Inclusion Criteria:
General and Demographic Criteria
- Age of 18 through 50 years.
- Access to a participating HVTN CRS and willingness to be followed for the planned duration of the study.
- Ability and willingness to provide informed consent.
- Assessment of understanding: volunteer demonstrates understanding of this study and that in a previous trial with an adenovirus type 5 (Ad5) vector there was an association of increased HIV acquisition with receipt of that study product; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly.
- Willing to be contacted annually after completion of scheduled clinic visits for a total of 3 years following initial study injection.
- Agrees not to enroll in another study of an investigational research agent until the last scheduled clinic visit.
- Good general health as shown by medical history, physical exam, and screening laboratory tests.
HIV-Related Criteria
- Willingness to receive HIV test results.
- Willingness to discuss HIV infection risks and amenable to HIV risk reduction counseling.
- Assessed as "low risk" for HIV acquisition per low risk guidelines (see Appendix M), agrees to discuss HIV infection risks, agrees to risk reduction counseling, and agrees to avoid behavior associated with high risk of HIV exposure through the final study visit. Low risk may include persons stably taking PrEP as prescribed for 6 months or longer.
Laboratory Inclusion Values
Hemogram/Complete blood count (CBC)
Hemoglobin
- 11.0 g/dL for volunteers who were assigned female sex at birth
- 13.0 g/dL for volunteers who were assigned male sex at birth and transgender male who have been on hormone therapy for more than 6 consecutive months
- 12.0 g/dL for transgender female who have been on hormone therapy for more than 6 consecutive months
For transgender participants who have been on hormone therapy for less than 6 consecutive months, determine hemoglobin eligibility based on the sex assigned at birth
- White blood cell count = 2,500 to 12,000 cells/mm3 with normal differential, or differential approved by Investigator of Record (IoR) or designee as not clinically significant
- Total lymphocyte count ≥ 650 cells/mm3 with normal differential, or differential approved by Investigator of Record (IoR) or designee as not clinically significant
- Remaining differential either within institutional normal range or with site physician approval.
- Platelets = 125,000 to 550,000 cells/mm3.
Chemistry
- Alanine aminotransferase (ALT) < 1.25 times the institutional upper limit of normal;
- Creatinine <1.1 times the institutional upper limit of normal
Virology
- Negative HIV-1 and -2 blood test: US volunteers must have a negative FDA-approved enzyme immunoassay (EIA) or chemiluminescent microparticle immunoassay (CMIA).
- Negative Hepatitis B surface antigen (HBsAg).
- Negative anti-Hepatitis C virus antibodies (anti-HCV), or negative HCV nucleic acid test if the anti-HCV is positive
Urine
Normal urine:
- Negative or trace urine protein, and
- Negative, trace, or 1+ blood/hemoglobin on urine dipstick. If 1+ hemoglobin is present on dipstick, a microscopic urinalysis with red blood cells levels within institutional normal range is required.
Reproductive Status
Volunteers who were assigned female sex at birth: negative serum or urine beta human chorionic gonadotropin (β-HCG) pregnancy test at screening (ie, prior to randomization) and prior to study product administration on the day of study product administration. Persons who are NOT of reproductive potential due to having undergone hysterectomy or bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing.
Reproductive status: A volunteer who was assigned female sex at birth must agree to use effective contraception for sexual activity that could lead to pregnancy from at least 21 days prior to enrollment until two months following final product administration.
- Condoms (male or female) with or without a spermicide,
- Diaphragm or cervical cap with spermicide,
- Intrauterine device (IUD),
- Hormonal contraception,
- Tubal ligation, or
- Any other contraceptive method approved by the HVTN 139 PSRT
- Successful vasectomy in any partner assigned male sex at birth (considered successful if a volunteer reports that a male partner has [1] documentation of azoospermia by microscopy, or [2] a vasectomy more than 2 years ago with no resultant pregnancy despite sexual activity postvasectomy);
- Or not be of reproductive potential, such as having reached menopause (no menses for 1 year) or having undergone hysterectomy, or bilateral oophorectomy;
- Or be sexually abstinent.
Volunteers who were assigned female sex at birth must also agree not to seek pregnancy through alternative methods, such as artificial insemination or in vitro fertilization until two months after the last product administration
Exclusion Criteria:
- Blood products received within 120 days before first vaccination.
- Investigational research agents received within 30 days before first vaccination.
- Body mass index (BMI) ≥ 40; or BMI ≥ 35 with 2 or more of the following: age > 45, systolic blood pressure > 140 mm Hg, diastolic blood pressure > 90 mm Hg, current tobacco smoker, known hyperlipidemia.
- Intent to participate in another study of an investigational research agent or any other study that requires non-HVTN HIV antibody testing during the planned duration of the HVTN 139 study.
- Pregnant or breastfeeding.
- Active duty and reserve US military personnel.
