Deborah Persaud,Anne Coletti,Bryan S Nelson,Jennifer Jao,Edmund V Capparelli,Diane Costello,Camlin Tierney,Adeodata R Kekitiinwa,Teacler Nematadzira,Boniface N Njau,John Moye,Patrick Jean-Philippe,Violet Korutaro,Annet Nalugo,Tapiwa Mbengeranwa,Tinashe Chidemo,Blandina T Mmbaga,Philoteus A Sakasaka,Mark Cotton,Cheryl Jennings,Carly Hoffmann,Laura Hovind,Yvonne Bryson,Ellen G Chadwick,
{"title":"早期ART治疗后子宫内HIV-1患儿无ART缓解(IMPAACT P1115):一项多中心、开放标签、1/2期概念验证研究","authors":"Deborah Persaud,Anne Coletti,Bryan S Nelson,Jennifer Jao,Edmund V Capparelli,Diane Costello,Camlin Tierney,Adeodata R Kekitiinwa,Teacler Nematadzira,Boniface N Njau,John Moye,Patrick Jean-Philippe,Violet Korutaro,Annet Nalugo,Tapiwa Mbengeranwa,Tinashe Chidemo,Blandina T Mmbaga,Philoteus A Sakasaka,Mark Cotton,Cheryl Jennings,Carly Hoffmann,Laura Hovind,Yvonne Bryson,Ellen G Chadwick, ","doi":"10.1016/s2352-3018(25)00189-4","DOIUrl":null,"url":null,"abstract":"BACKGROUND\r\nWe hypothesised that initiating antiretroviral therapy (ART) soon after birth could limit HIV-1 reservoirs and promote ART-free remission. This study aims to assess remission in children with in-utero HIV-1 infection who received very early ART as neonates by performing analytical treatment interruption (ATI).\r\n\r\nMETHODS\r\nIMPAACT P1115 is an ongoing, open-label, proof-of-concept study at 30 research sites in 11 countries across Africa, Asia, and the Americas. Neonates (≥34 weeks gestational age) at high risk for in-utero HIV-1 were eligible. Neonates born to mothers with untreated HIV-1 (cohort 1) or mothers who might have been on ART (cohort 2) initiated three-drug oral nevirapine-based ART (6mg/kg per dose orally twice a day) within 48 h of birth (cohort 1), three-drug nevirapine-based prophylaxis (≥8 mg/kg per dose orally once a day), or nevirapine-based ART after HIV-1 diagnosis by age 10 days (cohort 2). Coformulated ritonavir 75 mg/m2 and lopinavir 300 mg/m2 orally twice a day was added when age appropriate for those with confirmed in-utero HIV-1. Nevirapine was discontinued 12 weeks after two consecutive plasma viral loads were below the assay limit. Children at least 2 years of age maintaining undetectable HIV-1 RNA since week 48 and who tested HIV-1 antibody negative, HIV-1 DNA not detected, and normal CD4 count and percentage qualified for ATI. The primary outcome was ART-free remission, defined as no HIV-1 RNA in plasma for 48 weeks or more off ART. A two-sided exact 95% CI was calculated to estimate the probability of remission. This study is registered with ClinicalTrials.gov (NCT02140255).\r\n\r\nFINDINGS\r\nAmong 54 children with in-utero HIV-1 enrolled between Jan 23, 2015, and Dec 14, 2017, six (11%) children (four girls, two boys; one in cohort 1, five in cohort 2) met criteria and underwent ATI at a median age of 5·5 years. Two children had early rebound at 3·4 weeks and 9·4 weeks. Four reached ART-free remission (67%; exact 95% CI 22-96), one of whom had late viral rebound at 79·3 weeks. All three children with viral rebound successfully resuppressed HIV-1 RNA below the assay limit on ART. Mild symptoms of acute retroviral syndrome occurred in two participants during rebound and resolved with ART resumption.\r\n\r\nINTERPRETATION\r\nThis study shows that ART-free remission for 48 weeks or longer is achievable with very early ART in children with in-utero HIV-1, but close monitoring for viral rebound and acute retroviral syndrome during ATI is needed. These findings, observed in resource-constrained countries, exhibit the feasibility of testing at birth and initiating very early ART, show the potential to limit HIV-1 reservoirs for ART-free remission, and inform future remission strategies.\r\n\r\nFUNDING\r\nThe US National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the US National Institute of Mental Health.","PeriodicalId":48725,"journal":{"name":"Lancet Hiv","volume":"61 1","pages":""},"PeriodicalIF":13.0000,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"ART-free HIV-1 remission in children with in-utero HIV-1 after very early ART (IMPAACT P1115): a multicentre, open-label, phase 1/2 proof-of-concept study.