Correcting mortality estimates among children and youth on antiretroviral therapy in southern Africa: A comparative analysis between a multi-country tracing study and linkage to a health information exchange.

OBJECTIVES: The objective of this study is to assess the outcomes of children, adolescents and young adults with HIV reported as lost to follow-up, correct mortality estimates for children, adolescents and young adults with HIV for unascertained outcomes in those loss to follow-up (LTFU) based on tracing and linkage data separately using data from the International epidemiology Databases to Evaluate AIDS in Southern Africa. METHODS: We included data from two different populations of children, adolescents and young adults with HIV; (1) clinical data from children, adolescents and young adults with HIV aged ≤24 years from Lesotho, Malawi, Mozambique, Zambia and Zimbabwe; (2) clinical data from children, adolescents and young adults with HIV aged ≤14 years from the Western Cape (WC) in South Africa. Outcomes of patients lost to follow-up were available from (1) a tracing study and (2) linkage to a health information exchange. For both populations, we compared six methods for correcting mortality estimates for all children, adolescents and young adults with HIV. RESULTS: We found substantial variations of mortality estimates among children, adolescents and young adults with HIV reported as lost to follow-up versus those retained in care. Ascertained mortality was higher among lost and traceable children, adolescents and young adults with HIV and lower among lost and linkable than those retained in care (mortality: 13.4% [traced] vs. 12.6% [retained-other Southern Africa countries]; 3.4% [linked] vs. 9.4% [retained-WC]). A high proportion of lost to follow-up children, adolescents and young adults with HIV had self-transferred (21.0% and 47.0%) in the traced and linked samples, respectively. The uncorrected method of non-informative censoring yielded the lowest mortality estimates among all methods for both tracing (6.0%) and linkage (4.0%) approaches at 2 years from ART start. Among corrected methods using ascertained data, multiple imputation, incorporating ascertained data (MI(asc.)) and inverse probability weighting with logistic weights were most robust for the tracing approach. In contrast, for the linkage approach, MI(asc.) was the most robust. CONCLUSIONS: Our findings emphasise that lost to follow-up is non-ignorable and both tracing and linkage improved outcome ascertainment: tracing identified substantial mortality in those reported as lost to follow-up, whereas linkage did not identify out-of-facility deaths, but showed that a large proportion of those reported as lost to follow-up were self-transfers.

HIV Drug Resistance in Newly Diagnosed Young Children in the Western Cape, South Africa.

BACKGROUND: Pretreatment of HIV drug resistance among children living with HIV (CLHIV) can compromise antiretroviral therapy (ART) effectiveness. Resistance may be transmitted directly from mothers or acquired following exposure to antiretrovirals consumed through breastfeeding or administered as prophylaxis. METHODS: We performed resistance testing in children aged <3 years, newly diagnosed with HIV in Western Cape, South Africa (2021-2022), who either (1) acquired HIV via possible breastfeeding transmission from mothers who received ART (any regimen) during pregnancy/postpartum and/or (2) were exposed to protease inhibitors or integrase strand transfer inhibitors (INSTIs) in utero. Possible breastfeeding transmission was defined as testing HIV-polymerase chain reaction positive at age >28 days, after previously testing negative. We used surveillance drug-resistance mutation lists to define mutations. RESULTS: We included 135 CLHIV. Most mothers started ART prepregnancy (73%). Overall, 57% (77/135) of children had resistance mutations detected. Nonnucleoside reverse transcriptase inhibitor-associated, nucleoside reverse transcriptase inhibitor-associated, protease inhibitor-associated and INSTI-associated mutations were found in 55% (74/135), 10% (13/135), <1% (1/135) and <1% (1/122) of children tested, respectively. One child with breastfeeding transmission had high-level INSTI resistance detected at HIV diagnosis, aged 18 months (E138K and G118R mutations). CONCLUSIONS: Although not clinically relevant, nonnucleoside reverse transcriptase inhibitor-associated mutations were common. Dolutegravir is currently the preferred first-line treatment for adults and CLHIV age ≥4 weeks, and although very low INSTI resistance levels have been observed in adults, limited data exist on genotyping the integrase region in children. Pretreatment INSTI resistance in children is likely to be unusual, but future surveillance, including longitudinal studies with paired mother-child resistance testing, is needed.

