Evaluating the Safety and Immune Response to Two HIV Vaccine Regimens in Healthy, HIV-Uninfected Adults in the United States and South Africa
Evaluating the Safety and Immune Response to Two HIV Vaccine Regimens in Healthy, HIV-Uninfected Adults in the United States and South Africa
The purpose of this study is to evaluate the safety and immune response to two different HIV
 vaccine regimens in healthy, HIV-uninfected people in the United States and South Africa.
This study will evaluate the safety, tolerability, and immune response to two different
 vaccine schedules of a prime with either DNA HIV vaccine (DNA-HIV-PT123), or NYVAC HIV
 vaccine (NYVAC-HIV-PT1 and NYVAC-HIV-PT4) followed by a boost combination of NYVAC HIV
 vaccine (PT1 & PT4) and AIDSVAX B/E. Study researchers will also evaluate whether body mass
 index (BMI) and/or sex impact the immunogenicity of the vaccine regimens in participants from
 South Africa, and look at regional differences in immunologic responses between United States
 and South African participants.

 The study will enroll 264 healthy, HIV-uninfected people, ages 18-50, in the United States
 and South Africa.

 Participants will be randomly assigned to one of three groups and receive either one of the
 vaccine regimens or placebo. Participants will receive injections according to their assigned
 group schedule at study entry (Month 0) and Months 1, 3, and 6.

 Participants will remain in the clinic for 30 minutes after receiving the vaccines for
 observation and monitoring. For 7 days after receiving the vaccines, participants will record
 their symptoms and report them to study researchers.

 Study visits will occur at study entry, and Months 1, 1.5, 3, 3.5, 6, 6.5, 9, and 12. All
 study visits will include a physical examination, HIV risk reduction counseling, and
 interviews and/or questionnaires. Select study visits will include urine collection, an
 electrocardiogram (ECG), blood collection, a pregnancy test for female participants, and HIV
 testing. At some visits, some participants may also provide samples of cervical fluid, rectal
 fluid, and/or semen. Study researchers will contact participants by telephone or e-mail once
 a year for 3 years following the first vaccination for follow-up health monitoring.
Inclusion Criteria:

 -  Access to a participating HIV Vaccine Trials Network (HVTN) clinical research site
 (CRS) and willingness to be followed for the planned duration of the study

 -  Ability and willingness to provide informed consent

 -  Assessment of understanding: participant demonstrates understanding of this study;
 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 before the
 last required protocol clinic visit

 -  Good general health as shown by medical history, physical exam, and screening
 laboratory tests

 -  Willingness to receive HIV test results

 -  Willingness to discuss HIV infection risks, amenable to HIV risk reduction counseling,
 and committed to maintaining behavior consistent with low risk of HIV exposure through
 the last required protocol clinic visit

 -  Assessed by the clinic staff as being at "low risk" for HIV infection

 -  Hemoglobin greater than or equal to 11.0 g/dL for participants who were born female
 and greater than or equal to 13.0 g/dL for participants who were born male

 -  White blood cell count equal to 3,300 to 12,000 cells/mm^3

 -  Total lymphocyte count greater than or equal to 800 cells/mm^3

 -  Remaining differential either within institutional normal range or with site physician
 approval

 -  Platelets equal to 125,000 to 550,000/mm^3

 -  Chemistry panel: alanine aminotransferase (ALT), aspartate aminotransferase (AST), and
 alkaline phosphatase less than 1.25 times the institutional upper limit of normal
 (IULN); creatinine less than or equal to 1.1 times the IULN

 -  Cardiac Troponin T or I (cTnT or cTnI) does not exceed the IULN

 -  Negative HIV-1 and -2 blood test: U.S. participants must have a negative Food and Drug
 Administration (FDA)-approved enzyme immunoassay (EIA). Non-U.S. sites may use locally
 available assays that have been approved by HVTN Laboratory Operations.

 -  Negative hepatitis B surface antigen (HBsAg)

 -  Negative anti-hepatitis C virus antibodies (anti-HCV), or negative HCV polymerase
 chain reaction (PCR) if the anti-HCV is positive

 -  Normal urine:

 1. Negative urine glucose, and

 2. Negative or trace urine protein, and

 3. Negative or trace urine hemoglobin (if trace hemoglobin is present on dipstick, a
 microscopic urinalysis with red blood cells levels within institutional normal
 range).

 -  Participants who were born female: negative serum or urine beta human chorionic
 gonadotropin (β-HCG) pregnancy test performed prior to vaccination on the day of
 initial vaccination

 -  Reproductive status: a participant who was born female must agree to consistently use
 effective contraception for sexual activity that could lead to pregnancy from at least
 21 days prior to enrollment through the last required protocol clinic visit. More
 information on this criterion can be found in the protocol.

