pilot peg-interferon-a2b in decreasing viral dna in hiv

Conditions: HIV-1 Infection

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 \ 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 (\ 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

Keywords: hiv-1 interferon alpha integrated dna latent reservoir