Reducing Proviral HIV DNA With Interferon-a

• Status: Unknown status
• Trial end date: 2018-07-24
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to determine if treatment with pegylated interferon alpha 2b (peg-IFN-α2b) will reduce the amount of integrated HIV DNA in peripheral blood cells and tissues of individuals with chronic HIV infection receiving antiretroviral treatment (ART).

A reduction and/or clearance of the latent viral reservoir (i.e.: virus that remains dormant in HIV-infected subjects receiving suppressive treatment ) is considered essential for HIV eradication.

By measuring the changes in integrated proviral HIV DNA, which is considered a surrogate measure of the latent reservoir, the investigators will establish if peg-IFN-α2b treatment should be considered as a component of future viral eradication strategies.

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

Details

• Lead Sponsor: The Wistar Institute
• Collaborators: Merck Sharp & Dohme Corp.; National Institute of Allergy and Infectious Diseases (NIAID); National Institutes of Health (NIH)
• Treatments: Interferon alpha-2; Interferon-alpha; Interferons; Peginterferon alfa-2b

Criteria

Inclusion criteria

• 18-65 years of age

• Body weight ≥ 125 and ≤ 300 lbs

• Confirmed diagnosis of HIV-1 infection by western blot or by a documented HIV-1 viral load at screening.

• Currently receiving ART and on ART for ≥ 1 year

• VL < 50 copies/ml for ≥ 1 year, with at least 2 measurements in the previous year. 1 viral "blip" with VL< 400 copies/ml allowed if 1 or more measurements of < 50 copies/ml are available no more than 3 months before and 3 months after the "blip" without change in ART

• HIV viral load of <50 copies/ml at screening.

• CD4 >450 cells/µL at screening.

• a negative electrocardiogram (EKG, see section 7.4) for: a) men >45 years or women > 55 years of age b) younger subjects of either sex with two risk factors for coronary artery disease [smoking, hypertension (BP >140/90 or on antihypertensive medications), low HDL (<40 mg/dl), family history of premature CHD (<55 yrs males/<65 females, c) subjects with a Framingham score > 15% (men) or 10% (women)

Exclusion criteria Current or prior medications

• Confirmed clinical history of developing resistance to ART regimens that resulted in treatment changes

• Receiving didanosine as part of the participant's ART regimen at the time of screening

• Ongoing treatment with Isoniazid, Pyrazinamide, Rifabutin, Rifampicin, Ganciclovir, Valgancyclovir, Oxymetholone, Thalidomide or Theophylline.

• Ongoing treatment with anticoagulants

• Use of any investigational drug within 30 days prior to screening

• History or current use of immunomodulatory therapy for over 2 weeks during the 6 months prior to enrollment, including, but not limited to: IFN-α or γ (recombinant or pegylated), systemic corticosteroids (inhaled steroids allowed at the discretion of the Investigator); systemic cancer chemotherapy/irradiation; cyclosporin; tacrolimus (FK-506); OKT-3; any Interleukin, including IL-2; cyclophosphamide; methotrexate; IVIG (gamma globulin); G/M-CSF; hydroxyurea; thalidomide; pentoxifylline; thymopentin; thymosin; dithiocarbonate; polyribonucloside.

• History of adverse or allergic reactions to any type-1 interferon (e.g. IFN-α2a, IFN-α2b, IFN-β)

Current or prior clinical conditions

• History of severe depression, including history of suicidal ideation or attempt, or ongoing moderate depression determined by PHQ-9 at screening

• Type I diabetes mellitus, or type II diabetes mellitus that is not controlled with oral agents and/or insulin (i.e.: subjects with a history of diabetes mellitus and HA1C of > 9 in the last 3 months or at screening).

• Prior diagnosis of multiple sclerosis or other neurodegenerative disorders

• Significant co-existing lab abnormalities including: a) Anemia (Hgb <9.1 mg/dl men, <8.9 mg/dl women); b) Ongoing coagulopathy/clotting disorder; c) WBC <2000 cells/µl; d) Absolute neutrophil count (ANC) <1200 cells/ µl; e) Platelet count <60,000 cells/ µl; f) Liver disease (AST/ALT > 2.5x OR total bilirubin > 1.5x upper limits of norm (ULN), (if not receiving atazanavir) or direct bilirubin > 0.6 (if receiving atazanavir); g) Pancreatic disease (amylase : > 1.5 ULN, lipase > 1.5 ULN, triglycerides > 750 mg/dl); h Renal disease (creatinine > 2x ULN or creatinine clearance <60mg/dl (by Crockoff-Gault)

• Chronic HCV infection (HCV viremia), or HBV Ag positive and/ or HBV viremia (Notice:

subjects with prior HCV infection with a documented sustained virologic response with treatment finishing >1 year prior to screening are eligible for enrollment).

• Liver cirrhosis or hepatic decompensation with Child Pugh score > 6

• History of major organ transplantation with an existing functional graft.

• Evidence of OI or other active infectious diseases or active malignancies

• Active Autoimmune diseases, including autoimmune hepatitis

• History of retinopathy or clinically significant ophthalmologic disease on eye exam performed within 60 days prior to initiation of IFN

• Significant EKG abnormalities (see section 7.4)

Other conditions

• Pregnancy or breastfeeding

• A planned pregnancy during study participation

• Lack of one of three strategies for birth control during study participation: a) Barrier contraceptives (male or female condoms with or without a spermicidal agent, diaphragm or cervical cap with spermicidal); b) Non-hormonal Intrauterine Devices (IUDs); c) Hormonal-based, including hormonal IUDs, in combination with barrier contraceptives.

• Body weight < 125 lbs or > 300 lbs

• Other conditions, such as active drug/alcohol abuse or dependence,that in the opinion of the Investigator would interfere with study compliance.