Prevention of mother-to-child-transmission of HIV in Khayelitsha: a contemporary review of services 20 years later

Background: It's been 20 years since the Western Cape (WC) province of South Africa launched its first Prevention of Mother-To-Child-Transmission of HIV(PMTCT) pilot programme in Khayelitsha. The programme evolved alongside the World Health Organization (WHO) guidelines; in 2013 the recommended guidelines in the province was WHO Option B+( life-long antiretroviral therapy (ART) irrespective of CD4 count, and exclusive breastfeeding for the first 6 months of life). Alongside the explanation of the PMTCT programme, the province gradually implemented patient administrative systems in all fixed public health facilities; these systems all shared a unique patient identifier called the folder number. The digitization of folder number lead to the establishment of the Provincial Health Data Centre (PHDC), an African health information exchange (HIE) developed and hosted in the WC Department of Health. The HIE also integrated data from disease management information systems (Three Interlinked Electronic Registers (TIER) and the Electronic Tuberculosis Register (ETR)), allowing the ability to track the cohort of pregnant women living with HIV who attend public health services across the Western Cape. Here we report the latest analysis of vertical HIV transmission in the era of WHO Option B+ with the advantage of a maturing consolidated African HIE. The primary aim of the study was to describe coverage of the PMTCT care cascade, including the implementation of maternal viral load monitoring and early infant diagnosis, among HIV positive women who presented antenatal care, or delivered in the absence of antenatal care, at a public health facility in Khayelitsha subdistrict in 2017; and to quantify MTCT risk factors and outcomes among this cohort up to 12 months post-partum. Methods: Patient-level consolidated PHDC data were used to draw an observational cohort consisting of all live-born and linked mother-infant pairs in which the mother was HIV positive, at any point prior to her first antenatal visit up to 12 months post-partum and attended antenatal care, or in the absence of antenatal care delivered in Khayelitsha in 2017. The PHDC provided a single summative record per pregnancy for each woman (linked to her infant after birth) which enabled the assessment of PMTCT uptake from her first antenatal visit through delivery to infant early infant diagnosis (EID) of HIV-PCR testing and PHDC ascertainment of HIV up to the end of the index period (i.e. 12 months post-partum). iii Using this cohort of HIV-exposed infants, a protocol was designed (Section A: Protocol) to assess the outcomes of the implementation of WHO Option B+(lifelong ART for all HIV positive pregnant women; and periodic re-testing of HIV negative women) under the latest EID guidelines of routine birth HIV-PCR (within 1 week of birth), and repeat testing at 10 weeks (between 2 and 14 weeks of birth) or a first HIV-test at 10 weeks if the infant had not been tested at birth. Continuous variables were converted to categorical variables according to pre-set thresholds, all categorical variables were described using proportions, and frequency tables were used for comparison. Timing of ART initiation was categorized as a binary variable which was assigned 1 if the mother started ART before the first antenatal visits, and 0 of she started ART at the first antenatal visit or anytime during the pregnancy. Viral load was categorised according to coverage and suppression status; virologic suppression was defined as having a viral load of 1000 copies/ml or less after 3 months on ART. Analysis was performed in using R studio; descriptive statistics were used to assess coverage along the PMTCT care cascade, and logistic regression was run to quantify a priori defined risk factors associated with MTCT. Results: The study cohort of 2 576 mother-infant pairs (2548 women living with HIV (WLHIV)) presented in the manuscript was a young cohort with a median age of 30 years (interquartile range of 26 – 34), in which most women delivered vaginally (70.5%), and 78.3% attended at least one antenatal visit before delivery. Most WLHIV (88.3%) presented to their first pregnancy related visit (antenatal care or delivery) already knowing their status, of whom 77.9% were already on ART. 94.5% of women diagnosed prior to birth were initiated on ART prior; 85.0% of these women received a viral load test antenatally, of whom 88.0% were virologically suppressed. Early infant diagnosis coverage was sub-optimal with birth HIV-PCR (within 7 days of birth) coverage of 79.21% among HIV exposed infants (HEI); an even lower proportion (57.9%) of HEI who tested negative at birth had a repeat test around 10-weeks. HIV-PCR ascertained MTCT was 0.8% at 10 weeks, consolidated data from the PHDC suggested an MTCT of 1.8% by the end of the index period (the PHDC HIV episode identified an additional 16 HIVexposed (HEI) infants with HIV who were not detected by laboratory tests). PWLHIV who started ART prior to the first antenatal visit had 50% reduced risk of MTCT compared to those who started ART during the pregnancy. Women who were not suppressed antenatally had a 5- fold (aOR = 5.3, 95% CI: 2.5 – 12.3) increased MTCT risk compared to those were suppressed antenatally. Women who did not attend ANC were at highest risk of transmission (aOR=1.6,95%CI: 0.7 – 3.6). iv Conclusion: Although women most women present to care already knowing their HIV status, ART initiation and uptake of viral load testing is very low at presentation but improved significantly during pregnancy, evidence of maturing PMCT services. National and Provincial MTCT is likely to be underestimated as it relies solely on PCR results; the uptake of the birth PCR among HIV-exposed infants is still not 100% (where it should be) and the uptake of a repeat tests among infants that tested negative is even lower. PHDC data, which consolidates HIV data from multiple sources, revealed a higher MTCT than HIV-PCR testing alone