Vaccines and other Injections
- HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 139 PSRT will determine eligibility on a case-by-case basis.
- Previous receipt of monoclonal antibodies (mAbs), whether licensed or investigational. Exceptions may be made by the HVTN 139 PSRT on a case-by-case basis.
- Non-HIV experimental vaccine(s) received within the last 1 year in a prior vaccine trial. Exceptions may be made by the HVTN 139 PSRT for vaccines that have subsequently undergone licensure by the FDA. For volunteers who have received control/placebo in an experimental vaccine trial, the HVTN 139 PSRT will determine eligibility on a case-by-case basis. For volunteers who have received an experimental vaccine(s) greater than 1 years ago, eligibility for enrollment will be determined by the HVTN 139 PSRT on a case-by-case basis.
- Live attenuated vaccines received within 30 days before first vaccination or scheduled within 28 days after injection (eg, measles, mumps, and rubella [MMR]; oral polio vaccine [OPV]; varicella; yellow fever; live attenuated influenza vaccine).
- Any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination (eg, tetanus, pneumococcal, Hepatitis A or B).
- Allergy treatment with antigen injections within 30 days before first vaccination or that are scheduled within 14 days after first vaccination.
Immune System
- Immunosuppressive medications received within 168 days before first vaccination (Not exclusionary: [1] corticosteroid nasal spray; [2] inhaled corticosteroids; [3] topical corticosteroids for mild, uncomplicated dermatologic condition; or [4] a single course of oral/parenteral prednisone or equivalent at doses < 60 mg/day and length of therapy < 11 days with completion at least 30 days prior to enrollment).
- Serious adverse reactions to vaccines or to vaccine components such as glycerol, sodium chloride, tris (hydroxymethyl)aminomethane including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. (Not excluded from participation: a volunteer who had a nonanaphylactic adverse reaction to pertussis vaccine as a child).
- Immunoglobulin received within 90 days before first vaccination (for mAb see criterion 8 above).
- Autoimmune disease, current or history. (Not exclusionary: well-controlled psoriasis that does not require systemic therapy)
- AESIs
Volunteers who currently have, or have a history of, any condition that could be considered an AESI for the products administered in this protocol (representative examples are listed in Appendix N). The exception to Appendix N is well-controlled psoriasis, which is not exclusionary (as above)
Clinical significant medical conditions
Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. A clinically significant condition or process includes but is not limited to:
- A process that would affect the immune response,
- A process that would require medication that affects the immune response,
- Any contraindication to repeated injections or blood draws,
- A condition that requires active medical intervention or monitoring to avert grave danger to the volunteer's health or well-being during the study period,
- A condition or process for which signs or symptoms could be confused with reactions to vaccine, or
- Any condition specifically listed among the exclusion criteria below.
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, assessment of safety or reactogenicity, or a volunteer's ability to give informed consent.
Psychiatric condition that precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years.
Current anti-tuberculosis (TB) prophylaxis or therapy.
Asthma exclusion criteria: Asthma is excluded if the participant has ANY of the following:
- Required either oral or parenteral corticosteroids for an exacerbation two or more times within the past year; OR
- Needed emergency care, urgent care, hospitalization, or intubation for asthma within the past year; OR
- Uses a short-acting rescue inhaler more than 2 days/week; OR
- Uses medium-to-high dose inhaled corticosteroids (greater than 250 mcg fluticasone or therapeutic equivalent) or more than one medication for maintenance therapy daily. For example, potential participants taking long acting bronchodilator/inhaled corticosteroid combinations for daily maintenance are excluded. [Note: Maintenance monotherapy with cromolyn, leukotriene receptor antagonist, or theophylline is not exclusionary.]; OR
- Meets any other asthma-related criteria that, in the judgement of the investigator, could lead to interference with study participation.
Diabetes mellitus type 1 or type 2. (Not exclusionary: type 2 cases controlled with diet alone or a history of isolated gestational diabetes)
Thyroidectomy, or thyroid disease (Not exclusionary: well-controlled non-autoimmune thyroid disease as defined in HVTN 139 Study Specific Procedures (SSP))
Hypertension:
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 in this protocol 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 volunteers, 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.
- Bleeding disorder (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions)
- Malignancy (Not excluded from participation: Volunteer who has had malignancy excised surgically and who, in the investigator's estimation, has a reasonable assurance of sustained cure, or who is unlikely to experience recurrence of malignancy during the period of the study).
- Seizure disorder: History of seizure(s) within past three years. Also exclude if volunteer has used medications in order to prevent or treat seizure(s) at any time within the past 3 years.
- Asplenia: any condition resulting in the absence of a functional spleen.
- History of angioedema, or anaphylaxis. (Not exclusionary: angioedema or anaphylaxis with known trigger and no episodes within five years.)
- History of generalized urticaria within past five years.