Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children
Autor: | Anna, Turkova, Ellen, White, Hilda A, Mujuru, Adeodata R, Kekitiinwa, Cissy M, Kityo, Avy, Violari, Abbas, Lugemwa, Tim R, Cressey, Philippa, Musoke, Ebrahim, Variava, Mark F, Cotton, Moherndran, Archary, Thanyawee, Puthanakit, Osee, Behuhuma, Robin, Kobbe, Steven B, Welch, Mutsa, Bwakura-Dangarembizi, Pauline, Amuge, Elizabeth, Kaudha, Linda, Barlow-Mosha, Shafic, Makumbi, Nastassja, Ramsagar, Chaiwat, Ngampiyaskul, Godfrey, Musoro, Lorna, Atwine, Afaaf, Liberty, Victor, Musiime, Dickson, Bbuye, Grace M, Ahimbisibwe, Suwalai, Chalermpantmetagul, Shabinah, Ali, Tatiana, Sarfati, Ben, Wynne, Clare, Shakeshaft, Angela, Colbers, Nigel, Klein, Sarah, Bernays, Yacine, Saïdi, Alexandra, Coelho, Tiziana, Grossele, Alexandra, Compagnucci, Carlo, Giaquinto, Pablo, Rojo, Deborah, Ford, Diana M, Gibb, Anna, Goodman |
---|---|
Rok vydání: | 2021 |
Předmět: |
Oral
Cyclopropanes Male Adolescent Pyridones Administration Oral HIV Infections 3-Ring Article Piperazines Drug Therapy Heterocyclic Compounds Oxazines Humans HIV Integrase Inhibitors Child Preschool Alkynes Anti-Retroviral Agents Benzoxazines Child Preschool Cholesterol Drug Therapy Combination Female HIV Protease Inhibitors Heterocyclic Compounds 3-Ring Viral Load HIV-1 General Medicine lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] Administration Combination |
Zdroj: | The New England Journal of Medicine, 385, 2531-2543 The New England Journal of Medicine, 385, 27, pp. 2531-2543 N Engl J Med |
ISSN: | 0028-4793 |
Popis: | Item does not contain fulltext 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 who were starting first- or second-line treatment, dolutegravir-based ART was superior to standard care. (Funded by ViiV Healthcare; ODYSSEY ClinicalTrials.gov number, NCT02259127; EUDRACT number, 2014-002632-14; and ISRCTN number, ISRCTN91737921.). |
Databáze: | OpenAIRE |
Externí odkaz: |