Fixed-dose combination dolutegravir, abacavir, and lamivudine versus ritonavir-boosted atazanavir plus tenofovir disoproxil fumarate and emtricitabine in previously untreated women with HIV-1 infection (ARIA)

week 48 results from a randomised, open-label, non-inferiority, phase 3b study

ARIA study team

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background Dolutegravir is a once-daily integrase strand transfer inhibitor with no need for pharmacokinetic boosting that is approved for the treatment of HIV-1 infection. Because women are often under-represented in HIV clinical trials, we addressed the safety and efficacy of dolutegravir in women with HIV-1. Methods The ARIA study is a randomised, open-label, multicentre, active-controlled, parallel-group, non-inferiority phase 3b study done in 86 hospital and university infectious disease clinics, local health clinics, and private infectious disease clinics in 12 countries and one US territory, in North America, South America, Europe, Africa, and Asia. Eligible participants were women aged 18 years or older who had HIV-1 RNA viral loads of 500 copies per mL or greater, had received 10 days or less of previous antiretroviral therapy, and had tested negative for the HLA-B*5701 allele. Pregnant women were excluded. Eligible women were randomly assigned (1:1) to receive either a single-tablet regimen of dolutegravir plus abacavir and lamivudine once a day (dolutegravir group) or a three-tablet combination of ritonavir-boosted atazanavir plus coformulated tenofovir disoproxil fumarate and emtricitabine once a day (atazanavir group). Random treatment group assignment was stratified by plasma HIV-1 RNA viral loads and CD4 cell count at baseline. The primary endpoint was the proportion of participants with HIV-1 RNA viral loads of less than 50 copies per mL at week 48 in all participants who received at least one dose of study medication (intention-to-treat exposed population). We used a non-inferiority margin of −12%. Investigators monitored adverse events to assess safety. This study is registered with ClinicalTrials.gov, number NCT01910402. Findings Between Aug 22, 2013, and Sept 22, 2015, of 705 women assessed, 499 were randomly assigned to either the dolutegravir group (n=250) or the atazanavir group (n=249); two participants from each group were randomised to treatment but did not receive study medication. At week 48, 203 (82%) of 248 participants in the dolutegravir group compared with 176 (71%) of 247 in the atazanavir group had HIV-1 RNA viral loads of less than 50 copies per mL (mean difference 10·5%, 95% CI 3·1–17·8, p=0·005). One participant in the atazanavir group had nucleoside reverse transcriptase inhibitor–associated resistance that led to reduced emtricitabine susceptibility. Adverse events were similar between the dolutegravir and atazanavir groups; the most common were nausea (46 [19%] of 248 in the dolutegravir group vs 49 [20%] of 247 in the atazanavir group) and headache (28 [11%] vs 32 [13%]). Fewer participants in the dolutegravir group than the atazanavir group reported drug-related adverse events (83 [33%] vs 121 [49%]) or adverse events that led to discontinuation (ten [4%] vs 17 [7%]). One death was reported in each treatment group, but neither was considered related to the study medications. Interpretation The non-inferior efficacy and similar safety profile of the dolutegravir combined regimen compared with the atazanavir regimen support the use of dolutegravir for HIV-1 infection in treatment-naive women. Funding ViiV Healthcare.

Original languageEnglish (US)
Pages (from-to)e536-e546
JournalThe Lancet HIV
Volume4
Issue number12
DOIs
StatePublished - Dec 1 2017

Fingerprint

Tenofovir
Ritonavir
HIV Infections
HIV-1
Viral Load
RNA
Safety
Tablets
Communicable Diseases
dolutegravir
Atazanavir Sulfate
lamivudine drug combination abacavir
Emtricitabine
Therapeutics