The Retrospective Implementation of Standardized In Utero HIV Exposure Definitions Using Routinely Collected Public Sector Data Across the Western Cape Province, South Africa.

Using the Data Evaluation and Preparation for HIV-Exposed Uninfected Child Cohorts project's standardized child HIV exposure definitions, 64%, 64% and 90% of children exposed to HIV in utero could be classified as HIV-uninfected with moderate or high certainty at the ages of 1 and 3 years and at the time of first infectious disease hospitalization, respectively. These definitions can be applied retrospectively to routine datasets with linked mother-child data.

COVID-19 Vaccine Uptake and Effectiveness by Time since Vaccination in the Western Cape Province, South Africa: An Observational Cohort Study during 2020-2022.

There are few data on the real-world effectiveness of COVID-19 vaccines and boosting in Africa, which experienced widespread SARS-CoV-2 infection before vaccine availability. We assessed the association between vaccination and severe COVID-19 in the Western Cape, South Africa, in an observational cohort study of >2 million adults during 2020-2022. We described SARS-CoV-2 testing, COVID-19 outcomes, and vaccine uptake over time. We used multivariable cox models to estimate the association of BNT162b2 and Ad26.COV2.S vaccination with COVID-19-related hospitalization and death, adjusting for demographic characteristics, underlying health conditions, socioeconomic status proxies, and healthcare utilization. We found that by the end of 2022, 41% of surviving adults had completed vaccination and 8% had received a booster dose. Recent vaccination was associated with notable reductions in severe COVID-19 during periods dominated by Delta, and Omicron BA.1/2 and BA.4/5 (sub)lineages. During the latest Omicron BA.4/5 wave, within 3 months of vaccination or boosting, BNT162b2 and Ad26.COV2.S were each 84% effective against death (95% CIs: 57-94 and 49-95, respectively). However, distinct reductions of effectiveness occurred at longer times post completing or boosting vaccination. Results highlight the importance of continued emphasis on COVID-19 vaccination and boosting for those at high risk of severe COVID-19, even in settings with widespread infection-induced immunity.

Virologic outcomes with tenofovir-lamivudine-dolutegravir in adults failing PI-based second-line ART.

Background: In South African antiretroviral guidelines, selected patients failing second-line protease inhibitor (PI)-based therapy qualify for genotypic resistance testing - those with PI resistance receive darunavir-based third-line regimens; those without PI resistance continue current regimen with adherence support. The Western Cape province, from September 2020, implemented a strategy of tenofovir-lamivudine-dolutegravir (TLD) for patients, provided there was no tenofovir resistance, irrespective of PI resistance. Objectives: To evaluate virologic outcomes with TLD among adults failing second-line PI regimens with no tenofovir resistance. Method: An observational cohort study comparing outcomes in patients switched to TLD with those continuing the same PI or switched to darunavir-based regimens. Follow-up was until virologic suppression (HIV-1 RNA < 400 copies/mL), or at the point of censoring. Results: One hundred and thirty-three patients switched to TLD, 101 to darunavir-based regimens, and 121 continued with the same PI. By 12 months, among patients with PI resistance, 42/47 (89%) in the TLD group had HIV-1 RNA < 400 copies/mL compared to 91/99 (92%) in the darunavir group (hazard ratio, 1.11; 95% confidence interval, 0.77-1.60). In patients without PI resistance, 66/86 (77%) in the TLD group had HIV-1 RNA < 400 copies/mL compared to 42/120 (35%) in those continuing with the same PI (hazard ratio, 4.03; 95% confidence interval, 2.71-5.98). Two patients receiving TLD developed virologic failure with high-level dolutegravir resistance. Conclusion: Amongst patients failing second-line PI with no PI resistance, switching to TLD was associated with higher virologic suppression, likely due to improved adherence. Virologic outcomes were similar in patients with PI resistance switched to darunavir-based regimens or TLD.

