Paediatric HIV-1 infection: updated strategies of prevention mother-to-child transmission

Lumaca, Alessandra; Galli, Luisa; Martino, Maurizio de; Chiappini, Elena

doi:10.1080/1120009x.2018.1451030

Cited by 8 publications

(6 citation statements)

References 56 publications

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“…All pregnant mothers should be screened for HIV in the first trimester: for infants born to mothers with unknown HIV status, a rapid HIV screening of mothers and/or infants should be performed as soon as possible, either during labor or after delivery, starting immediately the appropriate neonatal postexposure prophylaxis (PEP) if the test is positive [ 147 ].…”

Section: Human Immunodeficiency Virusmentioning

confidence: 99%

Pregnancy and viral infections: Mechanisms of fetal damage, diagnosis and prevention of neonatal adverse outcomes from cytomegalovirus to SARS-CoV-2 and Zika virus

Auriti

Rose

Santisi

et al. 2021

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Section: Human Immunodeficiency Virusmentioning

confidence: 99%

Pregnancy and viral infections: Mechanisms of fetal damage, diagnosis and prevention of neonatal adverse outcomes from cytomegalovirus to SARS-CoV-2 and Zika virus

Auriti

Rose

Santisi

et al. 2021

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…Prevention of mother-to-child human immunodeficiency virus (HIV) transmission during pregnancy, delivery, and breastfeeding by using antiretroviral therapy (ART) has proven to be extremely beneficial in reducing the number of new HIV-1 infections in children. − The antiretroviral (ARV) drug regimens used for pregnant women and neonates include nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), or integrase strand transcriptase inhibitors (INSTIs) with treatment frequency and duration dependent on the risk factors involved. , However, these treatments have their challenges with modulating metabolic pathways in both the mother and the newborn resulting in dyslipidemia, glucose intolerance, and abnormal mitochondrial function or adrenal dysfunction. − The PI ritonavir-boosted lopinavir regimen, also known as Kaletra, is used during pregnancy or as a prophylactic treatment for neonates and has been associated with premature birth and transient adrenal insufficiency in newborns. ,− Previous studies have shown elevated plasma concentrations of adrenal steroid hormones including 17α-hydroxy progesterone (17-OHP), dehydroepiandrosterone (DHEA), and dehydroepiandrosterone 3-sulfate (DHEA-S) in neonates receiving the Kaletra treatment (Figure ). ,, Several hypotheses regarding the mechanism of adrenal hormonal imbalance and the associated life-threatening symptoms observed in newborns subjected to Kaletra therapy have been proposed.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of CYP3A7 DHEA-S Oxidation by Lopinavir and Ritonavir: An Alternative Mechanism for Adrenal Impairment in HIV Antiretroviral-Treated Neonates

Kandel

Lampe

2021

Chem. Res. Toxicol.

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Prophylactic antiretroviral therapy (ART) in HIV infected pregnant mothers and their newborns can dramatically reduce mother-to-child viral transmission and seroconversion in the neonate. The ritonavir-boosted lopinavir regimen, known as Kaletra, has been associated with premature birth and transient adrenal insufficiency in newborns, accompanied by increases in plasma dehydroepiandrosterone 3-sulfate (DHEA-S). In the fetus and neonates, cytochrome P450 CYP3A7 is responsible for the metabolism of DHEA-S into 16α-hydroxy DHEA-S, which plays a critical role in growth and development. In order to determine if CYP3A7 inhibition could lead to the adverse outcomes associated with Kaletra therapy, we conducted in vitro metabolic studies to determine the extent and mechanism of CYP3A7 inhibition by both ritonavir and lopinavir and the relative intrinsic clearance of lopinavir with and without ritonavir in both neonatal and adult human liver microsomes (HLMs). We identified ritonavir as a potent inhibitor of CYP3A7 oxidation of DHEA-S (IC 50 = 0.0514 μM), while lopinavir is a much weaker inhibitor (IC 50 = 5.88 μM). Furthermore, ritonavir is a time-dependent inhibitor of CYP3A7 with a K I of 0.392 μM and a k inact of 0.119 min –1 , illustrating the potential for CYP3A mediated drug–drug interactions with Kaletra. The clearance rate of lopinavir in neonatal HLMs was much slower and comparable to the rate observed in adult HLMs in the presence of ritonavir, suggesting that the addition of ritonavir in the cocktail therapy may not be necessary to maintain effective concentrations of lopinavir in neonates. Our results suggest that several of the observed adverse outcomes of Kaletra therapy may be due to the direct inhibition of CYP3A7 by ritonavir and that the necessity for the inclusion of this drug in the therapy may be obviated by the lower rate of lopinavir clearance in the neonatal liver. These results may lead to a reconsideration of the use of ritonavir in neonatal antiretroviral therapy.

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“…In a cross-sectional study conducted on HIV-exposed infants, Yitayew et al [30] reported that ARV drugs given to the mother during pregnancy and the administration of an ARV prophylaxis to the infant was the two most significant factors in avoiding perinatal HIV transmission. In a systematic review, Lumaca et al [31] reported that an optimal ART regimen and the use of intrapartum ZDV for pregnant women are recommended to reduce perinatal HIV transmission. One mother in this study who gave birth at another hospital received an intrapartum prophylaxis with IV ZDV.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of infants with HIV infected mothers and perinatal transmission in Turkey: A single-center experience

Yakut

Kepenekli

2021

North Clin Istanbul

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A ccording to data from the Joint United Nations Program on HIV/AIDS (UNAIDS), 36.7 million people worldwide are infected with HIV and 1.8 million are newly diagnosed [1]. The first AIDS case was reported in Turkey in 1985. The Turkish Ministry of Health reports that in Turkey, there are 21,988 patients with a diagnosis of HIV or AIDS and that 718 of these people are children or adolescents [2]. Perinatal transmission, also known as vertical or motherto-child transmission, is the main route of HIV infection in children. It is estimated that there are 2 million children living with HIV infection worldwide [3]. Pediatric HIV infection can occur during pregnancy, delivery, or breastfeeding. The rate of transmission without intervention ranges from 15% to 35% [4,5]. However, perinatal transmission of HIV can be prevented by taking precautions in the perinatal period, and the probability of transmission can be reduced to below 2% with plasma HIV viral load suppression [6,7]. Prevention of perinatal transmission of HIV is possible using the following measures: Antiretroviral therapy (ART) throughout the pregnancy, cesarean ABSTRACT OBJECTIVE: The most common route of HIV infection in children is through perinatal transmission. In this study, we aimed to evaluate the characteristics of infants with HIV-infected mothers and perinatal HIV transmission. METHODS:We conducted a retrospective, single-center study of HIV-exposed infants in between December 2017 and October 2019 in a Marmara University Pendik Training and Research Hospital. RESULTS:A total of 18 infants were examined. All babies were born by cesarean section, and none of them were breastfed. Seventeen mothers were diagnosed with HIV before pregnancy. These mothers had received antiretroviral therapy (ART) during pregnancy, and their viral loads before delivery were negative. An antiretroviral prophylaxis with oral zidovudine was started in all infants within their 1 st day of birth and continued for at least 6 weeks. All infants were tested for their HIV viral load within the first 48 h of birth, with negative results, and 12 infants were tested for anti-HIV antibodies at the 18 th month, again with negative results. In this study, we determined that none of the infants had been infected with HIV. CONCLUSION:Our findings highlight the importance of initiating ART for all HIV-infected pregnant women and the importance of protection modalities during pregnancy, delivery, and the postnatal period for the prevention of perinatal transmission of HIV.

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Paediatric HIV-1 infection: updated strategies of prevention mother-to-child transmission

Cited by 8 publications

References 56 publications

Pregnancy and viral infections: Mechanisms of fetal damage, diagnosis and prevention of neonatal adverse outcomes from cytomegalovirus to SARS-CoV-2 and Zika virus

Pregnancy and viral infections: Mechanisms of fetal damage, diagnosis and prevention of neonatal adverse outcomes from cytomegalovirus to SARS-CoV-2 and Zika virus

Inhibition of CYP3A7 DHEA-S Oxidation by Lopinavir and Ritonavir: An Alternative Mechanism for Adrenal Impairment in HIV Antiretroviral-Treated Neonates

Evaluation of infants with HIV infected mothers and perinatal transmission in Turkey: A single-center experience

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