A longitudinal analysis of neonatal and infant diagnostic HIV-PCR uptake and associations during three sequential policy periods in Mitchell’s Plain, Cape Town

Background: Despite technological and programmatic advances in the prevention of vertical transmission of HIV and early infant diagnosis (EID), paediatric HIV continues to have a significant impact on infant and child survival in low- and middle-income countries. Many EID programmes follow the WHO recommendation of initial infant HIV testing with a nucleic acid assay at 4-6 weeks old. In general this strategy has been poorly implemented with substantial attrition after birth such that, according to UNAIDS, only 51% of HIV-exposed infants received a virological test in the first two months of life in 2015. In addition, there is concern about the sensitivity of the nucleic acid assays at six weeks in the context of exposure to prolonged multidrug antiretroviral therapy as infant post-exposure prophylaxis, and in breast milk. HIV-PCR testing at birth has been promoted as a means of maximizing the number of infants who receive an HIV test as well as identifying in utero-infected infants in whom HIV infection may follow an aggressive course. Evidence from pilot studies and modelling data was sufficiently compelling for the WHO to include a conditional recommendation for the addition of a birth HIV-PCR (either routine or targeted at high risk groups) to its EID algorithms in 2015. The Western Cape introduced targeted birth HIV testing for high risk infants in August 2014 and expanded this in line with the South African National Prevention of Mother-to-Child Transmission Guidelines, to include all HIV-exposed infants in December 2015. Methods: Between 2013 and 2016 we conducted an implementation science project to iteratively assess the implementation and effectiveness of the vertical transmission prevention of HIV in a chain of referral facilities in Cape Town (i.e. from primary to tertiary care). The e-register provided a single longitudinal record for each woman (linked to her infant after birth) and enabled assessment of HIV testing and treatment from first antenatal visit through delivery to infant HIV testing. Using a cohort of HIV-exposed live infants from this database, a protocol was designed (Section A: Protocol) to assess the implementation and outcome of effectively three different EID policy periods in the facility chain. i.e. an initial period of birth HIV-PCR at the clinician’s discretion if evidence of HIV infection; a period of targeted birth testing of high risk infants and lastly, of routine birth HIV-PCR for all HIV-exposed infants. A critical review of the literature appraised published assessments of birth HIV testing programmes in low- and middle-income countries (Section B: Literature Review) with the aim of assessing in utero transmission rates, follow-up testing and transmission rates and the resources required for implementation. Studies that modelled the impact of birth HIV testing were specifically reviewed. The manuscript (Section C: Manuscript) presented an analysis of the HIV-infected/exposed mother/infant dyads from the e-register of the Closing the Gaps study. Using this database adherence to guidelines in each period was assessed as well as the outcome of HIV-PCR at four delivery sites and the impact of the policies on return for follow-up EID. Results: South Africa is the first country in sub-Saharan Africa to implement birth HIV testing and most of the studies in support of this strategy were generated here. There was limited literature which highlighted the need for further investigation into the implementation and effectiveness of such programmes. No prospective data addressed targeted birth testing and those reporting on more routine birth HIV-PCR demonstrated success in timeous diagnosis and treatment although significant additional project resources were required. The retrospective laboratory data indicated that receipt of a birth HIV-PCR reduced the likelihood for follow-up at later testing time-points. This is important as the modelling studies suggested that the clinical and financial benefits of adding birth testing to existing algorithms would be lost if follow-up was poor. In the cohort of 2012 HIV-exposed infants in the study presented in the manuscript, the proportion who received birth testing increased with the progression of the EID policies but guideline implementation was poor, especially in primary care, with only 60% of infants being tested as recommended. The proportion of infants with positive HIV-PCR decreased as the pool of HIV-exposed infants undergoing testing expanded, being highest during the periods of targeted birth testing. In concurrence with the South African literature, receipt of a birth HIV-PCR decreased the likelihood of follow-up testing at 6-10 weeks. Among infants tested at 6-10 weeks old, the proportion who were positive for the first time at this time- point increased with the introduction of routine birth testing for all HIV-exposed infants, emphasizing the importance of the follow-up EID time-points. Conclusion: Virological testing at birth effectively increased the number of HIV-exposed infants who received an HIV test and was effective in identifying in utero infection in high risk infants (who could start treatment early with the attendant benefits.) The Western Cape EID policies were incompletely implemented in the study facilities over this time with many infants not being tested as indicated. Birth HIV-PCR decreased follow-up testing, an unintended consequence of serious concern. Adherence to the provincial and national guidelines needs to be re-enforced at delivery sites and at the primary care facilities where follow-up EID occurs

Provider-initiated HIV testing and counselling for children

Mary-Ann Davies and Emma Kalk reflect on recent research by Rashida Ferrand and colleagues into barriers to provider-initiated HIV testing for older children in Zimbabwe. Please see later in the article for the Editors' Summar

Identifying HIV infection in South African women: How does a fourth generation HIV rapid test perform?

