Pilot Peg-Interferon-a2b in Decreasing Viral DNA in HIV
Condition: HIV-1 Infection
MeSH terms: Infections
Intervention: Pegylated Interferon alpha 2b
Intervention description: 1µg/kg/week
Intervention MeSH terms: Interferons; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2b
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: HIV-1; Interferon alpha; Integrated DNA; Latent reservoir

Summary:

      We propose to test our primary hypothesis that treatment with Peg-IFN-α-2b will result in a
      decrease in integrated HIV DNA in peripheral blood and tissue in chronically HIV-infected
      immune-reconstituted individuals (see section 3.1) in a prospective, interventional, 1-arm,
      open label clinical trial. To this end, we propose to enroll 25 HIV-1-infected subjects
      (please refer to power calculations in section 10.1 below) currently stably suppressed (> 1y
      with VL < 50 copies/ml) on ART and with CD4 count > 450 cells/µl.

      We hypothesize that 20 weeks of treatment with Peg-IFN-alpha-2b, in the presence of HIV
      reactivation (i.e.: ART interruption), will result in activation of intrinsic and/or
      immune-mediated anti-HIV mechanisms resulting in a decrease in the levels of viral reservoir
      in chronically HIV-infected, immune-reconstituted individuals.
    

Eligibility criteria:

        Inclusion Criteria:

          -  18-65 years of age

          -  Body weight between 125 and 299 lbs

          -  Confirmed diagnosis of HIV-1 infection by western blot or by a documented HIV-1 viral
             load

          -  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

          -  HIV viral load of <50 copies/ml at screening.

          -  CD4 >450 cells/µL at screening.

          -  A negative ECG if >45yrs men/>55yrs women years of age or if below these years of age
             but with two added 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)] or a Framingham score > 15% (men) or 10%
             (women))

        Exclusion Criteria:

          -  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 Isoniazide, pyrazinamide, Rifabutin, Rifampicin, Diadenosine
             Ganciclovir, Valgancyclovir, Oxymetholone, Thalidomide or Theophylline.

          -  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-alpha or gamma
             (recombinant or pegylated), systemic corticosteroids (nasal or pulmonary steroids will
             be allowed; 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; polyribonucleotide.

          -  History of adverse or allergic reactions to any type-1 interferon (e.g. IFN-alpha2a,
             IFN-α2b, IFN-beta)

          -  History of severe depression, 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.

          -  Prior diagnosis of multiple sclerosis or other neurodegenerative disorders

          -  Significant co-existing lab abnormalities including:

               1. Anemia (Hgb <9.1 mg/dl men, <8.9 mg/dl women)

               2. WBC <2000 cells/µl

               3. Absolute neutrophil count (ANC) <1200 cells/ µl

               4. Platelet count <60,000 cells/ µl

               5. Liver disease (AST/ALT > 2.5x, Total Bilirubin > 1.5x upper limits of norm (ULN),
                  or Total Bilirubin >3x ULN if receiving indinavir OR Atazanavir)

               6. Renal disease (creatinine > 2x upper normal limits 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 6 months prior to initiation of IFN

          -  Pregnancy, actively attempting to become pregnant, or breastfeeding

          -  Body weight under 125 lbs or over 300 lbs

          -  Other conditions, such as active drug/alcohol abuse or dependence which would
             interfere with study compliance