A Safety and Immunogenicity Study of a Plasmid DNA Prime and MVA Boost Vaccine in HIV-1 (Human Immunodeficiency Virus-1) Infected Adults on ART

Inclusion Criteria:

• Age 18 through 50 years
• Time between start of ART and last documented negative HIV antibody test within 18 months; or time from negative detuned HIV-1 antibody assay to start of ART within 13 months; or time between evolution of Western blot from indeterminate to positive (as defined by CDC/ASTPHLD) in the presence of a positive antibody test and initiation of ART is within 18 months
• No changes to ART treatment within 4 weeks of study entry
• Documentation of level of plasma HIV-1 RNA and CD4+ counts prior to beginning ART; pretreatment HIV-RNA must be at least 8 wks following diagnosis of acute HIV-1 infection
• On stable suppressive ART, defined as HIV-1 RNA < 50 copies/mL (PCR) or < 75 copies/mL (bDNA) for a minimum of 6 months prior to starting vaccination so that at least two measures must have occurred within the 6 months preceding vaccination (One may be from the chart and one at screening)
• No history of virologic failure, failure defined as HIV-1 RNA > 50 copies/mL (PCR) or > 75 copies/mL (bDNA), after achieving suppression below those levels or failure to reach HIV-1 RNA < 50 copies/mL (PCR) or < 75 copies/mL (bDNA) on initial antiretroviral regimen (Substitutions due to intolerance are allowed)
• CD4+ > 500 cells/µL
• Nadir CD4+ > 350 cells/µL unless measured in the setting of acute infection

• Laboratory values:

  • Hemoglobin ≥ 10g/dL (male) or 9g/dL (women)
  • ANC > 1000 cells/µL
  • ALT, AST ≤ 2.5 ULN
  • Total bilirubin < 1.5 x ULN (≤ 5 x ULN on atazanavir)
  • Fasting glucose ≤ 125 mg/dL
  • Serum creatine < 1.5 x ULN
  • Creatinine clearance ≥ 60 mL/min (Cockcroft-Gault)
  • Serum creatine phosphokinase (CPK) ≤ 1.5 x ULN
  • UA negative for hemoglobin and glucose and no greater than 1+ protein
  • Any abnormalities must be assessed by the investigator as not clinically significant
• ECG without evidence of current or past MI, or ischemic heart disease
• Willing to provide signed informed consent
• Female subjects must have a negative serum or urine β-HCG pregnancy test at screening
• Female subjects of reproductive potential (not having reached menopause or not having undergone hysterectomy, bilateral oophorectomy, or tubal ligation) who engage in sexual activity that could lead to pregnancy must agree to avoid pregnancy and agree to consistently use contraception for at least 21 days prior to first vaccination until the last protocol visit.

• Contraception is defined as using at least one of the following methods:

  • Condoms (male or female)
  • Diaphragm or cervical cap
  • Intrauterine device (IUD)
  • Hormonal contraceptive with one of the following: condoms, diaphragm or cervical cap
• Male subjects participating in the study must agree to not attempt to impregnate a female, or participate in sperm donation programs
• Males engaging in sexual activity that could lead to pregnancy must use a condom from the date of receipt of the first study vaccine until the last protocol visit
• Male and female subjects participating in the study must agree to use condoms for protection against HIV-1 transmission throughout the study
• Participants must be willing to comply with all study requirements and expected to be available for the duration of the study
• Participants must be willing to temporarily discontinue antiretroviral therapy for up to 12 weeks post-vaccinations

Exclusion Criteria:

• Known infection with HIV-1 subtype other than Clade B
• Receipt of chemotherapy for active malignancy in the past 12 months
• Prior vaccinations with any HIV-1 vaccine
• Prior vaccination against smallpox within the last 15 years

• History of or known cardiac disease including:

  • myocardial infarction
  • angina pectoris
  • congestive heart failure
  • cardiomyopathy
  • pericarditis
  • stroke or transient ischemic attack
  • symptoms suggestive of cardiac disease in the opinion of the investigator
• History of myositis
• Diagnosis of HIV-associated nephropathy
• Evidence of active hepatitis B or C infection, including positive HBsAG or positive hepatitis C antibody
• Framingham Global Risk Assessment Score consistent with high short-term (10 year) cardiac risk
• Receipt of immunomodulatory agents, systemic corticosteroids (including nonprescription street steroids), gamma globulin, or investigational agents (other than H1N1 influenza vaccine) within 6 months of screening
• Any immunization within 1 month of screening
• Creatine supplements within 14 days of baseline and unwillingness to discontinue use throughout the trial
• Changes in ART regimen prior to entry due to virologic failure (not including toxicity)
• Pregnancy or breastfeeding
• Any clinically significant diseases (other than HIV-1 infection) or clinically significant findings during the screening medical history or physical examination that, in the investigator's opinion, would compromise participant safety
• Active alcohol or substance abuse, defined as use that is likely to interfere with the ability of the subject to adhere to medications, return for study visits or lead to adverse events
• Allergy to chicken egg derived products
• Contraindication to intramuscular injection such as anticoagulant therapy or thrombocytopenia
• Unwilling to forego vigorous exercise 3 days prior to each vaccination