The cyclical cascade of HIV care: Temporal care engagement trends within a population-wide cohort.

BACKGROUND: The traditional HIV treatment cascade aims to visualise the journey of each person living with HIV from diagnosis, through initiation on antiretroviral therapy (ART) to treatment success, represented by virological suppression. This representation has been a pivotal tool in highlighting and quantifying sequential gaps along the care continuum. There is longstanding recognition, however, that this may oversimplify the complexity of real-world engagement with HIV services in settings with mature high-burden HIV epidemics. A complementary "cyclical" cascade has been proposed to represent the processes of disengagement at different points on the care continuum, with multiple pathways to re-engagement, although the feasibility of implementing this at scale has been uncertain. This study aimed to populate, refine, and explore the utility of a cyclical representation of the HIV cascade, using routine data from a high-burden HIV setting. METHODS AND FINDINGS: This observational cohort study leveraged person-level data on all people living with HIV in the Western Cape (WC), South Africa, who accessed public health services in the 2 years prior to 31 December 2023. Programme data from disease registers were complemented by data from pharmacy and laboratory systems. At study closure, 494 370 people were included, constituting 93% of those of those estimated to be living with HIV in the province, of whom 355 104 were on ART. Substantial disengagement from HIV care was evident at every point on the cascade. Early treatment emerged as a period of higher risk of disengagement, but it did not account for the majority of disengagement. Almost all those currently disengaged had prior experience of treatment. While re-engagement was also common, overall treatment coverage had increased slowly over 5 years. The transition to dolutegravir-based regimens was dramatic with good virological outcomes for those in care, notwithstanding a clearly discernible impact of the Coronavirus Disease 2019 (COVID-19) pandemic on viral load (VL) testing. People currently engaged and disengaged in care are similar with respect to age and gender. Those who died or disengaged recently were previously distributed across a range of cascade statuses, and a substantial proportion of those newly initiating and re-initiating treatment were no longer on treatment 6 months later. The main limitation of this study was incomplete evidence of HIV testing, linkage to HIV-specific services, and out-of-facility mortality. CONCLUSIONS: Using routine data, it was possible to populate and automate a cyclical cascade of HIV care that continuously captured the nonlinear care journeys of individuals living with HIV. In this generalised mature HIV epidemic, most people are treatment experienced. Disengagement is common and occurs at various points along the cascade, making it challenging to identify high-impact intervention opportunities. While historical HIV cascades remain valuable for target setting and service monitoring, they can be complemented with insights from more detailed cyclical cascades.

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.

ART history prior to conception: trends and association with postpartum disengagement from HIV care in Khayelitsha, South Africa (2013-2019): a retrospective cohort study.

INTRODUCTION: In recent years, the expansion of HIV treatment eligibility has resulted in an increase in people with antiretroviral therapy (ART) experience prior to pregnancy but little is known about postpartum engagement in care in this population. We examined differences in disengagement from HIV care after delivery by maternal ART history before conception. METHODS: We analysed data from people living with HIV (aged 15-49) in Khayelitsha, South Africa, with ≥1 live birth between April 2013 and March 2019. We described trends over time in ART history prior to estimated conception, classifying ART history groups as: (A) on ART with no disengagement (>270 days with no evidence of HIV care); (B) returned before pregnancy following disengagement; (C) restarted ART in pregnancy after disengagement; and (D) ART new start in pregnancy. We used Kaplan-Meier curves and proportional-hazards models (adjusted for maternal age, number of pregnancy records and year of delivery) to examine the time to disengagement from delivery to 2 years postpartum. RESULTS: Among 7309 pregnancies (in 6680 individuals), the proportion on ART (A) increased from 19% in 2013 to 41% in 2019. The proportions of those who returned (B) and restarted (C) increased from 2% to 13% and from 2% to 10%, respectively. There was a corresponding decline in the proportion of new starts (D) from 77% in 2013 to 36% in 2019. In the first recorded pregnancy per person in the study period, 26% (95% CI 25-27%) had disengaged from care by 1 year and 34% (95% CI 33-36%) by 2 years postpartum. Individuals who returned (B: aHR 2.10, 95% CI 1.70-2.60), restarted (C: aHR 3.32, 95% CI 2.70-4.09) and newly started ART (D: aHR 2.41, 95% CI 2.12-2.74) had increased hazards of postpartum disengagement compared to those on ART (A). CONCLUSIONS: There is a growing population of people with ART experience prior to conception and postpartum disengagement varies substantially by ART history. Antenatal care presents an important opportunity to understand prior ART experiences and an entry into interventions for strengthened engagement in HIV care.

