Chidamide in Combination With Antiretroviral Therapy for Eradication of the Latent HIV-1 Reservoir
Condition: Chronic HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      HIV replication can be effectively suppressed and acquired immunodeficiency syndrome(AIDS)
      can be prevented with highly active antiretroviral therapy (HAART). However, HIV-infected
      people must remain on treatment continuously to avoid viral rebound and progression to AIDS.
      HIV persistence is thought to stem primarily from the presence of integrated copies of the
      proviral genome within long-lived cells. Because active viral gene expression causes cell
      death due to viral cytopathic effects and the immune response, long-lived cells likely harbor
      transcriptionally silent, latent provirus. HIV-1 persistence in long-lived cellular
      reservoirs remains a major barrier to a cure. HDACi have the potential to activate ("Kick")
      these latently infected cells. This will make the HIV infected cells visible to the immune
      system; the immune response and antiretrovirals(ARVs) will be able to attack and eliminate
      ("Kill") the infected cells. The purpose of this study is to evaluate the safety and efficacy
      of multi-dose Chidamide in combination with antiretroviral therapy in HIV-infected adults
      with suppressed viral load.
    

Detailed description: 
      Every participant will receive oral Chidamide on Day 0, 3, 7, 10, 14, 17, 21, 24. In Step 1,
      the dose of Chidamide will be 10 mg each time, for Step 2 30 mg each time. Participants will
      be enrolled into Step 1 first; if the dose given to Step 1 is well tolerated and no safety
      concerns are noted, Step 2 will be enrolled. All participants will keep their antiretroviral
      therapy during this study.

      Each step of this study will last for 56 days, involving 14 study visits(Screening, Day 0, 2,
      3, 8, 11, 14, 15, 17, 21, 24, 26, 27, 56) for every participant. At the screening visit,
      participants will give a medical history and will undergo a physical exam; blood samples will
      be collected. Participants will undergo pharmacokinetic (PK) sampling which will require that
      blood be drawn at 0, 1, 2, 6, 12, 24, 48, 72h after the first dose. For multi-dose PK
      studies, blood samples will be collected at the same time points after the last dose.
      Participants will undergo pharmacodynamic (PD) sampling which will require that blood be
      drawn at 0, 6, 12, 24, 48, 72h after the first dose. For steady-state concentration PK and PD
      studies, blood samples will be collected 5-30 minutes before Chidamide administration on Day
      14, 17, 21. If participants agree, their blood samples may be stored for future research.
    

Intervention name(s): Chidamide
Intervention type(s): Drug
Intervention description(s): Chidamide will be given by mouth on Day 0, 3, 7, 10, 14, 17, 21, 24.
Other intervention name(s): CS055; HBI-8000
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Chidamide; Histone Deacetylase Inhibitor; HIV-1 Reservoir; Chronic HIV infections; Antiretroviral Therapy; HIV Eradication