Optimizing Research Methods to Understand HIV-Exposed Uninfected Infant and Child Morbidity: Report of the Second HEU Infant and Child Workshop

CITATION: Slogrove, A. L., et al. 2016. Optimizing research methods to understand HIV-exposed uninfected infant and child morbidity : report of the second HEU infant and child workshop. Frontiers in Immunology, 7:576, doi:10.3389/fimmu.2016.00576.The original publication is available at http://journal.frontiersin.orgThe first HIV Exposed Uninfected (HEU) Infant and Child Workshop was held in Vancouver in July 2015, hosted by the Child and Family Research Institute at the British Columbia Children’s Hospital and University of British Columbia. This event brought together 50 clinicians, epidemiologists, and basic scientists to review current knowledge of HEU infants, their clinical course, immunologic differences, and risk for neurodevelopmental and infectious morbidity. This Frontiers in Immunology Research Topic, “Immune mechanisms underlying the increased morbidity and mortality of HIVexposed uninfected (HEU) children,” is a product of the first HEU workshop synthesizing the evidence in the field. It was clear from the first workshop that there is a committed community of researchers who have identified the need to understand the mechanisms of increased morbidity and mortality in HEU infants and children, but evidence to intervene and mitigate these risks is lacking. In high HIV burden countries, all infants and children, irrespective of HIV exposure, are vulnerable to high rates of infant and child mortality (1). In this context, the essential question is whether HEU children are any different than HIV-unexposed uninfected (HUU) children experiencing similar nutritional, environmental, and social constraints to health. To this end, particular research methodological principles require reinforcing in future HEU research. It was these methodological challenges and possible solutions that formed the theme of the second HEU Infant and Child Workshop attended by 75 HEU researchers and hosted by the KwaZulu-Natal Research Institute for Tuberculosis and HIV at the University of KwaZulu-Natal in Durban, South Africa. We report on the specific methodological challenges tackled during the workshop and steps to move forward.http://journal.frontiersin.org/journal/immunology/section/hiv-and-aids#aboutPublisher's versio

Being prepared to evaluate pregnancy PrEP

CITATION: Slogrove, A. L. 2019. Being prepared to evaluate pregnancy PrEP. Journal of the International AIDS Society, 22(12). doi:10.1002/jia2.25435The original publication is available at https://onlinelibrary.wiley.com/journal/17582652Pregnant and breastfeeding women in high HIV-incidence set-tings are at great risk for HIV-acquisition and stand to benefit tremendously from HIV pre-exposure prophylaxis (PrEP)scale-up [1]. The PrEP Implementation in Young women and Adolescents (PrIYA) programme is to be commended for addressing this challenge by integrating PrEP delivery into routine maternal child health and family planning services in16 clinics in Kisumu County, Kenya. Dettinger and colleagues used data from the PrIYA programme implementation to describe birth (weight and gestational age) and 6-week growth outcomes of infants born to women with and without pregnancy PrEP exposure, concluding that outcomes did not differ by PrEP exposure [2]. However, methodologic limitations of this evaluation challenge interpretation of the comparisons in birth weight, gestational age and 6-week growth outcomes between PrEP-exposed and PrEP-unexposed pregnancies.https://onlinelibrary.wiley.com/doi/10.1002/jia2.25435Publisher’s versio

Risk factors associated with the severity of pneumonia in a cohort of hospitalized children in a rural setting

Objectives: Pneumonia remains a leading cause of death in South African children under 5 years of age. Known risk factors for pneumonia have been the focus of public health strategies to mitigate disease. This study aimed to determine whether adverse household environmental factors were associated with severe compared to non-severe pneumonia in children admitted to Worcester Provincial Hospital (WPH), South Africa. Materials and Methods: We conducted a case–control study at WPH from January 1st to December 31st, 2019, including children aged 0–59 months admitted with pneumonia. Using the WHO definition, children were categorized as having severe or non-severe pneumonia. Structured interviews with consenting primary caregivers were conducted in both groups on weekdays throughout the year to collect demographic, social, maternal, infant, and household factors. We compared the odds of adverse household environmental factors including tobacco smoke exposure, indoor smoke exposure, and overcrowding in children with severe compared to non-severe pneumonia. Results: A total of 305 children were included, 134 (43.9%) cases with severe pneumonia and 171 (56.1%) controls with non-severe pneumonia. Baseline characteristics of children, including age (median 6.9 months; IQR 2.5–17.5), appropriate nutritional status (81.6%; n = 249), and HIV unexposed and uninfected status (81.3%; n = 248), were similar between groups. Caregiver characteristics, including age (median 28 years; IQR 23–33), secondary schooling (71.2%, n = 217), and HIV negative status (81%, n = 247), were also comparable between groups. There was no association in univariable or multivariable analysis between severe pneumonia and adverse household environmental factors including tobacco smoke exposure (aOR 0.73; 95% CI 0.44–1.21), overcrowding (aOR 0.65, 95% CI 0.39–1.08), and indoor smoke exposure (aOR 2.85; 95% CI 0.89–9.09). However, children with severe pneumonia had at least 5 times greater odds (aOR 5.42; 95% CI 1.10–26.65) of living in a household with a pit latrine toilet compared to any other toilet than children with non-severe pneumonia. Conclusion: Few factors were found to be associated with pneumonia severity, except for living in a household with a pit latrine toilet. This may represent socioeconomic vulnerability and the risk associated with developing severe pneumonia

