Evaluating the Safety of and Immune Response to an HIV Vaccine Followed by Booster, Administered by Two Devices, in HIV-Uninfected Adults

Inclusion Criteria: * Low risk of HIV infection (as defined by the Study Risk Assessment Tool captured during the medical history) * Amenable to HIV risk reduction counseling, committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit, and committed to 18 months of follow-up contact * Pass the Test of Understanding and demonstrate an understanding of STEP study results (HVTN 502/Merck 023 trial) * Assessed by the clinic staff as being at low risk of HIV infection on the basis of sexual behaviors within the 12 months prior to enrollment as follows: sexually abstinent, or had two or fewer mutually monogamous relationships with HIV-uninfected partners and who have not used illicit drugs, or had two or fewer partners believed to be HIV uninfected and who did not use illicit drugs and with whom he/she regularly uses condoms for sexual intercourse * Healthy men and women (determined by medical history, physical examination, and clinical judgment) * Available and willing to participate for 12 months for study visits and annual follow-up for 18 months after study completion * Must be willing to have photo or fingerprint taken for identification purposes * Must be willing to be taken home at enrollment visit and allow home visits, if needed * Able to read and willing to complete the informed consent process * Has the following laboratory criteria within 45 days prior to study entry: 1. Hemoglobin: Women: 11 mg/dL; Men: 12.5 mg/dL 2. White cell count: 2,500 to 11,000 cells/mm\^3 3. Platelets: 125,000 to 450,000 per mm\^3 4. Urinalysis: protein and blood less than 1+, glucose negative 5. Normal liver function tests to include alanine aminotransferase (ALT)/aspartate aminotransferase (AST), alkaline phosphatase, gamma-glutamyl transpeptidase (GGT) (less than or equal to 1.25 times the institutional upper limits of normal), creatine phosphokinase (CPK) (less than or equal to 600 IU/L), troponin I (less than 0.4 ng/mL), and creatinine (less than or equal to 1.25 times the institutional upper limits of normal) 6. Negative for HIV infection (enzyme linked immunosorbent assay \[ELISA\], Western blot \[WB\], and HIV polymerase chain reaction \[PCR\]) * Female participants must have a negative pregnancy test at the screening visit and have a negative pregnancy test immediately prior to each vaccine/placebo vaccination * Provide verbal assurance that adequate birth control measures have been followed for 45 days prior to the first vaccine/placebo vaccination and will continue to be followed for at least 3 months after the final vaccine/placebo vaccination. More information on this criterion can be found in the protocol. * Body mass index (BMI) less than 30 Exclusion Criteria: * Confirmed HIV-1 or HIV-2 infection * Engaged in excessive daily alcohol use, frequent binge drinking, or illicit drug use within the 12 months prior to study entry * History of new onset, sexually acquired infection, as determined by local, syndromic diagnostics standards or, as available, serologic and microbiologic diagnosis within the 12 months prior to study entry * Has a known current high-risk partner or had such a partner within the 12 months prior to study entry * Hepatitis B, hepatitis C, or syphilis infection; active syphilis documented by exam or serology unless positive serology is because of remote treated infection or positive rapid plasma reagin * Pregnant, planning on becoming pregnant during the study, or breastfeeding * Any clinically significant acute or chronic medical condition that, in the opinion of the investigator, would preclude study participation (e.g., history of seizure disorders, bleeding/clotting disorder, autoimmune disease, malignancy, tuberculosis, other systemic infections) * Major surgery within the 4 weeks prior to study entry * History of or known active heart disease including: 1. Previous myocardial infarction (heart attack) 2. Angina pectoris; congestive heart failure 3. Valvular heart disease, including mitral valve prolapse 4. Cardiomyopathy 5. Myo/pericarditis 6. Stroke or transient ischemic attack 7. Chest pain or shortness of breath with activity (such as walking up stairs) 8. Arrhythmia/episodic palpitations (not excluded: sinus arrhythmia) 9. Pacemaker 10. Other heart conditions under the care of a doctor * People who have 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, sister) who had coronary artery disease before the age of 50 years * Electrocardiogram (ECG) with clinically significant findings, or features that would interfere with the assessment of myo/pericarditis. More information on this criterion can be found in the protocol. * History of 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 12 months prior to study entry * High blood pressure: 1. If a person has been diagnosed with high blood pressure during screening or previously, exclude for high 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 diagnosed with high blood pressure during screening or previously, exclude for systolic blood pressure greater than or equal to 150 mm Hg at study entry or diastolic blood pressure greater than or equal to 100 mm Hg at study entry * Major psychiatric illness and/or substance abuse problems during the 12 months before study entry that, in the opinion of the investigator, would preclude study participation * Receipt of live attenuated vaccine within 30 days or inactivated/killed vaccine within 2 weeks of DNA vaccination * Use of experimental therapeutic agents within 30 days of study entry * Current or planned participation in another clinical study during the study period * Receipt of blood products or immunoglobulin in the 3 months before study entry * History of anaphylaxis or other serious adverse reactions to vaccines or egg products or amide type anesthetics (e.g., bupivacaine, novocaine, lidocaine, mepivacaine, neomycin, streptomycin) * History of chronic urticaria (recurrent hives) * Chronic or recurrent use of medications that modify host immune response (e.g., cancer chemotherapeutic agents, parenteral corticosteroids \[topical not an exclusion\]) * Recipient of an HIV vaccine candidate at any time and receipt of other experimental vaccine(s) within the 5 years before study entry. More information on this criterion can be found in the protocol. * A study site employee * Military personnel (will be excluded from participation in this study at all sites due to the potential for a false-positive HIV test result on mandatory HIV testing, which could have adverse affects on deployment status)