 months before, at the point of IC enrolment and 12 months after IC enrolment. Predictors of NCD control 12 months post IC enrolment were investigated using multivariable logistic regression. RESULTS: As of 31 August 2017, 247 HIV-infected patients in total had been enrolled into IC for at least 12 months. Of these, 221 (89.5%) had hypertension, 4 (1.6%) had diabetes mellitus and 22 (8.9%) had both diseases. Adherence was maintained before and after IC enrolment with mean adherence percentages of 92.2% and 94.2% respectively. HIV viral suppression rates were 98.6%, 99.5% and 99.4% at the three time points respectively. Retention in care was high with 6.9% lost to follow up at 12 months post IC enrolment. Across the 3 time-points, optimal blood pressure control was achieved in 43.1%, 58.9% and 49.4% of participants while optimal glycaemic control was achieved in 47.4%, 87.5% and 53.3% of participants with diabetes respectively. Multivariable logistic analyses showed no independent variables significantly associated with NCD control. CONCLUSION: Multimorbid adults living with HIV achieved high levels of HIV control in integrated HIV and NCD clubs. However, intensified interventions are needed to maintain NCD control in the long term.

Increased infectious-cause hospitalization among infants who are HIV-exposed uninfected compared with HIV-unexposed.

OBJECTIVES: Increased risk of morbidity and hospitalization has been observed in children who are HIV-exposed uninfected (HEU) compared with HIV-unexposed uninfected (HUU). Studies in the era of universal maternal antiretroviral treatment (ART) are limited. DESIGN: Prospective cohort. METHODS: We investigated hospitalization between 29 days and 12 months of life in a South African cohort of infants born between February 2017 and January 2019 (HEU = 455; HUU = 458). All mothers known with HIV during pregnancy received ART. We reviewed hospital records and classified and graded infectious diagnoses using a standardized tool. We examined factors associated with infectious-cause hospitalization using mixed-effects Poisson regression. RESULTS: Infants HEU vs. HUU had higher all-cause and infectious-cause hospitalization (13 vs. 7%, P = 0.004 and 10 vs. 6%, P = 0.014, respectively). Infectious causes accounted for most hospitalizations (77%). More infants HEU were hospitalized with severe or very severe infections than those HUU (9 vs. 6%; P = 0.031). Mortality (<1%) did not differ between groups. HIV exposure was a significant risk factor for infectious-cause hospitalization [adjusted incidence rate ratios (aIRRs) = 2.8; 95% confidence interval (CI) 1.5-5.4]. Although increased incidence of preterm birth (14 vs. 10%; P < 0.05) and shorter duration of breastfeeding (44 vs. 68% breastfed for ≥3 months, P < 0.001) among infants HEU vs. HUU contributed to increased hospitalization, they did not account for all the increased risk. CONCLUSION: Infectious-cause hospitalization incidence was higher among infants HEU vs. HUU, likely partly because of higher incidence of preterm birth and lower breastfeeding rates among infants HEU. The increased infectious disease burden in HEU infants has important implications for health services in sub-Saharan Africa.

Preterm birth and severe morbidity in hospitalized neonates who are HIV exposed and uninfected compared with HIV unexposed.

OBJECTIVES: Infants who are HIV exposed but uninfected (HEU) compared with HIV unexposed uninfected (HUU) have an increased risk of adverse birth outcomes, morbidity and hospitalization. In the era of universal maternal antiretroviral treatment, there are few insights into patterns of neonatal morbidity specifically. DESIGN: A prospective cohort study. METHODS: We compared neonatal hospitalizations among infants who were HEU (n = 463) vs. HUU (n = 466) born between 2017 and 2019 to a cohort of pregnant women from a large antenatal clinic in South Africa. We examined maternal and infant factors associated with hospitalization using logistic regression. RESULTS: Hospitalization rates were similar between neonates who were HEU and HUU (13 vs. 16%; P = 0.25). Overall, most hospitalizations occurred directly after birth (87%); infection-related causes were identified in 34%. The most common reason for hospitalization unrelated to infection was respiratory distress (25%). Very preterm birth (<32 weeks) (29 vs. 11%; P = 0.01) as well as very low birthweight (<1500 g) (34 vs. 16%; P = 0.02) occurred more frequently among hospitalized neonates who were HEU. Of those hospitalized, risk of intensive care unit (ICU) admission was higher in neonates who were HEU (53%) than HUU (27%) [risk ratio = 2.1; 95% confidence interval (95% CI) 1.3-3.3]. Adjusted for very preterm birth, the risk of ICU admission remained higher among neonates who were HEU (aRR = 1.8; 95% CI 1.1-2.9). CONCLUSION: Neonates who were HEU (vs. HUU) did not have increased all-cause or infection-related hospitalization. However, very preterm birth, very low birthweight and ICU admission were more likely in hospitalized neonates who were HEU, indicating increased severity of neonatal morbidity.

Consolidating strategic information to monitor progress against the UNAIDS 90-90-90 targets: evaluating the operational feasibility of an electronic HIV testing register in Cape Town, South Africa.