Background: HIV rapid tests (RT) play an important role in tackling the HIV pandemic in South Africa. Third generation RT that detect HIV antibodies are currently used to diagnose HIV infection at the point of care. Determine Combo (DC) is the first fourth generation RT that detects both p24 antigen (p24Ag) and HIV antibodies (Ab), theoretically reducing the window period and increasing detection rates. Early detection of maternal HIV infection is important to mitigate the high risk of vertical transmission associated with acute maternal infection. Objectives: We assessed the performance of the DC RT against third generation RT in antenatal and post-partum women. Methods: Third generation RT Advance Quality and Acon were used in a serial algorithm to diagnose HIV infection in antenatal and post-partum women over six months at a tertiary hospital in Johannesburg, South Africa. This data provided the reference against which the DC RT was compared on plasma and whole blood samples. Results: The 1019 participants comprised 345 (34%) antenatal and 674 (66%) post-partum women. Ninety women (8.8%) tested HIV-positive of whom 59 (66%) were tested antenatally, and 31 (34%) post-partum yielding prevalence rates of 17.1% and 4.6% respectively. The sensitivity and specificity of the Ab component of DC on plasma antenatally was 100% (93.8% – 100%) and 100% (98.6% – 100%) respectively and post-partum was 100% (88.9% – 100%) and 99.6% (98.8% – 99.9%) respectively. One false positive and not a single true positive p24Ag was detected. Of 505 post-partum women who tested HIV-negative 6–12 months prior to enrolment, 12 (2.4%) seroconverted. Conclusion: The fourth generation DC offered no advantage over current third generation RT in the diagnosis of HIV infection

HIV sero-conversion during late pregnancy – when to retest

The South African National Prevention of Mother-to-Child Transmission of HIV programme has resulted in significant reductions in vertical transmission, but new infant HIV infections continue to occur. We present two cases of HIV seroconversion during late pregnancy, demonstrating the limitations of the current programme. These could be mitigated by expanding the programme to include maternal testing at delivery and at immunisation clinic visits as we pursue the elimination of mother-to-child transmission

Survival and health of children who are HIV-exposed uninfected: study protocol for the CHERISH (Children HIV-Exposed Uninfected - Research to Inform Survival and Health) dynamic, prospective, maternal-child cohort study

INTRODUCTION: CHERISH is designed to establish a long-term sustainable system for measurement of in utero and postnatal exposures and outcomes in children who are HIV-exposed uninfected (HEU) and HIV-unexposed to compare survival, hospitalisation, growth and neurodevelopment in the Western Cape, South Africa. METHODS AND ANALYSIS: During 2022-2025, the CHERISH dynamic cohort is prospectively enrolling pregnant people with and without HIV at 24-36 weeks gestation from one urban and one rural community, following mother-child pairs, including children who are HEU (target N=1200) and HIV-unexposed (target N=600) for 3 years from the child's birth. In-person visits occur at enrolment, delivery, 12 months, 24 months and 36 months with intervening 3-monthly telephone data collection. Children and mothers without HIV are tested for HIV at all in-person visits. Data on exposures and outcomes are collected from routine standardised healthcare documentation, maternal interview, measurement (growth and neurodevelopment) at in-person visits and linkage to the Western Cape Provincial Health Data Centre (survival and hospitalisation). A priori adverse birth outcomes, advanced maternal HIV and maternal mental health are considered potential mediators of outcome disparities in children who are HEU and will be evaluated as such in multivariable models appropriate for each outcome. ETHICS AND DISSEMINATION: Mothers interested in joining the study are taken through a visual informed consent document for their and their child's participation, with the option to consent to anonymised de-identified data being contributed to a public data repository. All data is captured directly into an electronic database using alphanumeric identifiers devoid of identifying information. The cohort study is approved by Human Research Ethics Committees of Stellenbosch University (N20/08/084), University of Cape Town (723/2021) and Western Cape Government (WC_2021_09_007). Findings will be shared with participants, participating communities, local and provincial stakeholders, child health clinicians, researchers and policymakers at local, national and international forums and submitted for publication in peer-reviewed journals

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

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

Association between food intake and obesity in pregnant women living with and without HIV in Cape Town, South Africa: a prospective cohort study