\",\"authors\":\"Deborah Persaud,Anne Coletti,Bryan S Nelson,Jennifer Jao,Edmund V Capparelli,Diane Costello,Camlin Tierney,Adeodata R Kekitiinwa,Teacler Nematadzira,Boniface N Njau,John Moye,Patrick Jean-Philippe,Violet Korutaro,Annet Nalugo,Tapiwa Mbengeranwa,Tinashe Chidemo,Blandina T Mmbaga,Philoteus A Sakasaka,Mark Cotton,Cheryl Jennings,Carly Hoffmann,Laura Hovind,Yvonne Bryson,Ellen G Chadwick, \",\"doi\":\"10.1016/s2352-3018(25)00189-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"BACKGROUND\\r\\nWe hypothesised that initiating antiretroviral therapy (ART) soon after birth could limit HIV-1 reservoirs and promote ART-free remission. This study aims to assess remission in children with in-utero HIV-1 infection who received very early ART as neonates by performing analytical treatment interruption (ATI).\\r\\n\\r\\nMETHODS\\r\\nIMPAACT P1115 is an ongoing, open-label, proof-of-concept study at 30 research sites in 11 countries across Africa, Asia, and the Americas. Neonates (≥34 weeks gestational age) at high risk for in-utero HIV-1 were eligible. Neonates born to mothers with untreated HIV-1 (cohort 1) or mothers who might have been on ART (cohort 2) initiated three-drug oral nevirapine-based ART (6mg/kg per dose orally twice a day) within 48 h of birth (cohort 1), three-drug nevirapine-based prophylaxis (≥8 mg/kg per dose orally once a day), or nevirapine-based ART after HIV-1 diagnosis by age 10 days (cohort 2). Coformulated ritonavir 75 mg/m2 and lopinavir 300 mg/m2 orally twice a day was added when age appropriate for those with confirmed in-utero HIV-1. Nevirapine was discontinued 12 weeks after two consecutive plasma viral loads were below the assay limit. Children at least 2 years of age maintaining undetectable HIV-1 RNA since week 48 and who tested HIV-1 antibody negative, HIV-1 DNA not detected, and normal CD4 count and percentage qualified for ATI. The primary outcome was ART-free remission, defined as no HIV-1 RNA in plasma for 48 weeks or more off ART. A two-sided exact 95% CI was calculated to estimate the probability of remission. This study is registered with ClinicalTrials.gov (NCT02140255).\\r\\n\\r\\nFINDINGS\\r\\nAmong 54 children with in-utero HIV-1 enrolled between Jan 23, 2015, and Dec 14, 2017, six (11%) children (four girls, two boys; one in cohort 1, five in cohort 2) met criteria and underwent ATI at a median age of 5·5 years. Two children had early rebound at 3·4 weeks and 9·4 weeks. Four reached ART-free remission (67%; exact 95% CI 22-96), one of whom had late viral rebound at 79·3 weeks. All three children with viral rebound successfully resuppressed HIV-1 RNA below the assay limit on ART. Mild symptoms of acute retroviral syndrome occurred in two participants during rebound and resolved with ART resumption.\\r\\n\\r\\nINTERPRETATION\\r\\nThis study shows that ART-free remission for 48 weeks or longer is achievable with very early ART in children with in-utero HIV-1, but close monitoring for viral rebound and acute retroviral syndrome during ATI is needed. These findings, observed in resource-constrained countries, exhibit the feasibility of testing at birth and initiating very early ART, show the potential to limit HIV-1 reservoirs for ART-free remission, and inform future remission strategies.\\r\\n\\r\\nFUNDING\\r\\nThe US National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the US National Institute of Mental Health.\",\"PeriodicalId\":48725,\"journal\":{\"name\":\"Lancet Hiv\",\"volume\":\"61 1\",\"pages\":\"\"},\"PeriodicalIF\":13.0000,\"publicationDate\":\"2025-09-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Lancet Hiv\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/s2352-3018(25)00189-4\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Lancet Hiv","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/s2352-3018(25)00189-4","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
ART-free HIV-1 remission in children with in-utero HIV-1 after very early ART (IMPAACT P1115): a multicentre, open-label, phase 1/2 proof-of-concept study.
