Evaluating the Safety and Immune Response to Different Combinations of the DNA-HIV-PT123 and AIDSVAX® B/E Vaccines in Healthy, HIV-Uninfected Adults

The purpose of this study is to evaluate the safety, tolerability, and immunogenicity of the
combination of two different experimental HIV vaccines—the DNA-HIV-PT123 vaccine and the
AIDSVAX® B/E vaccine—administered in different sequences or simultaneously, in healthy
adults who are not infected with HIV.

Participants will be randomly assigned to four groups. Depending on which group participants
are in, they will receive different combinations of the DNA-HIV-PT123 vaccine, the AIDSVAX®
B/E vaccine, a placebo for DNA-HIV-PT123 vaccine, and/or a placebo for AIDSVAX® B/E vaccine.
Study visits will occur at study entry, Week 2, and Months 1, 1.5, 3, 3.5, 6, 6.5, 9, and
12. All participants will receive their assigned combinations of vaccines at study entry and
Months 1, 3, and 6. At each vaccination visit, participants will receive one injection in
each upper arm. Following each vaccination, participants will remain in the clinic for 30
minutes for monitoring. All study visits will include a physical examination, HIV risk
reduction counseling, and questionnaires and assessments. Select study visits will also
include a urine collection, a blood collection, a pregnancy test for participants who were
born female, and HIV testing and counseling.

Inclusion Criteria:

General and Demographic 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

- 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

HIV-Related Criteria:

- Willingness to receive HIV test results

- Willingness to discuss HIV infection risks and amenable to HIV risk reduction
counseling

- Assessed by the clinic staff as being at "low risk" for HIV infection and committed
to maintaining behavior consistent with low risk of HIV exposure through the last
required protocol clinic visit

Laboratory Inclusion Values

Hemogram/Complete Blood Count (CBC)

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

- Chemistry panel: alanine aminotransferase (ALT) less than 1.25 times the
institutional upper limit of normal (IULN) and creatinine less than or equal to IULN

Virology

- Negative HIV-1 and -2 blood test: participants must have a negative Food and Drug
Administration (FDA)-approved enzyme immunoassay (EIA)

- Negative hepatitis B surface antigen (HBsAg)

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

Urine

- Normal urine:

- Negative urine glucose, and

- Negative or trace urine protein, and

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

Reproductive Status

- 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. Persons who are NOT of reproductive potential due to having
undergone total hysterectomy with bilateral oophorectomy (verified by medical
records) are not required to undergo pregnancy testing.

- 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;

- Or not be of reproductive potential, such as having reached menopause (no menses
for 1 year) or having undergone hysterectomy, bilateral oophorectomy, or tubal
ligation;

- Or be sexually abstinent. More information on this criterion is available 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:

General

- 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 before
the last required protocol clinic visit

- Pregnant or breastfeeding

Vaccines and Other Injections

- HIV vaccine(s) received in a prior HIV vaccine trial. For participants who have
received control/placebo in an HIV vaccine trial, the HVTN 105 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 FDA. For participants who have received control/placebo in an experimental vaccine
trial, the HVTN 105 PSRT will determine eligibility on a case-by-case basis. For
participants who have received an experimental vaccine(s) more than 5 years ago,
eligibility for enrollment will be determined by the HVTN 105 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

Immune System

- 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 history of 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

Clinically Significant Medical Conditions

- 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 is
available 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 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 other than mild or moderate, well-controlled asthma. More information on this
criterion is available 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:

- If a participant 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 less than
or equal to 140 mm Hg systolic and less than or equal to 90 mm Hg diastolic,
with or without medication, with only isolated, brief instances of higher
readings, which must be less than or equal to 150 mm Hg systolic and less than
or equal to 100 mm Hg diastolic. For these participants, blood pressure must be
less than or equal to 140 mm Hg systolic and less than or equal to 90 mm Hg
diastolic at enrollment.

- If a participant 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.

- 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 the 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