Background Although global nutrition/dietary transition resulting from industrialisation and urbanisation has been identified as a major contributor to widespread trends of obesity, there is limited data in pregnant women, including those living with HIV in South Africa. We examined food-based dietary intake in pregnant women with and without HIV at first antenatal care (ANC) visit, and associations with maternal overweight/obesity and gestational weight gain (GWG). Methods In an urban South African community, consecutive women living with (n = 479) and without (n = 510) HIV were enrolled and prospectively followed to delivery. Interviewer-administered non-quantitative food frequency questionnaire was used to assess dietary intake (starch, protein, dairy, fruits, vegetables, legumes, oils/fats) at enrolment. Associations with maternal body mass index (BMI) and GWG were examined using logistic regression models. Results Among women (median age 29 years, IQR 25–34), the prevalence of obesity (BMI ≥ 30 kg/m2) at first ANC was 43% and that of excessive GWG (per IOM guidelines) was 37% overall; HIV prevalence was 48%. In women without HIV, consumption of potato (any preparation) (aOR 1.98, 95% CI 1.02–3.84) and pumpkin/butternut (aOR 2.13, 95% CI 1.29–3.49) for 1–3 days a week increased the odds of overweight/obesity compared to not consuming any; milk in tea/coffee (aOR 6.04, 95% CI 1.37–26.50) increased the odds of excessive GWG. Consumption of eggs (any) (aOR 0.52, 95% CI 0.32–0.86) for 1–3 days a week reduced the odds of overweight/obesity while peanut and nuts consumption for 4–7 days a week reduced the odds (aOR 0.34, 95% CI 0.14–0.80) of excessive GWG. In women with HIV, consumption of milk/yoghurt/maas to drink/on cereals (aOR 0.35, 95% CI 0.18–0.68), tomato (raw/cooked) (aOR 0.50, 95% CI 0.30–0.84), green beans (aOR 0.41, 95% CI 0.20–0.86), mixed vegetables (aOR 0.49, 95% CI 0.29–0.84) and legumes e.g. baked beans, lentils (aOR 0.50, 95% CI 0.28–0.86) for 4–7 days a week reduced the odds of overweight/obesity; tomato (raw/cooked) (aOR 0.48, 95% CI 0.24–0.96) and mixed vegetables (aOR 0.38, 95% CI 0.18–0.78) also reduced the odds of excessive GWG. Conclusions Diet modification may promote healthy weight in pregnant women living with and without HIV

Growth patterns of infants with in- utero HIV and ARV exposure in Cape Town, South Africa and Lusaka, Zambia

Background Infants born HIV-exposed yet remain uninfected (HEU) are at increased risk of poorer growth and health compared to infants born HIV-unexposed (HU). Whether maternal antiretroviral treatment (ART) in pregnancy ameliorates this risk of poorer growth is not well understood. Furthermore, whether risks are similar across high burden HIV settings has not been extensively explored. Methods We harmonized data from two prospective observational studies conducted in Cape Town, South Africa, and Lusaka, Zambia, to compare weight-for-age (WAZ), length-for-age (LAZ) and weight-for-length (WLZ) Z-scores between infants who were HEU and HU, converting infant anthropometric measures using World Health Organisation Growth Standards adjusted for age and sex. Linear mixed effects models were fit to identify risk factors for differences in anthropometrics at 6–10 weeks and 6 months by infant HIV exposures status and by timing of exposure to maternal ART, either from conception or later in gestation. Results Overall 773 mother-infant pairs were included across two countries: women living with HIV (WLHIV), 51% (n = 395) with 65% on ART at conception and 35% initiating treatment in pregnancy. In linear mixed effects models, WAZ and WLZ at 6–10 weeks were lower among infants who were HEU vs HU [β = − 0.29 (95% CI: − 0.46, − 0.12) and [β = − 0.42 (95% CI: − 0.68, − 0.16)] respectively after adjusting for maternal characteristics and infant feeding with a random intercept for country. At 6 months, LAZ was lower [β = − 0.28 CI: − 0.50, − 0.06)] among infants who were HEU, adjusting for the same variables, with no differences in WAZ and WLZ. Within cohort evaluations identified different results with higher LAZ among infants who were HEU from Zambia at 6–10 weeks, [β = + 0.34 CI: + 0.01, + 0.68)] and lower LAZ among infants who were HEU from South Africa [β = − 0.30 CI: − 0.59, − 0.01)] at 6 months, without other anthropometric differences at either site. Conclusion Infant growth trajectories differed by country, highlighting the importance of studying contextual influences on outcomes of infants who were HEU

COVID-19 in pregnancy in South Africa : tracking the epidemic and defining the natural history

South Africa (SA) has seen a rapid increase in COVID-19 infections in recent weeks, with cases exceeding 40 000 in early June and anticipated to escalate rapidly as lockdown is eased. The country also has the largest HIV burden globally, and poor maternal and child health indices in many parts. Although early indications were that COVID-19 infection does not worsen pregnancy and birth outcomes, recent reports have raised fresh concerns. Preterm birth, neonatal pneumonia[9-11] and cases of vertical transmission and postpartum infections have been reported, including in SA. Some maternal deaths related to COVID-19 have occurred, possibly linked to haemodynamic changes immediately postpartum and/or to the thrombogenic nature of both pregnancy and COVID- 19. Maternal wellbeing in pregnant women with COVID-19 infection is a major concern, as these women often have high anxiety about infecting their newborn child, and may experience challenging interactions with healthcare providers and community stigma. Most evidence on COVID-19 and pregnancy to date is limited to case series, involves only symptomatic women without HIV, and is almost exclusively from high-income countries. Cohort data across a range of settings and population groups are the only means of fully understanding the natural history, clinical disease spectrum and risks of COVID-19 in pregnant women, fetuses and infants.http://www.samj.org.zaam2021Obstetrics and Gynaecolog