Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
CONCISE COMMUNICATION
No adverse safety or virological changes 2 years
following vorinostat in HIV-infected individuals on
antiretroviral therapy
Talia M. Mota
a,b,f
, Thomas A. Rasmussen
d,f
, Ajantha Rhodes
a,f
,
Surekha Tennakoon
a,f
, Ashanti Dantanarayana
a,f
, Fiona Wightman
a,f
,
Michelle Hagenauer
e,f
, Janine Roney
e,f
, Tim Spelman
a,c,f
,
Damian F.J. Purcell
a,b,f
, James McMahon
c,e,f
, Jennifer F. Hoy
e,f
,
H. Miles Prince
e,f
, Julian H. Elliott
c,e,f
and Sharon R. Lewin
a,e,f
Objective: To determine the long-term effects of vorinostat on safety and virological
parameters in HIV-infected individuals on suppressive antiretroviral therapy (ART).
Design: Prospective longitudinal observational extended follow-up of 20 HIV-infected
individuals on ART previously enrolled in a clinical trial of daily vorinostat 400 mg for
14 days. Extended follow-up included visits at 6, 12, 18 and 24 months postenrolment
in the initial clinical trial.
Methods: Cell-associated unspliced HIV RNA, total HIV DNA and plasma HIV RNA
were quantified by PCR, and CD4
þ
and CD8
þ
T cells quantified by flow cytometry.
Changes over time in each parameter were assessed using the Wilcoxon matched pair
signed-rank test and generalized estimating equations for trend modelling.
Results: We recorded a total of 31 adverse events (26 grade 1 and five grade 2) in all
study participants (n ¼ 20). There were no significant changes in the number of CD4
þ
or
CD8
þ
T cells or plasma HIV RNA over time. In 12 participants for whom baseline samples
were available, there were no significant changes in total HIV DNA, cell-associated
unspliced HIV RNA, plasma RNA or CD4
þ
and CD8
þ
T cells at 6, 12, 18 or 24 months.
Conclusion: Extended follow-up for 24 months did not reveal any long-term toxicity or
changes in markers of HIV persistence or transcription in participants on ART who had
received 14 days of vorinostat.
Copyright ß 2017 Wolters Kluwer Health, Inc. All rights reserved.
AIDS 2017, 31:1137–1141
Keywords: acetylation, histone deacetylase inhibitors, HIV, HIV latency, latency
reversal, vorinostat
a
The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital,
b
Department
of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne,
c
Centre
for Population Health, Burnet Institute, Melbourne, Victoria, Australia,
d
Department of Infectious Diseases, Aarhus University
Hospital, Aarhus, Denmark,
e
Department of Infectious Diseases, Alfred Health and Monash University, and
f
Peter MacCallum
Cancer Centre, Victorian Comprehensive Cancer Centre, Melbourne, Victoria, Australia.
Correspondence to Professor Sharon R. Lewin, FRACP, PhD, Director, The Peter Doherty Institute for Infection and Immunity, The
University of Melbourne and Royal Melbourne Hospital, 786-798 Elizabeth Street, Melbourne 3010, VIC, Australia.
E-mail: sharon.lewin@unimelb.edu.au
Received: 20 December 2016; revised: 19 January 2017; accepted: 20 January 2017.
DOI:10.1097/QAD.0000000000001442
ISSN 0269-9370 Copyright Q 2017 Wolters Kluwer Health, Inc. All rights reserved.
1137