NCT01319383

A Phase I/II Investigation of the Effect of Vorinostat (VOR) on HIV RNA Expression in the Resting CD4+ T Cells of HIV-Infected Patients Receiving Stable Antiretroviral Therapy

Completed Phase 1/Phase 2 Results posted Last updated 30 May 2017

What this trial tests

Phase 1/Phase 2 trial testing Vorinostat in HIV-1 Infection in 25 participants. Completed in 31 March 2016.

Timeline

1 February 2011

Primary endpoint
31 March 2016

31 March 2016

Quick facts

Lead sponsor	University of North Carolina, Chapel Hill
Phase	Phase 1/Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	25
Start date	1 February 2011
Primary completion	31 March 2016
Estimated completion	31 March 2016
Sites	1 location across United States

Drugs / interventions tested

• Vorinostat (VORINOSTAT) — full drug profile →

Conditions studied

• HIV-1 Infection — all drugs for HIV-1 Infection →

Sponsor

University of North Carolina, Chapel Hill

Who can join

Adults 18 to 65, any sex, with HIV-1 Infection. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Number of Participants Exhibiting an in Vivo Resting CD4+ T Cell- Associated HIV RNA (RCVL) Increase After Receiving a Single Dose of VOR 400 mg PO
  Time frame: Arm1: Baseline, Visit 5 and Arm 2: Baseline and Visit 3
  Participants in Arm 1 and 2 were analyzed in Step 2 for an in vivo increase in resting CD4+ T cell- associated HIV RNA (RCVL) after administration of a single dose of VOR 400 mg PO
• Number of Participants Exhibiting an in Vivo Resting CD4+ T-cell-associated HIV RNA (Rc-RNA) Increase Following Each of Two Multiple Dose Cycles (11 Doses/Cycle)
  Time frame: Baseline, Visit 18, Visit 29
  Participants in Arm 1, Step 3 were analyzed for an in vivo increase in the resting CD4+ T cell- associated HIV RNA (RCVL) after 11 doses of VOR 400 mg PO. This cycle was repeated after a 5 - 8 week rest period for a 2nd series and measurement.
• Number of Participants With a Significant in Vivo Response in Resting Cell Infection (RCI) and HIV RNA After Paired Doses
  Time frame: Baseline, Visit 6
  Induction of significant in vivo RCI and RCLV response after 2 doses of VOR 400 mg PO administered 48 hours apart or 72 hours apart
• Number of Participants Exhibiting an in Vivo Resting CD4+ T-cell-associated HIV RNA (Rc-RNA) Increase Following Multiple (n = 10) Interval Doses
  Time frame: Baseline, Visit 9
  Participants in Arm 2, Step 4 were analyzed for an in vivo increase in the resting CD4+ T cell- associated HIV RNA (RCVL) after administration of 10 doses of VOR 400 mg PO, given 72 hours apart.

Sponsor's own description

The purpose of this study is to compare HIV RNA expression and infection within resting (CD4)+ cells in HIV-infected patients on stable ART before and after a single exposure to Vorinostat (VOR), after exposure to short intervals of VOR, and after repeated short interval exposure to VOR dosed over several weeks.

Hypotheses:

1. The frequency of resting CD4+ T cell- associated HIV RNA (RCVL) will be increased following single and repeated exposure to VOR when given at appropriate intervals, and
2. That repeated exposure to VOR will reduce the frequency of HIV infection within resting CD4+ T cells (RCI)

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. HIV-1 transcription and latency: an update.
   Van Lint C, Bouchat S, Marcello A. · · 2013 · cited 256× · PMID 23803414 · DOI 10.1186/1742-4690-10-67
2. Eradicating HIV-1 infection: seeking to clear a persistent pathogen.
   Archin NM, Sung JM, Garrido C, Soriano-Sarabia N, et al · · 2014 · cited 230× · PMID 25402363 · DOI 10.1038/nrmicro3352
3. Barriers to a cure for HIV: new ways to target and eradicate HIV-1 reservoirs.
   Katlama C, Deeks SG, Autran B, Martinez-Picado J, et al · · 2013 · cited 228× · PMID 23541541 · DOI 10.1016/s0140-6736(13)60104-x
4. HIV-1 expression within resting CD4+ T cells after multiple doses of vorinostat.
   Archin NM, Bateson R, Tripathy MK, Crooks AM, et al · · 2014 · cited 203× · PMID 24620025 · DOI 10.1093/infdis/jiu155
5. Interval dosing with the HDAC inhibitor vorinostat effectively reverses HIV latency.
   Archin NM, Kirchherr JL, Sung JA, Clutton G, et al · · 2017 · cited 161× · PMID 28714868 · DOI 10.1172/jci92684
6. Expanded cytotoxic T-cell lymphocytes target the latent HIV reservoir.
   Sung JA, Lam S, Garrido C, Archin N, et al · · 2015 · cited 77× · PMID 25589335 · DOI 10.1093/infdis/jiv022
7. Control of viral infections by epigenetic-targeted therapy.
   Nehme Z, Pasquereau S, Herbein G. · · 2019 · cited 73× · PMID 30917875 · DOI 10.1186/s13148-019-0654-9
8. Ongoing Clinical Trials of Human Immunodeficiency Virus Latency-Reversing and Immunomodulatory Agents.
   Delagrèverie HM, Delaugerre C, Lewin SR, Deeks SG, et al · · 2016 · cited 68× · PMID 27757411 · DOI 10.1093/ofid/ofw189