A Randomized Trial of Vorinostat with Treatment Interruption after Initiating Antiretroviral Therapy During Acute HIV-1 Infection

Journal of Virus Eradication
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Kroon EDMB, Ananworanich J, Paggliuzza A, Rhodes A, Phanuphak N, Trautmann L, Mitchell JL, Chintanaphol M, Intasan J, Pinyakorn S, Benjapornpong K, Chang JJ, Colby DJ, Chomchey N, Fletcher JLK, Eubanks K, Yang H, Kapson J, Dantanarayana A, Tennakoon S, Gorelick RJ, Maldarelli F, Robb ML, Kim JH, Spudich S, Chomont N, Phanuphak P, Lewin SR and de Souza MS.

J VIRUS ERAD. 2020:100004

DOI: https://doi.org/10.1016/j.jve.2020.100004

Abstract

Objective

and Design: A randomized, open-label pilot study in individuals treated with anti-retroviral therapy (ART) since acute HIV infection (AHI) with a regimen including a histone deacetylase inhibitor to induce HIV from latency and control HIV replication during subsequent treatment interruption (TI).

Methods

Fifteen participants who initiated ART at AHI were randomized to vorinostat/hydroxychloroquine/maraviroc (VHM) plus ART (n=10) or ART alone (n=5). The VHM arm received three 14-day vorinostat cycles within 10 weeks before TI. ART was resumed for plasma viral load (VL) >1,000 HIV RNA copies/mL. Primary outcome was proportion of participants on VHM+ART versus ART only with VL <50 copies/mL for 24 weeks after TI.

Results

Fifteen participants on ART (median: 178 weeks: range 79-295) enrolled. Two on VHM+ART experienced serious adverse events. Fourteen participants underwent TI; all experienced VL rebound with no difference in time between arms: VHM+ART (n=9) median: 4 weeks and ART only (n=5) median: 5 weeks. VHM induced a 2.2-fold increase in VL (p=0.008) by single-copy HIV RNA assay after the first cycle. Neopterin levels increased significantly following the first two cycles. After VHM treatment, the frequencies of peripheral blood mononuclear cells harboring total HIV DNA and cell-associated RNA were unchanged. All participants achieved VL suppression following ART re-initiation.

Conclusions

Administration of VHM increased HIV VL in plasma, but this was not sustained. VHM did not impact time to viral rebound following TI and had no impact on the size of the HIV reservoir, suggesting that HIV reservoir elimination will require alternative treatment strategies.

 

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