Antiviral Activity of Peg-IFN-Alpha-2A in Chronic HIV-1 Infection
Condition: HIV Infections
MeSH terms: Infections; Communicable Diseases
Intervention: Pegylated Interferon-alpha 2a, 180 mcg/week sc; Pegylated Interferon-alpha 2a, 90 mcg/week sc
Intervention description: Pegylated Interferon-alpha 2a, 90 mcg/week sc for 24 weeks, 5 weeks in combination with ART, then 7 weeks without ART to primary endpoint (VL < 400 c/ml at 12 weeks) and further 12 weeks without ART (24 weeks) to secondary endpoints; Pegylated Interferon-alpha 2a, 90 mcg/week sc for 24 weeks, 5 weeks in combination with ART, then 7 weeks without ART to primary endpoint (VL < 400 c/ml at 12 weeks) and further 12 weeks without ART (24 weeks) to secondary endpoints
Intervention MeSH terms: Interferons; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2a
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: HIV; HIV-1; Pegasys; Peg-IFN-Alpha-2A; Viral Suppression; ART cessation; Immune function; Innate Immunity; Toxicity; Immune-based therapy; Treatment interruption

Summary:

      The objective of the study is to compare two different doses of Peg-INF-α-2A (90 or 180
      ug/wk) for their ability to maintain viral control when initiated 5 weeks before ART
      (antiretroviral therapy) interruption in HIV positive, ART-suppressed subjects (viral load
      <50 copies/ml) as determined by observing the percentages of viral load measurements <400
      copies/ml between the two arms over a 24-week period, corresponding to the Pegasys
      monotherapy period (exclusive of dual ART/Pegasys 5-week period). Primary analysis will be an
      "intent to treat" analysis and will address the hypothesis that two different doses of
      Peg-INF-α-2A (90 and 180 ug/week) will be similarly effective at inhibiting viral
      replication.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female, age ≥ 18 but <65 years

          -  Able and willing to provide informed consent.

          -  HIV-1 infection documented by any licensed enzyme-linked immunosorbent assay (ELISA)
             test kit and confirmed by Western Blot at any time prior to or at study entry. HIV-1
             culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other
             than ELISA is acceptable as an alternative confirmatory test

          -  HIV RNA < 75 copies/ml on a regimen of a) 2 Nucleoside Reverse Transcriptase
             Inhibitors (NRTIs) and 1 non-nucleoside RTI (NNRTI) OR b) 2 NRTIs and Protease
             Inhibitor (PI) for at least 24 weeks OR c) 3 NRTIs

          -  HIV RNA < 75 copies/ml at screening

          -  > 6 months ≥ 400 CD4+ T cells/mm3 (CD4 nadir ≥ 200 cells)

          -  Female subjects with childbearing potential: negative pregnancy test (Beta human
             horionic gonadotropin (HCG)). Must agree to use appropriate contraceptive methods
             (barrier devices such as diaphragms or condoms + spermicidal or intrauterine device
             (IUD) or oral contraceptives) while on study.

          -  Karnofsky performance scale score of 80% or better

          -  Willing to adhere to the treatment and schedule approved by the study investigators in
             conjunction with the patient's primary provider.

          -  Willing to abstain from immunomodulatory drugs during the study period, with the
             exception of the study drug (Pegasys®).

          -  Patient Health Questionnaire (PHQ)-2 score < 2, OR PHQ-9 score< 10, OR PHQ-9 score
             10-14 AND medical provider's favorable opinion. In either case, score for PHQ-9
             question # 9 (suicidal ideation) must be 0.

          -  Thyroid stimulating hormone (TSH) within normal range, unless accompanied by thyroid
             profile consistent with normal thyroid function

          -  A negative cardiac stress test 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 Hight
             density lipoprotein (HDL)-associated cholesterol (<40 mg/dL), family history of
             premature Coronary heart disease (CHD) (<55 yrs males/<65 females)] or a Framingham
             score > 15% (men) or 10% (women))

        Exclusion Criteria:

          -  Currently pregnant or breast feeding.

          -  CD4 cell count < 400 or recorded CD4 nadir < 200 cells/mm3

          -  History of immunomodulatory therapy for over 2 weeks during the 6 months prior to
             enrollment, including, but not limited to: IFN-Alpha or Beta (recombinant or
             pegylated), systemic corticosteroids; 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;
             polyribonucleoside.

          -  Significant co-existing medical conditions including: Anemia (Hgb <9.1 men, <8.9
             women), Neutropenia (ANC < 1000), Thrombocytopenia (platelet count <50K), Liver
             disease (AST/ALT > 5x, Total Bilirubin > 1.5x upper limits of normal, or Total
             Bilirubin >3x upper limit of the norm (ULN) if receiving indinavir), Renal disease
             (creatinine > 2x upper normal limits), or other conditions, such as active
             drug/alcohol abuse or dependence which would interfere with study compliance.

          -  Any history of heart attacks, myocardial infarction or coronary arterial disease
             (MI/CAD). .

          -  Prior history of major depression or other severe psychiatric disorder/condition
             requiring treatment and/or hospitalization

          -  PHQ-9 score >14, OR PHQ-9 score > 10 - 14 and lack of medical provider's favorable
             opinion, or score for PHQ-9 answer # 9 (suicidal ideation) > 0.

          -  Evidence of chronic active Hepatitis B infection (Surface Antigen HBsAg) or Hepatitis
             C plymerase chain reaction (PCR) positivity at screening (cleared of HCV at entry >6
             months).

          -  Past evidence of medical conditions associated with chronic liver disease including
             genetic hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin
             exposures etc.

          -  History of neutropenia or other hematological abnormalities

          -  Type I diabetes mellitus, or type II diabetes mellitus that is not controlled with
             oral agents and/or insulin.

          -  Ongoing treatment with Isoniazide, Pyrazinamide, Rifabutin, Rifampicin, Diadenosine
             Ganciclovir, Valganciclovir, Oxymetholone, Thalidomide or Theophylline.

          -  History of autoimmune processes including Crohn's disease, ulcerative colitis, severe
             psoriasis, rheumatoid arthritis, myositis, hepatitis etc.

          -  History of major organ transplantation with an existing functional graft.

          -  Active coronary artery disease within 24 weeks prior to study

          -  Hemoglobinopathies such as sickle cell anemia or Thalassemia major.

          -  Hypersensitivity to Pegasys®or any of its components.