Immunoglobulin-free strategy to prevent HBV mother-to-child transmission in Cambodia (TA-PROHM): a single-arm, multicentre, phase 4 trial.

Alanine Transaminase Antiviral Agents / therapeutic use Cambodia DNA, Viral Female Hepatitis B / drug therapy Hepatitis B Surface Antigens / therapeutic use Hepatitis B e Antigens / therapeutic use Hepatitis B virus Humans Infant, Newborn Infectious Disease Transmission, Vertical / prevention & control Pregnancy Tenofovir / therapeutic use Viral Load

Journal

The Lancet. Infectious diseases

ISSN: 1474-4457

Titre abrégé: Lancet Infect Dis

Pays: United States

ID NLM: 101130150

Informations de publication

Date de publication:
08 2022

Historique:

received: 08 12 2021

revised: 12 02 2022

accepted: 10 03 2022

pubmed: 2 6 2022

medline: 27 7 2022

entrez: 1 6 2022

Statut: ppublish

Résumé

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 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 ≥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 ≤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. 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. 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. French Agency for Research on AIDS and Viral Hepatitis and Emerging Infectious diseases. For the French translation of the abstract see Supplementary Materials section.

Sections du résumé

BACKGROUND

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 ≥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 ≤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.

Identifiants

DOI: 10.1016/S1473-3099(22)00206-7 PMID: 35643089

pubmed: 35643089

pii: S1473-3099(22)00206-7

doi: 10.1016/S1473-3099(22)00206-7

pii:

doi:

Substances chimiques

Antiviral Agents 0

DNA, Viral 0

Hepatitis B Surface Antigens 0

Hepatitis B e Antigens 0

Tenofovir 99YXE507IL

Alanine Transaminase EC 2.6.1.2

Banques de données

ClinicalTrials.gov

['NCT02937779']

Types de publication

Clinical Trial, Phase IV Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

1181-1190

Investigateurs

Chanthy Keang (C)

Ousa Khan (O)

Boraneath Nang (B)

Vouch Leang Sreng (VL)

Sopheavet In (S)

Sineath Sun (S)

Linda Sov (L)

Bunrachana Nor (B)

Brembrey Hing (B)

Sokkim Seng (S)

Sophea Soum (S)

Leakhena Say (L)

Sao Sarady Ay (SS)

Daneth Thol (D)

Chhorn Chhouk (C)

Patrice Piola (P)

Janin Nouhin (J)

Anne-Marie Roque Afonso (AM)

Jean Charles Duclos Vallee (JC)

Channa Sann (C)

Leang Sim Kruy (LS)

Maud Lemoine (M)

Laurent Mandelbrot (L)

Stephane Blanche (S)

Alpha Diallo (A)

Christelle Paul (C)

Say Tiv (S)

Polinn Sar (P)

Lyvoin Nov (L)

Darapoline Vann (D)

Tha Chea (T)

Bunrith Touch (B)

Kongkea Neav (K)

Ekvitou Kong (E)

Ratha Chea (R)

Chanksolina Ouk (C)

Lyhour Meak (L)

Rayounette Krouch (R)

Naneth Chhan (N)

Sody Seang (S)

Veasna Nuon (V)

Leang Meng (L)

Sok Leakhena Tharith (SL)

Sovannara Hang (S)

Vanrithy Som (V)

Rithy Som (R)

Phirak Seng (P)

Malys Lim (M)

Kimchhorn Srey (K)

Sok Rothavy Uch (SR)

Pichthyda Hou (P)

Satha Bo (S)

Eanghor Ieang (E)

Kimchhorng Korn (K)

Chan Reatrey Noun (CR)

Sokhoeun Soy (S)

Thou Khim (T)

Vutha Sou (V)

Sokha Pol (S)

Samreth Nget (S)

Marina Sun (M)

Phearom Uon (P)

Kim Teng Ya (KT)

Kimsreng Lean (K)

Kim Ean Eang (KE)

Sophal Ung (S)

Rauin Rith (R)

Charya Mom (C)

Chanthea Keang (C)

Soklyda Sam (S)

Sokneth Chuong (S)

Chanmony Nam (C)

Sophya Khuon (S)

Sidet Cheang (S)

Sopheak Lean (S)

Arnaud Tarantola (A)

Isabelle Fournier (I)

Nicolas Rouveau (N)

Maria-Camila Calvo Cortez (MC)

Commentaires et corrections

Type : CommentIn

Informations de copyright

Déclaration de conflit d'intérêts

Declaration of interests We declare no competing interests.