Journal
JOURNAL OF VIRUS ERADICATION
Volume 6, Issue 3, Pages -Publisher
MEDISCRIPT LTD
DOI: 10.1016/j.jve.2020.100004
Keywords
Acute HIV infection; Vorinostat; Maraviroc; HIV remission; Latency reversal
Categories
Funding
- Henry M Jackson Foundation for the Advancement of Military Medicine, Inc. [W81XWH-07-2-0067, W81XWH-11-2-0174]
- US Department of the Army [W81XWH-07-2-0067, W81XWH-11-2-0174]
- Thai Red Cross AIDS Research Centre
- US Army Medical Research Acquisition Activity (Fort Detrick, MD, USA)
- Thai Government Pharmaceutical Organization
- Gilead
- Merck
- ViiV Healthcare
- National Institute of Neurologic Disorders and Stroke [1R01NS084911-01]
- federal funds from the National Cancer Institute, National Institutes of Health [HHSN261200800001E]
- National Institute of Allergy and Infectious Diseases [1R01AI108433]
- National Health and Medical Research Council of Australia (NHMRC Program) [GNT1052979]
- National Institutes for Health Delaney AIDS Research Enterprise [DARE AI096109, AI126611]
- American Foundation for AIDS Research
- Cooper Human Systems, Nashua, NH, USA
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Objective and Design: A randomized, open-label pilot study in individuals treated with antiretroviral 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 thorn 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 thorn ART experienced serious adverse events. Fourteen participants underwent TI; all experienced VL rebound with no difference in time between arms: VHM thorn 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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