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

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

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

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

Unmasking the vulnerabilities of uninfected children exposed to HIV

Although programmes to reduce vertical transmission of HIV mean fewer children are acquiring HIV, more needs to be done to understand the longer term outcomes of exposure.http://www.bmj.com/thebmjPaediatrics and Child Healt

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

The epidemiology of adolescents living with perinatally acquired HIV: A cross-region global cohort analysis

Background Globally, the population of adolescents living with perinatally acquired HIV (APHs) continues to expand. In this study, we pooled data from observational pediatric HIV cohorts and cohort networks, allowing comparisons of adolescents with perinatally acquired HIV in “real-life” settings across multiple regions. We describe the geographic and temporal characteristics and mortality outcomes of APHs across multiple regions, including South America and the Caribbean, North America, Europe, sub-Saharan Africa, and South and Southeast Asia. Methods and findings Through the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER), individual retrospective longitudinal data from 12 cohort networks were pooled. All children infected with HIV who entered care before age 10 years, were not known to have horizontally acquired HIV, and were followed up beyond age 10 years were included in this analysis conducted from May 2016 to January 2017. Our primary analysis describes patient and treatment characteristics of APHs at key time points, including first HIV-associated clinic visit, antiretroviral therapy (ART) start, age 10 years, and last visit, and compares these characteristics by geographic region, country income group (CIG), and birth period. Our secondary analysis describes mortality, transfer out, and lost to follow-up (LTFU) as outcomes at age 15 years, using competing risk analysis. Among the 38,187 APHs included, 51% were female, 79% were from sub-Saharan Africa and 65% lived in low-income countries. APHs from 51 countries were included (Europe: 14 countries and 3,054 APHs; North America: 1 country and 1,032 APHs; South America and the Caribbean: 4 countries and 903 APHs; South and Southeast Asia: 7 countries and 2,902 APHs; sub-Saharan Africa, 25 countries and 30,296 APHs). Observation started as early as 1982 in Europe and 1996 in sub-Saharan Africa, and continued until at least 2014 in all regions. The median (interquartile range [IQR]) duration of adolescent follow-up was 3.1 (1.5–5.2) years for the total cohort and 6.4 (3.6–8.0) years in Europe, 3.7 (2.0–5.4) years in North America, 2.5 (1.2–4.4) years in South and Southeast Asia, 5.0 (2.7–7.5) years in South America and the Caribbean, and 2.1 (0.9–3.8) years in sub-Saharan Africa. Median (IQR) age at first visit differed substantially by region, ranging from 0.7 (0.3–2.1) years in North America to 7.1 (5.3–8.6) years in sub-Saharan Africa. The median age at ART start varied from 0.9 (0.4–2.6) years in North America to 7.9 (6.0–9.3) years in sub-Saharan Africa. The cumulative incidence estimates (95% confidence interval [CI]) at age 15 years for mortality, transfers out, and LTFU for all APHs were 2.6% (2.4%–2.8%), 15.6% (15.1%–16.0%), and 11.3% (10.9%–11.8%), respectively. Mortality was lowest in Europe (0.8% [0.5%–1.1%]) and highest in South America and the Caribbean (4.4% [3.1%–6.1%]). However, LTFU was lowest in South America and the Caribbean (4.8% [3.4%–6.7%]) and highest in sub-Saharan Africa (13.2% [12.6%–13.7%]). Study limitations include the high LTFU rate in sub-Saharan Africa, which could have affected the comparison of mortality across regions; inclusion of data only for APHs receiving ART from some countries; and unavailability of data from high-burden countries such as Nigeria. Conclusion To our knowledge, our study represents the largest multiregional epidemiological analysis of APHs. Despite probable under-ascertained mortality, mortality in APHs remains substantially higher in sub-Saharan Africa, South and Southeast Asia, and South America and the Caribbean than in Europe. Collaborations such as CIPHER enable us to monitor current global temporal trends in outcomes over time to inform appropriate policy responses

The pattern and pathways of infectious morbidity in South African HIV exposed uninfected infants

Background: Universal infant morbidity risk factors (poor birth outcomes, suboptimal breastfeeding, poverty) occur more frequently in HIV exposed uninfected (HEU) than HIV unexposed uninfected (HUU) infants. HEU infants’ unique exposures, including in utero exposure to HIV products and maternal immune compromise, may potentiate HEU infants’ infectious morbidity risk. The primary objective was to determine whether HEU infants experience greater infectious morbidity than HUU infants through HIV exposure-specific pathways beyond universal infant morbidity risk factors. Methods: This prospective cohort study identified low risk HIV-infected and HIV-uninfected mothers and their term newborns from a single community midwife unit in Kraaifontein, South Africa. The primary outcome, at least one infectious cause hospitalization or death before six months of age, was classified according to modified WHO case-definitions and compared between HEU and HUU infants. Complete outcome determination on all infants was possible through linkage with the electronic provincial hospital administration system and mortality registry. Adjusted odds ratios (aOR) were calculated by multivariable logistic regression including stratified analyses conditioned on breastfeeding. Results: One hundred and seventy six (94 HEU, 82 HUU) mother-infant pairs were included. HIV-infected mothers were older (median 27.8 vs. 24.7 years, p<0.01) and HEU infants less often breastfed (35/94 (37%) vs. 81/82 (99%), p<0.001). The groups were similar on maternal education, antenatal course, household characteristics, birth weight, gestational age and immunizations. Incidence rate ratio of all-cause sick clinic visits in HEU compared to HUU infants was 0.82 (95% CI 0.58,1.16). The primary outcome occurred in 17 (18%) HEU and 10 (12%) HUU infants (p=0.38), giving an aOR of 1.45 (95% CI 0.44,4.55). In stratified analysis comparing only infants with any breastfeeding, HEU infants had an aOR for a very severe infectious cause hospitalization or death of 4.2 (95% CI 1.00,19.2, p=0.05). Seven of 17(41%) HEU and 1/10 (10%) HUU primary outcome events occurred after 90 days of age (p=0.07). Conclusion: Amongst term infants with similar social circumstances, a higher probability of very severe infectious morbidity was observed in breastfed HEU compared to breastfed HUU infants. HEU infant risk may be driven through HIV exposure-specific pathways unrelated to universal infant morbidity risk factors.Medicine, Faculty ofPopulation and Public Health (SPPH), School ofGraduat

HIV exposed uninfected (HEU) infants with excess infectious morbidity

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Antiretroviral and Antituberculosis therapy in HIV-TB co-infected children

HIV-infected children experience a high burden of tuberculosis. With recent advances in international pediatric HIV treatment guidelines significant numbers of infants and children will require simultaneous treatment for both TB and HIV. This article attempts to concisely outline strategies for effective co-treatment of both infections. Rifamycins, an essential component of short course TB chemotherapy, alter the metabolism of a number of antiretroviral drugs. These interactions and their consequences are considered. Options for antiretroviral therapy and the optimal timing of its initiation in the presence of antituberculosis therapy are discussed. © 2011 Bentham Science Publishers Ltd.Revie