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1.
Pharmacokinetics of HIV-Integrase Inhibitors During Pregnancy: Mechanisms, Clinical Implications and Knowledge Gaps.
van der Galiën, R, Ter Heine, R, Greupink, R, Schalkwijk, SJ, van Herwaarden, AE, Colbers, A, Burger, DM
Clinical pharmacokinetics. 2019;(3):309-323
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Abstract
Prevention of mother-to-child transmission of HIV and optimal maternal treatment are the most important goals of antiretroviral therapy in pregnant women with HIV. These goals may be at risk due to possible reduced exposure during pregnancy caused by physiological changes. Limited information is available on the impact of these physiological changes. This is especially true for HIV-integrase inhibitors, a relatively new class of drugs, recommended first-line agents and hence used by a large proportion of HIV-infected patients. Therefore, the objective of this review is to provide a detailed overview of the pharmacokinetics of HIV-integrase inhibitors in pregnancy. Second, this review defines potential causes for the change in pharmacokinetics of HIV-integrase inhibitors during pregnancy. Despite increased clearance, for raltegravir 400 mg twice daily and dolutegravir 50 mg once daily, exposure during pregnancy seems adequate; however, for elvitegravir, the proposed minimal effective concentration is not reached during pregnancy. Lower exposure to these drugs may be caused by increased hormone levels and, subsequently, enhanced drug metabolism during pregnancy. The pharmacokinetics of bictegravir and cabotegravir, which are under development, have not yet been evaluated in pregnant women. New studies need to prospectively assess whether adequate exposure is reached in pregnant women using these new HIV-integrase inhibitors. To further optimize antiretroviral treatment in pregnant women, studies need to unravel the underlying mechanisms behind the changes in the pharmacokinetics of HIV-integrase inhibitors during pregnancy. More knowledge on altered pharmacokinetics during pregnancy and the underlying mechanisms contribute to the development of effective and safe antiretroviral therapy for HIV-infected pregnant women.
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Pre-exposure prophylaxis for HIV prevention during pregnancy and lactation: forget not the women and children.
Horgan, L, Blyth, CC, Bowen, AC, Nolan, DA, McLean-Tooke, AP
The Medical journal of Australia. 2019;(6):281-284
Abstract
Pregnancy is known to be a time of increased susceptibility to acquiring to human immunodeficiency virus (HIV) infection and this increased maternal risk places the unborn child at risk of vertical transmission. Pre-exposure prophylaxis (PrEP) involves the provision of antiretroviral therapy to an HIV-negative individual with ongoing risk of HIV exposure to limit the likelihood of HIV transmission. The inclusion of PrEP as part of a comprehensive strategy is recognised as an effective and safe means of reducing HIV infection in serodiscordant couples, thereby reducing the risk of vertical transmission of HIV. Current data suggest that PrEP is safe to continue during pregnancy and breastfeeding in HIV-negative women who remain vulnerable to acquiring HIV. The recent Pharmaceutical Benefits Scheme subsidisation of PrEP has reduced the financial and practical obstacles of PrEP provision, and a subsequent increase in patient awareness and acceptance of PrEP is expected. The framework for appropriately identifying and managing at-risk pregnant and lactating women requiring PrEP is poorly defined and warrants further clarification to better support clinicians and this patient group. This review discusses the current recommendations highlighting the gaps in the guidelines and makes some recommendations for future guideline development.
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Microbial transmission from mother to child: improving infant intestinal microbiota development by identifying the obstacles.
Van Daele, E, Knol, J, Belzer, C
Critical reviews in microbiology. 2019;(5-6):613-648
Abstract
Industrialisation has introduced several lifestyle changes and medical advancements but their impact on intestinal microbiota acquisition is often overlooked. Even though these consequential changes in the microbiota could contribute to the disease burden that accompanies industrialisation, such as obesity and atopic disease. A healthy intestinal microbiota is acquired early in life but its exact origin is not fully elucidated. The maternal microbiota is a likely source because the infant and mother intestinal microbiota share identical strains. Successfully transmitting microbes from mother to child requires microbes in the maternal donor, contact between the maternal source and the infant, and an acquiring infant recipient. Transmission can be altered by changes to any of those three transmission determinants: (1) maternal microbiota sources are shaped by the mother's genotype, diet, health status and perturbing antimicrobial exposure; (2) maternal contact is reduced through C-section and formula feeding and (3) engraftment in the infant recipient is determined by host habitat filtering, the established microbes and antibiotic disruptions. This review gives an overview of the possible maternal transmission routes, the disruptions thereof, and the missing links that should be addressed in future research to investigate the maternal transmissions that are crucial for obtaining a healthy infant microbiota.
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4.
Management Algorithm for Interrupting Mother-to-Child Transmission of Hepatitis B Virus.
