TY  - JOUR
PY  - 2021//
TI  - Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children
JO  - New England journal of medicine
A1  - Turkova, A.
A1  - White, E.
A1  - Mujuru, H.A.
A1  - Kekitiinwa, A.R.
A1  - Kityo, C.M.
A1  - Violari, A.
A1  - Lugemwa, A.
A1  - Cressey, T.R.
A1  - Musoke, P.
A1  - Variava, E.
A1  - Cotton, M.F.
A1  - Archary, M.
A1  - Puthanakit, T.
A1  - Behuhuma, O.
A1  - Kobbe, R.
A1  - Welch, S.B.
A1  - Bwakura-Dangarembizi, M.
A1  - Amuge, P.
A1  - Kaudha, E.
A1  - Barlow-Mosha, L.
A1  - Makumbi, S.
A1  - Ramsagar, N.
A1  - Ngampiyaskul, C.
A1  - Musoro, G.
A1  - Atwine, L.
A1  - Liberty, A.
A1  - Musiime, V.
A1  - Bbuye, D.
A1  - Ahimbisibwe, G.M.
A1  - Chalermpantmetagul, S.
A1  - Ali, S.
A1  - Sarfati, T.
A1  - Wynne, B.
A1  - Shakeshaft, C.
A1  - Colbers, A.
A1  - Klein, N.
A1  - Bernays, S.
A1  - Saïdi, Y.
A1  - Coelho, A.
A1  - Grossele, T.
A1  - Compagnucci, A.
A1  - Giaquinto, C.
A1  - Rojo, P.
A1  - Ford, D.
A1  - Gibb, D.M.
SP  - 2531
EP  - 2543
VL  - 385
IS  - 27
N2  - BACKGROUND Children with human immunodeficiency virus type 1 (HIV-1) infection have limited options for effective antiretroviral treatment (ART). <br><br>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. <br><br>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 followup 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). <br><br>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.<p /> <p>Language: en</p>
LA  - en
SN  - 0028-4793
UR  - http://dx.doi.org/10.1056/NEJMoa2108793
ID  - ref1
ER  -