INCLUSION CRITERIA:
1. Male, age 18 to 45 years, who is circumcised (as documented at screening examination) and who, in the 24 weeks prior to randomization, experienced 1 or more of the following HIV risk criteria; male-to-female transgender volunteers who have not used hormone therapy for 90 days prior to the first study vaccination and who agree not to use hormonal therapy until the study is unblinded are allowed to participate:
-unprotected anal intercourse with 1 or more HIV-l-infected male or MTF transgender partner(s);
-unprotected anal intercourse with 2 or more male or MTF transgender partners;
-unprotected anal intercourse with a male or MTF transgender partner who had 2 or more other partners in the same 6 month timeframe; or
-anal intercourse with 3 or more male or MTF transgender partners.
2. Negative HIV-1 and -2 blood test (FDA-approved enzyme immunoassay [EIA])
3. Ad5 nAb titer < 1:18
4. ALT less than or equal to 2.5 upper limit of normal
5. Within reach of a participating study site and willing to be followed for the planned duration of the study, including long-term safety surveillance contact for 5 years after enrollment
6. Able and willing to provide informed consent
7. Assessment of understanding: demonstrates understanding of this study and the Step Study, results; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly
8. Willing to receive HIV test results
9. Willing to discuss HIV infection risks and amenable to risk reduction counseling
10. Good general health as shown by medical history, physical exam, and screening laboratory tests
11. Agrees not to enroll in another study of an investigational research agent prior to unblinding of the HVTN 505 study without first discussing with the site PI
EXCLUSION CRITERIA:
1. Volunteer has received any of the following:
-HIV vaccine(s) received in a prior HIV vaccine trial. For potential participants who have received control/placebo in an HIV vaccine trial, the HVTN 505 PSRT will determine eligibility on a case-by-case basis.
-Immunosuppressive medications received within 168 days before first vaccination. (Not excluded: [1] corticosteroid nasal spray for allergic rhinitis; topical corticosteroids for mild, uncomplicated dermatitis; or oral/parenteral corticosteroids given for non-chronic conditions not expected to recur [length of therapy 10 days or less with completion at least 30 days prior to enrollment].)
-Blood products within 90 days before first vaccination
-Immunoglobulin within 90 days before first vaccination
-Live attenuated vaccines other than influenza vaccine within 30 days before first vaccination or scheduled within 14 days after injection (eg, measles, mumps, and rubella [MMR]; oral polio vaccine [OPV]; varicella; yellow fever)
-Influenza vaccine or any vaccines that are not live attenuated vaccines within 14 days before first vaccination (eg, influenza 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
-Investigational research agents within 90 days before first vaccination
2. Volunteer has used PEP greater than or equal to 3 times in the past 12 months or has used PEP within the 60 days prior to first vaccination
3. Volunteer has used PrEP greater than or equal to 6 times within the 6 months prior to first vaccination, or for 30 consecutive days within the 60 days prior to first vaccination
4. Volunteer has been circumcised within 90 days prior to first vaccination or displays evidence that surgical site is not fully healed
5. History of serious adverse reactions to vaccines including anaphylaxis and related symptoms such as hives, respirator), difficult), angioedema, and/or abdominal pain. (Not excluded: a participant who had a nonanaphylactic adverse reaction to pertussis vaccine as a child.)
6. Current anti-tuberculosis prophylaxis or therapy
7. 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 participant'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 (eg, recurrent cellulitis, small area of psoriasis, etc.); or
-Any condition specifically listed among the exclusion criteria below.
8. Any medical, psychiatric, or 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 participant's ability to give informed consent
9. 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.
10. Autoimmune disease
11. Immunodeficiency
12. Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions)
13. History of malignancy (Not excluded: a participant with a surgical excision and subsequent observation period that in the investigator's estimation has a reasonable assurance of sustained cure or is unlikely to recur during the period of the study.)
14. Seizure disorder (Not excluded: a participant with a history of seizures who has not required medications or had a seizure within the past 3 years.)
15. Asthma other than mild, well-controlled asthma. Exclude a participant who:
-Generally uses a bronchodilator (beta2 agonist) daily, or
-In the past year, has (any of the following):
--Had > 1 exacerbation of symptoms treated with oral steroids (Note: oral steroid use is exclusionary within 168 days before first vaccination.);
--Routinely used moderate to high dose inhaled corticosteroids (eg, more than the equivalent of 250 mcg fluticasone; 400 mcg budesonide; 500 mcg beclomethasone; or 1000 mcg triamcinolone/flunisolide, as a daily dose) or theophylline for asthma; or
--Needed emergency care, urgent care, hospitalization, or intubation for asthma.
16. Angioedema within the last 3 years if episodes are considered serious or have required medication within the last 2 years
National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 11/25/2009