부산대학교 도서관

Summary Background Prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is based on administration of vaccine and immunoglobulins (HBIg) to newborns at birth and maternal antiviral prophylaxis for those with an HBV-DNA viral load of at 5*3 log.sub.10 IU/mL or more. Many low-income and middle-income countries face difficulty in accessing HBIg and HBV-DNA quantification. The aim of this study was to evaluate the effectiveness of an HBIg-free strategy to prevent MTCT of HBV. Methods TA-PROHM was a single-arm, multicentre, phase 4 trial done in five maternity units in Cambodia. Pregnant women who were positive for hepatitis B surface antigen (HBsAg), aged 18 years or older were included. Women who were HCV or HIV positive, had creatinine clearance of less than 30 mL/min, severe gravid disease, and planned to give birth outside the study sites were excluded. From Oct 4, 2017, to Jan 9, 2019, HBsAg positive pregnant women who tested positive for hepatitis B e antigen (HBeAg) with a rapid diagnostic test were eligible to receive tenofovir disoproxil fumarate. From Jan 9, 2019, women who were HBeAg negative with an alanine aminotransferase concentration of [greater than or equal to]40 IU/L were also eligible to receive tenofovir disoproxil fumarate. Women in the tenofovir disoproxil fumarate eligible group received 300 mg of tenofovir disoproxil fumarate orally once a day from the 24th week of gestation until 6 weeks postpartum. The primary outcome was the overall proportion of infants who were HBsAg positive at 6 months of life, confirmed by positive HBV DNA quantification. For the primary outcome, the proportion (95% CI) of infants with HBsAg at 6 months was stratified according to infant's HBIg status, duration of maternal tenofovir disoproxil fumarate treatment (>4 weeks and [less than or equal to]4 weeks), and study period (before and after the change in therapeutic algorithm) and was measured in a modified intention-to-treat analysis, which excluded infants lost to follow-up or who were withdrawn before 6 months. The study is registered with ClinicalTrials.gov, NCT02937779. Findings From Oct 4, 2017, to Nov 27, 2020, 21 251 pregnant women were screened for HBsAg, of whom 1194 (6%) were enrolled in the study: 338 (28%) were eligible to receive tenofovir disoproxil fumarate. For the tenofovir disoproxil fumarate eligible group, four (1% [95% CI 0*34--3*20]) of 317 infants had HBV infection at 6 months; in the subgroup of 271 children who did not receive HBIg, four (1% [0*40--3*74]) had HBV infection at 6 months. In absence of HBIg, MTCT HBV transmission occurred in none (0% [0--1*61]) of 227 women who received tenofovir disoproxil fumarate for more than 4 weeks before giving birth and three (8% [1*75--22*47]) of 36 women who received tenofovir disoproxil fumarate for less than 4 weeks. In the tenofovir disoproxil fumarate ineligible group, seven (1% [0*40--2*02]) of 712 infants had HBV infection at 6 months; in the subgroup of 567 children who did not receive HBIg, six (1% [0*39--2*30]) had HBV infection at 6 months. Interpretation An immunoglobulin-free strategy using an HBeAg rapid diagnosis test and alanine aminotransferase-based algorithm to assess eligibility for tenofovir, is effective at preventing MTCT of HBV when tenofovir was initiated at least 4 weeks before birth. Funding French Agency for Research on AIDS and Viral Hepatitis and Emerging Infectious diseases. Translation For the French translation of the abstract see Supplementary Materials section. Author Affiliation: (a) Grant Management Office, University of Health Sciences, Phnom Penh, Cambodia (b) French Agency for Research on AIDS, Viral Hepatitis and Emerging Infectious diseases (ANRS-MIE), Phnom Penh, Cambodia (c) Epidemiology and Public Health Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia (d) INSERM US19, SC10 Essais The[combining acute accent]rapeutiques et Maladies Infectieuses, Villejuif, France (e) Maternity Department, Calmette hospital, Phnom Penh, Cambodia (f) Maternity Department, Jayavarman VII hospital, Siem Reap, Cambodia (g) Hepatology Department, Calmette hospital, Phnom Penh, Cambodia (h) National Maternal and Child Health Center, Phnom Penh, Cambodia (i) Maternity Department, Kompong Cham Provincial Hospital, Kompong Cham, Cambodia (j) Maternity Department, Takeo Referral Hospital, Takeo, Cambodia (k) Virology Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia (l) INSERM-Centre d'Investigation Clinique-Cochin-Hôtel Dieu, Paris France (m) ANRS-Maladies Infectieuses Emergentes, Paris France (n) Direction Department, Foundation Children's Hospital Kantha Bopha, Dr med Beat Richner, Phnom Penh, Cambodia (o) University Paris Saclay, Assistance Publique--Hôpitaux de Paris, Le Kremlin Bicêtre, France * Correspondence to: Dr Olivier Segeral, ANRS, University of Health Sciences, Phnom-Penh, Cambodia Byline: Olivier Segeral, PhD [oliseg@hotmail.com] (a,b), Bunnet Dim, MD (c), Christine Durier, PhD (d), Sovann Nhoueng, MSc (c), Kearena Chhim, MD (e), Saren Sovann, MSc (c), Sophal Yom, MD (f), Chanlina Vong, MD (g), Song Yin, MSc (c), Bandith Ros, MD (f), Vutha Ky, MD (g), Sothy Pech, MD (h), Bunthoeun Nem, MD (i), Kay Hout (j), Julia Guillebaud, MSc (k), Eamkim Ear, MSc (c), Layana Caroupaye-Caroupin, MPH (d), Claire Rekacewicz, MD (l), Laura Fernandez, MPH (m), Denis Laurent, PhD (n), Chantana Yay, MD (n), Rattana Kim, MD (h), Laurence Meyer, PhD (o), Samsorphea Chhun, MD (e), Chanthy Keang, Ousa Khan, Boraneath Nang, Vouch Leang Sreng, Sopheavet In, Sineath Sun, Linda Sov, Bunrachana Nor, Brembrey Hing, Sokkim Seng, Sophea Soum, Leakhena Say, Sao Sarady Ay, Daneth Thol, Chhorn Chhouk, Patrice Piola, Janin Nouhin, Anne-Marie Roque Afonso, Jean Charles Duclos Vallee, Channa Sann, Leang Sim Kruy, Maud Lemoine, Laurent Mandelbrot, Stephane Blanche, Alpha Diallo, Christelle Paul, SAY Tiv, Polinn Sar, Lyvoin Nov, Darapoline Vann, Tha Chea, Bunrith Touch, Kongkea Neav, Ekvitou Kong, Ratha Chea, Chanksolina Ouk, Lyhour Meak, Rayounette Krouch, Naneth Chhan, Sody Seang, Veasna Nuon, Leang Meng, Sok Leakhena Tharith, Sovannara Hang, Vanrithy Som, Rithy Som, Phirak Seng, Malys Lim, Kimchhorn Srey, Sok Rothavy Uch, Pichthyda Hou, Satha Bo, Eanghor Ieang, Kimchhorng Korn, Chan Reatrey Noun, Sokhoeun Soy, Thou Khim, Vutha Sou, Sokha Pol, Samreth Nget, Marina Sun, Phearom Uon, Kim Teng Ya, Kimsreng Lean, Kim Ean Eang, Sophal Ung, Rauin Rith, Charya Mom, Chanthea Keang, Soklyda Sam, Sokneth Chuong, Chanmony Nam, Sophya Khuon, Sidet Cheang, Sopheak Lean, Arnaud Tarantola, Isabelle Fournier, Nicolas Rouveau, Maria-Camila Calvo cortez