Therapeutic Vaccine for HIV
Condition: HIV; Therapeutic Vaccine
Intervention: rVSV; IL-12 pDNA adjuvant; HIV-Mag pDNA; Placebo
Intervention description: Attenuated recombinant vesicular stomatitis virus containing HIV-1 gag gene; plasmid DNA containing human IL-12 gene; plasmid DNA vaccine containing genes encoding multiple HIV-1 proteins
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: HIV-MAG pDNA Prime; HIV Therapy; Therapeutic Vaccine

Summary:

      Background:

      - In most people who have human immunodeficiency virus (HIV), the immune system cannot
      control or cure the infection. Antiretroviral therapy drugs can keep the amount of HIV virus
      low for a long time. However, this treatment does not remove the virus from the body. In the
      vast majority of patients antiretroviral therapy also will not protect the body from the
      virus once treatment stops. Researchers want to see if therapeutic vaccination can help
      people with HIV. Therapeutic vaccination means giving vaccines to treat an infection that
      someone already has (HIV, in this case). It may help the body's immune system attack the
      infection. This study will look at different measures of HIV infection after receiving either
      therapeutic vaccination or a placebo.

      Objectives:

      - To see whether therapeutic vaccination is safe and can affect how the body responds to HIV
      infection.

      Eligibility:

      - Individuals between 18 and 65 years of age who have HIV and are taking antiretroviral
      therapy drugs.

      Design:

        -  Participants will be screened with a physical exam and medical history. Blood and urine
           samples will be collected.

        -  During the screening visit and throughout the study until week 56, participants will
           continue to take their HIV medications.

        -  Participants will be divided into two groups. One group will have the study vaccines.
           The other will have a placebo.

        -  The first study vaccine or placebo will be given in weeks 4, 12, and 36. The second
           study vaccine or the placebo will be given in weeks 24 and 48. Blood samples and other
           tests will be given at each visit.

        -  After the study visit at week 56, participants will stop their HIV medications until
           week 72. From weeks 58 through 72, they will come in every 2 weeks for study visits;
           each visit will take about 1 hour to complete. These visits will look at the body s
           response to the vaccines and their HIV viral load. After week 72, participants will
           re-start their HIV medications.

        -  There will be follow-up study visits from weeks 76 to 96, with blood tests and other
           studies.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. Age, 18-65 years.

               2. Institution of cART within 12 weeks of being diagnosed with acute or early HIV-1
                  infection.

                  Acute HIV-1 infection is defined as:

                    1. Detectable plasma HIV-1 RNA levels of greater than 2000 copies/mL with a
                       negative result from an HIV-1 EIA, or

                    2. Positive result from an HIV-1 EIA with a negative or indeterminate result
                       from an HIV-1 western blot that subsequently evolves to a confirmed positive
                       result, or

                    3. Negative result from an HIV-1 EIA within the past 4 months and HIV-1 RNA
                       levels of greater than 400,000 copies/mL, in the setting of a potential
                       exposure to HIV-1.

                  Early HIV-1 Infection is defined as:

                    1. Negative result from an HIV-1 EIA within 6 months prior to a positive result
                       from an HIV-1 EIA and an HIV-1 western blot.

                    2. Negative result from a rapid HIV-1 test within 1 month prior to a positive
                       result from an HIV-1 EIA and an HIV-1 western blot.

                    3. Presence of low level of HIV antibodies as determined by having a positive
                       EIA or a positive Western blot with a non-reactive detuned EIA according to
                       a serologic testing algorithm for recent infection.

               3. CD4+ cell count greater than 450 cells/mm3 at screening.

               4. Documentation of continuous cART treatment with suppression of plasma viral level
                  below the limit of detection for greater than 1 year. Subjects with a single blip
                  (i.e., detectable viral levels on cART) prior to randomization may be included
                  provided they satisfy the following criteria:

                    1. The blips are less than 400 copies/mL, and

                    2. Succeeding viral levels return to levels below the limit of detection on
                       subsequent testing.

               5. Willingness to undergo ATI.

               6. Laboratory values within pre-defined limits at screening:

                    -  Absolute neutrophil count greater than 1,000/mm3.

                    -  Hemoglobin levels greater than 10.0 g/dL for men and greater than 9.0 g/dL
                       for women.

                    -  Platelet count greater than 100,000/mm3.