Association between tuberculosis and pregnancy outcomes: a retrospective cohort study of women in Cape Town, South Africa

Background Tuberculosis (TB) remains a leading cause of mortality among women of childbearing age and a significant contributor to maternal mortality. Pregnant women with TB are at high risk of adverse pregnancy outcomes. This study aimed to determine risk factors for an adverse pregnancy outcome among pregnant women diagnosed with TB. Methods Using TB programmatic data, this retrospective cohort analysis included all women who were routinely diagnosed with TB in the public sector between October 2018 and March 2020 in two health subdistricts of Cape Town, and who were documented to be pregnant during their TB episode. Adverse pregnancy outcome was defined as either a live birth of an infant weighing <2500 g and/or with a gestation period <37 weeks or as stillbirth, miscarriage, termination of pregnancy, maternal or early neonatal death. Demographics, TB and pregnancy characteristics were described by HIV status. Logistic regression was used to determine risk factors for adverse pregnancy outcome. Results Of 248 pregnant women, half (52%) were living with HIV; all were on antiretroviral therapy at the time of their TB diagnosis. Pregnancy outcomes were documented in 215 (87%) women, of whom 74 (34%) had an adverse pregnancy outcome. Being older (35–44 years vs 25–34 years (adjusted OR (aOR): 3.99; 95% CI: 1.37 to 11.57), living with HIV (aOR: 2.72; 95% CI: 0.99 to 4.63), having an unfavourable TB outcome (aOR: 2.29; 95% CI: 1.03 to 5.08) and having presented to antenatal services ≤1 month prior to delivery (aOR: 10.57; 95% CI: 4.01 to 27.89) were associated with higher odds of an adverse pregnancy outcome. Conclusions Pregnancy outcomes among women with TB were poor, irrespective of HIV status. Pregnant women with TB are a complex population who need additional support prior to, during and after TB treatment to improve TB treatment and pregnancy outcomes. Pregnancy status should be considered for inclusion in TB registries

Risk factors for Coronavirus disease 2019 (Covid-19) death in a population cohort study from the Western Cape province, South Africa

Risk factors for coronavirus disease 2019 (COVID-19) death in sub-Saharan Africa and the effects of human immunodeficiency virus (HIV) and tuberculosis on COVID-19 outcomes are unknown. We conducted a population cohort study using linked data from adults attending public-sector health facilities in the Western Cape, South Africa. We used Cox proportional hazards models, adjusted for age, sex, location, and comorbidities, to examine the associations between HIV, tuberculosis, and COVID-19 death from 1 March to 9 June 2020 among (1) public-sector “active patients” (≥1 visit in the 3 years before March 2020); (2) laboratory-diagnosed COVID-19 cases; and (3) hospitalized COVID-19 cases. We calculated the standardized mortality ratio (SMR) for COVID-19, comparing adults living with and without HIV using modeled population estimates.Among 3 460 932 patients (16% living with HIV), 22 308 were diagnosed with COVID-19, of whom 625 died. COVID19 death was associated with male sex, increasing age, diabetes, hypertension, and chronic kidney disease. HIV was associated with COVID-19 mortality (adjusted hazard ratio [aHR], 2.14; 95% confidence interval [CI], 1.70–2.70), with similar risks across strata of viral loads and immunosuppression. Current and previous diagnoses of tuberculosis were associated with COVID-19 death (aHR, 2.70 [95% CI, 1.81–4.04] and 1.51 [95% CI, 1.18–1.93], respectively). The SMR for COVID-19 death associated with HIV was 2.39 (95% CI, 1.96–2.86); population attributable fraction 8.5% (95% CI, 6.1–11.1)

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

Abstract 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

Association between tuberculosis and pregnancy outcomes: a retrospective cohort study of women in Cape Town, South Africa

