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Background: Pregnancy and polymorphisms in drug disposition genes alter the clearance of key antiretrovirals used as part of regimens for prevention of mother-to-child transmission of HIV (PMTCT). The clinical significance of these in women initiating therapy late in pregnancy has not been investigated. The primary objective of the Viral and Antiretroviral Dynamics in HIV Mother-To-Child Transmission Fluids (VADICT) study is to investigate viral and antiretroviral dynamics in matrices associated with mother-to-child transmission (MTCT) (plasma, genital fluid and breastmilk) in women (stratified by CYP2B6 genotypes) who initiate antiretroviral therapy (ART) before or early in pregnancy versus late in pregnancy or early postpartum. Methods: A cohort of HIV-1 infected women who initiated ART containing 600 mg efavirenz before or early in pregnancy (n = 120), during the third trimester (n = 60), or early postpartum (n = 60) will be studied.  Eligible patients will be recruited from four hospitals in Benue State, North Central Nigeria and followed until the end of breastfeeding. Procedures at follow up visits will include sample collection for drug quantification and HIV-1 RNA and DNA in plasma, genital fluid and breastmilk; adherence monitoring; and newborn and infant assessment. Using newborn exposure to maternal efavirenz at birth for validation, prenatal pharmacogenetics of efavirenz will be explored using physiologically-based pharmacokinetic modelling. Three integrated methods will be used to monitor patterns and correlates of adherence across pregnancy and the breastfeeding period. A population pharmacokinetic-pharmacodynamic model will be developed to describe the observed data and simulate what to expect in women initiating ART containing 400 mg efavirenz (recently approved for non-pregnant adults) late in pregnancy or early postpartum. Discussion: This study will help in understanding residual MTCT in women receiving ART and reasons for the rise in MTCT risk during the breastfeeding period. Trial registration: ClinicalTrials.gov: NCT03284645 (15/09/2017)

The COVID-19 pandemic is disrupting health systems globally. Maternity care disruptions have been surveyed, but not those related to vulnerable small newborns. We aimed to survey reported disruptions to small and sick newborn care worldwide and undertake thematic analysis of healthcare providers' experiences and proposed mitigation strategies. Using a widely disseminated online survey in three languages, we reached out to neonatal healthcare providers. We collected data on COVID-19 preparedness, effects on health personnel and on newborn care services, including kangaroo mother care (KMC), as well as disruptors and solutions. We analysed 1120 responses from 62 countries, mainly low and middle-income countries (LMICs). Preparedness for COVID-19 was suboptimal in terms of guidelines and availability of personal protective equipment. One-third reported routine testing of all pregnant women, but 13% had no testing capacity at all. More than 85% of health personnel feared for their own health and 89% had increased stress. Newborn care practices were disrupted both due to reduced care-seeking and a compromised workforce. More than half reported that evidence-based interventions such as KMC were discontinued or discouraged. Separation of the mother-baby dyad was reported for both COVID-positive mothers (50%) and those with unknown status (16%). Follow-up care was disrupted primarily due to families' fear of visiting hospitals (~73%). Newborn care providers are stressed and there is lack clarity and guidelines regarding care of small newborns during the pandemic. There is an urgent need to protect life-saving interventions, such as KMC, threatened by the pandemic, and to be ready to recover and build back better.

BackgroundCOVID-19 is disrupting health services for mothers and newborns, particularly in low- and middle-income countries (LMIC). Preterm newborns are particularly vulnerable. We undertook analyses of the benefits of kangaroo mother care (KMC) on survival among neonates weighing ≤2000 g compared with the risk of SARS-CoV-2 acquired from infected mothers/caregivers.MethodsWe modelled two scenarios over 12 months. Scenario 1 compared the survival benefits of KMC with universal coverage (99%) and mortality risk due to COVID-19. Scenario 2 estimated incremental deaths from reduced coverage and complete disruption of KMC. Projections were based on the most recent data for 127 LMICs (~90% of global births), with results aggregated into five regions.FindingsOur worst-case scenario (100% transmission) could result in 1,950 neonatal deaths from COVID-19. Conversely, 125,680 neonatal lives could be saved with universal KMC coverage. Hence, the benefit of KMC is 65-fold higher than the mortality risk of COVID-19. If recent evidence of 10% transmission was applied, the ratio would be 630-fold. We estimated a 50% reduction in KMC coverage could result in 12,570 incremental deaths and full disruption could result in 25,140 incremental deaths, representing a 2·3-4·6% increase in neonatal mortality across the 127 countries.InterpretationThe survival benefit of KMC far outweighs the small risk of death due to COVID-19. Preterm newborns are at risk, especially in LMICs where the consequences of disruptions are substantial. Policymakers and healthcare professionals need to protect services and ensure clearer messaging to keep mothers and newborns together, even if the mother is SARS-CoV-2-positive.FundingEunice Kennedy Shriver National Institute of Child Health & Human Development; Bill & Melinda Gates Foundation; Elma Philanthropies; Wellcome Trust; and Joint Global Health Trials scheme of Department of Health and Social Care, Department for International Development, Medical Research Council, and Wellcome Trust.

Background: Pregnancy and polymorphisms in drug disposition genes alter the clearance of key antiretrovirals used as part of regimens for prevention of mother-to-child transmission of HIV (PMTCT). The clinical significance of these in women initiating therapy late in pregnancy has not been investigated. The primary objective of the Viral and Antiretroviral Dynamics in HIV Mother-To-Child Transmission Fluids (VADICT) study is to investigate viral and antiretroviral dynamics in matrices associated with mother-to-child transmission (MTCT) (plasma, genital fluid and breastmilk) in women (stratified by CYP2B6 genotypes) who initiate antiretroviral therapy (ART) before or early in pregnancy versus late in pregnancy or early postpartum. Methods: A cohort of HIV-1 infected women who initiated ART containing 600 mg efavirenz before or early in pregnancy (n = 120), during the third trimester (n = 60), or early postpartum (n = 60) will be studied.  Eligible patients will be recruited from four hospitals in Benue State, North Central Nigeria and followed until the end of breastfeeding. Procedures at follow up visits will include sample collection for drug quantification and HIV-1 RNA and DNA in plasma, genital fluid and breastmilk; adherence monitoring; and newborn and infant assessment. Using newborn exposure to maternal efavirenz at birth for validation, prenatal pharmacogenetics of efavirenz will be explored using physiologically-based pharmacokinetic modelling. Three integrated methods will be used to monitor patterns and correlates of adherence across pregnancy and the breastfeeding period. A population pharmacokinetic-pharmacodynamic model will be developed to describe the observed data and simulate what to expect in women initiating ART containing 400 mg efavirenz (recently approved for non-pregnant adults) late in pregnancy or early postpartum. Discussion: This study will help in understanding residual MTCT in women receiving ART and reasons for the rise in MTCT risk during the breastfeeding period. Trial registration: ClinicalTrials.gov: NCT03284645 (15/09/2017)