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

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dc.contributor.authorCompagnucci, Alexandra
dc.contributor.authorChan, Man K
dc.contributor.authorSaïdi, Yacine
dc.contributor.authorCressey, Tim R
dc.contributor.authorBamford, Alasdair
dc.contributor.authorRiault, Yoann
dc.contributor.authorCoelho, Alexandra
dc.contributor.authorNolan, Aoife
dc.contributor.authorChalermpantmetagul, Suwalai
dc.contributor.authorMorkunaite, Gabija
dc.contributor.authorAmuge, Pauline
dc.contributor.authorMusiime, Victor
dc.contributor.authorViolari, Avy
dc.contributor.authorCotton, Mark
dc.contributor.authorKekitiinwa, Adeodata R
dc.contributor.authorKaudha, Elizabeth
dc.contributor.authorGroenewald, Marisa
dc.contributor.authorLiberty, Afaaf A
dc.contributor.authorKanjanavanit, Suparat
dc.contributor.authorVolokha, Alla
dc.contributor.authorBologna, Rosa
dc.contributor.authorPavia Ruz, Noris
dc.contributor.authorPrieto Tato, Luis
dc.contributor.authorPaioni, Paolo
dc.contributor.authorMarques, Laura
dc.contributor.authorReliquet, Véronique
dc.contributor.authorNiehues, Tim
dc.contributor.authorWelch, Steven B
dc.contributor.authorFord, Deborah
dc.contributor.authorGiaquinto, Carlo
dc.contributor.authorGibb, Diana M
dc.contributor.authorBabiker, Abdel
dc.contributor.authorRamos Amador, Jose Tomas
dc.contributor.departmentPaediatricsen_US
dc.contributor.roleMedical and Dentalen_US
dc.contributor.trustauthorWelch, Steven
dc.date.accessioned2023-07-20T13:12:14Z
dc.date.available2023-07-20T13:12:14Z
dc.date.issued2023-06-02
dc.description.abstractBackground: 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 < 0.001), 0.66 kg/m2 (95% CI: 0.3, 1.0; p < 0.001)]. Interpretation: 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: Fondazione Penta Onlus, Gilead, Janssen, INSERM/ANRS and UK MRC. ViiV-Healthcare provided Dolutegravir.en_US
dc.identifier.citationCompagnucci A, Chan MK, Saïdi Y, Cressey TR, Bamford A, Riault Y, Coelho A, Nolan A, Chalermpantmetagul S, Morkunaite G, Amuge P, Musiime V, Violari A, Cotton M, Kekitiinwa AR, Kaudha E, Groenewald M, Liberty AA, Kanjanavanit S, Volokha A, Bologna R, Pavia Ruz N, Prieto Tato L, Paioni P, Marques L, Reliquet V, Niehues T, Welch SB, Ford D, Giaquinto C, Gibb DM, Babiker A, Ramos Amador JT; SMILE-PENTA17-ANRS 152 Trial Group. 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. EClinicalMedicine. 2023 Jun 2;60:102025. doi: 10.1016/j.eclinm.2023.102025.en_US
dc.identifier.doi10.1016/j.eclinm.2023.102025
dc.identifier.eissn2589-5370
dc.identifier.pmid37304494
dc.identifier.urihttp://hdl.handle.net/20.500.14200/1295
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/journals/3674/en_US
dc.relation.urlhttps://www.sciencedirect.com/science/journal/25895370en_US
dc.rights© 2023 The Authors.
dc.source.journaltitleEClinicalMedicine
dc.subjectPaediatricsen_US
dc.subjectMicrobiology. Immunologyen_US
dc.subjectCommunicable diseases
dc.titleNucleoside/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 trialen_US
dc.typeArticle
dspace.entity.typePublication
oa.grant.openaccessnaen_US
rioxxterms.versionNAen_US
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