Hou, J, Cui, F, Ding, Y, Dou, X, Duan, Z, Han, G, Jia, J, Mao, Q, Li, J, Li, Z, et al
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2019;(10):1929-1936.e1
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Abstract
In areas where hepatitis B virus (HBV) is endemic, mother-to-child transmission (MTCT) is the major route of infection of children. Blocking MTCT of HBV therefore would reduce its prevalence. The China Foundation of Hepatitis Prevention and Control organized a team of specialists in infectious diseases, hepatology, immunology, obstetrics, and public health to develop an algorithm for interrupting MTCT of HBV, based on the most recent hepatitis B guidelines and latest evidence. This algorithm comprises 10 steps and has been adopted in clinical practice in China. Four aspects (screening, antiviral intervention during pregnancy, immunoprophylaxis, and postvaccination serologic testing) are the core components of preventing MTCT. Although the combination of passive and active immunization in newborns of hepatitis B surface antigen-positive mothers reduces MTCT of HBV, this immunoprophylaxis cannot completely eradicate MTCT. In the past decade, administration of antiviral agents to pregnant women has been shown to be safe and effective in reducing MTCT of HBV in combination with immunoprophylaxis. Aiming to achieve zero MTCT, this algorithm recommends the use of antivirals during pregnancy by women with high viral loads. Preventing MTCT is key to achieving the goal of eliminating HBV as a public health threat by 2030. Implementation and enhancement of the standardized algorithm for pregnant women with chronic HBV infection and their infants is urgently needed to prevent MTCT.
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Does U=U for breastfeeding mothers and infants? Breastfeeding by mothers on effective treatment for HIV infection in high-income settings.
Waitt, C, Low, N, Van de Perre, P, Lyons, F, Loutfy, M, Aebi-Popp, K
The lancet. HIV. 2018;(9):e531-e536
Abstract
Can the campaign Undetectable=Untransmittable (U=U), established for the sexual transmission of HIV, be applied to the transmission of HIV through breastfeeding? European AIDS Clinical Society and, to some extent, American guidelines now state that mothers with HIV who wish to breastfeed should be supported, with increased clinical and virological monitoring. This Viewpoint summarises existing evidence on transmission of HIV through breastfeeding, differences in HIV dynamics and viral load between breastmilk and plasma, and the effects of antiretroviral therapy on infants. At present, insufficient evidence exists to make clear recommendations for the required frequency of clinical and virological monitoring for mother and infant in a breastfeeding relationship or for the action to be taken in the event of viral rebound. We propose a roadmap for collaborative research to provide the missing evidence required to enable mothers who wish to breastfeed to make a fully informed choice.
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6.
Ebola Infection in Pregnancy: A Global Perspective and Lessons Learned.
Haddad, LB, Horton, J, Ribner, BS, Jamieson, DJ
Clinical obstetrics and gynecology. 2018;(1):186-196
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Abstract
The 2014 to 2016 Ebola outbreak, primarily based in 3 West African countries, had far-reaching global effects. Importantly, the crisis highlighted large gaps in reproductive health services in affected countries and inadequate health care system preparedness for obstetrical patients in the setting of highly contagious infectious diseases. We aim to review Ebola virus effects with a focus on the obstetrical implications in the context of this recent Ebola outbreak, discuss the lessons learned following this outbreak and propose current measures specific to obstetrics that should be considered in preparation for the next concerning emergent infectious disease.
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Vitamin A supplements for reducing mother-to-child HIV transmission.
Wiysonge, CS, Ndze, VN, Kongnyuy, EJ, Shey, MS
The Cochrane database of systematic reviews. 2017;(9):CD003648
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Abstract
BACKGROUND Strategies to reduce the risk of mother-to-child transmission of the human immunodeficiency virus (HIV) include lifelong antiretroviral therapy (ART) for HIV-positive women, exclusive breastfeeding from birth for six weeks plus nevirapine or replacement feeding plus nevirapine from birth for four to six weeks, elective Caesarean section delivery, and avoiding giving children chewed food. In some settings, these interventions may not be practical, feasible, or affordable. Simple, inexpensive, and effective interventions (that could potentially be implemented even in the absence of prenatal HIV testing programmes) would be valuable. Vitamin A, which plays a role in immune function, is one low-cost intervention that has been suggested in such settings. OBJECTIVES To summarize the effects of giving vitamin A supplements to HIV-positive women during pregnancy and after delivery. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) up to 25 August 2017, and checked the reference lists of relevant articles for eligible studies. SELECTION CRITERIA We included randomized controlled trials conducted in any setting that compared vitamin A supplements to placebo or no intervention among HIV-positive women during pregnancy or after delivery, or both. DATA COLLECTION AND ANALYSIS At least two review authors independently assessed study eligibility and extracted data. We expressed study results as risk ratios (RR) or mean differences (MD) as appropriate, with their 95% confidence intervals (CI), and conducted random-effects meta-analyses. This is an update of a review last published in 2011. MAIN RESULTS Five trials met the inclusion criteria. These were conducted in Malawi, South Africa, Tanzania, and Zimbabwe between 1995 and 2005 and none of the participants received ART. Women allocated to intervention arms received vitamin A supplements at a variety of doses (daily during pregnancy; a single dose immediately after delivery, or daily doses during pregnancy plus a single dose after delivery). Women allocated to comparison arms received identical placebo (6601 women, 4 trials) or no intervention (697 women, 1 trial). Four trials (with 6995 women) had low risk of bias and one trial (with 303 women) had high risk of attrition bias.The trials show that giving vitamin A supplements to HIV-positive women during pregnancy, the immediate postpartum period, or both, probably has little or no effect on mother-to-child transmission of HIV (RR 1.07, 95% CI 0.91 to 1.26; 4428 women, 5 trials, moderate certainty evidence) and may have little or no effect on child death by two years of age (RR 1.06, 95% CI 0.92 to 1.22; 3883 women, 3 trials, low certainty evidence). However, giving vitamin A supplements during pregnancy may increase the mean birthweight (MD 34.12 g, 95% CI -12.79 to 81.02; 2181 women, 3 trials, low certainty evidence) and probably reduces the incidence of low birthweight (RR 0.78, 95% CI 0.63 to 0.97; 1819 women, 3 trials, moderate certainty evidence); but we do not know whether vitamin A supplements affect the risk of preterm delivery (1577 women, 2 trials), stillbirth (2335 women, 3 trials), or maternal death (1267 women, 2 trials). AUTHORS' CONCLUSIONS Antepartum or postpartum vitamin A supplementation, or both, probably has little or no effect on mother-to-child transmission of HIV in women living with HIV infection and not on antiretroviral drugs. The intervention has largely been superseded by ART which is widely available and effective in preventing vertical transmission.
