Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children.

Administration, Oral Adolescent Alkynes / therapeutic use Anti-Retroviral Agents / adverse effects Benzoxazines / therapeutic use Child Child, Preschool Cholesterol / blood Cyclopropanes / therapeutic use Drug Therapy, Combination Female HIV Infections / drug therapy HIV Integrase Inhibitors / administration & dosage HIV Protease Inhibitors / therapeutic use HIV-1 / isolation & purification Heterocyclic Compounds, 3-Ring / administration & dosage Humans Male Oxazines / administration & dosage Piperazines / administration & dosage Pyridones / administration & dosage Viral Load / drug effects

Journal

The New England journal of medicine

ISSN: 1533-4406

Titre abrégé: N Engl J Med

Pays: United States

ID NLM: 0255562

Informations de publication

Date de publication:
30 12 2021

Historique:

entrez: 29 12 2021

pubmed: 30 12 2021

medline: 13 1 2022

Statut: ppublish

Résumé

Children with human immunodeficiency virus type 1 (HIV-1) infection have limited options for effective antiretroviral treatment (ART). We conducted an open-label, randomized, noninferiority trial comparing three-drug ART based on the HIV integrase inhibitor dolutegravir with standard care (non-dolutegravir-based ART) in children and adolescents starting first- or second-line ART. The primary end point was the proportion of participants with virologic or clinical treatment failure by 96 weeks, as estimated by the Kaplan-Meier method. Safety was assessed. From September 2016 through June 2018, a total of 707 children and adolescents who weighed at least 14 kg were randomly assigned to receive dolutegravir-based ART (350 participants) or standard care (357). The median age was 12.2 years (range, 2.9 to 18.0), the median weight was 30.7 kg (range, 14.0 to 85.0), and 49% of the participants were girls. By design, 311 participants (44%) started first-line ART (with 92% of those in the standard-care group receiving efavirenz-based ART), and 396 (56%) started second-line ART (with 98% of those in the standard-care group receiving boosted protease inhibitor-based ART). The median follow-up was 142 weeks. By 96 weeks, 47 participants in the dolutegravir group and 75 in the standard-care group had treatment failure (estimated probability, 0.14 vs. 0.22; difference, -0.08; 95% confidence interval, -0.14 to -0.03; P = 0.004). Treatment effects were similar with first- and second-line therapies (P = 0.16 for heterogeneity). A total of 35 participants in the dolutegravir group and 40 in the standard-care group had at least one serious adverse event (P = 0.53), and 73 and 86, respectively, had at least one adverse event of grade 3 or higher (P = 0.24). At least one ART-modifying adverse event occurred in 5 participants in the dolutegravir group and in 17 in the standard-care group (P = 0.01). In this trial involving children and adolescents with HIV-1 infection who were starting first- or second-line treatment, dolutegravir-based ART was superior to standard care. (Funded by ViiV Healthcare; ODYSSEY ClinicalTrials.gov number, NCT02259127; EUDRACT number, 2014-002632-14; and ISRCTN number, ISRCTN91737921.).

Sections du résumé

BACKGROUND

Children with human immunodeficiency virus type 1 (HIV-1) infection have limited options for effective antiretroviral treatment (ART).

METHODS

We conducted an open-label, randomized, noninferiority trial comparing three-drug ART based on the HIV integrase inhibitor dolutegravir with standard care (non-dolutegravir-based ART) in children and adolescents starting first- or second-line ART. The primary end point was the proportion of participants with virologic or clinical treatment failure by 96 weeks, as estimated by the Kaplan-Meier method. Safety was assessed.

RESULTS

From September 2016 through June 2018, a total of 707 children and adolescents who weighed at least 14 kg were randomly assigned to receive dolutegravir-based ART (350 participants) or standard care (357). The median age was 12.2 years (range, 2.9 to 18.0), the median weight was 30.7 kg (range, 14.0 to 85.0), and 49% of the participants were girls. By design, 311 participants (44%) started first-line ART (with 92% of those in the standard-care group receiving efavirenz-based ART), and 396 (56%) started second-line ART (with 98% of those in the standard-care group receiving boosted protease inhibitor-based ART). The median follow-up was 142 weeks. By 96 weeks, 47 participants in the dolutegravir group and 75 in the standard-care group had treatment failure (estimated probability, 0.14 vs. 0.22; difference, -0.08; 95% confidence interval, -0.14 to -0.03; P = 0.004). Treatment effects were similar with first- and second-line therapies (P = 0.16 for heterogeneity). A total of 35 participants in the dolutegravir group and 40 in the standard-care group had at least one serious adverse event (P = 0.53), and 73 and 86, respectively, had at least one adverse event of grade 3 or higher (P = 0.24). At least one ART-modifying adverse event occurred in 5 participants in the dolutegravir group and in 17 in the standard-care group (P = 0.01).

