Overview

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.