학술논문
Nucleoside/nucleotide reverse transcriptase inhibitor sparing regimen with once daily integrase inhibitor plus boosted darunavir is non-inferior to standard of care in virologically-suppressed children and adolescents living with HIV – Week 48 results of the randomised SMILE Penta-17-ANRS 152 clinical trialResearch in context
Document Type
article
Author
Alexandra Compagnucci; Man K. Chan; Yacine Saïdi; Tim R. Cressey; Alasdair Bamford; Yoann Riault; Alexandra Coelho; Aoife Nolan; Suwalai Chalermpantmetagul; Gabija Morkunaite; Pauline Amuge; Victor Musiime; Avy Violari; Mark Cotton; Adeodata R. Kekitiinwa; Elizabeth Kaudha; Marisa Groenewald; Afaaf A. Liberty; Suparat Kanjanavanit; Alla Volokha; Rosa Bologna; Noris Pavia Ruz; Luis Prieto Tato; Paolo Paioni; Laura Marques; Véronique Reliquet; Tim Niehues; Steven B. Welch; Deborah Ford; Carlo Giaquinto; Diana M. Gibb; Abdel Babiker; Jose Tomas Ramos Amador; A. Compagnucci; Y. Saidi; Y. Riault; A. Coelho; C. Kouakam; L. Picault; M. Ndiaye; L. Meyer; C. Cagnot; S. Circosta; L. Léger; S. Simanic; A. Arulananthan; D.M. Gibb; A. Babiker; M. Chan; D. Ford; F. Hudson; L. Harper; A. Bamford; A. Nolan; K. Widuch; S. Townsend; N. Van-Looy; L. Gao; E. Little; A. Turkova; S. Fabiane; J. Calvert; J. Blackstone; K. Scott; J. Inshaw; A. Nunn; A. Nardone; D. Bilardi; T.R. Cressey; S. Chalermpantmetagul; W. Khamduang; G. Jourdain; N. Ngo Giang Huong; D. Chinwong; C. Saenjum; R. Peongjakta; P. Sukrakanchana; L. Laomanit; A. Kaewbundit; J. Khamkon; K. Than-in-at; C. Meeboon; W. Sripaoraya; N. Krueduangkam; N. Kruenual; W. Khamjakkaew; S. Klinprung; C. Giaquinto; G. Morkunaite; D. Hirt; L. Prieto Tato; T. Niehues; D. Plonné; C. Morén; T. Noguera; M.A. Muñoz Fernández; R. Bologna; S. Arazi; A.G. Fedullo; M. Taicz; E. Vicentini; M. Moragas; A. Mangano; M. Dell’Orso; M. Gatto; V. Reliquet; A. Soria; E. Paredes; N. Chereau; M. Tching Sin; L. Flet; A. Rodallec; C. Hemon; N. Elenga; M.D. Terrine; N. Blaise; S. Augustin; P. Mespoulhe; H. Pouchain; N. Pavia-Ruz; R. Muñoz- Hernández; A. Neri-Macias; M.D. Jarillo-Quijada; C. Espinosa-Sotero; L. Marques; C. Teixeira; A. Fernandes; R. Nunes; H. Nascimento; J. Tuna; A. Padrao; I. Ferraz; A.C. Mendes; C. Correira; H. Pinheiro; A.C. Matos; A.C. Sampaio; A. Oliveira; A. Caldeira; M. Tavares; A. Reis Melo; C. Castro; C. Faria; C. Prucha; R. Ribeiro; F. Monteiro; M.F. Candeias; T. Silva Milhiero; E. Gomes Neves; R. Corte-Real; M. Morgado; D. Mendes; M. Cardão; A. Violari; N. Ramsagar; A. Liberty; M. Nyati; L. Maseko; M. Khunene; S. Mkhize; Z. Essack; N. Akoojee; U. Singh; Y. Fourie; S. Govender; A. Vadee; R. Lakha; J. Erasmus; A. Mamiane; T. Daniel; P. Bhana; N. Maduna; M. Cotton; M. Groenewald; G. Slade; J. Coetzee; L. Ganger; S. Weldon; M. Wessels; L. Hoorn; S. Pieterse; C. Makola; K. Smith; M. Isaacs; A. Cweya; S. Fry; S. Barnabas; M. Theunissen; N. Nduna; M. Smuts; P. Rojo Conejo; C. Epalza; M. Fernández; M.J. Mellado Peña; T. Sainz Costa; L. Escosa García; P. Gomez Salcedo; C. Fortuny Guasch; T. Noguera Julian; C. Estepa; M. Cubells; E. Sans; E. Bruno; L. Prieto; P. Mendez García; A. Murciano Cabeza; M. Coto; R. Torrent; M. Torres Arauz; M. Navarro Gómez; A. Mur; S. Guillén Martin; M. Moreno; J.T. Ramos