 -  Participants who were born female must also agree not to seek pregnancy through
 alternative methods, such as artificial insemination or in vitro fertilization until
 after the last required protocol clinic visit

 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) greater than or equal to 40; or BMI greater than or equal to 35
 with 2 or more of the following: age greater than 45, systolic blood pressure greater
 than 140 mm Hg, diastolic blood pressure greater than 90 mm Hg, or known
 hyperlipidemia

 -  Intent to participate in another study of an investigational research agent during the
 planned duration of this study

 -  Pregnant or breastfeeding

 -  HIV vaccine(s) received in a prior HIV vaccine trial. For participants who have
 received control/placebo in an HIV vaccine trial, the HVTN 101 Protocol Safety Review
 Team (PSRT) will determine eligibility on a case-by-case basis.

 -  Non-HIV experimental vaccine(s) received within the last 5 years in a prior vaccine
 trial. Exceptions may be made for vaccines that have subsequently undergone licensure
 by the FDA or (South Africa) Medicines Control Council (MCC). For participants who
 have received control/placebo in an experimental vaccine trial, the HVTN 101 PSRT will
 determine eligibility on a case-by-case basis. For participants who have received an
 experimental vaccine(s) greater than 5 years ago, eligibility for enrollment will be
 determined by the HVTN 101 PSRT on a case-by-case basis.

 -  Live attenuated vaccines other than influenza vaccine received within 30 days before
 first vaccination or scheduled within 14 days after injection (e.g., measles, mumps,
 and rubella [MMR]; oral polio vaccine [OPV]; varicella; yellow fever)

 -  Influenza vaccine or any vaccines that are not live attenuated vaccines and were
 received within 14 days prior to first vaccination (e.g., 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

 -  Immunosuppressive medications received within 168 days before first vaccination. (Not
 excluded: [1] corticosteroid nasal spray; [2] inhaled corticosteroids; [3] topical
 corticosteroids for mild, uncomplicated dermatitis; or [4] a single course of
 oral/parenteral corticosteroids at doses less than 2 mg/kg/day and length of therapy
 less than 11 days with completion at least 30 days prior to enrollment.)

 -  Serious adverse reactions to vaccines including anaphylaxis and related symptoms such
 as hives, respiratory difficulty, angioedema, and/or abdominal pain. (Not excluded: a
 participant who had a nonanaphylactic adverse reaction to pertussis vaccine as a
 child.)

 -  Immunoglobulin received within 60 days before first vaccination

 -  Autoimmune disease (Not excluded: mild, well-controlled psoriasis)

 -  Immunodeficiency

 -  Untreated or incompletely treated syphilis infection

 -  Clinically significant medical condition, physical examination findings, clinically
 significant abnormal laboratory results, or past medical history with clinically
 significant implications for current health. More information on this criterion can be
 found in the protocol.

 -  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 participant's ability to give
 informed consent

 -  Psychiatric condition that precludes compliance with the protocol. Specifically
 excluded are people 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 other than mild, well-controlled asthma. More information on this criterion can
 be found in the protocol.

 -  Diabetes mellitus type 1 or type 2, including cases controlled with diet alone. (Not
 excluded: history of isolated gestational diabetes.)

 -  Thyroidectomy, or thyroid disease requiring medication during the last 12 months

 -  Hypertension:

 1. 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.
 More information on this criterion can be found in the protocol.

 2. If a person has NOT been found to have elevated blood pressure or hypertension
 during screening or previously, exclude for systolic blood pressure greater than
 or equal to 150 mm Hg at enrollment or diastolic blood pressure greater than or
 equal to 100 mm Hg at enrollment.

 -  History of myocarditis, pericarditis, cardiomyopathy, congestive heart failure with
 permanent sequelae, or clinically significant arrhythmia (including any arrhythmia
 requiring medication, treatment, or clinical follow-up)

 -  Electrocardiogram (ECG) with clinically significant findings, or features that would
 interfere with the assessment of myo/pericarditis, as determined by the contract ECG
 lab, cardiologist, or study clinician. More information on this criterion can be found
 in the protocol.

 -  Participants who have 2 or more of the following cardiac risk factors: (1) participant
 report of history of elevated blood cholesterol defined as fasting low-density
 lipoprotein (LDL) greater than 160 mg/dL; (2) first degree relative (e.g., mother,
 father, brother, or sister) who had coronary artery disease before the age of 50
 years); (3) current smoker; or (4) BMI greater than or equal to 35

 -  Allergy to eggs or egg products

 -  Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or
 platelet disorder requiring special precautions)

 -  Malignancy (Not excluded: participant 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 3 years. Also exclude if
 participant 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 hereditary angioedema, acquired angioedema, or idiopathic angioedema