1. 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
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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, and N. Sibanda
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HIV ,Children ,Adolescents ,Randomised ,Paediatrics ,Dual therapy ,Medicine (General) ,R5-920 - 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
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- 2023
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