CONCLUSIONS

In this trial involving children and adolescents with HIV-1 infection who were starting first- or second-line treatment, dolutegravir-based ART was superior to standard care. (Funded by ViiV Healthcare; ODYSSEY ClinicalTrials.gov number, NCT02259127; EUDRACT number, 2014-002632-14; and ISRCTN number, ISRCTN91737921.).

Identifiants

DOI: 10.1056/NEJMoa2108793 PMID: 34965338 PMC: PMC7614690

pubmed: 34965338

doi: 10.1056/NEJMoa2108793

pmc: PMC7614690

mid: EMS175950

doi:

Substances chimiques

Alkynes 0

Anti-Retroviral Agents 0

Benzoxazines 0

Cyclopropanes 0

HIV Integrase Inhibitors 0

HIV Protease Inhibitors 0

Heterocyclic Compounds, 3-Ring 0

Oxazines 0

Piperazines 0

Pyridones 0

Cholesterol 97C5T2UQ7J

dolutegravir DKO1W9H7M1

efavirenz JE6H2O27P8

Banques de données

ClinicalTrials.gov

['NCT02259127']

EudraCT

['2014-002632-14']

ISRCTN

['ISRCTN91737921']

Types de publication

Comparative Study Equivalence Trial Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

2531-2543

Subventions

Organisme : Medical Research Council

ID : MC_UU_12023/23

Pays : United Kingdom

Organisme : Medical Research Council

ID : MC_UU_00004/03

Pays : United Kingdom

Investigateurs

Carlo Giaquinto (C)

Tiziana Grossele (T)

Daniel Gomez-Pena (D)

Davide Bilardi (D)

Giulio Vecchia (G)

Shabinah S Ali (SS)

Abdel Babiker (A)

Shazia Begum (S)

Chiara Borg (C)

Anne-Marie Borges Da Silva (AM)

Joanna Calvert (J)

Man Chan (M)

Nimisha Dudakia (N)

Deborah Ford (D)

Joshua Gasa (J)

Diana M Gibb (DM)

Nasir Jamil (N)

Sarah Lensen (S)

Emma Little (E)

Fatima Mohamed (F)

Samuel Montero (S)

Cecilia L Moore (CL)

Rachel Oguntimehin (R)

Anna Parker (A)

Reena Patel (R)

Tasmin Phillips (T)

Tatiana Sarfati (T)

Karen Scott (K)

Clare Shakeshaft (C)

Moira Spyer (M)

Margaret Thomason (M)

Anna Turkova (A)

Rebecca Turner (R)

Nadine Van Looy (N)

Ellen White (E)

Ian White (I)

Kaja Widuch (K)

Helen Wilkes (H)

Ben Wynne (B)

Alexandra Compagnucci (A)

Yacine Saidi (Y)

Yoann Riault (Y)

Alexandra Coelho (A)

Laura Picault (L)

Christelle Kouakam (C)

Tim R Cressey (TR)

Suwalai Chalermpantmetagul (S)

Dujrudee Chinwong (D)

Gonzague Jourdain (G)

Rukchanok Peongjakta (R)

Praornsuda Sukrakanchana (P)

Wasna Sirirungsi (W)

Cissy M Kityo (CM)

Victor Musiime (V)

Elizabeth Kaudha (E)

Annet Nanduudu (A)

Emmanuel Mujyambere (E)

Paul Ocitti Labeja (PO)

Charity Nankunda (C)

Juliet Ategeka (J)

Peter Erim (P)

Collin Makanga (C)

Esther Nambi (E)

Abbas Lugemwa (A)

Lorna Atwine (L)

Edridah Keminyeto (E)

Deogratiuos Tukwasibwe (D)

Shafic Makumbi (S)

Emily Ninsiima (E)

Mercy Tukamushaba (M)

Rogers Ankunda (R)

Ian Natuhurira (I)

Miriam Kasozi (M)

Baker Rubinga (B)

Diana Antonia Rutebarika (DA)

Rashida Nazzinda (R)

Shamim Nakabuye (S)

Julius Tumusiime (J)

Alice Mulindwa (A)

Ritah Mbabazi (R)

Milly Ndigendawani (M)

Edward Bagirigomwa (E)

Eddie Rubanga (E)

David Eram (D)

Maria Nannungi (M)

Chrispus Katemba (C)

Disan Mulima (D)

Josephine Namusanje (J)

Mariam Nabalamba (M)

Priscilla Kyobutungi (P)

Phyllis Mwesigwa Rubondo (PM)

Robinah Kibenge (R)

Claire Nasaazi (C)

Roy Clark Basiimwa (RC)

Enock Babu (E)

Alex Musiime (A)

Faith Mbasani (F)

Martin Ojok (M)

Odoch Denis (O)

David Baliruno (D)

Katabalwa Juliet (K)

Ouma Benson (O)

Barbara Ainebyona (B)

Adeodata R Kekitiinwa (AR)

Pauline Amuge (P)

Dickson Bbuye (D)

Justine Nalubwama (J)

Winnie Akobye (W)

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Informations de copyright

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