BACKGROUND
We hypothesised that initiating antiretroviral therapy (ART) soon after birth could limit HIV-1 reservoirs and promote ART-free remission. This study aims to assess remission in children with in-utero HIV-1 infection who received very early ART as neonates by performing analytical treatment interruption (ATI).
METHODS
IMPAACT P1115 is an ongoing, open-label, proof-of-concept study at 30 research sites in 11 countries across Africa, Asia, and the Americas. Neonates (≥34 weeks gestational age) at high risk for in-utero HIV-1 were eligible. Neonates born to mothers with untreated HIV-1 (cohort 1) or mothers who might have been on ART (cohort 2) initiated three-drug oral nevirapine-based ART (6mg/kg per dose orally twice a day) within 48 h of birth (cohort 1), three-drug nevirapine-based prophylaxis (≥8 mg/kg per dose orally once a day), or nevirapine-based ART after HIV-1 diagnosis by age 10 days (cohort 2). Coformulated ritonavir 75 mg/m2 and lopinavir 300 mg/m2 orally twice a day was added when age appropriate for those with confirmed in-utero HIV-1. Nevirapine was discontinued 12 weeks after two consecutive plasma viral loads were below the assay limit. Children at least 2 years of age maintaining undetectable HIV-1 RNA since week 48 and who tested HIV-1 antibody negative, HIV-1 DNA not detected, and normal CD4 count and percentage qualified for ATI. The primary outcome was ART-free remission, defined as no HIV-1 RNA in plasma for 48 weeks or more off ART. A two-sided exact 95% CI was calculated to estimate the probability of remission. This study is registered with ClinicalTrials.gov (NCT02140255).
FINDINGS
Among 54 children with in-utero HIV-1 enrolled between Jan 23, 2015, and Dec 14, 2017, six (11%) children (four girls, two boys; one in cohort 1, five in cohort 2) met criteria and underwent ATI at a median age of 5·5 years. Two children had early rebound at 3·4 weeks and 9·4 weeks. Four reached ART-free remission (67%; exact 95% CI 22-96), one of whom had late viral rebound at 79·3 weeks. All three children with viral rebound successfully resuppressed HIV-1 RNA below the assay limit on ART. Mild symptoms of acute retroviral syndrome occurred in two participants during rebound and resolved with ART resumption.
INTERPRETATION
This study shows that ART-free remission for 48 weeks or longer is achievable with very early ART in children with in-utero HIV-1, but close monitoring for viral rebound and acute retroviral syndrome during ATI is needed. These findings, observed in resource-constrained countries, exhibit the feasibility of testing at birth and initiating very early ART, show the potential to limit HIV-1 reservoirs for ART-free remission, and inform future remission strategies.
FUNDING
The US National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the US National Institute of Mental Health.
期刊介绍:
The Lancet HIV is an internationally trusted source of clinical, public health, and global health knowledge with an Impact Factor of 16.1. It is dedicated to publishing original research, evidence-based reviews, and insightful features that advocate for change in or illuminates HIV clinical practice. The journal aims to provide a holistic view of the pandemic, covering clinical, epidemiological, and operational disciplines. It publishes content on innovative treatments and the biological research behind them, novel methods of service delivery, and new approaches to confronting HIV/AIDS worldwide. The Lancet HIV publishes various types of content including articles, reviews, comments, correspondences, and viewpoints. It also publishes series that aim to shape and drive positive change in clinical practice and health policy in areas of need in HIV. The journal is indexed by several abstracting and indexing services, including Crossref, Embase, Essential Science Indicators, MEDLINE, PubMed, SCIE and Scopus.