HIV infection documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral assay.
A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load.
WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment.
- Ages ≥ 18 to ≤ 45 years old
- Able and willing to give written informed consent.
- Able and willing to provide adequate locator information.
- Able and willing to comply with time requirements for protocol-specified visits and evaluations.
- Able and willing to commit to all study visits including follow-up through Week 24.
- Continuous ART prior to screening, defined as not missing more than 4 total days and never more than 2 consecutive days in the last 3 months.
- On a stable ART regimen defined as no changes in any ART medication within the 3 months prior to screening.
Permitted ART regimens include:
- 1) At least 3 ART agents (not counting ritonavir or cobicistat as one of the agents if less than a 200mg total daily dose). One of the agents must include an integrase inhibitor, NNRTI (Non-Nucleoside Reverse Transcriptase Inhibitors), or a boosted-PI (protease inhibitor).
- 2) Two ART agents in which one of the agents is either a boosted protease inhibitor or an integrase inhibitor.
NOTE: Other potent fully suppressive antiretroviral combinations will be considered on a case-by-case basis.
NOTE: Changes in drug formulation or dose are allowed (e g, TDF to TAF, ritonavir to cobicistat or separate ART agent dosing to fixed-dose combination), but none within 30 days prior to screening.
NOTE: Prior changes in, or elimination of, medications for easier dosing schedule, intolerance, toxicity, an improved side effect profile or within a drug class are permitted if an alternative suppressive regimen was maintained, but not within 3 months prior to screening.
- Ability and willingness of participant to continue ART throughout the study.
- Plasma HIV-1 RNA <50 copies/mL at 3 time points in the previous 24 months prior to screening and never ≥50 copies/mL on 2 consecutive time points in the last 24 months.
- At least 1 documented HIV-1 RNA result <50 copies/mL ≥24 months but ≤ 36 months prior to screening.
- Plasma HIV-1 RNA level <50 copies/mL on an FDA-approved HIV RNA assay performed at a US CLIA Certified Laboratory (or its equivalent).
- CD4 cell count ≥ 350 cells/mm3, performed at any US laboratory that has a CLIA certification or its equivalent.
No history of auto-immune disease, auto-immune manifestations or chronic inflammatory conditions including but not limited to inflammatory bowel diseases, scleroderma, severe psoriasis, myocarditis, uveitis, pneumonitis, systemic lupus erythematosus, rheumatoid arthritis, optic neuritis, myasthenia gravis, adrenal insufficiency, autoimmune thyroiditis, hypophysitis, or sarcoidosis.
Note: The following conditions are not exclusionary: vitiligo, resolved childhood atopic dermatitis, Graves' disease with subsequent return to a euthyroid state (clinically and by laboratory testing).
- Hepatitis C (HCV) antibody negative result at screening or, if the participant is HCV antibody positive, a negative HCV RNA at screening.
- Hepatitis B surface antigen (HBsAg) negative at screening.
- Adequate vascular access for leukapheresis.
- Able and willing to receive IM injections without difficulty.
- All women must have a negative serum pregnancy test at screening regardless of reproductive potential.
All participants must agree not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization, egg donation) while on study and for 4 months after their vaccination.
Note: Women of child bearing potential is defined as women who have not been post-menopausal for at least 24 consecutive months, i.e., who have had menses within the preceding 24 months, or women who have not undergone surgical sterilization, specifically hysterectomy and/or bilateral oophorectomy or bilateral salpingectomy
All men and women participating in sexual activity that could lead to pregnancy must agree to consistently use at least one of the following forms of birth control for at least 21 days prior to Visit 4 (Day 0) and for 4 months after their vaccination:
- Condoms (male or female) with or without a spermicidal agent
- Diaphragm or cervical cap with spermicide
- Intrauterine device (IUD)
- Tubal ligation
- Hormone-based contraceptive
NOTE: For female participants receiving ritonavir or cobicistat, estrogen-based contraceptives are not reliable and an alternative method should be suggested.
Men and women who are not of reproductive potential are eligible without requiring the use of contraceptives. Acceptable documentation detailing sterilization and menopause are specified below.
Note: Men who have sex with men only will not be required to use contraception.
Written or oral documentation communicated by clinician or clinician's staff of one of the following:
- Physician report/letter
- Operative report or other source documentation in the patient record (a laboratory report of azoospermia is required to document successful vasectomy)
- Discharge summary
- Follicle stimulating hormone-release factor (FSH) measurement elevated into the menopausal range as established by the reporting laboratory
- Agrees not to enroll on another study of an investigational research agent during the study period.
- Willingness to defer routine vaccination except for influenza from screening through 28 days after vaccination at Day 0.
- Adequate organ function as indicated by the following laboratory values:
Hematological: Absolute neutrophil count (ANC) ≥ 1,000 /mcL; Platelets ≥ 100,000/mcL; Hemoglobin ≥ 12 g/dL (male) and ≥ 11.5 g/dL (females)
Chemistries: Serum potassium levels within normal limits; Serum magnesium levels ≥ 1.4 mEq/L; Glucose - Screening serum glucose ≤ Grade 1 (fasting or non-fasting)
Hepatic: Serum total bilirubin - Total bilirubin <1.1 x ULN. If total bilirubin is elevated, direct bilirubin must be <2 x ULN
If the participant is on an atazanavir -containing therapy then a direct bilirubin should be measured instead of the total bilirubin and must be ≤1.0mg/dL.
- If the HIV provider or study investigator is unable, as assessed by the study PI or protocol team, to construct a fully active alternative regimen based on previous resistance testing and/or treatment history.