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.

Self-transfers, Hospital Admissions and Mortality Among Children and Adolescents Lost to Follow-up From Antiretroviral Therapy Programs in the Western Cape, South Africa Between 2004 and 2019: Linkage to Provincial Records.

BACKGROUND: Pediatric programs face a high rate of loss to follow-up (LTFU) among children and adolescents living with HIV (CAHIV). We assessed true outcomes and predictors of these among CAHIV who were LTFU using linkage to the Western Cape Provincial Health Data Centre at Western Cape sites of the International epidemiology Databases to Evaluate AIDS-Southern Africa collaboration. METHODS: We examined factors associated with self-transfer, hospital admission and mortality using competing risks regression in a retrospective cohort of CAHIV initiating antiretroviral therapy <15 years old between 2004 and 2019 and deemed LTFU (no recorded visit at the original facility for ≥180 days from the last visit date before database closure and not known to have officially transferred out or deceased). RESULTS: Of the 1720 CAHIV deemed LTFU, 802 (46.6%) had self-transferred and were receiving care elsewhere within the Western Cape, 463 (26.9%) had been hospitalized and 45 (2.6%) CAHIV had died. The overall rates of self-transfer, hospitalization, mortality and LTFU were 9.4 [95% confidence interval (CI): 8.8-10.1], 5.4 (95% CI: 5.0-6.0), 0.5 (95% CI: 0.4-0.7) and 4.8 (95% CI: 4.4-5.3) per 100 person-years respectively. Increasing duration on antiretroviral therapy before LTFU was associated with self-transfers while male sex, older age at last visit (≥10 years vs. younger) were associated with hospital admission and immune suppression at last visit was associated with 5 times higher mortality. CONCLUSIONS: Nearly half of CAHIV classified as LTFU had self-transferred to another health facility, a quarter had been hospitalized and a small proportion had died.

Correction: Early mortality in tuberculosis patients initially lost to follow up following diagnosis in provincial hospitals and primary health care facilities in Western Cape, South Africa.

[This corrects the article DOI: 10.1371/journal.pone.0252084.].

COVID-19 vaccine uptake and effectiveness by time since vaccination in the Western Cape province, South Africa: An observational cohort study during 2020-2022.

Background: There are few data on the real-world effectiveness of COVID-19 vaccines and boosting in Africa, which experienced high levels of SARS-CoV-2 infection in a mostly vaccine-naïve population, and has limited vaccine coverage and competing health service priorities. We assessed the association between vaccination and severe COVID-19 in the Western Cape, South Africa. Methods: We performed an observational cohort study of >2 million adults during 2020-2022. We described SARS-CoV-2 testing, COVID-19 outcomes, and vaccine uptake over time. We used multivariable cox models to estimate the association of BNT162b2 and Ad26.COV2.S vaccination with COVID-19-related hospitalisation and death, adjusting for demographic characteristics, underlying health conditions, socioeconomic status proxies and healthcare utilisation. Results: By end 2022, only 41% of surviving adults had completed vaccination and 8% a booster dose, despite several waves of severe COVID-19. Recent vaccination was associated with notable reductions in severe COVID-19 during distinct analysis periods dominated by Delta, Omicron BA.1/2 and BA.4/5 (sub)lineages: within 6 months of completing vaccination or boosting, vaccine effectiveness was 46-92% for death (range across periods), 45-92% for admission with severe disease or death, and 25-90% for any admission or death. During the Omicron BA.4/5 wave, within 3 months of vaccination or boosting, BNT162b2 and Ad26.COV2.S were each 84% effective against death (95% CIs: 57-94 and 49-95, respectively). However, there were distinct reductions of VE at larger times post completing or boosting vaccination. Conclusions: Continued emphasis on regular COVID-19 vaccination including boosting is important for those at high risk of severe COVID-19 even in settings with widespread infection-induced immunity.