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

CIHR canadian HIV trials network HIV workshop: ethical research through community participation and strengthening scientific validity

The CIHR canadian HIV trials network mandate includes strengthening capacity to conduct and apply clinical research through training and mentoring initiatives of HIV researchers by building strong networks and  partnerships on the African continent. At the17th International Conference on AIDS and Sexually Transmitted Infections in Africa (ICASA), the CTN facilitated a two-day workshop to address ethical issues in the conduct of HIV research, and career enhancing strategies for young African HIV researchers. Conference attendees were allowed to attend whichever session was of interest to them. We report on the topics covered, readings shared and participants’ evaluation of the workshop. The scientific aspects of ethical research in HIV and career enhancement strategies are relevant issues to conference attendees.Key words: Capacity building, ethics, HIV research, South Afric

Widening the lens to ensure children who are Human Immunodeficiency Virus (HIV) exposed are alive, HIV free, and thriving

CITATION: Slogrove, A. L. & Powis, K. M. 2021. Widening the Lens to Ensure Children Who Are Human Immunodeficiency Virus (HIV) Exposed Are Alive, HIV Free, and Thriving. Clinical infectious diseases, 72(4): 595–597. doi:10.1093/cid/ciaa079The original publication is available at https://academic.oup.com/cid/The “Start Free” component of the “Start Free Stay Free AIDS Free” framework, launched in 2016 by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the US President’s Emergency Plan for AIDS Relief (PEPFAR), aims to secure a human immunodeficiency virus (HIV)–free beginning for every child by ending new HIV infections among children [1]. Aligned with this, the Sustainable Development Goals challenge the global community to not only secure child survival, but ensure that children thrive and live transformative lives, contributing to societal transformation [2]. For the 1.3 million children born each year to women with HIV (ie, HIV exposed), this means doing more than ensuring an HIV-free start [3].https://academic.oup.com/cid/article/72/4/595/5715074?login=truePublishers versio

Recognition of infants at high risk for vertical HIV transmission at delivery in rural Western Cape Province, South Africa

Background. Despite South Africa’s substantial reduction in vertical HIV transmission (VHT), national paediatric HIV elimination is not yet attained. National and Western Cape Province (WC) HIV guidelines recommend enhanced postnatal prophylaxis for infants at high risk for VHT, identified in the WC 2015/2016 guidelines by any single high-risk criterion (maternal antiretroviral therapy (ART) <12 weeks, absent/ unsuppressed maternal HIV viral load (HIV-VL) <12 weeks before/including delivery, spontaneous preterm labour, prolonged rupture of membranes, chorioamnionitis). Accuracy of high-risk infant identification is unknown. Objectives. Primarily, to determine the proportion of infants at high risk for VHT, the accuracy of labour-ward risk classification, the criteria determining high-risk statuses and the criteria missed among unrecognised high-risk infants; secondarily, to determine maternal factors associated with high-risk infants. Methods. Infants born to women living with HIV at a rural regional hospital (May 2016 - April 2017) were retrospectively evaluated using data from the labour ward VHT register, standardised maternity case records, National Health Laboratory Service database and WC Provincial Health Data Centre. The study-derived risk status for each infant was determined using documented presence/absence of risk criteria and compared with labour ward assigned risk to determine accuracy. Proportions of high-risk and unrecognised high-risk infants with each high-risk criterion were determined. Maternal characteristics associated with having a high-risk infant were evaluated using multivariable logistic regression. Results. For liveborn infants, labour ward assigned risk classifications were 40% (n=75/188) high risk, 50% (n=94/188) low risk and 10% (n=19/188) unclassified. Study-derived risk was high risk for 69% (n=129/188) and low risk for 31% (n=59/188), yielding a high-risk classification sensitivity of 51% (95% confidence interval (CI) 42 - 60) and specificity of 69% (95% CI 56 - 80). Absent/unsuppressed HIVVL 4 antenatal visits (38% v. 81%, p<0.01) and first antenatal visit <20 weeks’ gestation (57% v. 77%, p=0.01). Only the number of antenatal visits remained associated with having a high-risk infant after adjusting for gestation at first visit and timing of HIV diagnosis and ART initiation: each additional antenatal visit conferred a 39% (95% CI 25 - 50) reduction in the odds of having a high-risk infant. Conclusion. Labour ward risk classification failed to recognise half of high-risk infants. Infant high-risk status as well as non-detection thereof were driven by suboptimal maternal HIV-VL monitoring. Reinforcing visit frequency later in pregnancy may improve antenatal HIV-VL monitoring, and point-of-care HIV-VL monitoring at delivery could improve recognition of virally unsuppressed mothers and their high-risk infant

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