Background Tuberculosis (TB) remains a leading cause of mortality among women of childbearing age and a significant contributor to maternal mortality. Pregnant women with TB are at high risk of adverse pregnancy outcomes. This study aimed to determine risk factors for an adverse pregnancy outcome among pregnant women diagnosed with TB.Methods Using TB programmatic data, this retrospective cohort analysis included all women who were routinely diagnosed with TB in the public sector between October 2018 and March 2020 in two health subdistricts of Cape Town, and who were documented to be pregnant during their TB episode. Adverse pregnancy outcome was defined as either a live birth of an infant weighing &lt;2500 g and/or with a gestation period &lt;37 weeks or as stillbirth, miscarriage, termination of pregnancy, maternal or early neonatal death. Demographics, TB and pregnancy characteristics were described by HIV status. Logistic regression was used to determine risk factors for adverse pregnancy outcome.Results Of 248 pregnant women, half (52%) were living with HIV; all were on antiretroviral therapy at the time of their TB diagnosis. Pregnancy outcomes were documented in 215 (87%) women, of whom 74 (34%) had an adverse pregnancy outcome. Being older (35–44 years vs 25–34 years (adjusted OR (aOR): 3.99; 95% CI: 1.37 to 11.57), living with HIV (aOR: 2.72; 95% CI: 0.99 to 4.63), having an unfavourable TB outcome (aOR: 2.29; 95% CI: 1.03 to 5.08) and having presented to antenatal services ≤1 month prior to delivery (aOR: 10.57; 95% CI: 4.01 to 27.89) were associated with higher odds of an adverse pregnancy outcome.Conclusions Pregnancy outcomes among women with TB were poor, irrespective of HIV status. Pregnant women with TB are a complex population who need additional support prior to, during and after TB treatment to improve TB treatment and pregnancy outcomes. Pregnancy status should be considered for inclusion in TB registries

Determining antenatal medicine exposures in South African women: a comparison of three methods of ascertainment

Background In the absence of clinical trials, data on the safety of medicine exposures in pregnancy are dependent on observational studies conducted after the agent has been licensed for use. This requires an accurate history of antenatal medicine use to determine potential risks. Medication use is commonly determined by self-report, clinician records, and electronic pharmacy data; different data sources may be more informative for different types of medication and resources may differ by setting. We compared three methods to determine antenatal medicine use (self-report, clinician records and electronic pharmacy dispensing records [EDR]) in women attending antenatal care at a primary care facility in Cape Town, South Africa in a setting with high HIV prevalence. Methods Structured, interview-administered questionnaires recorded self-reported medicine use. Data were collected from clinician records and EDR on the same participants. We determined agreement between these data sources using Cohen’s kappa and, lacking a gold standard, used Latent Class Analysis to estimate sensitivity, specificity and positive predictive value (PPV) for each data source. Results Between 55% and 89% of 967 women had any medicine use documented depending on the data source (median number of medicines/participant = 5 [IQR 3–6]). Agreement between the datasets was poor regardless of class except for antiretroviral therapy (ART; kappa 0.6–0.71). Overall, agreement was better between the EDR and self-report than with either dataset and the clinician records. Sensitivity and PPV were higher for self-report and the EDR and were similar for the two. Self-report was the best source for over-the-counter, traditional and complementary medicines; clinician records for vaccines and supplements; and EDR for chronic medicines. Conclusions Medicine use in pregnancy was common and no single data source included all the medicines used. ART was the most consistently reported across all three datasets but otherwise agreement between them was poor and dependent on class. Using a single data collection method will under-estimate medicine use in pregnancy and the choice of data source should be guided by the class of the agents being investigated

Cohort Profile: The Western Cape Pregnancy Exposure Registry (WCPER)

Purpose: The Western Cape Pregnancy Exposure Registry (PER) was established at two public sector healthcare sentinel sites in the Western Cape province, South Africa, to provide ongoing surveillance of drug exposures in pregnancy and associations with pregnancy outcomes. Participants: Established in 2016, all women attending their first antenatal visit at primary care obstetric facilities were enrolled and followed to pregnancy outcome regardless of the site (ie, primary, secondary, tertiary facility). Routine operational obstetric and medical data are digitised from the clinical stationery at the healthcare facilities. Data collection has been integrated into existing services and information platforms and supports routine operations. The PER is situated within the Provincial Health Data Centre, an information exchange that harmonises and consolidates all health-related electronic data in the province. Data are contributed via linkage across a unique identifier. This relationship limits the missing data in the PER, allows validation and avoids misclassification in the population-level data set. Findings to date: Approximately 5000 and 3500 pregnant women enter the data set annually at the urban and rural sites, respectively. As of August 2021, >30 000 pregnancies have been recorded and outcomes have been determined for 93%. Analysis of key obstetric and neonatal health indicators derived from the PER are consistent with the aggregate data in the District Health Information System. Future plans: This represents significant infrastructure, able to address clinical and epidemiological concerns in a low/middle-income setting