The purpose of this study is to determine the safety of and immune response to an investigational HIV vaccine, VRC-HIVADV014-00-VP, with or without a second investigational HIV vaccine, VRC-HIVDNA016-00-VP, in HIV uninfected adults.

The worldwide HIV/AIDS epidemic may only be controlled through development of a safe and effective vaccine that will prevent HIV infection. This study will evaluate the safety and immunogenicity of an experimental adenovirus-vectored multiclade HIV vaccine, VRC-HIVADV014-00-VP, followed with either a similarly structured DNA plasmid HIV vaccine, VRC-HIVDNA016-00-VP, or a placebo. The DNA plasmids in both vaccines code for proteins from HIV subtypes A, B, and C, which together represent 90% of new HIV infections in the world. HIV uninfected volunteers will be recruited in Kenya and Rwanda.

Volunteers will participate in this study for 1 year. Participants will be randomly assigned to one of four groups:

• Group A participants will receive a low dose of the adenovirus-vectored vaccine or placebo at study entry.
• Group B participants will receive a higher dose of the adenovirus-vectored vaccine or placebo at study entry.
• Group C participants will receive the DNA plasmid vaccine or placebo at study entry and Months 1 and 2. They will receive either a low dose of the adenovirus-vectored vaccine or placebo at Month 6.
• Group D participants will receive the DNA plasmid vaccine or placebo at study entry and Months 1 and 2. They will receive either a higher dose of the adenovirus-vectored vaccine or placebo at Month 6.

All participants will undergo vital signs measurements before and after receiving each vaccination.

Participants in Groups A and B will have 9 study visits over 12 months. A physical exam, adverse events reporting, and medical and medication history will occur at each visit. HIV testing and counseling and blood and urine collection will occur at selected visits.

Participants in Groups C and D will have 17 study visits over 12 months. A physical exam, adverse events reporting, and medical and medication history will occur at each visit. HIV testing and counseling and blood and urine collection will occur at selected visits.

Inclusion Criteria:

• Willing to follow all the requirements of the study and available for follow-up for the duration of the study
• Have understanding of the study and provide written informed consent
• Willing to undergo HIV testing and counseling and willing to receive HIV test results
• Willing to use acceptable forms of contraception

Exclusion Criteria:

• HIV infected
• Hepatitis B virus infected
• Hepatitis C virus infected
• Active or untreated syphilis
• Participated in high-risk behavior for HIV infection within 6 months prior to study entry. More information on this criterion can be found in the protocol.
• Any clinically significant abnormality in history or upon examination (e.g., immunodeficiency or autoimmune disease; use of systemic corticosteroids, immunosuppressive, antiviral, anticancer, or other medications considered significant by the investigator) within 6 months prior to study entry
• Any clinically significant acute or chronic medical condition that, in the opinion of the investigator, would make the volunteer unsuitable for the study
• Live attenuated vaccines within 30 days prior to study entry OR plan to receive a live attenuated vaccine within 60 days after vaccination in this study
• Subunit or killed vaccines within 14 days prior to study entry OR plan to receive a subunit or killed vaccine within 14 days after vaccination in this study
• Blood transfusion or blood products within 120 days prior to study entry
• Immunoglobulin within 60 days prior to study entry
• Participation in another investigational product clinical trial in the 3 months prior to study entry OR expected to participate in another investigational trial during this study
• Any other investigational HIV vaccine at any time
• History of severe local or systemic reactogenicity to vaccines or history of severe allergic reactions
• Major psychiatric illness, including any history of schizophrenia or severe psychosis, bipolar disorder requiring therapy, or suicide attempt or suicidal thoughts within the 3 years prior to study entry
• Uncontrolled hypertension
• Pregnant, breastfeeding, or plan to become pregnant