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 - 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 - Presti, Rachel M.
N1 - Publisher Copyright:
© 2017 Elsevier Ltd
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
U2 - 10.1016/S2352-3018(17)30095-4
DO - 10.1016/S2352-3018(17)30095-4
M3 - Article
C2 - 28729158
AN - SCOPUS:85024474883
SN - 2352-3018
VL - 4
SP - e536-e546
JO - The Lancet HIV
JF - The Lancet HIV
IS - 12
ER -