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[Mother-to-child transmission of hepatitis B virus despite postexposure prophylaxis: A review of the literature and description of 11 observations].
Biot, B, Laverdure, N, Lacaille, F, Lachaux, A
Archives de pediatrie : organe officiel de la Societe francaise de pediatrie. 2017;(2):135-139
Abstract
Chronic hepatitis B virus (HBV) infection leads to a risk of developing cirrhosis and hepatocellular carcinoma. In France, where the prevalence of HBV is low, mother-to-child transmission is the cause of chronic infection in more than one-third of cases. After exposure, the risk of chronic infection is the highest for newborns (90 %). The World Health Organization implemented a global immunization program in 1991, applied in France in 1994. A significant number of children are infected each year, however, and failure of postexposure prophylaxis is reported in 4-10 % of newborns. We report 11 children with chronic HBV infection due to failure of serovaccination, followed up in two centers between 1993 and 2015. We discuss maternal screening, serovaccination, and follow-up conditions, as well as the role of maternal viral load, amniocentesis, and mode of delivery as risk factors. These observations confirm that serovaccination failures are related to the nonobservance of recommendations for maternal screening or postexposure prophylaxis, and to a high maternal viral load (>106 copies/mL). We therefore recommend improving the screening strategy, with control of the hepatitis B antigen in early pregnancy, and discussion of treatment with a nucleoside analog during the last trimester of pregnancy. Serovaccination should be enforced. Its efficacy should be controlled when the child reaches 9 months of age, in order to organize the follow-up if infection occurs.
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Postnatal Cytomegalovirus Infection Through Human Milk in Preterm Infants: Transmission, Clinical Presentation, and Prevention.
Hamprecht, K, Goelz, R
Clinics in perinatology. 2017;(1):121-130
Abstract
Cytomegalovirus (CMV) is reactivated in the lactating breast in up to 96% of CMV seropositive mothers. There is a relevant entity of postnatally acquired symptomatic CMV infection and disease of preterm infants through raw breast milk (BM). Actual data support negative influence on long-term cognitive development. Concerning prevention, only heat inactivation eliminates virus infectivity, and short-term heat inactivation is most preservative; this can be applied effectively under routine conditions. Short-term heat inactivation for 5 minutes at 62°C maintains the benefits of feeding BM without the disadvantages of CMV transmission.
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Advances in therapy for the prevention of HIV transmission from mother to child.
Moretton, MA, Bertera, F, Lagomarsino, E, Riedel, J, Chiappetta, DA, Höcht, C
Expert opinion on pharmacotherapy. 2017;(7):657-666
Abstract
Actually, ~17.8 million women and 1.8 million children (<15 years) are currently infected with the Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS). Particularly, the majority of pediatric infections (>90%) resulted from 'HIV mother-to-child transmission' (MTCT), both in pregnancy, labour, delivery and later by breastfeeding. Due to its high pediatric incidence, MTCT represents a public health concern. Areas covered: In this review, we focus on available treatments and antiretroviral drugs recommended by the World Health Organization, and the main clinical investigations in antiretroviral pharmacotherapy to prevent the MTCT. Expert opinion: The MTCT has been improved dramatically in the last few years mainly due to prophylactic perinatal antiretroviral therapy for pregnant women living with HIV. However, there is still a milestone to reach since HIV MTCT remains as a public health challenge associated with MTCT though breastfeeding (post-natal transmission). In this context, different strategies could be employed as an attempt to reduce pediatric HIV infections. One of them involves the improvement of patient adherence to the HIV therapy. One possible solution is the development of novel long-acting formulations for prophylaxis of mothers and children, and a second possible solution is increase the inclusion of mothers and infants in care programs to more effectively prevent the vertical transmission.