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Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children

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Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children. / Turkova, Anna; White, Ellen; Mujuru, Hilda A; Kekitiinwa, Adeodata R; Kityo, Cissy M; Violari, Avy; Lugemwa, Abbas; Cressey, Tim R; Musoke, Philippa; Variava, Ebrahim; Cotton, Mark F; Archary, Moherndran; Puthanakit, Thanyawee; Behuhuma, Osee; Kobbe, Robin; Welch, Steven B; 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 M; 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 M; ODYSSEY Trial Team.

In: NEW ENGL J MED, Vol. 385, No. 27, 30.12.2021, p. 2531-2543.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

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, Gibb, DM & ODYSSEY Trial Team 2021, 'Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children', NEW ENGL J MED, vol. 385, no. 27, pp. 2531-2543. https://doi.org/10.1056/NEJMoa2108793

APA

Turkova, A., White, E., Mujuru, H. A., Kekitiinwa, A. R., Kityo, C. M., Violari, A., Lugemwa, A., Cressey, T. R., Musoke, P., Variava, E., Cotton, M. F., Archary, M., Puthanakit, T., Behuhuma, O., Kobbe, R., Welch, S. B., Bwakura-Dangarembizi, M., Amuge, P., Kaudha, E., ... ODYSSEY Trial Team (2021). Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children. NEW ENGL J MED, 385(27), 2531-2543. https://doi.org/10.1056/NEJMoa2108793

Vancouver

Turkova A, White E, Mujuru HA, Kekitiinwa AR, Kityo CM, Violari A et al. Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children. NEW ENGL J MED. 2021 Dec 30;385(27):2531-2543. https://doi.org/10.1056/NEJMoa2108793

Bibtex

@article{5bc4985bc77645b08db793c698c06599,
title = "Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children",
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.).",
keywords = "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/drug therapy, HIV Integrase Inhibitors/administration & dosage, HIV Protease Inhibitors/therapeutic use, HIV-1/isolation & purification, Heterocyclic Compounds, 3-Ring/administration & dosage, Humans, Male, Oxazines/administration & dosage, Piperazines/administration & dosage, Pyridones/administration & dosage, Viral Load/drug effects",
author = "Anna Turkova and Ellen White and Mujuru, {Hilda A} and Kekitiinwa, {Adeodata R} and Kityo, {Cissy M} and Avy Violari and Abbas Lugemwa and Cressey, {Tim R} and Philippa Musoke and Ebrahim Variava and Cotton, {Mark F} and Moherndran Archary and Thanyawee Puthanakit and Osee Behuhuma and Robin Kobbe and Welch, {Steven B} and Mutsa Bwakura-Dangarembizi and Pauline Amuge and Elizabeth Kaudha and Linda Barlow-Mosha and Shafic Makumbi and Nastassja Ramsagar and Chaiwat Ngampiyaskul and Godfrey Musoro and Lorna Atwine and Afaaf Liberty and Victor Musiime and Dickson Bbuye and Ahimbisibwe, {Grace M} and Suwalai Chalermpantmetagul and Shabinah Ali and Tatiana Sarfati and Ben Wynne and Clare Shakeshaft and Angela Colbers and Nigel Klein and Sarah Bernays and Yacine Sa{\"i}di and Alexandra Coelho and Tiziana Grossele and Alexandra Compagnucci and Carlo Giaquinto and Pablo Rojo and Deborah Ford and Gibb, {Diana M} and {ODYSSEY Trial Team} and Cornelius Rau and Ulf Schulze-Sturm",
note = "Copyright {\textcopyright} 2021 Massachusetts Medical Society.",
year = "2021",
month = dec,
day = "30",
doi = "10.1056/NEJMoa2108793",
language = "English",
volume = "385",
pages = "2531--2543",
journal = "NEW ENGL J MED",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "27",

}

RIS

TY - JOUR

T1 - Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children

AU - Turkova, Anna

AU - White, Ellen

AU - Mujuru, Hilda A

AU - Kekitiinwa, Adeodata R

AU - Kityo, Cissy M

AU - Violari, Avy

AU - Lugemwa, Abbas

AU - Cressey, Tim R

AU - Musoke, Philippa

AU - Variava, Ebrahim

AU - Cotton, Mark F

AU - Archary, Moherndran

AU - Puthanakit, Thanyawee

AU - Behuhuma, Osee

AU - Kobbe, Robin

AU - Welch, Steven B

AU - Bwakura-Dangarembizi, Mutsa

AU - Amuge, Pauline

AU - Kaudha, Elizabeth

AU - Barlow-Mosha, Linda

AU - Makumbi, Shafic

AU - Ramsagar, Nastassja

AU - Ngampiyaskul, Chaiwat

AU - Musoro, Godfrey

AU - Atwine, Lorna

AU - Liberty, Afaaf

AU - Musiime, Victor

AU - Bbuye, Dickson

AU - Ahimbisibwe, Grace M

AU - Chalermpantmetagul, Suwalai

AU - Ali, Shabinah

AU - Sarfati, Tatiana

AU - Wynne, Ben

AU - Shakeshaft, Clare

AU - Colbers, Angela

AU - Klein, Nigel

AU - Bernays, Sarah

AU - Saïdi, Yacine

AU - Coelho, Alexandra

AU - Grossele, Tiziana

AU - Compagnucci, Alexandra

AU - Giaquinto, Carlo

AU - Rojo, Pablo

AU - Ford, Deborah

AU - Gibb, Diana M

AU - ODYSSEY Trial Team

AU - Rau, Cornelius

AU - Schulze-Sturm, Ulf

N1 - Copyright © 2021 Massachusetts Medical Society.

PY - 2021/12/30

Y1 - 2021/12/30

N2 - 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.).

AB - 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.).

KW - Administration, Oral

KW - Adolescent

KW - Alkynes/therapeutic use

KW - Anti-Retroviral Agents/adverse effects

KW - Benzoxazines/therapeutic use

KW - Child

KW - Child, Preschool

KW - Cholesterol/blood

KW - Cyclopropanes/therapeutic use

KW - Drug Therapy, Combination

KW - Female

KW - HIV Infections/drug therapy

KW - HIV Integrase Inhibitors/administration & dosage

KW - HIV Protease Inhibitors/therapeutic use

KW - HIV-1/isolation & purification

KW - Heterocyclic Compounds, 3-Ring/administration & dosage

KW - Humans

KW - Male

KW - Oxazines/administration & dosage

KW - Piperazines/administration & dosage

KW - Pyridones/administration & dosage

KW - Viral Load/drug effects

U2 - 10.1056/NEJMoa2108793

DO - 10.1056/NEJMoa2108793

M3 - SCORING: Journal article

C2 - 34965338

VL - 385

SP - 2531

EP - 2543

JO - NEW ENGL J MED

JF - NEW ENGL J MED

SN - 0028-4793

IS - 27

ER -