Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: a phase 1/2, single group, clinical trial

Thomas Aagaard Rasmussen, Martin Tolstrup, Christel Brinkmann, Rikke Olesen, Christian Erikstrup, Ajantha Solomon, Anni Winkelmann, Sarah E Palmer, Charles A Dinarello, Maria Jose Buzon, Mathias Lichterfeld, Sharon Ruth Lewin, Lars Jorgen Ostergaard, Ole Schmeltz Sogaard

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Abstract

Background: Activating the expression of latent virus is an approach that might form part of an HIV cure. We assessed the ability of the histone deacetylase inhibitor panobinostat to disrupt HIV-1 latency and the safety of this strategy. Methods: In this phase 1/2 clinical trial, we included aviraemic adults with HIV treated at Aarhus University Hospital, Denmark. Participants received oral panobinostat (20 mg) three times per week every other week for 8 weeks while maintaining combination antiretroviral therapy. The primary outcome was change from baseline of cell-associated unspliced HIV RNA. Secondary endpoints were safety, plasma HIV RNA, total and integrated HIV DNA, infectious units per million CD4 T cells, and time to viral rebound during an optional analytical treatment interruption of antiretroviral therapy. This trial is registered with ClinicalTrial.gov, number NCT01680094. Findings: We enrolled 15 patients. The level of cell-associated unspliced HIV RNA increased signifi cantly at all timepoints when patients were taking panobinostat (p
Original languageEnglish
Pages (from-to)e13 - e21
Number of pages9
JournalThe Lancet HIV
Volume1
Issue number1
DOIs
Publication statusPublished - 2014

Cite this

Rasmussen, Thomas Aagaard ; Tolstrup, Martin ; Brinkmann, Christel ; Olesen, Rikke ; Erikstrup, Christian ; Solomon, Ajantha ; Winkelmann, Anni ; Palmer, Sarah E ; Dinarello, Charles A ; Buzon, Maria Jose ; Lichterfeld, Mathias ; Lewin, Sharon Ruth ; Ostergaard, Lars Jorgen ; Sogaard, Ole Schmeltz. / Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: a phase 1/2, single group, clinical trial. In: The Lancet HIV. 2014 ; Vol. 1, No. 1. pp. e13 - e21.
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title = "Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: a phase 1/2, single group, clinical trial",
abstract = "Background: Activating the expression of latent virus is an approach that might form part of an HIV cure. We assessed the ability of the histone deacetylase inhibitor panobinostat to disrupt HIV-1 latency and the safety of this strategy. Methods: In this phase 1/2 clinical trial, we included aviraemic adults with HIV treated at Aarhus University Hospital, Denmark. Participants received oral panobinostat (20 mg) three times per week every other week for 8 weeks while maintaining combination antiretroviral therapy. The primary outcome was change from baseline of cell-associated unspliced HIV RNA. Secondary endpoints were safety, plasma HIV RNA, total and integrated HIV DNA, infectious units per million CD4 T cells, and time to viral rebound during an optional analytical treatment interruption of antiretroviral therapy. This trial is registered with ClinicalTrial.gov, number NCT01680094. Findings: We enrolled 15 patients. The level of cell-associated unspliced HIV RNA increased signifi cantly at all timepoints when patients were taking panobinostat (p",
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Rasmussen, TA, Tolstrup, M, Brinkmann, C, Olesen, R, Erikstrup, C, Solomon, A, Winkelmann, A, Palmer, SE, Dinarello, CA, Buzon, MJ, Lichterfeld, M, Lewin, SR, Ostergaard, LJ & Sogaard, OS 2014, 'Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: a phase 1/2, single group, clinical trial', The Lancet HIV, vol. 1, no. 1, pp. e13 - e21. https://doi.org/10.1016/S2352-3018(14)70014-1

Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: a phase 1/2, single group, clinical trial. / Rasmussen, Thomas Aagaard; Tolstrup, Martin; Brinkmann, Christel; Olesen, Rikke; Erikstrup, Christian; Solomon, Ajantha; Winkelmann, Anni; Palmer, Sarah E; Dinarello, Charles A; Buzon, Maria Jose; Lichterfeld, Mathias; Lewin, Sharon Ruth; Ostergaard, Lars Jorgen; Sogaard, Ole Schmeltz.

In: The Lancet HIV, Vol. 1, No. 1, 2014, p. e13 - e21.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: a phase 1/2, single group, clinical trial

AU - Rasmussen, Thomas Aagaard

AU - Tolstrup, Martin

AU - Brinkmann, Christel

AU - Olesen, Rikke

AU - Erikstrup, Christian

AU - Solomon, Ajantha

AU - Winkelmann, Anni

AU - Palmer, Sarah E

AU - Dinarello, Charles A

AU - Buzon, Maria Jose

AU - Lichterfeld, Mathias

AU - Lewin, Sharon Ruth

AU - Ostergaard, Lars Jorgen

AU - Sogaard, Ole Schmeltz

PY - 2014

Y1 - 2014

N2 - Background: Activating the expression of latent virus is an approach that might form part of an HIV cure. We assessed the ability of the histone deacetylase inhibitor panobinostat to disrupt HIV-1 latency and the safety of this strategy. Methods: In this phase 1/2 clinical trial, we included aviraemic adults with HIV treated at Aarhus University Hospital, Denmark. Participants received oral panobinostat (20 mg) three times per week every other week for 8 weeks while maintaining combination antiretroviral therapy. The primary outcome was change from baseline of cell-associated unspliced HIV RNA. Secondary endpoints were safety, plasma HIV RNA, total and integrated HIV DNA, infectious units per million CD4 T cells, and time to viral rebound during an optional analytical treatment interruption of antiretroviral therapy. This trial is registered with ClinicalTrial.gov, number NCT01680094. Findings: We enrolled 15 patients. The level of cell-associated unspliced HIV RNA increased signifi cantly at all timepoints when patients were taking panobinostat (p

AB - Background: Activating the expression of latent virus is an approach that might form part of an HIV cure. We assessed the ability of the histone deacetylase inhibitor panobinostat to disrupt HIV-1 latency and the safety of this strategy. Methods: In this phase 1/2 clinical trial, we included aviraemic adults with HIV treated at Aarhus University Hospital, Denmark. Participants received oral panobinostat (20 mg) three times per week every other week for 8 weeks while maintaining combination antiretroviral therapy. The primary outcome was change from baseline of cell-associated unspliced HIV RNA. Secondary endpoints were safety, plasma HIV RNA, total and integrated HIV DNA, infectious units per million CD4 T cells, and time to viral rebound during an optional analytical treatment interruption of antiretroviral therapy. This trial is registered with ClinicalTrial.gov, number NCT01680094. Findings: We enrolled 15 patients. The level of cell-associated unspliced HIV RNA increased signifi cantly at all timepoints when patients were taking panobinostat (p

UR - http://www.thelancet.com/pdfs/journals/lanhiv/PIIS2352-3018%2814%2970014-1.pdf

U2 - 10.1016/S2352-3018(14)70014-1

DO - 10.1016/S2352-3018(14)70014-1

M3 - Article

VL - 1

SP - e13 - e21

JO - The Lancet HIV

JF - The Lancet HIV

SN - 2405-4704

IS - 1

ER -