Abstract

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 post enrolment in the initial clinical trial.

METHODS: Cell-associated unspliced (CA-US) HIV RNA, total HIV DNA and plasma HIV RNA were quantified by PCR and, CD4+ and CD8+ T cells quantified by flow cytometry. Changes over time in each parameter were assessed using Wilcoxon matched pair signed-rank test and Generalised Estimating Equations for trend modelling.

RESULTS: We recorded a total of 31 adverse events (26 grade 1 and 5 grade 2) in all study participants (n = 20). There were no significant changes in the number of CD4+ or CD8+ 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, CA-US HIV RNA, plasma RNA, or CD4 and CD8+ T cells at 6, 12, 18 or 24 months.

CONCLUSIONS: 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.