Amador; I. Garcia; C. Kalhert; T. Wachinger; B. Wohlwend; S. Hafner; G. Dollenmaier; P. Paioni; R. Signorell; J. Boni; A. Duppenthaler; B. Mann; C. Saegesser; M. Barbani; C. Ngampiyaskul; P. Greetanukroh; P. Khannak; P. Tearsansern; W. Chamjamrat; N. Chanto; T. Thapwai; K. Thungkham; P. Puangmalai; C. Ruklao; P. Ounchanum; S. Khusuwan; S. Denjanta; Y. Thaweesombat; J. Thewsoongnoen; K. Kaewmamueng; P. Kamboua; S. Pongprapass; W. Srisuk; A. Kongponoi; J. Limplertjareanwanich; S. Kanjanavanit; C. Saewtrakool; P. Yingyong; D. Chutima; R. Junkaew; T. Chankun; U. Srirompotong; P. Sudsaard; K. Kongsuk; T. Petpranee; S. Srirojana; D. Donngernl; A. Kamkoonmongkol; N. Na Kalasin; P. Phunkhum; A.R. Kekitiinwa; P. Amuge; D. Bbuye; J. Nalubwama; S. Namanda; M. Nsibuka Kisekka; A. Kirabira; L. Lawrence; G. Agaba; G. Ahimbisibwe; A. Nalugo; F. Namuli; R. Kadhuba; R. Namuddu; I. Nabwire; L. Kiyimba; A. Baita; J. Tikabibamu; L. Nakandi; G.P. Kisitu; N. Nabukeera Barung; C.M. Kityo; V. Musiime; E. Kaudha; A. Nanduudu; E. Mujyambere; S.P. Labeja Ocitti; J. Ategeka; E. Nambi; R. Nazzinda; D. Rutebarika; R. Basiimwa; R. Mbabazi; P. Kyobutungi; M. Nabalamba; A. Nakalyango; J. Tumusiime; S. Nakabuye; J. Mwebaza; S. Oruk; J. Namusanje; A. Musiime; L. Mugarura; M. Ojok; J. Kitabalwa; C. Katemba; M. Nannungi; E. Bagirigomwa; D. Odoch; E. Rubanga; D. Mulima; E.L. Babu; D. Baliruno; C. Inyakuwal; E.D. Williams; A. Mulindwa; A. Uyungrwoth; I. Raus; O. Mostovenko; T. Stepchenkova; A. Volokha; N. Primak; J. Kenny; A. Callaghan; M. Ahmad; S. Vergnano; M. Ross; F. Manyi; D. Nayagam; S. Hawkins; C. Ball; E. Hamlyn; C. Gilmour; S. Gilmour-White; S. Doshi; E. Fuller; A. Adebayo; K. Tupper; E. Nsirim; S. Welch; J. Daglish; L. Thrasyvoulou; E. Irvine; K. Gandhi; Y. Vaughn-Gordon; N. Sibanda
Source
EClinicalMedicine, Vol 60, Iss , Pp 102025- (2023)
Subject
Language
English
ISSN
2589-5370
Abstract
Summary: Background: Integrase inhibitor (INSTI) with boosted darunavir (DRV/r), a regimen with a high-resistance barrier, avoiding NRTI toxicities, might be a switching option in children living with HIV (CLWHIV). Methods: SMILE is a randomised non-inferiority trial evaluating safety and antiviral efficacy of once-daily INSTI + DRV/r vs. continuing on current standard-of-care (SOC) triple ART (2NRTI + boosted PI/NNRTI) in virologically-suppressed CLWHIV aged 6–18 years. The primary outcome is the proportion with confirmed HIV-RNA ≥50 copies/mL by week 48, estimated by Kaplan–Meier method. Non-inferiority margin was 10%. Registration number for SMILE are: ISRCTN11193709, NCT #: NCT02383108. Findings: Between 10th June 2016 and 30th August 2019, 318 participants were enrolled from Africa 53%, Europe 24%, Thailand 15% and Latin America 8%, 158 INSTI + DRV/r [153 Dolutegravir (DTG); 5 Elvitegravir (EVG)], 160 SOC. Median (range) age was 14.7 years (7.6–18.0); CD4 count 782 cells/mm3 (227–1647); 61% female. Median follow-up was 64.3 weeks with no loss to follow-up. By 48 weeks, 8 INSTI + DRV/r vs. 12 SOC had confirmed HIV-RNA ≥50 copies/mL; difference (INSTI + DRV/r-SOC) −2.5% (95% CI: −7.6, 2.5%), showing non-inferiority. No major PI or INSTI resistance mutations were observed. There were no differences in safety between arms. By week 48, difference (INSTI + DRV/r-SOC) in mean CD4 count change from baseline was −48.3 cells/mm3 (95% CI: −93.4, −3.2; p = 0.036). Difference (INSTI + DRV/r-SOC) in mean HDL change from baseline was −4.1 mg/dL (95% CI: −6.7, −1.4; p = 0.003). Weight and Body Mass Index (BMI) increased more in INSTI + DRV/r than SOC [difference: 1.97 kg (95% CI: 1.1, 2.9; p