Reducing the Residual Reservoir of HIV-1 Infected Cells in Patients Receiving Antiretroviral Therapy

• Status: Recruiting
• Trial end date: 2021-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This study is a prospective, open-label, randomized, three-arm, dose-escalation exploratory pilot clinical trial involving HIV-1 infected participants treated with suppressive combination antiretroviral combination therapy (cART). The study will test whether combined treatment with the histone deacetylase inhibitor panobinostat and the immunomodulatory cytokine Interferon-alpha2a can reduce the residual reservoir of HIV-1 infected cells that persist during treatment with currently available antiretroviral drugs.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Massachusetts General Hospital
• Collaborators: Genentech, Inc.; Novartis
• Treatments: Histone Deacetylase Inhibitors; Interferon alpha-2; Interferon-alpha; Interferons; Panobinostat; Peginterferon alfa-2a

Criteria

Inclusion Criteria:

• Ability and willingness to provide informed consent

• HIV-1 infection prior to entry

• Receiving suppressive ART therapy for a minimum of 24 consecutive months prior to screening with no interruption of therapy (same ART regimen for at least 12 weeks prior to screening)

• Documented suppressed HIV-1 RNA (plasma HIV-1 RNA values <50 copies/ml)

• CD4 T cell count ≥ 400 cells/mm3

• Negative Hepatitis B surface antigen (HBsAg) or Negative HBV DNA PCR

• Negative anti-Hepatitis C virus antibodies (anti-HCV) or negative HCV PCR if anti-HCV antibodies are positive

• Negative TB Test (if positive, completed a recommended treatment course for latent TB)

• Vaccinated for pneumococcal disease within last 5 years

• No clinically significant eye disease

• No evidence of clinical coronary heart disease

• Not pregnant, planning to become pregnant, or breastfeeding

• Willingness to continue to use contraceptives for 90 days after completing treatment

• If male, willingness to use a condom during intercourse while taking panobinostat and total of 80 hours after stopping treatment

• Not pregnant, planning to become pregnant, or breastfeeding

• No evidence of coronary heart disease

Exclusion Criteria:

• HIV-1 RNA > 50 copies/mL within 24 months of screening

• Severe psychiatric disease, chronic liver disease, past or current evidence of immunologically mediated disease

• Severe retinopathy due to diabetes, hypertension, cytomegalovirus or macular degeneration

• Evidence of coronary heart disease

• History of active thyroid disease requiring medication

• Breastfeeding

• Presence of a bacterial, fungal, viral or protozoal infection requiring systemic anti-infective therapy

• Uncontrolled seizure disorders

• History or other evidence of severe illness or other conditions

• History of malignancy of any organ system within the past 5 years

• Female participants who are pregnant or nursing

• History of solid organ transplantation with an existing functional graft

• Use of any immunomodulatory agents within 30 days prior to study enrollment or planned use during the trial

• Active drug or alcohol use or dependence

• Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the participant in case of participation in the study

• Use of HIV protease inhibitor or other strong or moderately strong CYP3A4 inhibitors

• History of anaphylaxis, allergy or serious adverse reactions to Interferon-alpha2a/Interferon-alpha2b or panobinostat

• Has taken: interleukins, systemic interferons or systemic chemotherapy