                    -  Prothrombin time (PT) and partial thromboplastin time (PTT) less than 1.5
                       upper limit of normal (ULN).

                    -  Estimated or a measured creatinine clearance rate of greater than 60 mL/min
                       as determined by the NIH Clinical Center laboratory.

                    -  AST and ALT levels of less than 2.5 x ULN.

               7. Willingness to have samples stored for future research.

               8. Women of childbearing potential must have a negative pregnancy test result.

                    -  They must agree to use an adequate form of contraception:

                         -  Hormonal contraception.

                         -  Male or female condoms with or without a spermicidal

                         -  Diaphragm or cervical cap with a spermicidal.

                         -  Intrauterine device.

        EXCLUSION CRITERIA:

          1. Allergy to amide-type local anesthetics (bupivacaine (Marcaine), lidocaine
             (Xylocaine), Mepivacaine (Polocaine/Carbocaine), etidocaine (Duranest), prilocaine
             (Citanest, EMLA cream).

          2. Chronic hepatitis B, as evidenced by a positive test for hepatitis B surface antigen
             (HBsAg), or chronic hepatitis C virus (HCV) infection, as evidenced by a positive test
             for HCV RNA. Subjects with a positive test for HCV antibody and a negative test for
             HCV RNA are eligible.

          3. Changes in cART regimen due to virologic breakthrough.

          4. HIV immunotherapy or vaccine(s) received within 1 year prior to screening.

          5. Any licensed or experimental non-HIV vaccination (e.g., hepatitis B, influenza,
             pneumococcal polysaccharide) received within 4 weeks prior to study entry.

          6. Interruption of cART for greater than 3 months since its initiation. 8. Any active
             malignancy that may require systemic chemotherapy or radiation therapy.

          7. Pregnancy or planned pregnancy during the study period or breastfeeding.

          8. Any active malignancy that may require systemic chemotherapy or radiationtherapy.

          9. Immunosuppressive medications received within 6 months before the first study
             vaccination (Not excluded: (1) corticosteroid nasal spray for allergic rhinitis; (2)
             topical corticosteroids for mild, uncomplicated dermatitis; or (3) oral/parenteral
             corticosteroids administered for non-chronic conditions not expected to recur (length
             of therapy less than or equal to10 days, with completion in greater than or equal to
             30 days prior to enrollment).

         10. Evidence of hepatic decompensation in subjects with cirrhosis: history of ascites,
             hepatic encephalopathy, or bleeding esophageal varices, or screening laboratory
             results with any of the following:

               1. International normalized ratio of greater than or equal to1.5 x ULN.

               2. Serum albumin less than 3.2 g/dL.

               3. Serum total bilirubin greater than 1.8 x ULN, unless history of Gilbert's disease
                  or deemed related to treatment with atazanavir.

         11. History or other clinical evidence of:

               1. Significant or unstable cardiac disease (e.g., angina, congestive heart failure,
                  recent myocardial infarction, significant arrhythmia).

               2. Severe illness, malignancy, immunodeficiency other than HIV, or any other
                  conditions that, in the opinion of the investigator, would make the subject
                  unsuitable for the study.

               3. AIDS-defining condition.

         12. Known allergy or sensitivity to the components of the investigational therapy.

         13. History of significant cardiac arrhythmia (e.g., supraventricular tachycardia,
             ventricular tachycardia, and atrial fibrillation/flutter).

         14. Active drug or alcohol use or any dependence other pattern of behaivor that, in the
             opinion of the investigator, would interfere with adherence to study requirements.

         15. Any active systemic inflammatory or autoimmune disease or condition.

         16. Presence of implanted electronic medical device (e.g., pacemaker, implantable cardiac
             defibrillator) or surgical/traumatic metal implant in the upper limb and/or upper
             torso.

         17. Neurological or neuropsychiatric disorder that may interfere with the assessment of
             safety (e.g., frequent recurring headaches, for example, a pattern of greater than 1
             headache/month affecting activities of daily living/work, frequent or
             severe/complicated migraines, cluster headaches); or history of encephalitis,
             narcolepsy, stroke with sequelae, moderate/severe major depressive disorder,
             moderate/severe bipolar disorder, seizure disorder.

         18. Deltoid skinfold measurements (by caliper) of greater than 40 mm.

         19. Body mass index greater than 40.