A model-based approach to estimating the prevalence of disease combinations in South Africa.

BACKGROUND: The development of strategies to better detect and manage patients with multiple long-term conditions requires estimates of the most prevalent condition combinations. However, standard meta-analysis tools are not well suited to synthesising heterogeneous multimorbidity data. METHODS: We developed a statistical model to synthesise data on associations between diseases and nationally representative prevalence estimates and applied the model to South Africa. Published and unpublished data were reviewed, and meta-regression analysis was conducted to assess pairwise associations between 10 conditions: arthritis, asthma, chronic obstructive pulmonary disease (COPD), depression, diabetes, HIV, hypertension, ischaemic heart disease (IHD), stroke and tuberculosis. The national prevalence of each condition in individuals aged 15 and older was then independently estimated, and these estimates were integrated with the ORs from the meta-regressions in a statistical model, to estimate the national prevalence of each condition combination. RESULTS: The strongest disease associations in South Africa are between COPD and asthma (OR 14.6, 95% CI 10.3 to 19.9), COPD and IHD (OR 9.2, 95% CI 8.3 to 10.2) and IHD and stroke (OR 7.2, 95% CI 5.9 to 8.4). The most prevalent condition combinations in individuals aged 15+ are hypertension and arthritis (7.6%, 95% CI 5.8% to 9.5%), hypertension and diabetes (7.5%, 95% CI 6.4% to 8.6%) and hypertension and HIV (4.8%, 95% CI 3.3% to 6.6%). The average numbers of comorbidities are greatest in the case of COPD (2.3, 95% CI 2.1 to 2.6), stroke (2.1, 95% CI 1.8 to 2.4) and IHD (1.9, 95% CI 1.6 to 2.2). CONCLUSION: South Africa has high levels of HIV, hypertension, diabetes and arthritis, by international standards, and these are reflected in the most prevalent condition combinations. However, less prevalent conditions such as COPD, stroke and IHD contribute disproportionately to the multimorbidity burden, with high rates of comorbidity. This modelling approach can be used in other settings to characterise the most important disease combinations and levels of comorbidity.

Reducing Initial Loss to Follow-up Among People With Bacteriologically Confirmed Tuberculosis: LINKEDin, a Quasi-experimental Study in South Africa.

Every person diagnosed with tuberculosis (TB) needs to initiate treatment. The World Health Organization estimated that 61% of people who developed TB in 2021 were included in a TB treatment registration system. Initial loss to follow-up (ILTFU) is the loss of persons to care between diagnosis and treatment initiation/registration. LINKEDin, a quasi-experimental study, evaluated the effect of 2 interventions (hospital recording and an alert-and-response patient management intervention) in 6 subdistricts across 3 high-TB burden provinces of South Africa. Using integrated electronic reports, we identified all persons diagnosed with TB (Xpert MTB/RIF positive) in the hospital and at primary health care facilities. We prospectively determined linkage to care at 30 days after TB diagnosis. We calculated the risk of ILTFU during the baseline and intervention periods and the relative risk reduction in ILTFU between these periods. We found a relative reduction in ILTFU of 42.4% (95% CI, 28.5%-53.7%) in KwaZulu Natal (KZN) and 22.3% (95% CI, 13.3%-30.4%) in the Western Cape (WC), with no significant change in Gauteng. In KZN and the WC, the relative reduction in ILTFU appeared greater in subdistricts where the alert-and-response patient management intervention was implemented (KZN: 49.3%; 95% CI, 32.4%-62%; vs 32.2%; 95% CI, 5.4%-51.4%; and WC: 34.2%; 95% CI, 20.9%-45.3%; vs 13.4%; 95% CI, 0.7%-24.4%). We reported a notable reduction in ILTFU in 2 provinces using existing routine health service data and applying a simple intervention to trace and recall those not linked to care. TB programs need to consider ILTFU a priority and develop interventions specific to their context to ensure improved linkage to care.

