HIV-1 Infection
Conditions
Keywords
HIV-1, Interferon alpha, Integrated DNA, Latent reservoir
Brief 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 \< 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.
Interventions
1µg/kg/week
Sponsors
University of Pennsylvania
Merck Sharp & Dohme LLC
The Wistar Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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: 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Copies of HIV DNA Per CD4+ T Cell at Week 24 | Week 3 and 24 | Difference in copies of HIV DNA per CD4+ T cell between baseline and week 24, assessed by Alu-HIVgag polymerase chain reaction |
Countries
United States
Participant flow
Recruitment details
22 screened
Participants by arm
| Arm | Count |
|---|---|
| Interferon Alpha pegylated Interferon alpha 2b (Pegintron) 1 µg/kg per week, 20 weeks
Pegylated Interferon alpha 2b: 1µg/kg/week | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Interferon Alpha |
|---|---|
| Age, Continuous | 47 years |
| CD4 count | 591 cells/ul |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 11 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
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
Time frame: Week 3 and 24
Population: outcome measure available only for 17 individuals
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Interferon Alpha | Change From Baseline in Copies of HIV DNA Per CD4+ T Cell at Week 24 | Baseline | 113 HIV DNA copies per CD4+ T cell |
| Interferon Alpha | Change From Baseline in Copies of HIV DNA Per CD4+ T Cell at Week 24 | Week 24 | 98 HIV DNA copies per CD4+ T cell |
p-value: 0.0797signed rank test