No Treatment versus 24 or 60 Weeks of Antiretroviral Treatment during Primary HIV Infection: The Randomized Primo-SHM Trial

BACKGROUND: The objective of this study was to assess the benefit of temporary combination antiretroviral therapy (cART) during primary HIV infection (PHI). METHODS AND FINDINGS: Adult patients with laboratory evidence of PHI were recruited in 13 HIV treatment centers in the Netherlands and randomly...

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Autores principales: Grijsen, Marlous L., Steingrover, Radjin, Wit, Ferdinand W. N. M., Jurriaans, Suzanne, Verbon, Annelies, Brinkman, Kees, van der Ende, Marchina E., Soetekouw, Robin, de Wolf, Frank, Lange, Joep M. A., Schuitemaker, Hanneke, Prins, Jan M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3313945/
https://www.ncbi.nlm.nih.gov/pubmed/22479156
http://dx.doi.org/10.1371/journal.pmed.1001196
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author Grijsen, Marlous L.
Steingrover, Radjin
Wit, Ferdinand W. N. M.
Jurriaans, Suzanne
Verbon, Annelies
Brinkman, Kees
van der Ende, Marchina E.
Soetekouw, Robin
de Wolf, Frank
Lange, Joep M. A.
Schuitemaker, Hanneke
Prins, Jan M.
author_facet Grijsen, Marlous L.
Steingrover, Radjin
Wit, Ferdinand W. N. M.
Jurriaans, Suzanne
Verbon, Annelies
Brinkman, Kees
van der Ende, Marchina E.
Soetekouw, Robin
de Wolf, Frank
Lange, Joep M. A.
Schuitemaker, Hanneke
Prins, Jan M.
author_sort Grijsen, Marlous L.
collection PubMed
description BACKGROUND: The objective of this study was to assess the benefit of temporary combination antiretroviral therapy (cART) during primary HIV infection (PHI). METHODS AND FINDINGS: Adult patients with laboratory evidence of PHI were recruited in 13 HIV treatment centers in the Netherlands and randomly assigned to receive no treatment or 24 or 60 wk of cART (allocation in a 1∶1∶1 ratio); if therapy was clinically indicated, participants were randomized over the two treatment arms (allocation in a 1∶1 ratio). Primary end points were (1) viral set point, defined as the plasma viral load 36 wk after randomization in the no treatment arm and 36 wk after treatment interruption in the treatment arms, and (2) the total time that patients were off therapy, defined as the time between randomization and start of cART in the no treatment arm, and the time between treatment interruption and restart of cART in the treatment arms. cART was (re)started in case of confirmed CD4 cell count <350 cells/mm(3) or symptomatic HIV disease. In total, 173 participants were randomized. The modified intention-to-treat analysis comprised 168 patients: 115 were randomized over the three study arms, and 53 randomized over the two treatment arms. Of the 115 patients randomized over the three study arms, mean viral set point was 4.8 (standard deviation 0.6) log(10) copies/ml in the no treatment arm, and 4.0 (1.0) and 4.3 (0.9) log(10) copies/ml in the 24- and 60-wk treatment arms (between groups: p<0.001). The median total time off therapy in the no treatment arm was 0.7 (95% CI 0.0–1.8) y compared to 3.0 (1.9–4.2) and 1.8 (0.5–3.0) y in the 24- and 60-wk treatment arms (log rank test, p<0.001). In the adjusted Cox analysis, both 24 wk (hazard ratio 0.42 [95% CI 0.25–0.73]) and 60 wk of early treatment (hazard ratio 0.55 [0.32–0.95]) were associated with time to (re)start of cART. CONCLUSIONS: In this trial, temporary cART during PHI was found to transiently lower the viral set point and defer the restart of cART during chronic HIV infection. TRIAL REGISTRATION: Current Controlled Trials ISRCTN59497461 Please see later in the article for the Editors' Summary