ASJC Scopus subject areas

  • Epidemiology
  • Immunology
  • Infectious Diseases
  • Virology

Cite this

@article{2ef377bd51244a3da32d878aa0fc8ae0,
title = "Fixed-dose combination dolutegravir, abacavir, and lamivudine versus ritonavir-boosted atazanavir plus tenofovir disoproxil fumarate and emtricitabine in previously untreated women with HIV-1 infection (ARIA): week 48 results from a randomised, open-label, non-inferiority, phase 3b study",
abstract = "Background Dolutegravir is a once-daily integrase strand transfer inhibitor with no need for pharmacokinetic boosting that is approved for the treatment of HIV-1 infection. Because women are often under-represented in HIV clinical trials, we addressed the safety and efficacy of dolutegravir in women with HIV-1. Methods The ARIA study is a randomised, open-label, multicentre, active-controlled, parallel-group, non-inferiority phase 3b study done in 86 hospital and university infectious disease clinics, local health clinics, and private infectious disease clinics in 12 countries and one US territory, in North America, South America, Europe, Africa, and Asia. Eligible participants were women aged 18 years or older who had HIV-1 RNA viral loads of 500 copies per mL or greater, had received 10 days or less of previous antiretroviral therapy, and had tested negative for the HLA-B*5701 allele. Pregnant women were excluded. Eligible women were randomly assigned (1:1) to receive either a single-tablet regimen of dolutegravir plus abacavir and lamivudine once a day (dolutegravir group) or a three-tablet combination of ritonavir-boosted atazanavir plus coformulated tenofovir disoproxil fumarate and emtricitabine once a day (atazanavir group). Random treatment group assignment was stratified by plasma HIV-1 RNA viral loads and CD4 cell count at baseline. The primary endpoint was the proportion of participants with HIV-1 RNA viral loads of less than 50 copies per mL at week 48 in all participants who received at least one dose of study medication (intention-to-treat exposed population). We used a non-inferiority margin of −12{\%}. Investigators monitored adverse events to assess safety. This study is registered with ClinicalTrials.gov, number NCT01910402. Findings Between Aug 22, 2013, and Sept 22, 2015, of 705 women assessed, 499 were randomly assigned to either the dolutegravir group (n=250) or the atazanavir group (n=249); two participants from each group were randomised to treatment but did not receive study medication. At week 48, 203 (82{\%}) of 248 participants in the dolutegravir group compared with 176 (71{\%}) of 247 in the atazanavir group had HIV-1 RNA viral loads of less than 50 copies per mL (mean difference 10·5{\%}, 95{\%} CI 3·1–17·8, p=0·005). One participant in the atazanavir group had nucleoside reverse transcriptase inhibitor–associated resistance that led to reduced emtricitabine susceptibility. Adverse events were similar between the dolutegravir and atazanavir groups; the most common were nausea (46 [19{\%}] of 248 in the dolutegravir group vs 49 [20{\%}] of 247 in the atazanavir group) and headache (28 [11{\%}] vs 32 [13{\%}]). Fewer participants in the dolutegravir group than the atazanavir group reported drug-related adverse events (83 [33{\%}] vs 121 [49{\%}]) or adverse events that led to discontinuation (ten [4{\%}] vs 17 [7{\%}]). One death was reported in each treatment group, but neither was considered related to the study medications. Interpretation The non-inferior efficacy and similar safety profile of the dolutegravir combined regimen compared with the atazanavir regimen support the use of dolutegravir for HIV-1 infection in treatment-naive women. Funding ViiV Healthcare.",
author = "{ARIA study team} and Catherine Orrell and Hagins, {Debbie P.} and Elena Belonosova and Norma Porteiro and Sharon Walmsley and Vicen{\cc} Falc{\'o} and Man, {Choy Y.} and Alicia Aylott and Buchanan, {Ann M.} and Brian Wynne and Cindy Vavro and Michael Aboud and Smith, {Kimberly Y.} and Cahn, {Pedro Enrique} and Cassetti, {Lidia Isabel} and {Porteiro Barreira}, Norma and Angel, {Jonathan Benjamin} and {de Pokomandy}, Alexandra and Marianne Harris and Rachlis, {Anita R.} and Clotilde Allavena and Oliver Bouchaud and Caroline Gatey and Agathe Rami and Salvatore Casari and {Di Perri}, Giovanni and Adriano Lazzarin and Franco Maggiolo and Giovanni Penco and Tiziana Quirino and Giuliano Rizzardini and Andrade-Villanueva, {Jaime Federico} and Sierra-Madero, {Juan G.} and Teresa Branco and Rosario Serrao and Teofilo, {Eugenio JR} and Ivan Melendez-Rivera and Lizette Santiago and Zorrilla, {Carmen D.} and Chernova, {Oksana E.} and Vadim Pokrovsky and Rakhmanova, {Aza Gasanovna} and Olga Tsybakova and Eugene Voronin and Tasneem Vally and Farisani, {Livhuwani ML} and Sebopa, {Boitumelo Lucrecia} and Barros, {Carlos Aguado} and {Cano S{\'a}nchez}, Alfredo and Sandkovsky, {Uriel S}",
year = "2017",
month = "12",
day = "1",
doi = "10.1016/S2352-3018(17)30095-4",
language = "English (US)",
volume = "4",
pages = "e536--e546",
journal = "The Lancet HIV",
issn = "2352-3018",
publisher = "Elsevier Limited",
number = "12",