BACKGROUND: HIV diagnosis in South Africa is based on a point-of-care testing (PoCT) algorithm with paper-based record-keeping. Aggregated testing data are reported routinely. To facilitate improved HIV case-based surveillance, the Western Cape Province implemented a unique pilot intervention to digitise PoCT results, at an individual level, and generate an electronic register using the newly developed Provincial Health Data Centre (PHDC). We describe the intervention (phased) and present an evaluation of the operational feasibility of the intervention. We also offer implementation insights into establishing electronic capture of individual level testing data. METHODS: Cross-sectional analyses were conducted on records of all patients attending a local Community Health Centre who had an HIV-PoCT during the study period. Data from the intervention were linked to the PHDC using a unique identifier and compared with aggregate data from the paper-based register. Correlation coefficients were calculated to quantify the correlation between the two monthly datasets. To support an understanding of the findings, the Department of Health project management team generated reflections on the implementation process, which were then grouped thematically into implementation lessons. RESULTS: In total, 11,337 PoCT records were digitised (70% (7954) during Phase I; and 30% (3383) during Phase II). Linkage of forms to the PHDC was 96% in Phase I and 98% in Phase II. Comparison with aggregate data showed high correlation during Phase I, but notable divergence during Phase II. Divergence in Phase II was due to stringent data quality requirements and high clinical staff turnover. Factors supporting implementation success in Phase I included direct oversight of data capturing by a manager with clinical and operational insight. Implementation challenges included operational, health system, and high cost-related issues. CONCLUSIONS: We demonstrate that rapid digitisation of HIV PoCT data, without compromising currently collected aggregate data, is operationally feasible, and can contribute to person-level longitudinal HIV case-based surveillance. To take to scale, we will need to improve PoCT platforms and clerical and administrative systems. Although we highlight challenges, we demonstrate that electronic HIV testing registers can successfully replace manual registers and improve efforts to monitor and evaluate HIV testing strategies.

Utility of digitising point of care HIV test results to accurately measure, and improve performance towards, the UNAIDS 90-90-90 targets.

INTRODUCTION: High rates of pre-treatment loss to care among persons diagnosed with HIV persist. Linkage to care can be improved through active digitally-based surveillance. Currently, record-keeping for HIV diagnoses in South Africa is paper-based. Aggregated testing data are reported routinely, and only discordant findings result in a specimen being tested at a laboratory and digitised. The Western Cape Province in South Africa has a Provincial Health Data Centre (PHDC) where person-level routine electronic data are consolidated in a single database, leveraging the existence of a unique patient identifier. To facilitate improved HIV surveillance, a pre-carbonated point-of-care test (PoCT) form was piloted, where one copy was routed to a central point and digitised for PHDC inclusion. METHODS: We evaluated the utility of the intervention using cross-sectional and retrospective cohort analyses, as well as comparisons with aggregate data. Data were linked to the Patient Master Index of the PHDC using unique identifiers. Prior evidences of HIV within the PHDC were used to differentiate newly diagnosed patients and those retesting, as well as linkage to care and treatment. RESULTS: From May 2017 to June 2018, 11337 digitised point-of-care HIV testing records were linked to the PHDC. Overall, 96% of records in the aggregate dataset were digitised, with 97% linked to the PHDC. Of those tested, 79% were female (median age 27 years). Linkage demonstrated that 51.3% (95% CI 48.4-54.1%) of patients testing HIV-positive were retesting. Of those newly diagnosed, 81% (95% CI 77.9-84.3%) were linked to HIV care and 25% (95% CI 21.6-28.7%) were initiated on antiretroviral therapy immediately. CONCLUSION: Digitisation of PoCT results provides individuated HIV testing data to assist in linkage to care and in differentiating newly diagnosed patients from positive patients retesting. Actionable and accurate data can improve the measurement of performance towards the UNAIDS 90-90-90 targets.

Safety and Effectiveness of Isoniazid Preventive Therapy in Pregnant Women Living with Human Immunodeficiency Virus on Antiretroviral Therapy: An Observational Study Using Linked Population Data.

BACKGROUND: Isoniazid preventive therapy (IPT) is widely used to protect against tuberculosis (TB) in people living with human immunodeficiency virus (HIV). Data on the safety and efficacy of IPT in pregnant women living with HIV (PWLHIV) are mixed. We used an individual-level, population-wide health database to examine associations between antenatal IPT exposure and adverse pregnancy outcomes, maternal TB, all-cause mortality, and liver injury during pregnancy through 12 months postpartum. METHODS: We used linked routine electronic health data generated in the public sector of the Western Cape, South Africa, to define a cohort of PWLHIV on antiretroviral therapy. Pregnancy outcomes were assessed using logistic regression; for maternal outcomes we applied a proportional hazards model with time-updated IPT exposure. RESULTS: Of 43 971 PWLHIV, 16.6% received IPT. Women who received IPT were less likely to experience poor pregnancy outcomes (adjusted odds ratio [aOR], 0.83 [95% confidence interval {CI}, .78-.87]); this association strengthened with IPT started after the first trimester compared with none (aOR, 0.71 [95% CI, .65-.79]) or with first-trimester exposure (aOR, 0.64 [95% CI, .55-.75]). IPT reduced the risk of TB by approximately 30% (aHR, 0.71 [95% CI, .63-.81]; absolute risk difference, 1518/100 000 women). The effect was modified by CD4 cell count with protection conferred if CD4 count was ≤350 cells/µL (aHR, 0.51 [95% CI, .41-.63]) vs 0.93 [95% CI, .76-1.13] for CD4 count >350 cells/µL). CONCLUSIONS: This analysis of programmatic data is reassuring regarding the safety of antenatal IPT, with the greatest benefits against TB disease observed in women with CD4 count ≤350 cells/µL.