- Women of childbearing age/potential must not be breast feeding, pregnant, or planning pregnancy any time from enrollment to 4 months after vaccination at Day 0.
- Body Mass Index (BMI) ≥40 kg/m2
- Untreated syphilis infection (defined as a positive rapid plasma reagin (RPR) without clear documentation of treatment).
- Current treatment for HCV with antiviral therapy or participants who have received HCV treatment within 6 months prior to screening.
- HIV RNA ≥150 copies/mL in the 6 months prior to screening.
- Received any infusion blood product, immune globulin, or hematopoetic growth factors within 6 months prior to screening.
- Use of any of the following within 90 days prior to screening: immunomodulatory, cytokine, or growth stimulating factors such as systemic cytotoxic chemotherapy, , immune globulin, interferon, cyclosporine, methotrexate, azathioprine, anti-CD25 antibody, IFN, interleukins, interleukin-2 (IL-2), hydroxyurea, thalidomide, sargramostim (granulocyte macrophage-colony stimulating factor [GM-CSF]), growth factors, dinitrochlorobenzene (DNCB), thymosin alpha, thymopentin, inosiplex, polyribonucleoside, or diticarb sodium, coumadin, warfarin, or other Coumadin derivative anticoagulants.
- Intent to use immunomodulators (e.g., IL-2, IL-12, interferons or TNF modifiers) during the course of the study.
Use of systemic corticosteroids or topical steroids over a total area exceeding 15 cm2 within 30 days prior to screening, or anticipated need for periodic use of corticosteroids during the study.
NOTE: For participants receiving ritonavir or cobicistat, (either as a booster or protease inhibitor [PI]) as part of their ART regimen, the concomitant use of oral/systemic/topical/inhaled/ intranasal corticosteroids is prohibited.
- Use of any prior HIV vaccine (prophylactic and/or therapeutic).
- Any experimental non-HIV vaccination within 1 year prior to screening.
- Prior immunization with a recombinant Adenovirus or MVA vaccine
- Prior immunization with small pox vaccine.
- Live attenuated vaccines received within 60 days prior to screening (i.e., varicella; measles, mumps, rubella [MMR]; yellow fever, oral polio, shingles).
- Receipt of other vaccines, excluding influenza vaccine, within the previous 28 days of screening.
- History of prior IgG therapy or immunization with any experimental immunogens (antibodies) within 6 months of screening.
Use of any investigational treatment within 6 months prior to screening, with the exception of Phase II studies of antiretroviral agents.
NOTE: Co-enrollment with other studies under an IND using an FDA approved medication that are not otherwise listed as prohibited will be considered on a case-by-case basis.
- For any serious illness requiring systemic treatment or hospitalization, the participant must either complete therapy or be clinically stable on therapy, in the opinion of the site investigator, for at least 90 days prior to screening.
- Treatment for an active HIV-related opportunistic infection within 90 days prior to screening.
History of malignancy within the last 5 years.
NOTE: A history of non-melanoma skin cancer (e.g., basal cell carcinoma or squamous cell skin cancer) is not exclusionary with documentation of complete resection at least 3 months prior to enrollment).
- Immune deficiency other than that caused by HIV infection.
- Any medical, psychiatric, occupational or other condition that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence or assessment of safety.
- If a person has been found to have elevated blood pressure or hypertension during screening or previously, exclude for blood pressure that is not well controlled. Well-controlled blood pressure is defined as consistently ≤ 140 mm Hg systolic and ≤ 90 mm Hg diastolic, with or without medication, with only isolated, brief instances of higher readings, which must be ≤ 150 mm Hg systolic and ≤ 100 mm Hg diastolic. For these participants, blood pressure must be ≤ 140 mm Hg systolic and ≤ 90 mm Hg diastolic at enrollment.
- If a person has NOT been found to have elevated blood pressure or hypertension during screening or previously, exclude for systolic blood pressure ≥ 150 mm Hg at enrollment or diastolic blood pressure ≥ 100 mm Hg at enrollment.
Note: Elevated BP occurring during research leukapheresis procedures completed within the past 12 months are excluded from this requirement. Other isolated incidences of elevated BP should be reviewed by study PI to determine whether exclusionary. Isolated elevations must be noted as acceptable and signed by study PI or designee.
- Seizure disorder or any history of prior seizure.
- History of unexplained syncope or fainting episodes within 12 months of study screening.
History of Asplenia - absence of normal spleen function as indicated by:
- Sickle cell disease
- Bleeding disorder including factor deficiency, coagulopathy or platelet disorder that requires special precautions (easy bruising without a formal diagnosis is not exclusionary).
- Allergy to eggs and/or egg products.
- History of anaphylaxis or severe adverse reaction to vaccines including symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain.
- History of hereditary angioedema, acquired angioedema or idiopathic angioedema.
- Known or suspected hypersensitivity to any vaccine component.
Unstable asthma (e.g. sudden acute attacks occurring without an obvious trigger) or asthma requiring:
- Daily steroid or long acting beta-agonist prevention
- Hospitalization in the last two years
- Extensive tattoos or depo-provera injection at the site of administration (upper left or right medial deltoid muscles).
- History of allergy to latex.
- Active chronic skin problems such as eczema or psoriasis.
- Known psychiatric or substance abuse disorder/dependence that, in the opinion of the site investigator, would interfere with cooperation with the requirements of the trial.
- Compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric illness or a physical illness, e.g., infectious disease.
- Prisoner recruitment and participation is not permitted.
- Inability to communicate effectively with study personnel.