Maternal and birth outcomes in pregnant people with and without HIV in the Western Cape, South Africa.

INTRODUCTION: We evaluated associations of HIV and antiretroviral therapy (ART) with birth and maternal outcomes at a province-wide-level in the Western Cape, South Africa, in a recent cohort before dolutegravir-based first-line ART implementation. METHODS: This retrospective cohort study included pregnant people delivering in 2018-2019 with data in the Western Cape Provincial Health Data Centre which integrates individual-level data on all public sector patients from multiple electronic platforms using unique identifiers. Adverse birth outcomes (stillbirth, low birth weight (LBW), very LBW (VLBW)) and maternal outcomes (early and late pregnancy-related deaths, early and late hospitalizations) were compared by HIV/ART status and adjusted prevalence ratios (aPRs) calculated using log-binomial regression. RESULTS: Overall 171,960 pregnant people and their singleton newborns were included, 19% (N = 32 015) identified with HIV. Amongst pregnant people with HIV (PPHIV), 60% (N = 19 157) were on ART preconception, 29% (N = 9276) initiated ART during pregnancy and 11% (N = 3582) had no ART. Adjusted for maternal age, multiparity, hypertensive disorders and residential district, stillbirths were higher only for PPHIV not on ART [aPR 1.31 (95%CI 1.04-1.66)] compared to those without HIV. However, LBW and VLBW were higher among all PPHIV, with aPRs of 1.11-1.22 for LBW and 1.14-1.54 for VLBW. Pregnancy-initiated ART was associated with early pregnancy-related death (aPR 3.21; 95%CI 1.55-6.65), and HIV with or without ART was associated with late pregnancy-related death (aPRs 7.89-9.01). CONCLUSIONS: Even in the universal ART era, PPHIV experienced higher rates of LBW and VLBW newborns, and higher late pregnancy-related death regardless of ART status than pregnant people without HIV.

Change in HIV-related characteristics of children hospitalised with infectious diseases in Western Cape, South Africa, 2008-2021: a time trend analysis.

INTRODUCTION: With the scaling up of vertical HIV transmission prevention programmes, the HIV-related population profile of children in South Africa has shifted. We described temporal changes in HIV-related characteristics of children, aged ≤3 years (up to the third birthday), with infectious disease hospitalisations across the Western Cape province. METHODS: We used routinely collected electronic data to identify children born in the Western Cape with infectious disease hospital records for lower respiratory tract infections, diarrhoea, meningitis and tuberculous meningitis, from 2008 to 2021. Linked maternal and child unique identifiers were used to extract pregnancy, HIV-related, laboratory, pharmacy and hospitalisation data. We described temporal changes in child HIV exposure and acquisition status, timing of maternal HIV diagnosis and antiretroviral therapy (ART) start, infant exposure to maternal ART and timing thereof, and maternal CD4 and HIV viral load closest to delivery. We used logistic and multinomial regression to assess changes in characteristics between the Pre-Option B+ (2008-2013), Option B+ (2013-2016) and Universal ART periods (2016-2021). RESULTS: Among 52,811 children aged ≤3 years with hospitalisations, the proportion living with HIV dreased from 7.0% (2008) to 1.1% (2021), while those exposed to HIV and uninfected increased from 14.0% (2008) to 16.1% (2021) with a peak of 18.3% in 2017. Among mothers with HIV (n = 9873), the proportion diagnosed with HIV and starting ART before pregnancy increased from 20.2% to 69.2% and 5.8% to 59.0%, respectively, between 2008 and 2021. Children hospitalised during the Universal ART period had eight times higher odds (Odds Ratio: 8.41; 95% CI: 7.36-9.61) of exposure to maternal ART versus children admitted Pre-Option B+. Among mothers of children exposed to HIV and uninfected with CD4 records (n = 7523), the proportion with CD4 <350 cells/µl decreased from 90.6% (2008) to 27.8% (2021). CONCLUSIONS: In recent years, among children hospitalised with infectious diseases, there were fewer children with perinatally acquired HIV, while an increased proportion of those without HIV acquisition are exposed to maternal HIV and ART. There is a need to look beyond paediatric HIV prevalence and consider child exposure to HIV and ART among children without HIV, when assessing the HIV epidemic's impact on child health services.

