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

GV-TH-01 is an open label Phase 1 study of 9 HIV-1 infected adults with suppressed viremia
who started anti-retroviral therapy (ART) within 18 months of a negative HIV antibody test.
This study has 3 phases. The first phase is the vaccination phase, where patients are
vaccinated with pGA2/JS7 (JS7)DNA and MVA62B vaccines on a prime/boost regimen at weeks 1 and
9 (JS7 DNA vaccine) and weeks 17 and 25 (MVA62B). Both vaccines express Gag, Pol, and Env.
The second phase of the study is a treatment interruption phase, whereby ART is interrupted
for a 12 week period approximately 8 weeks following the last vaccination. The third phase
occurs after the 12 week treatment interruption phase and is called the treatment
reinstitution phase, because subjects reinstitute ART and are followed for an additional 24
weeks. The primary objective is to evaluate the safety of the vaccines during the three
phases of the study. A secondary objective is to evaluate the immunogenicity of the vaccines
during the vaccination phase of the study.

Inclusion Criteria:

- Age 18-50 yrs.

- ART started within 18 mo. of last documented negative HIV Ab test, or within 13 mo. of
last negative detuned HIV-1 Ab assay, or within 18 mo. of evolution of Western blot
from indeterminate to positive in the presence of a positive Ab test

- No changes to ART treatment within 4 wks. of study entry

- Documentation of level of plasma HIV-1 RNA and CD4+ counts prior to ART

- On stable suppressive ART [HIV-1 RNA < 50 copies/mL (PCR) or < 75 copies/mL (bDNA) for
at least 6 mo. prior to starting vaccination]

- No history of virologic failure

- 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

- Females: a negative serum or urine β-HCG pregnancy test at screening

- Female subjects of reproductive potential 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.

- 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

- Agreement 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 wks. post-vaccinations

Exclusion Criteria:

- Known infection with HIV-1 subtype other than Clade B

- Chemotherapy for active malignancy in the past 12 mo.

- Prior vaccinations with any HIV-1 vaccine

- Prior vaccination against smallpox within the last 15 yrs.

- History of or known cardiac disease

- History of myositis

- Diagnosis of HIV-associated nephropathy

- Evidence of active HBV or HCV infection

- Framingham Global Risk Assessment Score consistent with high short-term (10 yr.)
cardiac risk

- Receipt of immunomodulatory agents, systemic corticosteroids (including
nonprescription street steroids), gamma globulin, or investigational agents (other
than H1N1 influenza vaccine) within 6 mo. of screening

- Any immunization within 1 mo. of screening and within 2 wks. of any inoculation in
this study

- 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 abuses

- Allergy to chicken egg derived products

- Contraindication to intramuscular injection

- Unwilling to forego vigorous exercise 3 days prior to each vaccination