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Non-inferiority of simplified dolutegravir monotherapy compared to continued combination antiretroviral therapy that was initiated during primary HIV infection: a randomized, controlled, multi-site, open-label, non-inferiority trial


Braun, Dominique L; Turk, Teja; Tschumi, Fabian; Grube, Christina; Hampel, Benjamin; Depmeier, Carsten; Schreiber, Peter W; Brugger, Silvio D; Greiner, Michael; Steffens, Daniela; de Torrenté-Bayard, Cornelia; Courlet, Perrine; Neumann, Kathrin; Kuster, Herbert; Flepp, Markus; Bertisch, Barbara; Decosterd, Laurent; Böni, Jürg; Metzner, Karin J; Kouyos, Roger D; Günthard, Huldrych F (2019). Non-inferiority of simplified dolutegravir monotherapy compared to continued combination antiretroviral therapy that was initiated during primary HIV infection: a randomized, controlled, multi-site, open-label, non-inferiority trial. Clinical Infectious Diseases:Epub ahead of print.

Abstract

Background Patients who start combination antiretroviral therapy (cART) during primary HIV-1 infection show a smaller HIV-1 latent reservoir, less immune activation and a smaller viral diversity compared to patients who start cART during chronic infection. We conducted a pilot study to test whether these properties would allow sustained virological suppression after simplification of cART to dolutegravir monotherapy. Methods EARLY-SIMPLIFIED is a randomized, open label, non-inferiority trial. Patients who started cART <180 days after estimated date of a documented primary HIV-1 infection and had a HIV-1 RNA <50 copies/mL plasma for at least 48 weeks were randomized (2:1) to monotherapy with dolutegravir 50 mg once-daily or to continuation of cART. The primary efficacy endpoint was the proportion of patients with <50 HIV-1 RNA copies/mL on or before week 48; non-inferiority margin 10%. Results Of the 101 patients randomized, 68 were assigned to simplification to dolutegravir monotherapy and 33 to continuation of cART. At week 48 in the per-protocol population, 67/67 (100%) had virological response in the dolutegravir monotherapy group versus 32/32 (100%) in the cART group (difference 0.00%, 95%-CI [-100%, 4.76%]). This showed non-inferiority of the dolutegravir monotherapy at the pre-specified level. Conclusion In this pilot study consisting of patients who initiated cART <180 days after the estimated day of a documented primary HIV-1 infection and had <50 HIV-1 RNA copies/mL for at least 48 weeks, monotherapy with once-daily dolutegravir was non-inferior to cART. Our results suggest that future simplification studies should use a stratification according to time of HIV infection and start of first cART.

Abstract

Background Patients who start combination antiretroviral therapy (cART) during primary HIV-1 infection show a smaller HIV-1 latent reservoir, less immune activation and a smaller viral diversity compared to patients who start cART during chronic infection. We conducted a pilot study to test whether these properties would allow sustained virological suppression after simplification of cART to dolutegravir monotherapy. Methods EARLY-SIMPLIFIED is a randomized, open label, non-inferiority trial. Patients who started cART <180 days after estimated date of a documented primary HIV-1 infection and had a HIV-1 RNA <50 copies/mL plasma for at least 48 weeks were randomized (2:1) to monotherapy with dolutegravir 50 mg once-daily or to continuation of cART. The primary efficacy endpoint was the proportion of patients with <50 HIV-1 RNA copies/mL on or before week 48; non-inferiority margin 10%. Results Of the 101 patients randomized, 68 were assigned to simplification to dolutegravir monotherapy and 33 to continuation of cART. At week 48 in the per-protocol population, 67/67 (100%) had virological response in the dolutegravir monotherapy group versus 32/32 (100%) in the cART group (difference 0.00%, 95%-CI [-100%, 4.76%]). This showed non-inferiority of the dolutegravir monotherapy at the pre-specified level. Conclusion In this pilot study consisting of patients who initiated cART <180 days after the estimated day of a documented primary HIV-1 infection and had <50 HIV-1 RNA copies/mL for at least 48 weeks, monotherapy with once-daily dolutegravir was non-inferior to cART. Our results suggest that future simplification studies should use a stratification according to time of HIV infection and start of first cART.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2 January 2019
Deposited On:29 Jan 2019 10:29
Last Modified:29 Jan 2019 10:31
Publisher:Oxford University Press
ISSN:1058-4838
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/cid/ciy1131
PubMed ID:30601950

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