}

TY - JOUR

T1 - Fixed-dose combination dolutegravir, abacavir, and lamivudine versus ritonavir-boosted atazanavir plus tenofovir disoproxil fumarate and emtricitabine in previously untreated women with HIV-1 infection (ARIA)

T2 - week 48 results from a randomised, open-label, non-inferiority, phase 3b study

AU - ARIA study team

AU - Orrell, Catherine

AU - Hagins, Debbie P.

AU - Belonosova, Elena

AU - Porteiro, Norma

AU - Walmsley, Sharon

AU - Falcó, Vicenç

AU - Man, Choy Y.

AU - Aylott, Alicia

AU - Buchanan, Ann M.

AU - Wynne, Brian

AU - Vavro, Cindy

AU - Aboud, Michael

AU - Smith, Kimberly Y.

AU - Cahn, Pedro Enrique

AU - Cassetti, Lidia Isabel

AU - Porteiro Barreira, Norma

AU - Angel, Jonathan Benjamin

AU - de Pokomandy, Alexandra

AU - Harris, Marianne

AU - Rachlis, Anita R.

AU - Allavena, Clotilde

AU - Bouchaud, Oliver

AU - Gatey, Caroline

AU - Rami, Agathe

AU - Casari, Salvatore

AU - Di Perri, Giovanni

AU - Lazzarin, Adriano

AU - Maggiolo, Franco

AU - Penco, Giovanni

AU - Quirino, Tiziana

AU - Rizzardini, Giuliano

AU - Andrade-Villanueva, Jaime Federico

AU - Sierra-Madero, Juan G.

AU - Branco, Teresa

AU - Serrao, Rosario

AU - Teofilo, Eugenio JR

AU - Melendez-Rivera, Ivan

AU - Santiago, Lizette

AU - Zorrilla, Carmen D.

AU - Chernova, Oksana E.

AU - Pokrovsky, Vadim

AU - Rakhmanova, Aza Gasanovna

AU - Tsybakova, Olga

AU - Voronin, Eugene

AU - Vally, Tasneem

AU - Farisani, Livhuwani ML

AU - Sebopa, Boitumelo Lucrecia

AU - Barros, Carlos Aguado

AU - Cano Sánchez, Alfredo

AU - Sandkovsky, Uriel S

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Background Dolutegravir is a once-daily integrase strand transfer inhibitor with no need for pharmacokinetic boosting that is approved for the treatment of HIV-1 infection. Because women are often under-represented in HIV clinical trials, we addressed the safety and efficacy of dolutegravir in women with HIV-1. Methods The ARIA study is a randomised, open-label, multicentre, active-controlled, parallel-group, non-inferiority phase 3b study done in 86 hospital and university infectious disease clinics, local health clinics, and private infectious disease clinics in 12 countries and one US territory, in North America, South America, Europe, Africa, and Asia. Eligible participants were women aged 18 years or older who had HIV-1 RNA viral loads of 500 copies per mL or greater, had received 10 days or less of previous antiretroviral therapy, and had tested negative for the HLA-B*5701 allele. Pregnant women were excluded. Eligible women were randomly assigned (1:1) to receive either a single-tablet regimen of dolutegravir plus abacavir and lamivudine once a day (dolutegravir group) or a three-tablet combination of ritonavir-boosted atazanavir plus coformulated tenofovir disoproxil fumarate and emtricitabine once a day (atazanavir group). Random treatment group assignment was stratified by plasma HIV-1 RNA viral loads and CD4 cell count at baseline. The primary endpoint was the proportion of participants with HIV-1 RNA viral loads of less than 50 copies per mL at week 48 in all participants who received at least one dose of study medication (intention-to-treat exposed population). We used a non-inferiority margin of −12%. Investigators monitored adverse events to assess safety. This study is registered with ClinicalTrials.gov, number NCT01910402. Findings Between Aug 22, 2013, and Sept 22, 2015, of 705 women assessed, 499 were randomly assigned to either the dolutegravir group (n=250) or the atazanavir group (n=249); two participants from each group were randomised to treatment but did not receive study medication. At week 48, 203 (82%) of 248 participants in the dolutegravir group compared with 176 (71%) of 247 in the atazanavir group had HIV-1 RNA viral loads of less than 50 copies per mL (mean difference 10·5%, 95% CI 3·1–17·8, p=0·005). One participant in the atazanavir group had nucleoside reverse transcriptase inhibitor–associated resistance that led to reduced emtricitabine susceptibility. Adverse events were similar between the dolutegravir and atazanavir groups; the most common were nausea (46 [19%] of 248 in the dolutegravir group vs 49 [20%] of 247 in the atazanavir group) and headache (28 [11%] vs 32 [13%]). Fewer participants in the dolutegravir group than the atazanavir group reported drug-related adverse events (83 [33%] vs 121 [49%]) or adverse events that led to discontinuation (ten [4%] vs 17 [7%]). One death was reported in each treatment group, but neither was considered related to the study medications. Interpretation The non-inferior efficacy and similar safety profile of the dolutegravir combined regimen compared with the atazanavir regimen support the use of dolutegravir for HIV-1 infection in treatment-naive women. Funding ViiV Healthcare.

