Therapeutic Intensification Plus Immunomodulation to Decrease the HIV-1 Viral Reservoir
Condition: HIV Infection
MeSH terms: HIV Infections
Intervention: DNA + HIV-rAd5 vaccine; ART intensification (raltegravir); ART intensification (maraviroc)
Intervention description: 4 mg subcutaneous injection at weeks 8 (DNA prime), 12 (DNA prime), 16 (DNA prime), and 32 (HIV-rAd5); raltegravir 400 mg PO BID for 56 weeks; maraviroc 150, 300, or 600 mg PO BID (depending on PK interactions with other medications) for 56 weeks
Intervention MeSH terms: Raltegravir Potassium; Maraviroc
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 28.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: HIV-1 infection; Treatment intensification; Immunomodulation; HIV-rAd5 vaccine

Summary:

      The objective of this study is to discover a new approach in which human immunodeficiency
      virus (HIV) can be eradicated from an infected individual by intensified antiretroviral
      treatment coupled with immunomodulation. The hypothesis is that eradication is possible only
      if very potent antiretroviral drugs are delivered in conjunction with an immunomodulatory
      agent that simultaneously attack the viral reservoirs.
    

Eligibility criteria:

        Inclusion Criteria:

          -  HIV-1 infection

          -  At least 3 years of ART without interruption (less than one month cumulative)

          -  ART regimen unchanged in the 3 months prior to screening

          -  One HIV plasma viral load (RNA) documented at least 3 years prior to entry, and at
             least 2 HIV plasma viral load (RNA) documented per year thereafter

          -  HIV plasma viral load (RNA) ≤ 500 copies/mL at least 3 years prior to entry, and HIV
             plasma viral load < 500 copies/mL for >90% of the measures thereafter

          -  HIV plasma viral load (RNA) below the limit of detection for all values within the
             past year (one virologic blip allowed)

          -  HIV plasma viral load below the limit of detection within 60 days of entry

          -  CD4+ count ≥ 350 cells/mm3 within 60 days of entry

          -  Proviral DNA ≥10 and ≤1000 copies/106 PBMCs within 75 days of entry

          -  Adeno5 neutralizing antibody titers of 250 or less within 75 days of entry

          -  Hemoglobin ≥ 10 g/dL within 60 days of entry

          -  Platelets ≥ 100,000 per microliter within 60 days of entry

          -  Hepatic transaminases (ALT and AST) ≤ 2.5 x ULN within 60 days of entry

          -  Creatinine clearance > 50 mL/min by the Cockcroft-Gault equation within 60 days of
             entry

        Exclusion Criteria:

          -  Sexually active men and women who will not practice at least one form of barrier birth
             control (male partner using condoms, female partner using condoms, other barrier
             contraception, etc)

          -  Pregnancy

          -  Inability or unwillingness to provide informed consent

          -  HBsAg positive

          -  HCV antibody positive or HCV RNA detectable

          -  Previous use of an integrase inhibitor (ie raltegravir) or a CCR5 inhibitor (ie
             maraviroc, vicriviroc). Use of raltegravir for non-treatment failure indications such
             as intensification or toxicity switches is allowed.

          -  Immunologic therapeutic intervention (e.g. IL-2) within the past year

          -  Participation in another clinical drug or device trial where the last dose of drug was
             within the past 30 days or an investigational medical device is currently implanted

          -  Diagnosis of cancer within the last 5 years (except basal cell cutaneous cancers and
             cutaneous KS not requiring systemic therapy)

          -  Co-morbid condition with an expected survival of less than 12 months

          -  History of hypersensitivity to vaccination

          -  History of autoimmune disease, such as systemic lupus erythematosis (SLE) or
             Hashimoto's thyroiditis

          -  Active drug or alcohol use or dependence that, in the opinion of the site
             investigator, would interfere with adherence to study requirements