Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/31332
Title: Psychosocial predictors of non-adherence and treatment failure in a large scale multi-national trial of antiretroviral therapy for HIV: data from the ACTG A5175/PEARLS trial
Authors: Safren, Steven A.
Biello, Katie B.
Smeaton, Laura
Mimiaga, Matthew J.
Walawander, Ann
Lama, Javier R.
Rana, Aadia
Nyirenda, Mulinda
Kayoyo, Virginia M.
Samaneka, Wadzanai
Joglekar, Anjali
Celentano, David
Martinez, Ana
Remmert, Jocelyn E.
Nair, Aspara
Lalloo, Umesh G.
Kumarasamy, Nagalingeswaran
Hakim, James
Campbell, Thomas B.
PEARLS (ACTG A5175) Study Team
Affilliation: Massachusetts General Hospital. Boston, MA, USA / Harvard Medical School. Boston, MA, USA / The Fenway Institute. Fenway Health. Boston, MA, USA.
The Fenway Institute. Fenway Health. Boston, MA, USA / Harvard School of Public Health. Boston, MA, USA.
Harvard School of Public Health. Boston, MA, USA.
Massachusetts General Hospital. Boston, MA, USA / Harvard Medical School. Boston, MA, USA / The Fenway Institute. Fenway Health. Boston, MA, USA / Harvard School of Public Health. Boston, MA, USA.
Frontier Science and Technology Research Foundation. Amherst, NY, USA.
Asociación Civil Impacta Salud y Educación. Lima, Peru.
Alpert Medical School. The Miriam Hospital. Providence, RI, USA.
College of Medicine. Johns Hopkins Research Project. Blantyre, Malawi.
University of North Carolina Project. Lilongwe, Malawi.
University of Zimbabwe-University of California San Francisco Collaborative Research Program. Harare, Zimbabwe.
National AIDS Research Institute. Pune, India.
Johns Hopkins Bloomberg School of Public Health. Baltimore, MD, USA.
NIH/NIAD/DAIDS Pharmaceutical Affairs. Bethesda, MD, USA.
Massachusetts General Hospital. Boston, MA, USA.
Frontier Science and Technology Research Foundation. Amherst, NY, USA.
University of KwaZulu-Natal. Nelson R. Mandela School of Medicine. Durban, South Africa.
YRGCARE Medical Centre. Chennai, India.
University of Zimbabwe. Harare, Zimbabwe.
University of Colorado Denver. Aurora, CO, USA.
Abstract: Background: Dolutegravir (GSK1349572), a once-daily HIV integrase inhibitor, has shown potent antiviral response and a favourable safety profi le. We evaluated safety, efficacy, and emergent resistance in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV-1 with at least two-class drug resistance. Methods: ING111762 (SAILING) is a 48 week, phase 3, randomised, double-blind, active-controlled, non-inferiority study that began in October, 2010. Eligible patients had two consecutive plasma HIV-1 RNA assessments of 400 copies per mL or higher (unless >1000 copies per mL at screening), resistance to two or more classes of antiretroviral drugs, and had one to two fully active drugs for background therapy. Participants were randomly assigned (1:1) to once-daily dolutegravir 50 mg or twice-daily raltegravir 400 mg, with investigator-selected background therapy. Matching placebo was given, and study sites were masked to treatment assignment. The primary endpoint was the proportion of patients with plasma HIV-1 RNA less than 50 copies per mL at week 48, evaluated in all participants randomly assigned to treatment groups who received at least one dose of study drug, excluding participants at one site with violations of good clinical practice. Non-inferiority was prespecified with a 12% margin; if non-inferiority was established, then superiority would be tested per a prespecified sequential testing procedure. A key prespecified secondary endpoint was the proportion of patients with treatment-emergent integrase-inhibitor resistance. The trial is registered at ClinicalTrials.gov, NCT01231516. Findings: Analysis included 715 patients (354 dolutegravir; 361 raltegravir). At week 48, 251 (71%) patients on dolutegravir had HIV-1 RNA less than 50 copies per mL versus 230 (64%) patients on raltegravir (adjusted difference 7·4%, 95% CI 0·7 to 14·2); superiority of dolutegravir versus raltegravir was then concluded (p=0·03). Significantly fewer patients had virological failure with treatment-emergent integrase-inhibitor resistance on dolutegravir (four vs 17 patients; adjusted difference –3·7%, 95% CI –6·1 to –1·2; p=0·003). Adverse event frequencies were similar across groups; the most commonly reported events for dolutegravir versus raltegravir were diarrhoea (71 [20%] vs 64 [18%] patients), upper respiratory tract infection (38 [11%] vs 29 [8%]), and headache (33 [9%] vs 31 [9%]). Safety events leading to discontinuation were infrequent in both groups (nine [3%] dolutegravir, 14 [4%] raltegravir). Interpretation: Once-daily dolutegravir, in combination with up to two other antiretroviral drugs, is well tolerated with greater virological eff ect compared with twice-daily raltegravir in this treatment-experienced patient group. Funding: ViiV Healthcare.
Keywords: HIV
Antiretroviral therapy
Issue Date: 2014
Publisher: Public Library of Science
Citation: SAFREN, Steven A. et al. Psychosocial predictors of non-adherence and treatment failure in a large scale multi-national trial of antiretroviral therapy for HIV: data from the ACTG A5175/PEARLS trial. Plos One, v. 9, p. 1-10, Aug. 2014.
Description: Beatriz Grinsztejn (Fiocruz/INI) - Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento.
DOI: 10.1371/journal.pone.0104178
ISSN: 1932-6203
Copyright: open access
Appears in Collections:INI - Artigos de Periódicos

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