A Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of a 6-Plasmid Multiclade HIV-1 DNA Vaccine, VRC-HIVDNA016-00-VP, in Uninfected Adult Volunteers

Study start date: August 2, 2004

* INCLUSION CRITERIA: A participant must meet all of the following criteria: 18 to 44 years old. Available for clinical follow-up through Week 32 of the study. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process. Complete an Assessment of Understanding prior to enrollment and verbalize understanding of all questions answered incorrectly. Able and willing to complete the informed consent process. Willing to receive HIV test results and willing to abide by NIH guidelines for partner notification of positive HIV results. Willing to donate blood for sample storage to be used for future research. Willing to discuss HIV infection risks and amenable to risk reduction counseling. In good general health without clinically significant medical history and has satisfactorily completed screening. Physical examination and laboratory results without clinically significant findings within the 28 days prior to enrollment. Laboratory Criteria within 28 days prior to enrollment: Hemoglobin greater than or equal to 11.5 g/dL for women; greater than or equal to 13.5 g/dL for men. WBC equal to 3,300-12,000 cells/mm(3). Differential either within institutional normal range or accompanied by site physician approval. Total lymphocyte count greater than or equal to 800 cells/mm(3). Platelets equal 125,000 - 550,000/mm(3). ALT (SGPT) less than or equal to 1.25 x upper limit of normal. Serum creatinine less than or equal to upper limit of normal. Normal urinalysis defined as negative glucose, negative or trace protein, and negative or trace hemoglobin (blood). Negative FDA-approved HIV blood test. Negative Hepatitis B surface antigen. Negative anti-HCV. Female Specific Criteria: Negative beta-HCG pregnancy test (urine or serum) on day of enrollment for women presumed to be of reproductive potential. A female participant must meet any of the following criteria: No reproductive potential because of menopause (one year without menses) or because of a hysterectomy, bilateral oophorectomy, or tubal ligation, OR Participant agrees to be heterosexually inactive at least 21 days prior to enrollment and through Week 32 of the study, OR Participant agrees to consistently practice contraception at least 21 days prior to enrollment and through Week 32 of the study by one of the following methods: Condoms, male or female, with or without a spermicide; Diaphragm or cervical cap with spermicide; Intrauterine device; Contraceptive pills or patch, Norplant, Depo-Provera or other FDA-approved contraceptive method; Male partner has previously undergone a vasectomy for which there is documentation. EXCLUSION CRITERIA: A volunteer will be excluded if one or more of the following conditions apply: Women: Woman who is breast-feeding or planning to become pregnant during the 32 weeks of study participation. Volunteer has received any of the following substances: HIV vaccines in a prior clinical trial; Immunosuppressive medications or cytotoxic medications or inhaled corticosteroids within the past six months (with the exception of corticosteroid nasal spray for allergic rhinitis or topical corticosteroids for an acute uncomplicated dermatitis); Blood products within 120 days prior to HIV screening; Immunoglobulin within 60 days prior to HIV screening; Investigational research agents within 30 days prior to initial study vaccine administration; Live attenuated vaccines within 30 days prior to initial study vaccine administration. Medically indicated subunit or killed vaccines, e.g. influenza, pneumococcal, or allergy treatment with antigen injections, within 14 days of study vaccine administration; Current anti-TB prophylaxis or therapy. Volunteer has a history of any of the following clinically significant conditions: Serious adverse reactions to vaccines such as anaphylaxis, hives, respiratory difficulty, angioedema, or abdominal pain. Autoimmune disease or immunodeficiency. Asthma that is unstable or required emergent care, urgent care, hospitalization or intubation during the past two years or that requires the use of oral or intravenous corticosteroids. Diabetes mellitus (type I or II), with the exception of gestational diabetes. History of thyroidectomy or thyroid disease that required medication within the past 12 months. Serious angioedema episodes within the previous 3 years or requiring medication in the previous two years. Hypertension that is not well controlled by medication or is more than 150/100 at enrollment. Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws. Syphilis infection that is active or a positive serology due to a syphilis infection treated less than six months ago. Malignancy that is active or treated malignancy for which there is not reasonable assurance of sustained cure or malignancy that is likely to recur during the period of the study. Seizure disorder other than: 1. febrile seizures under the age of two, 2. seizures secondary to alcohol withdrawal more than 3 years ago, or 3. a singular seizure not requiring treatment within the last 3 years. Asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen. Psychiatric condition that precludes compliance with the protocol; past or present psychoses; past or present bipolar disorder requiring therapy that has not been well controlled on medication for the past two years; disorder requiring lithium; or suicidal ideation occurring within five years prior to enrollment. Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent.