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Costa B, Gouveia MJ, Vale N. Safety and Efficacy of Antiviral Drugs and Vaccines in Pregnant Women: Insights from Physiologically Based Pharmacokinetic Modeling and Integration of Viral Infection Dynamics. Vaccines (Basel) 2024; 12:782. [PMID: 39066420 PMCID: PMC11281481 DOI: 10.3390/vaccines12070782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2024] [Revised: 07/11/2024] [Accepted: 07/15/2024] [Indexed: 07/28/2024] Open
Abstract
Addressing the complexities of managing viral infections during pregnancy is essential for informed medical decision-making. This comprehensive review delves into the management of key viral infections impacting pregnant women, namely Human Immunodeficiency Virus (HIV), Hepatitis B Virus/Hepatitis C Virus (HBV/HCV), Influenza, Cytomegalovirus (CMV), and SARS-CoV-2 (COVID-19). We evaluate the safety and efficacy profiles of antiviral treatments for each infection, while also exploring innovative avenues such as gene vaccines and their potential in mitigating viral threats during pregnancy. Additionally, the review examines strategies to overcome challenges, encompassing prophylactic and therapeutic vaccine research, regulatory considerations, and safety protocols. Utilizing advanced methodologies, including PBPK modeling, machine learning, artificial intelligence, and causal inference, we can amplify our comprehension and decision-making capabilities in this intricate domain. This narrative review aims to shed light on diverse approaches and ongoing advancements, this review aims to foster progress in antiviral therapy for pregnant women, improving maternal and fetal health outcomes.
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Affiliation(s)
- Bárbara Costa
- PerMed Research Group, Center for Health Technology and Services Research (CINTESIS), 4200-450 Porto, Portugal;
- CINTESIS@RISE, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
- Department of Community Medicine, Health Information and Decision (MEDCIDS), Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
- Centre for Parasite Biology and Immunology, Department of Infectious Diseases, National Health Institute Dr. Ricardo Jorge, 4000-055 Porto, Portugal;
| | - Maria João Gouveia
- Centre for Parasite Biology and Immunology, Department of Infectious Diseases, National Health Institute Dr. Ricardo Jorge, 4000-055 Porto, Portugal;
- Center for the Study in Animal Science (CECA/ICETA), University of Porto, 4051-401 Porto, Portugal
| | - Nuno Vale
- PerMed Research Group, Center for Health Technology and Services Research (CINTESIS), 4200-450 Porto, Portugal;
- CINTESIS@RISE, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
- Department of Community Medicine, Health Information and Decision (MEDCIDS), Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
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Zappulo E, Giaccone A, Schiano Moriello N, Gentile I. Pharmacological approaches to prevent vertical transmission of HIV and HBV. Expert Rev Clin Pharmacol 2022; 15:863-876. [PMID: 35876100 DOI: 10.1080/17512433.2022.2105202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Mother-to-child transmission (MTCT) is mainly responsible for the global pediatric HIV and HBV epidemic. Vertical transmission can be prevented and reduced through a series of interventions at the primary healthcare level, including extensive screening of pregnant women, administration of antivirals or immune-based treatments, counselling on type of delivery and breastfeeding. AREAS COVERED In this narrative review, approved therapeutic options for the treatment of pregnant women living with HIV or HBV are discussed with special focus on efficacy and safety profiles of each agent or drug class examined. The search was performed using Medline (via PubMed), Web of Science, and Google Scholar to identify studies assessing vertical transmission of both HIV and HBV. EXPERT OPINION Elimination of MTCT of both infections is firmly endorsed by major global commitments and the integration of tailored preventive interventions into maternal and newborn health services is of strategical importance to achieve this critical target. However, further research centered on antiviral-based and immunization trials among pregnant women is urgently needed to mitigate the risk of maternal and neonatal adverse outcomes, effectively prevent transmission to the offspring and finally eliminate the pediatric HIV and HBV epidemic, one of the key global health challenges of our time.
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Affiliation(s)
- Emanuela Zappulo
- Department of Clinical Medicine and Surgery, Infectious Diseases Unit, University of Naples Federico II, Naples, Italy
| | - Agnese Giaccone
- Department of Clinical Medicine and Surgery, Infectious Diseases Unit, University of Naples Federico II, Naples, Italy
| | - Nicola Schiano Moriello
- Department of Clinical Medicine and Surgery, Infectious Diseases Unit, University of Naples Federico II, Naples, Italy
| | - Ivan Gentile
- Department of Clinical Medicine and Surgery, Infectious Diseases Unit, University of Naples Federico II, Naples, Italy
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Veronese P, Dodi I, Esposito S, Indolfi G. Prevention of vertical transmission of hepatitis B virus infection. World J Gastroenterol 2021; 27:4182-4193. [PMID: 34326618 PMCID: PMC8311536 DOI: 10.3748/wjg.v27.i26.4182] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 03/29/2021] [Accepted: 06/02/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) is the leading cause of chronic viral hepatitis. Annually, almost two million children younger than 5 years acquire the infection, mostly through vertical or horizontal transmission in early life. Vertical transmission of HBV is a high efficacy phenomenon ranging, in the absence of any preventive interventions, from 70% to 90% for hepatitis e antigen positive mothers and from 10% to 40% for hepatitis e antigen-negative mothers. Maternal viraemia is a preeminent risk factor for vertical transmission of HBV. Maternal screening is the first step to prevent vertical transmission of HBV. Hepatitis B passive and active immunoprophylaxis at birth together with antiviral treatment of highly viraemic mothers are the key strategies for global elimination of HBV infection. Strategies are needed to promote implementation of birth-dose vaccination and hepatitis B immunoglobulins in low- and middle-income countries where the prevalence of the infection is at the highest.
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Affiliation(s)
- Piero Veronese
- Department of Medicine and Surgery, University of Parma, Parma 43121, Italy
| | - Icilio Dodi
- Department of Pediatrics, Pietro Barilla Children's Hospital, Parma 43121, Italy
| | - Susanna Esposito
- Department of Medicine and Surgery, University of Parma, Parma 43121, Italy
| | - Giuseppe Indolfi
- Department Neurofarba, University of Florence, Florence 50129, Italy
- Department Neurofarba, Meyer Children's University Hospital, Florence 50129, Italy
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High HBV Load Weakens Predictive Effect of Serum miR-122 on Response to Sorafenib in Hepatocellular Carcinoma Patients. JOURNAL OF ONCOLOGY 2021; 2021:9938207. [PMID: 34194500 PMCID: PMC8214498 DOI: 10.1155/2021/9938207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 05/26/2021] [Accepted: 06/03/2021] [Indexed: 11/17/2022]
Abstract
Background MiR-122 is a liver-specific microRNA. The aim of the study was to explore the association of serum miR-122 with response to sorafenib in hepatitis B virus- (HBV-) related hepatocellular carcinoma (HCC) patients and to further reveal the effect of the virus load on such potential relationship. Methods A total of 588 patients with HCC were retrospectively included. All of them were diagnosed with HBV-related locally advanced HCC and were treated with sorafenib. Therapeutic and prognostic information and other information were collected from medical records. Stored blood specimens that were obtained before sorafenib treatment were adopted to detect miR-122. Results The patients were divided into high-level group and low-level group according to the median of serum miR-122 level, and each group contained 294 patients. During the first 24 weeks after sorafenib treatment, the patients in the high-level group had more opportunities to experience progression-free survival (PFS) and overall survival (OS) than those in the low-level group (HR: 2.47, 95%CI: 1.24∼4.88; HR: 1.20, 95%CI: 1.09∼1.32). In the subgroup analysis, the relationship between serum miR-122 level and overall survival still existed in the patients with relatively lower HBV load (HR: 1.22, 95%CI: 1.09∼1.36), but not in the patients with higher HBV load (HR: 1.12, 95%CI: 0.93∼1.35). Conclusion Higher serum level of miR-122 at baseline was associated with a better response to sorafenib in HBV-related locally advanced HCC patients, and relatively high HBV load weakened such predictive effect mentioned above.
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Xu B, Xu C, Feng J, Chen J, Rui Y, Qiu Z, Zhu J, Tang J, Lou H, Chen T, Ge H, Ge X, Wang Z, Huang H, Pan M, Dai Y, Hu Y, Zhou YH. Reduced mother-to-child transmission of hepatitis B after implementation of completely charge-free active-passive immunoprophylaxis: an observational cohort study. Expert Rev Vaccines 2021; 20:899-905. [PMID: 33960275 DOI: 10.1080/14760584.2021.1927723] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Objectives: China has implemented universal hepatitis B vaccination since 2002 and provided charge-free hepatitis B immunoglobulin (HBIG) to infants of HBV-infected mothers since July 2011. We aimed to compare mother-to-child transmission (MTCT) in children born before and since July 2011.Methods: In total, 5,149 children of HBV-infected mothers were tested for HBV markers. Group one contained 1,160 children born during August 2002-June 2011 and group two contained 3,989 children born during July 2011-June 2016.Results: In total, 92 (1.8%, 95% confidence interval [95%CI] 1.4-2.2) children were infected with HBV. None (0%, 95%CI 0.0-0.1) of 3,716 children of mothers with negative hepatitis B e antigen (HBeAg) was infected, whereas 92 (6.4%, 95%CI 5.2-7.8) of 1,433 children of HBeAg-positive mothers were infected (p < 0.0001). Among children of HBeAg-positive mothers, MTCT occurred in 10.3% (19/185) (95%CI 6.3-15.6) in group one and 5.8% (73/1,248) (95%CI 4.6-7.3) in group two (p = 0.02).Conclusions: Implementing charge-free active-passive immunoprophylaxis greatly reduces MTCT of HBV in children of HBeAg-positive mothers, highlighting the importance of timely administration of both hepatitis B vaccine and HBIG to prevent MTCT. The still remaining MTCT suggests that reducing maternal virus load before delivery is an additional important measure.
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Affiliation(s)
- Biyun Xu
- Departments of Laboratory Medicine and Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Chenyu Xu
- Department of Obstetrics and Gynecology, Zhenjiang Fourth People's Hospital, Zhenjiang, Jiangsu, China
| | - Jing Feng
- Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing, China
| | - Jie Chen
- Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing, China
| | - Yanjing Rui
- Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing, China
| | - Ziyan Qiu
- Department of Mass Health Care, Sihong County Maternal and Child Health Hospital, Sihong, Jiangsu, China
| | - Jihua Zhu
- Department of Mass Health Care, Rugao Municipal Center for Maternal and Child Health Care and Family Planning, Jiangsu, Jiangsu, China
| | - Jie Tang
- Department of Obstetrics and Gynecology, Wujin Hospital, Changzhou, Jiangsu, China
| | - Haiqin Lou
- Department of Mass Health Care, Nantong Municipal Maternal and Child Health Hospital, Nantong, Jiangsu, China
| | - Tingmei Chen
- Department of Obstetrics and Gynecology, Zhenjiang Fourth People's Hospital, Zhenjiang, Jiangsu, China
| | - Hongyan Ge
- Department of Obstetrics and Gynecology, Zhenjiang Fourth People's Hospital, Zhenjiang, Jiangsu, China
| | - Xiaoyun Ge
- Department of Mass Health Care, Nantong Municipal Maternal and Child Health Hospital, Nantong, Jiangsu, China
| | - Zhihong Wang
- Department of Mass Health Care, Rugao Municipal Center for Maternal and Child Health Care and Family Planning, Jiangsu, Jiangsu, China
| | - Hongyu Huang
- Departments of Laboratory Medicine and Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Mingjie Pan
- Departments of Laboratory Medicine and Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Yimin Dai
- Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing, China
| | - Yali Hu
- Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing, China
| | - Yi-Hua Zhou
- Departments of Laboratory Medicine and Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China
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Liang LY, Wong VWS, Toyoda H, Tse YK, Yip TCF, Yuen BWY, Tada T, Kumada T, Lee HW, Lui GCY, Chan HLY, Wong GLH. Serum hepatitis B core-related antigen predicts hepatocellular carcinoma in hepatitis B e antigen-negative patients. J Gastroenterol 2020; 55:899-908. [PMID: 32556643 DOI: 10.1007/s00535-020-01700-z] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Accepted: 06/08/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND Hepatitis B core-related antigen (HBcrAg) is a novel serum viral marker. Recent studies showed that its level correlates with the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We aimed to evaluate the accuracy of serum HBsAg and HBcrAg levels at baseline to predict HCC. METHODS 1400 CHB patients who received nucleos(t)ide analogues (NA) treatment since December 2005 were included. Their stored serum samples at baseline were retrieved to measure HBsAg and HBcrAg levels. The primary endpoint was the cumulative incidence of HCC. RESULTS 85 (6.1%) patients developed HCC during a mean (± SD) follow-up duration of 45 ± 20 months. Serum HBcrAg level above 2.9 log10 U/mL at baseline was an independent factor for HCC in hepatitis B e antigen (HBeAg)-negative patients by multivariable analysis (adjusted hazard ratio 2.13, 95% CI 1.10-4.14, P = 0.025). HBcrAg above 2.9 log10 U/mL stratified the risk of HCC in HBeAg-negative patients with high PAGE-B score (P = 0.024 by Kaplan-Meier analysis), and possibly in cirrhotic patients (P = 0.08). Serum HBsAg level did not show any correlation with the risk of HCC in all patients or any subgroups. CONCLUSION Serum HBcrAg level predicts the risk of HCC accurately in NA-treated HBeAg-negative CHB patients.
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Affiliation(s)
- Lilian Yan Liang
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 9/F Prince of Wales Hospital, Shatin, Hong Kong
| | - Vincent Wai-Sun Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 9/F Prince of Wales Hospital, Shatin, Hong Kong
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR
| | | | - Yee-Kit Tse
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 9/F Prince of Wales Hospital, Shatin, Hong Kong
| | - Terry Cheuk-Fung Yip
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 9/F Prince of Wales Hospital, Shatin, Hong Kong
| | - Becky Wing-Yan Yuen
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 9/F Prince of Wales Hospital, Shatin, Hong Kong
| | | | | | - Hye-Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Grace Chung-Yan Lui
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 9/F Prince of Wales Hospital, Shatin, Hong Kong
| | - Henry Lik-Yuen Chan
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 9/F Prince of Wales Hospital, Shatin, Hong Kong
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR
| | - Grace Lai-Hung Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR.
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 9/F Prince of Wales Hospital, Shatin, Hong Kong.
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR.
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Huang H, Xu C, Liu L, Chen L, Zhu X, Chen J, Feng J, Chen T, Xu B, Yang J, Xu B, Pan M, Dai Y, Hu Y, Zhou YH. Increased protection of earlier use of immunoprophylaxis in preventing perinatal transmission of hepatitis B virus. Clin Infect Dis 2020; 73:e3317-e3323. [PMID: 32634824 DOI: 10.1093/cid/ciaa898] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Accepted: 06/24/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Passive-active immunoprophylaxis against mother-to-child transmission (MTCT) of hepatitis B virus (HBV) recommends administer hepatitis B immunoglobulin (HBIG) and birth dose hepatitis B vaccine in infants within 12 or 24 hours after birth. With this protocol, MTCT of HBV still occurs in 5-10% infants of HBV-infected mothers with positive hepatitis B e antigen (HBeAg). METHODS The present study aimed to investigate whether earlier administration of HBIG and hepatitis B vaccine after birth can further increase the protection efficacy. RESULTS Totally, 1140 HBV-infected pregnant women were enrolled, and 982 infants (9 twins) of 973 mothers were finally followed up at 9.6 ± 1.9 months age. HBIG and birth dose vaccine were administered in newborn infants with a median 0.17 hour (0.02-1.0) after birth. The overall rate of MTCT was 0.9% (9/982), with none (0%) of 607 infants of HBeAg-negative mothers and 9 (2.4%) of 375 infants of HBeAg-positive mothers. All nine HBV-infected infants were born to mothers with HBV DNA >2.75×106 IU/ml. Maternal HBV DNA levels >1×106 IU/ml was an independent risk factor (OR = 10.627, 95% CI: 2.135-+∞) for immunoprophylaxis failure. CONSLUSIONS Earlier use (within one hour after birth) of HBIG and hepatitis B vaccine can provide better protection efficacy against MTCT of HBV.
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Affiliation(s)
- Hongyu Huang
- Department of Experimental Medicine and Jiangsu Key Laboratory for Molecular Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Chenyu Xu
- Department of Obstetrics and Gynecology, Zhenjiang Fourth People's Hospital, Zhenjiang, China
| | - Lanhua Liu
- Department of Obstetrics and Gynecology, Taixing People's Hospital, Taizhou, China
| | - Liping Chen
- Department of Obstetrics and Gynecology, Nantong First People's Hospital, Nantong, China
| | - Xiaoqin Zhu
- Department of Obstetrics and Gynecology, Huai'an Maternal and Children's Hospital, Huai'an, China
| | - Jie Chen
- Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Jing Feng
- Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Tingmei Chen
- Department of Obstetrics and Gynecology, Zhenjiang Fourth People's Hospital, Zhenjiang, China
| | - Biao Xu
- Department of Obstetrics and Gynecology, Taixing People's Hospital, Taizhou, China
| | - Jishi Yang
- Department of Obstetrics and Gynecology, Taixing People's Hospital, Taizhou, China
| | - Biyun Xu
- Department of Biostatistics, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Mingjie Pan
- Department of Experimental Medicine and Jiangsu Key Laboratory for Molecular Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Yimin Dai
- Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Yali Hu
- Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Yi-Hua Zhou
- Department of Experimental Medicine and Jiangsu Key Laboratory for Molecular Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.,Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
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