Pilot Peg-Interferon-a2b in Decreasing Viral DNA in HIV

Study Overview
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Brief Summary
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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.

Official Title
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Pilot Study: Single Arm, Multi-site, Open-label Study to Assess the Effectiveness of Peg-IFN-a2b in Decreasing the Levels of Cell-associated Integrated Viral DNA in HIV Chronic Infection

Conditions
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HIV-1 Infection

Intervention / Treatment
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* Drug: Pegylated Interferon alpha 2b


Participation Criteria
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Eligibility Criteria
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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: Anemia (Hgb <9.1 mg/dl men, <8.9 mg/dl women) WBC <2000 cells/µl Absolute neutrophil count (ANC) <1200 cells/ µl Platelet count <60,000 cells/ µl 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) 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interferon alpha<br>pegylated Interferon alpha 2b (Pegintron) 1 µg/kg per week, 20 weeks | Drug: Pegylated Interferon alpha 2b<br>* 1µg/kg/week<br>* Other names: Pegintron;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Copies of HIV DNA Per CD4+ T Cell at Week 24 | Difference in copies of HIV DNA per CD4+ T cell between baseline and week 24, assessed by Alu-HIVgag polymerase chain reaction | Week 3 and 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-1, Interferon alpha, Integrated DNA, Latent reservoir