Antiviral Activity of Peg-IFN-Alpha-2A in Chronic HIV-1 Infection

• Status: Completed
• Trial end date: 2011-05-01
• Target enrollment: 0
• Participant gender: All

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.

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

Details

• Lead Sponsor: The Wistar Institute
• Collaborators: Hoffmann-La Roche; National Institute of Allergy and Infectious Diseases (NIAID); National Institutes of Health (NIH)
• Treatments: Antiviral Agents; Interferon alpha-2; Interferon-alpha; Interferons; Peginterferon alfa-2a

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.