AB - Background Dolutegravir is a once-daily integrase strand transfer inhibitor with no need for pharmacokinetic boosting that is approved for the treatment of HIV-1 infection. Because women are often under-represented in HIV clinical trials, we addressed the safety and efficacy of dolutegravir in women with HIV-1. Methods The ARIA study is a randomised, open-label, multicentre, active-controlled, parallel-group, non-inferiority phase 3b study done in 86 hospital and university infectious disease clinics, local health clinics, and private infectious disease clinics in 12 countries and one US territory, in North America, South America, Europe, Africa, and Asia. Eligible participants were women aged 18 years or older who had HIV-1 RNA viral loads of 500 copies per mL or greater, had received 10 days or less of previous antiretroviral therapy, and had tested negative for the HLA-B*5701 allele. Pregnant women were excluded. Eligible women were randomly assigned (1:1) to receive either a single-tablet regimen of dolutegravir plus abacavir and lamivudine once a day (dolutegravir group) or a three-tablet combination of ritonavir-boosted atazanavir plus coformulated tenofovir disoproxil fumarate and emtricitabine once a day (atazanavir group). Random treatment group assignment was stratified by plasma HIV-1 RNA viral loads and CD4 cell count at baseline. The primary endpoint was the proportion of participants with HIV-1 RNA viral loads of less than 50 copies per mL at week 48 in all participants who received at least one dose of study medication (intention-to-treat exposed population). We used a non-inferiority margin of −12%. Investigators monitored adverse events to assess safety. This study is registered with ClinicalTrials.gov, number NCT01910402. Findings Between Aug 22, 2013, and Sept 22, 2015, of 705 women assessed, 499 were randomly assigned to either the dolutegravir group (n=250) or the atazanavir group (n=249); two participants from each group were randomised to treatment but did not receive study medication. At week 48, 203 (82%) of 248 participants in the dolutegravir group compared with 176 (71%) of 247 in the atazanavir group had HIV-1 RNA viral loads of less than 50 copies per mL (mean difference 10·5%, 95% CI 3·1–17·8, p=0·005). One participant in the atazanavir group had nucleoside reverse transcriptase inhibitor–associated resistance that led to reduced emtricitabine susceptibility. Adverse events were similar between the dolutegravir and atazanavir groups; the most common were nausea (46 [19%] of 248 in the dolutegravir group vs 49 [20%] of 247 in the atazanavir group) and headache (28 [11%] vs 32 [13%]). Fewer participants in the dolutegravir group than the atazanavir group reported drug-related adverse events (83 [33%] vs 121 [49%]) or adverse events that led to discontinuation (ten [4%] vs 17 [7%]). One death was reported in each treatment group, but neither was considered related to the study medications. Interpretation The non-inferior efficacy and similar safety profile of the dolutegravir combined regimen compared with the atazanavir regimen support the use of dolutegravir for HIV-1 infection in treatment-naive women. Funding ViiV Healthcare.

UR - http://www.scopus.com/inward/record.url?scp=85024474883&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85024474883&partnerID=8YFLogxK

U2 - 10.1016/S2352-3018(17)30095-4

DO - 10.1016/S2352-3018(17)30095-4

M3 - Article

VL - 4

SP - e536-e546

JO - The Lancet HIV

JF - The Lancet HIV

SN - 2352-3018

IS - 12

ER -