Safety of and Immune Response to Vaccination With 2 Experimental HIV Vaccines in Healthy Adults
Safety of and Immune Response to Vaccination With 2 Experimental HIV Vaccines in Healthy Adults
The HIV Vaccine Trials Network (HVTN) is doing a study to test 2 experimental HIV vaccines in
 combination with 2 licensed vaccines for tetanus and hepatitis B. HIV is the virus that
 causes AIDS. Tetanus is an infection that causes muscular spasms. Hepatitis B is a virus that
 can cause liver failure.

 About 100 people will take part in this study at multiple sites. The US National Institutes
 of Health (NIH) is paying for the study.

 We are doing this study to answer several questions.

 -  Are the HIV study vaccines safe to give to people?

 -  Are people able to take the HIV study vaccines without becoming too uncomfortable?

 -  How do people's immune systems respond to the HIV study vaccines? (Your immune system
 protects you from disease.)

 -  Can people's immune responses to a tetanus or hepatitis B vaccines help us understand
 how their immune systems might respond to the HIV study vaccines?

 -  Is there a common immune response to licensed vaccines like the tetanus and hepatitis B
 vaccines?
Inclusion Criteria:

 -  Age of 18 to 40 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;
 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

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

 -  Willingness to receive tetanus and Hepatitis B vaccination

 -  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 ≥ 11.0 g/dL for volunteers who were born female, ≥ 13.0 g/dL for volunteers
 who were born male

 -  White blood cell count = 3,300 to 12,000 cells/mm3

 -  Total lymphocyte count ≥ 800 cells/mm3

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

 -  Platelets = 125,000 to 550,000/mm3

 -  Chemistry panel: alanine aminotransferase (ALT), aspartate aminotransferase (AST), and
 alkaline phosphatase < 1.25 times the institutional upper limit of normal; creatinine
 ≤ institutional upper limit of normal.

 -  Negative HIV-1 and -2 blood test: Sites may use locally available assays that have
 been approved by HVTN Laboratory Operations.

 -  Negative Hepatitis B surface antigen (HBsAg)

 -  Negative Hepatitis B core antibody (HBcAb)

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

 -  Normal urine:

 -  Negative urine glucose,

 -  Negative or trace urine protein, and

 -  Urinalysis (dipstick) for blood no greater than 1+ (if trace or 1+ hemoglobin is
 present on dipstick, a microscopic urinalysis with red blood cells levels within
 institutional normal range).

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

 -  Reproductive status: A volunteer who was born female must:

 -  Agree to consistently use effective contraception (see Appendix C) for sexual
 activity that could lead to pregnancy from at least 21 days prior to enrollment
 through the last required protocol clinic visit. Effective contraception for
 participants in South Africa is defined as using 2 methods, including the
 following:

 -  Condoms (male or female) with or without a spermicide,

 -  Diaphragm or cervical cap with spermicide,

 PLUS 1 of the following methods:

 -  Intrauterine device (IUD),

 -  Hormonal contraception (in accordance with South African contraception guidelines), or

 -  Successful vasectomy in the male partner (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, bilateral oophorectomy, or tubal
 ligation;

 -  Or be sexually abstinent.

 -  Volunteers 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) ≥ 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
 smoker, known hyperlipidemia

 -  Intent to participate in another study of an investigational research agent during the
 planned duration of the HVTN 097 study

 -  Pregnant, breastfeeding or lactating

 -  History of Hepatitis B viral infection

 -  History of tetanus disease 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 097 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 South Africa Medicines Control Council (MCC). For volunteers who have received
 control/placebo in an experimental vaccine trial, the HVTN 097 PSRT will determine
 eligibility on a case-by-case basis. For volunteers who have received an experimental
 vaccine(s) greater than 5 years ago, eligibility for enrollment will be determined by
 the HVTN 097 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 (eg, 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 (eg, pneumococcal, Hepatitis A)

 -  Any requirement to receive an HBV vaccine other than the HBV vaccine given during the
 study period.

 -  Allergy treatment with antigen injections within 30 days before first vaccination or
 that are scheduled within 14 days after first vaccination

 -  Known to have received a tetanus vaccination within the last 5 years prior to 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 < 2 mg/kg/day and length of therapy < 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
 volunteer who had a nonanaphylactic adverse reaction to pertussis vaccine as a child.)

 -  History of allergic reaction to yeast

 -  History of allergic reaction to HBV or tetanus vaccine or any component of the
 vaccines or placebo, including eggs, egg products, or neomycin

 -  Immunoglobulin received within 60 days before first vaccination

 -  Autoimmune disease

 -  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. 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-TB prophylaxis or therapy

 -  Asthma other than mild or moderate, well-controlled asthma. (Symptoms of asthma
 severity as defined in the most recent National Asthma Education and Prevention
 Program (NAEPP) Expert Panel report).

 Exclude a volunteer who:

 -  Uses a short-acting rescue inhaler (typically a β 2 agonist) daily, or

 -  Uses high dose inhaled corticosteroids, or

 -  In the past year has either of the following:

 -  Greater than 1 exacerbation of symptoms treated with oral/parenteral
 corticosteroids;

 -  Needed emergency care, urgent care, hospitalization, or intubation for asthma.

 -  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 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 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 diagnosed by a doctor (eg, factor deficiency, coagulopathy, or
 platelet disorder requiring special precautions)

 -  Malignancy (Not excluded: 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 hereditary angioedema, acquired angioedema, or idiopathic angioedema.