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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

2017; Elsevier BV; Volume: 4; Issue: 12 Linguagem: Inglês

10.1016/s2352-3018(17)30095-4

2405-4704

Catherine Orrell, Debbie Hagins, Elena Belonosova, Norma Porteiro, Sharon Walmsley, Vicenç Falcó, Choy Man, Alicia Aylott, Ann M. Buchanan, Brian Wynne, Cindy Vavro, Michael Aboud, Kimberly Y. Smith, Pedro Cahn, Lidia Isabel Cassetti, Norma Porteiro Barreira, Jonathan B. Angel, Alexandra de Pokomandy, Marianne Harris, Anita Rachlis, Sharon Walmsley, Clotilde Allavena, Oliver Bouchaud, Caroline Gatey, Agathe Rami, Salvatore Casari, Giovanni Di Perri, Adriano Lazzarin, Franco Maggiolo, Giovanni Penco, Tiziana Quirino, Giuliano Rizzardini, Jaime Andrade‐Villanueva, Juan Sierra‐Madero, Teresa Branco, Rosário Serrão, Eugénio Teófilo, Ivan Melendez-Rivera, Lizette Santiago, Carmen Zorrilla, Elena Belonosova, Oksana Chernova, Vadim Pokrovsky, Aza Rakhmanova, Olga Aleksandrovna Tsybakova, Eugene Voronin, Catherine Orrell, Tasneem Vally, Livhuwani ML. Farisani, Boitumelo Lucrecia Sebopa, Carlos Aguado Barros, Alfredo Cano Sánchez, Manuel Castaño, Vicens Falcó Ferrer, Juan González‐García, José Hernández‐Quero, Eugènia Negredo, Maria Jesús Pérez‐Elías, Daniel Podzamczer Palter, Joaquín Portilla, Pompeyo Viciana Fernández, Weerawat Manosuthi, Kiat Ruxrungtham, David H. Dockrell, Phillip Hay, Margaret Johnson, Nicola Mackie, Chloe Orkin, Stephen Taylor, Laveeza Bhatti, Indira Brar, Robert Owen Brennan, Jerry Cade, Beata Casańas, Kathleen Casey, Douglas Cunningham, Edwin DeJesus, Craig Dietz, Robin Dretler, Joseph J. Eron, Franco Antoni B. Felizarta, Kenneth H. Fife, Debbie Hagins, Margaret Hoffman-Terry, Mamta K. Jain, Marc Alexander Johnson, Clifford A. Kinder, Princy Kumar, Stanley T. Lewis, Cheryl McDonald, Armando Meza, Karam Mounzer, Cheryl Newman, Olayemi Osiyemi, Ronald Poblete, Rachel M. Presti, Moti Ramgopal, Joel Rosenstock, Rafik Samuel, Uriel Sandkovsky, Alyssa Shon, Daniel J. Skiest, Louis Sloan, Catherine B. Small, Pablo Tebas, Cornelius N. Van Dam,

HIV/AIDS Research and Interventions

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.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.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.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.ViiV Healthcare.