1. Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children.
- Author
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Turkova A, White E, Mujuru HA, Kekitiinwa AR, Kityo CM, Violari A, Lugemwa A, Cressey TR, Musoke P, Variava E, Cotton MF, Archary M, Puthanakit T, Behuhuma O, Kobbe R, Welch SB, Bwakura-Dangarembizi M, Amuge P, Kaudha E, Barlow-Mosha L, Makumbi S, Ramsagar N, Ngampiyaskul C, Musoro G, Atwine L, Liberty A, Musiime V, Bbuye D, Ahimbisibwe GM, Chalermpantmetagul S, Ali S, Sarfati T, Wynne B, Shakeshaft C, Colbers A, Klein N, Bernays S, Saïdi Y, Coelho A, Grossele T, Compagnucci A, Giaquinto C, Rojo P, Ford D, and Gibb DM
- Subjects
- Administration, Oral, Adolescent, Alkynes therapeutic use, Anti-Retroviral Agents adverse effects, Benzoxazines therapeutic use, Child, Child, Preschool, Cholesterol blood, Cyclopropanes therapeutic use, Drug Therapy, Combination, Female, HIV Infections virology, HIV Integrase Inhibitors administration & dosage, HIV Integrase Inhibitors adverse effects, HIV Protease Inhibitors therapeutic use, Heterocyclic Compounds, 3-Ring administration & dosage, Heterocyclic Compounds, 3-Ring adverse effects, Humans, Male, Oxazines administration & dosage, Oxazines adverse effects, Piperazines administration & dosage, Piperazines adverse effects, Pyridones administration & dosage, Pyridones adverse effects, Viral Load drug effects, Anti-Retroviral Agents therapeutic use, HIV Infections drug therapy, HIV Integrase Inhibitors therapeutic use, HIV-1 isolation & purification, Heterocyclic Compounds, 3-Ring therapeutic use, Oxazines therapeutic use, Piperazines therapeutic use, Pyridones therapeutic use
- Abstract
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.)., (Copyright © 2021 Massachusetts Medical Society.)
- Published
- 2021
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