The purpose of the study is to determine the safety of and immune response to the investigational HIV vaccine, EP HIV-1090, in HIV uninfected adults.

The worldwide HIV/AIDS epidemic may only be controlled through the development of a safe and effective vaccine that will prevent HIV infection. DNA vaccines are inexpensive to construct, readily produced in large quantities, and stable for long periods of time. EP HIV-1090 is a DNA HIV CTL vaccine; the proteins for which its genes code are designed to interact with CD8 cells (CTL) and cause CD8 cell proliferation. The DNA plasmids in EP HIV-1090 code for proteins conserved among HIV subtypes A, B, C, D, F, and G, which encompass the HLA subtypes of 85% of the worldwide general population.

Participants will be enrolled in this study for 1 year. Group 4 participants will receive EP HIV-1090 or placebo at study entry and Months 1, 3, and 6. There will be 11 study visits that will occur at screening; study entry; and Months 0.5, 1, 1.5, 3, 3.5, 6, 6.5, 9, and 12. A physical exam and risk reduction/pregnancy prevention counseling will occur at each visit. Participants will be asked about their adverse experiences from vaccination at each visit. Blood and urine collection will occur at selected visits.

Note: Groups 1, 2, 3, and 5 have permanently discontinued enrollment per the 12/26/06 letter of amendment.

Inclusion Criteria:

• Good general health
• Have access to a participating HIV Vaccine Trials Unit (HVTU) and are willing to be followed for the duration of the study
• Willing to receive HIV test results
• Have understanding of the study
• Willing to use acceptable forms of contraception
• Negative pregnancy test

Exclusion Criteria:

• HIV vaccines in a prior HIV vaccine trial
• Immunosuppressive medications within 168 days prior to first vaccination
• Blood products within 120 days prior to first vaccination
• Immunoglobulin within 60 days prior to first vaccination
• Live attenuated vaccines within 30 days prior to first vaccination
• Investigational research agents within 30 days prior to first vaccination
• Medically indicated subunit or killed vaccines within 14 days prior to first study vaccine administration, or allergy treatment with antigen injections within 30 days prior to first vaccination
• Current tuberculosis prophylaxis or therapy
• Clinically significant medical condition, abnormal physical exam findings, abnormal laboratory results, or past medical history that may affect current health
• Any medical, psychiatric, or social condition that would interfere with the study. More information about this criterion can be found in the protocol.
• Any job-related responsibility that would interfere with the study
• Serious adverse reaction to vaccines. A person who had an adverse reaction to pertussis vaccine as a child is not excluded.
• Autoimmune disease or immunodeficiency
• Active syphilis infection unless the participant has completed full treatment for syphilis 6 months prior to enrollment
• Unstable asthma
• Diabetes mellitus type 1 or 2
• Thyroid disease or thyroidectomy requiring treatment
• Serious angioedema within 3 years prior to enrollment
• Uncontrolled hypertension
• Body mass index (BMI) of 40 or greater
• BMI of 35 or greater if the participant is older than 45 years, has systolic blood pressure greater than 140 mm Hg, has diastolic blood pressure greater than 90 mm Hg, smokes, or has known hyperlipidemia
• Bleeding disorder
• Malignancy unless it has been surgically removed and, in the opinion of the investigator, is not likely to recur during the study period
• Seizure disorder requiring medication within the 3 years prior to enrollment
• Absence of the spleen
• Mental illness that would interfere with the study
• Other conditions that, in the judgment of the investigator, would interfere with the study
• Pregnancy, breastfeeding, or plans to become pregnant