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 trial.

Adolescents Children Darunavir Dolutegravir Dual therapy HIV Maintenance Paediatrics Randomised Simplification Virological suppressed

Journal

EClinicalMedicine

ISSN: 2589-5370

Titre abrégé: EClinicalMedicine

Pays: England

ID NLM: 101733727

Informations de publication

Date de publication:
Jun 2023

Historique:

received: 09 03 2023

revised: 11 05 2023

accepted: 11 05 2023

medline: 12 6 2023

pubmed: 12 6 2023

entrez: 12 6 2023

Statut: epublish

Résumé

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). 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. 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/mm In virologically-suppressed children, switching to INSTI + DRV/r was non-inferior virologically, with similar safety profile, to continuing SOC. Small but significant differences in CD4, HDL-cholesterol, weight and BMI were observed between INSTI + DRV/r vs. SOC although clinical relevance needs further investigation. SMILE data corroborate adult findings and provide evidence for this NRTI-sparing regimen for children and adolescents. Fondazione Penta Onlus, Gilead, Janssen, INSERM/ANRS and UK MRC. ViiV-Healthcare provided Dolutegravir.

Sections du résumé

Background UNASSIGNED

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 UNASSIGNED

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 UNASSIGNED

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/mm

Interpretation UNASSIGNED

In virologically-suppressed children, switching to INSTI + DRV/r was non-inferior virologically, with similar safety profile, to continuing SOC. Small but significant differences in CD4, HDL-cholesterol, weight and BMI were observed between INSTI + DRV/r vs. SOC although clinical relevance needs further investigation. SMILE data corroborate adult findings and provide evidence for this NRTI-sparing regimen for children and adolescents.

Funding UNASSIGNED

Fondazione Penta Onlus, Gilead, Janssen, INSERM/ANRS and UK MRC. ViiV-Healthcare provided Dolutegravir.

Identifiants

DOI: 10.1016/j.eclinm.2023.102025 PMID: 37304494 PMC: PMC10251070

pubmed: 37304494

doi: 10.1016/j.eclinm.2023.102025

pii: S2589-5370(23)00202-X

pmc: PMC10251070

doi:

Banques de données

ClinicalTrials.gov

['NCT02383108']

Types de publication

Journal Article

Langues

eng

Pagination

102025

Investigateurs

A Compagnucci (A)

Y Saidi (Y)

Y Riault (Y)

A Coelho (A)

C Kouakam (C)

L Picault (L)

M Ndiaye (M)

L Meyer (L)

C Cagnot (C)

S Circosta (S)

L Léger (L)

S Simanic (S)

A Arulananthan (A)

D M Gibb (DM)

A Babiker (A)

M Chan (M)

D Ford (D)

F Hudson (F)

L Harper (L)

A Bamford (A)

A Nolan (A)

K Widuch (K)

S Townsend (S)

N Van-Looy (N)

L Gao (L)

E Little (E)

A Turkova (A)

S Fabiane (S)

J Calvert (J)

J Blackstone (J)

K Scott (K)

J Inshaw (J)

A Nunn (A)

A Nardone (A)

D Bilardi (D)

T R Cressey (TR)

S Chalermpantmetagul (S)

W Khamduang (W)

G Jourdain (G)

N Ngo Giang Huong (N)

D Chinwong (D)

C Saenjum (C)

R Peongjakta (R)

P Sukrakanchana (P)

L Laomanit (L)

A Kaewbundit (A)

J Khamkon (J)

K Than-In-At (K)

C Meeboon (C)

W Sripaoraya (W)

N Krueduangkam (N)

N Kruenual (N)

W Khamjakkaew (W)

S Klinprung (S)

C Giaquinto (C)

G Morkunaite (G)

D Hirt (D)

L Prieto Tato (L)

T Niehues (T)

D Plonné (D)

C Morén (C)

T Noguera (T)

M A Muñoz Fernández (MA)

R Bologna (R)

S Arazi (S)

A G Fedullo (AG)

M Taicz (M)

E Vicentini (E)

M Moragas (M)

A Mangano (A)

M Dell'Orso (M)

M Gatto (M)

V Reliquet (V)

A Soria (A)

E Paredes (E)

N Chereau (N)

M Tching Sin (M)

L Flet (L)

A Rodallec (A)

C Hemon (C)

N Elenga (N)

M D Terrine (MD)

N Blaise (N)

S Augustin (S)

P Mespoulhe (P)

H Pouchain (H)

N Pavia-Ruz (N)

R Muñoz-Hernández (R)

A Neri-Macias (A)

M D Jarillo-Quijada (MD)

C Espinosa-Sotero (C)

L Marques (L)

C Teixeira (C)

A Fernandes (A)

R Nunes (R)

H Nascimento (H)

J Tuna (J)

A Padrao (A)

I Ferraz (I)

A C Mendes (AC)

C Correira (C)

H Pinheiro (H)

A C Matos (AC)

A C Sampaio (AC)

A Oliveira (A)

A Caldeira (A)

M Tavares (M)

A Reis Melo (A)

C Castro (C)

C Faria (C)

C Prucha (C)

R Ribeiro (R)

F Monteiro (F)

M F Candeias (MF)

T Silva Milhiero (T)

E Gomes Neves (E)

A Oliveira (A)

R Corte-Real (R)

M Morgado (M)

D Mendes (D)

M Cardão (M)

A Violari (A)

N Ramsagar (N)

A Liberty (A)

M Nyati (M)

L Maseko (L)

M Khunene (M)

S Mkhize (S)

Z Essack (Z)

N Akoojee (N)

U Singh (U)

Y Fourie (Y)

S Govender (S)

A Vadee (A)

R Lakha (R)

