Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children
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| Název: | Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children |
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| Autoři: | Turkova, Anna, White, Ellen, Mujuru, Hilda, Kekitiinwa, Adeodata, Kityo, Cissy, Violari, Avy, Lugemwa, Abbas, Cressey, Tim, Musoke, Philippa, Variava, Ebrahim, Cotton, Mark, Archary, Moherndran, Puthanakit, Thanyawee, Behuhuma, Osee, Kobbe, Robin, Welch, Steven, Bwakura-Dangarembizi, Mutsa, Amuge, Pauline, Kaudha, Elizabeth, Barlow-Mosha, Linda, Makumbi, Shafic, Ramsagar, Nastassja, Ngampiyaskul, Chaiwat, Musoro, Godfrey, Atwine, Lorna, Liberty, Afaaf, Musiime, Victor, Bbuye, Dickson, Ahimbisibwe, Grace, Chalermpantmetagul, Suwalai, Ali, Shabinah, Sarfati, Tatiana, Wynne, Ben, Shakeshaft, Clare, Colbers, Angela, Klein, Nigel, Bernays, Sarah, Saïdi, Yacine, Coelho, Alexandra, Grossele, Tiziana, Compagnucci, Alexandra, Giaquinto, Carlo, Rojo, Pablo, Ford, Deborah, Gibb, Diana, Leroy, Valeriane |
| Přispěvatelé: | Medical Research Council Clinical Trials Unit (MRC CTU), University College of London London (UCL), Institute of Clinical Trials and Methodology London (ICTM), University of Zimbabwe (UZ), Baylor College of Medicine (BCM), Baylor University, Bugema University Kampala, University of the Witwatersrand Johannesburg (WITS), Joint Clinical Research Centre, Chiang Mai University (CMU), Stellenbosch University, University of KwaZulu-Natal Durban, Afrique du Sud (UKZN), Chulalongkorn University Bangkok, Africa Health Research Institute Durban/Mtubatuba (AHRI), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf Hamburg (UKE), Equipe SPHERE (CERPOP), Centre d'Epidémiologie et de Recherche en santé des POPulations (CERPOP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), MC_UU_12023/23/MRC_/Medical Research Council/United KingdomMC_UU_00004/03/MRC_/Medical Research Council/United Kingdom |
| Zdroj: | ISSN: 0028-4793. |
| Informace o vydavateli: | CCSD Massachusetts Medical Society |
| Rok vydání: | 2021 |
| Sbírka: | Université Toulouse III - Paul Sabatier: HAL-UPS |
| Témata: | MESH: Administration, Oral, MESH: Adolescent, MESH: HIV Infections / virology, MESH: HIV Integrase Inhibitors / administration & dosage, MESH: Alkynes / therapeutic use, MESH: Anti-Retroviral Agents / adverse effects, MESH: Anti-Retroviral Agents / therapeutic use, MESH: Benzoxazines / therapeutic use, MESH: Child, Preschool, MESH: Cholesterol / blood, MESH: Cyclopropanes / therapeutic use, MESH: Drug Therapy, Combination, MESH: Female, MESH: HIV Infections / drug therapy, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie |
| Popis: | International audience ; 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 ... |
| Druh dokumentu: | article in journal/newspaper |
| Jazyk: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/34965338; PUBMED: 34965338; PUBMEDCENTRAL: PMC7614690 |
| DOI: | 10.1056/NEJMoa2108793 |
| Dostupnost: | https://hal.science/hal-04682062 https://doi.org/10.1056/NEJMoa2108793 |
| Rights: | http://hal.archives-ouvertes.fr/licences/copyright/ |
| Přístupové číslo: | edsbas.314A7640 |
| Databáze: | BASE |
Nájsť tento článok vo Web of Science | Abstrakt: | International audience ; 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 ... |
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| DOI: | 10.1056/NEJMoa2108793 |