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spelling pubmed-33139452012-04-04 No Treatment versus 24 or 60 Weeks of Antiretroviral Treatment during Primary HIV Infection: The Randomized Primo-SHM Trial Grijsen, Marlous L. Steingrover, Radjin Wit, Ferdinand W. N. M. Jurriaans, Suzanne Verbon, Annelies Brinkman, Kees van der Ende, Marchina E. Soetekouw, Robin de Wolf, Frank Lange, Joep M. A. Schuitemaker, Hanneke Prins, Jan M. PLoS Med Research Article BACKGROUND: The objective of this study was to assess the benefit of temporary combination antiretroviral therapy (cART) during primary HIV infection (PHI). METHODS AND FINDINGS: Adult patients with laboratory evidence of PHI were recruited in 13 HIV treatment centers in the Netherlands and randomly assigned to receive no treatment or 24 or 60 wk of cART (allocation in a 1∶1∶1 ratio); if therapy was clinically indicated, participants were randomized over the two treatment arms (allocation in a 1∶1 ratio). Primary end points were (1) viral set point, defined as the plasma viral load 36 wk after randomization in the no treatment arm and 36 wk after treatment interruption in the treatment arms, and (2) the total time that patients were off therapy, defined as the time between randomization and start of cART in the no treatment arm, and the time between treatment interruption and restart of cART in the treatment arms. cART was (re)started in case of confirmed CD4 cell count <350 cells/mm(3) or symptomatic HIV disease. In total, 173 participants were randomized. The modified intention-to-treat analysis comprised 168 patients: 115 were randomized over the three study arms, and 53 randomized over the two treatment arms. Of the 115 patients randomized over the three study arms, mean viral set point was 4.8 (standard deviation 0.6) log(10) copies/ml in the no treatment arm, and 4.0 (1.0) and 4.3 (0.9) log(10) copies/ml in the 24- and 60-wk treatment arms (between groups: p<0.001). The median total time off therapy in the no treatment arm was 0.7 (95% CI 0.0–1.8) y compared to 3.0 (1.9–4.2) and 1.8 (0.5–3.0) y in the 24- and 60-wk treatment arms (log rank test, p<0.001). In the adjusted Cox analysis, both 24 wk (hazard ratio 0.42 [95% CI 0.25–0.73]) and 60 wk of early treatment (hazard ratio 0.55 [0.32–0.95]) were associated with time to (re)start of cART. CONCLUSIONS: In this trial, temporary cART during PHI was found to transiently lower the viral set point and defer the restart of cART during chronic HIV infection. TRIAL REGISTRATION: Current Controlled Trials ISRCTN59497461 Please see later in the article for the Editors' Summary Public Library of Science 2012-03-27 /pmc/articles/PMC3313945/ /pubmed/22479156 http://dx.doi.org/10.1371/journal.pmed.1001196 Text en Grijsen et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Grijsen, Marlous L.
Steingrover, Radjin
Wit, Ferdinand W. N. M.
Jurriaans, Suzanne
Verbon, Annelies
Brinkman, Kees
van der Ende, Marchina E.
Soetekouw, Robin
de Wolf, Frank
Lange, Joep M. A.
Schuitemaker, Hanneke
Prins, Jan M.
No Treatment versus 24 or 60 Weeks of Antiretroviral Treatment during Primary HIV Infection: The Randomized Primo-SHM Trial
title No Treatment versus 24 or 60 Weeks of Antiretroviral Treatment during Primary HIV Infection: The Randomized Primo-SHM Trial
title_full No Treatment versus 24 or 60 Weeks of Antiretroviral Treatment during Primary HIV Infection: The Randomized Primo-SHM Trial
title_fullStr No Treatment versus 24 or 60 Weeks of Antiretroviral Treatment during Primary HIV Infection: The Randomized Primo-SHM Trial
title_full_unstemmed No Treatment versus 24 or 60 Weeks of Antiretroviral Treatment during Primary HIV Infection: The Randomized Primo-SHM Trial
title_short No Treatment versus 24 or 60 Weeks of Antiretroviral Treatment during Primary HIV Infection: The Randomized Primo-SHM Trial
title_sort no treatment versus 24 or 60 weeks of antiretroviral treatment during primary hiv infection: the randomized primo-shm trial
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3313945/
https://www.ncbi.nlm.nih.gov/pubmed/22479156
http://dx.doi.org/10.1371/journal.pmed.1001196
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