J Erasmus (J)

A Mamiane (A)

T Daniel (T)

P Bhana (P)

N Maduna (N)

M Cotton (M)

M Groenewald (M)

G Slade (G)

J Coetzee (J)

L Ganger (L)

S Weldon (S)

M Wessels (M)

L Hoorn (L)

S Pieterse (S)

C Makola (C)

K Smith (K)

M Isaacs (M)

A Cweya (A)

S Fry (S)

S Barnabas (S)

M Theunissen (M)

N Nduna (N)

M Smuts (M)

P Rojo Conejo (P)

C Epalza (C)

L Prieto Tato (L)

M Fernández (M)

M J Mellado Peña (MJ)

T Sainz Costa (T)

L Escosa García (L)

P Gomez Salcedo (P)

C Fortuny Guasch (C)

T Noguera Julian (T)

C Estepa (C)

M Cubells (M)

E Sans (E)

E Bruno (E)

L Prieto (L)

P Mendez García (P)

A Murciano Cabeza (A)

M Coto (M)

R Torrent (R)

M Torres Arauz (M)

M Navarro Gómez (M)

A Mur (A)

S Guillén Martin (S)

M Moreno (M)

J T Ramos Amador (JT)

I Garcia (I)

C Kalhert (C)

T Wachinger (T)

B Wohlwend (B)

S Hafner (S)

G Dollenmaier (G)

P Paioni (P)

R Signorell (R)

J Boni (J)

A Duppenthaler (A)

B Mann (B)

C Saegesser (C)

M Barbani (M)

C Ngampiyaskul (C)

P Greetanukroh (P)

P Khannak (P)

P Tearsansern (P)

W Chamjamrat (W)

N Chanto (N)

T Thapwai (T)

K Thungkham (K)

P Puangmalai (P)

C Ruklao (C)

P Ounchanum (P)

S Khusuwan (S)

S Denjanta (S)

Y Thaweesombat (Y)

J Thewsoongnoen (J)

K Kaewmamueng (K)

P Kamboua (P)

S Pongprapass (S)

W Srisuk (W)

A Kongponoi (A)

J Limplertjareanwanich (J)

S Kanjanavanit (S)

C Saewtrakool (C)

P Yingyong (P)

D Chutima (D)

R Junkaew (R)

T Chankun (T)

U Srirompotong (U)

P Sudsaard (P)

K Kongsuk (K)

T Petpranee (T)

S Srirojana (S)

D Donngernl (D)

A Kamkoonmongkol (A)

N Na Kalasin (N)

P Phunkhum (P)

A R Kekitiinwa (AR)

P Amuge (P)

D Bbuye (D)

J Nalubwama (J)

S Namanda (S)

M Nsibuka Kisekka (M)

A Kirabira (A)

L Lawrence (L)

G Agaba (G)

G Ahimbisibwe (G)

A Nalugo (A)

F Namuli (F)

R Kadhuba (R)

R Namuddu (R)

I Nabwire (I)

L Kiyimba (L)

A Baita (A)

J Tikabibamu (J)

L Nakandi (L)

G P Kisitu (GP)

N Nabukeera Barung (N)

C M Kityo (CM)

V Musiime (V)

E Kaudha (E)

A Nanduudu (A)

E Mujyambere (E)

S P Labeja Ocitti (SP)

J Ategeka (J)

E Nambi (E)

R Nazzinda (R)

D Rutebarika (D)

R Basiimwa (R)

R Mbabazi (R)

P Kyobutungi (P)

M Nabalamba (M)

A Nakalyango (A)

J Tumusiime (J)

S Nakabuye (S)

J Mwebaza (J)

S Oruk (S)

J Namusanje (J)

A Musiime (A)

L Mugarura (L)

M Ojok (M)

J Kitabalwa (J)

C Katemba (C)

M Nannungi (M)

E Bagirigomwa (E)

D Odoch (D)

E Rubanga (E)

D Mulima (D)

E L Babu (EL)

D Baliruno (D)

C Inyakuwal (C)

E D Williams (ED)

A Mulindwa (A)

A Uyungrwoth (A)

I Raus (I)

O Mostovenko (O)

T Stepchenkova (T)

A Volokha (A)

N Primak (N)

J Kenny (J)

A Callaghan (A)

M Ahmad (M)

S Vergnano (S)

M Ross (M)

F Manyi (F)

D Nayagam (D)

S Hawkins (S)

C Ball (C)

E Hamlyn (E)

C Gilmour (C)

S Gilmour-White (S)

S Doshi (S)

E Fuller (E)

A Adebayo (A)

K Tupper (K)

E Nsirim (E)

S Welch (S)

J Daglish (J)

L Thrasyvoulou (L)

E Irvine (E)

K Gandhi (K)

Y Vaughn-Gordon (Y)

N Sibanda (N)

Informations de copyright

Déclaration de conflit d'intérêts

ACom, YS, YR and ACoe declare that their institution Inserm received a grant for the trial through PENTA Foundation “agreement PENTA-Inserm” started 14th September 2014 and declare support for scientific meetings from PENTA Foundation. AVi declares funding given from PENTA Foundation to her institution for the conduct of the study. ABab declares a grant from Medical Research Council, UKRI to his Institution. PA and ADK declare sponsored study materials and participant recruitment costs from PENTA foundation. PA, ADK and CG declare a research grant for part of the study from Gilead and funded drug supply for the study from ViiV Healthcare. NPR declares a financial support for the research paid to her institution from PENTA Foundation and from Merck. NPR declares that her institution receives the drugs for the study from PENTA Foundation. NPR declares a support for attending ID week in 2022 from AstraZeneca. All other authors declare no competing interests.

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