Preferences for onward health data use in the electronic age among maternity patients and providers in South Africa: a qualitative study.

Despite the expanding digitisation of individual health data, informed consent for the collection and use of health data is seldom explicitly sought in public sector clinics in South Africa. This study aims to identify perceptions of informed consent practices for health data capture, access, and use in Gauteng and the Western Cape provinces of South Africa. Data collection from September to December 2021 included in-depth interviews with healthcare providers (n = 12) and women (n = 62) attending maternity services. Study findings suggest that most patients were not aware that their data were being used for purposes beyond the individualised provision of medical care. Understanding the concept of anonymised use of electronic health data was at times challenging for patients who understood their data in the limited context of paper-based folders and booklets. When asked about preferences for electronic data, patients overwhelmingly were in favour of digitisation. They viewed electronic access to their health data as facilitating rapid and continuous access to health information. Patients were additionally asked about preferences, including delivery of health information, onward health data use, and recontacting. Understanding of these use cases varied and was often challenging to convey to participants who understood their health data in the context of information inputted into their paper folders. Future systems need to be established to collect informed consent for onward health data use. In light of perceived ties to the care received, these systems need to ensure that patient preferences do not impede the content nor quality of care received.

Maternal weight trajectories and associations with infant growth in South African women.

BACKGROUND: Despite the close relationship between pre-pregnancy body mass index (BMI), gestational weight gain (GWG) and postpartum weight (PPW), these factors are often studied separately. There are no data characterising longitudinal weight trajectories among pregnant and postpartum women in urban African populations. We examined maternal weight trajectories from pregnancy through to 12 months postpartum, factors associated with higher weight trajectory class membership and associations of weight trajectories with infant growth at 12 months. METHODS: Data from 989 women were examined for weight trajectories from first antenatal care visit in pregnancy to 12 months postpartum using latent-class growth models. Baseline factors associated with class membership were assessed using multinomial logistic regression. Of the enrolled women, 613 of their infants were assessed for growth at 12 months. Anthropometry measurements for mothers and infants were conducted by a trained study nurse. Associations between maternal weight trajectory class and infant weight-for-age (WAZ), length-for-age (LAZ), weight-for-length (WLZ) at 12 months of age were analysed using linear regression. RESULTS: Four distinct classes of maternal weight trajectories were identified. The classes included consistent low (29%), consistent medium (37%), medium-high (24%) and consistent high (10%) trajectories. Similar to trends observed with medium-high trajectory, baseline factors positively associated with consistent high class membership included age (OR 1.05, 95% CI 1.01-1.09), pre-pregnancy BMI (OR 2.24, 95% CI 1.97-2.56), stage 1 hypertension (OR 3.28, 95% CI 1.68-6.41), haemoglobin levels (OR 1.39, 95% CI 1.11-1.74) and parity (OR 1.39, 95% CI 1.15-1.67); living with HIV (OR 0.47, 95% CI 0.30-0.74) was inversely associated. In adjusted analyses, compared to consistent medium weight trajectory, consistent low weight trajectory (mean difference -0.41, 95% CI -0.71;-0.12) was associated with decreased, and consistent high weight trajectory (mean difference 1.21, 95% CI 0.59-1.83) with increased infant WAZ at 12 months of age. CONCLUSION: Identification of unique longitudinal weight trajectory groupings might inform comprehensive efforts targeted at improving healthy maternal weight and infant outcomes.