Therapeutic Intensification Plus Immunomodulation to Decrease the HIV-1 Viral Reservoir

The objective of this study is to measure the impact of immunomodulation plus treatment intensification on the HIV reservoir in HIV-infected patients who have viral suppression on combination antiretroviral therapy. Treatment regimens first will be intensified by the addition of raltegravir and maraviroc for 8 week followed by immunomodulation with the NIH HIV-rAd5 vaccine plus DNA prime-boost for 24 weeks. The primary endpoint is measurement of change in peripheral cellular HIV DNA. A decrease of 0.5 log is considered significant. A secondary endpoints include change in HIV DNA in the rectal mucosa, immunologic changes in the peripheral blood and safety.

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