No adverse safety or virological changes 2 years following vorinostat in HIV-infected individuals on antiretroviral therapy

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 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 and CD8 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 = 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, cell-associated unspliced HIV RNA, plasma RNA or CD4 and CD8 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.

Figures

Fig. 1. Changes in total HIV DNA and CA-US HIV RNA over 24 months follow up after daily vorinostat for 14 days

(a) Total HIV DNA was measured per million cells and (b) fold changes (FC) in DNA were calculated relative to baseline values. (c) CA-US HIV RNA was measured relative to 18S RNA and (d) fold changes were calculated relative to baseline. Median and IQR are shown for each time point. Comparisons of RNA or DNA to baseline were made using the Wilcoxon test. There were no significant changes in these parameters over time.