Safety and Effectiveness of HIV-1 DNA Plasmid Vaccine and HIV-1 Recombinant Adenoviral Vector Vaccine in HIV-Uninfected, Circumcised Men and Male-to-Female (MTF) Transgender Persons Who Have Sex With Men

• HIV-1 infection diagnosis [ Time Frame: Measured at or after Day 196 post-enrollment through the Month 24 visit ] [ Designated as safety issue: No ]
  
• Viral load (VL) setpoint [ Time Frame: Measured at Week 10 through Week 20 after diagnosis of HIV infection ] [ Designated as safety issue: No ]
  VL setpoint defined as the average of all log˅10 plasma HIV-1 RNA values obtained at the Weeks 10, 12, 14, 16, and 20 study visits after the diagnosis of HIV infection and prior to initiation of antiretroviral therapy (ART), for HIV-infected participants who are diagnosed at or after Day 196 through the Month 24 study visit
  
  
• Local and systemic reactogenicity signs and symptoms and adverse events (AEs) and expedited adverse events (EAEs) [ Time Frame: Measured through participant's last follow-up contact, which may be up to 5 years after enrollment ] [ Designated as safety issue: Yes ]
  

• Early VL [ Time Frame: Measured from Weeks 2 through 8 post-HIV diagnosis ] [ Designated as safety issue: No ]

  If at least 80% of participants who contribute Week 28+ infections have at least one VL value at the Weeks 2 through 8 post-diagnosis visits and prior to initiation of ART, early VL will be defined as the average of all available log˅10 plasma HIV-1 RNA values obtained during this window and prior to initiation of ART.

  If fewer than 80%: early VL will be defined as the average of all available log˅10 plasma HIV-1 RNA values obtained at the diagnosis through Week 8 post-diagnosis visits and prior to initiation of ART.

  
  
• HIV-1 plasma RNA levels and CD4+ T-cell counts in HIV-1-infected participants [ Time Frame: Measured through Week 72 post-diagnosis ] [ Designated as safety issue: No ]
  
• Time to initiation of ART [ Time Frame: Measured throughout the 5 years after study entry ] [ Designated as safety issue: No ]
  
• Time to reach a VL of more than 100,000 copies/mL, CD4+ cell counts less than or equal to X cells/mm^3, HIV clinical disease progression, or death, with X set at 350, 500, and varied continuously over the range 350 to 500 cells/mm^3 [ Time Frame: Measured from Week 2 through Week 72 post-diagnosis ] [ Designated as safety issue: No ]
  
• Types of HIV-1 related clinical events [ Time Frame: Measured throughout the 5 years after study entry ] [ Designated as safety issue: Yes ]
  If and when HIV-1-infected participants experience an HIV-1-related clinical event will be recorded. The type of HIV-1-related clinical event will be recorded. This endpoint will also contribute to analysis of safety.
  
  
• Unfractionated HIV-1-specific interferon (IFN)-gamma enzyme-linked immunosorbent spot (ELISpot) responses [ Time Frame: Measured throughout the first 24 months after study entry ] [ Designated as safety issue: No ]
  
• HIV-1-specific flow cytometry responses [ Time Frame: Measured throughout the first 24 months after study entry ] [ Designated as safety issue: No ]
  
• HIV-1 binding enzyme-linked immunosorbent assay (ELISA) responses [ Time Frame: Measured throughout the first 24 months after study entry ] [ Designated as safety issue: No ]
  
• HIV-1 neutralization responses [ Time Frame: Measured throughout the first 24 months after study entry ] [ Designated as safety issue: No ]
  
• Immune response to the rAd5 vector [ Time Frame: Measured throughout the first 24 months after study entry ] [ Designated as safety issue: No ]
  Immune responses will be measured to the rAd5 vector by rAd5-specific multiparameter flow cytometry
  
  
• Social impacts [ Time Frame: Measured throughout the 5 years after study entry ] [ Designated as safety issue: No ]
  Social impact variables include both positive and negative experiences the participant encounters due to his participation in this study. Specific social impacts to be followed during the course of the study include social, travel, work, school, health care, life insurance, health insurance, housing, military, benefits, and any additional impacts identified by a participant.
  
  

In 2007, the Joint United Nations Programme on HIV/AIDS estimated that 33.2 million people were living with HIV/AIDS globally. The U.S. HIV prevalence data reported in October 2008 by the Centers for Disease Control and Prevention estimate that 1.1 million adults and adolescents were living with diagnosed or undiagnosed HIV infection in the United States at the end of 2006. Nearly half of all U.S. HIV infections (48.1%) were found in men who have sex with men (MSM). Given the difficulty of maintaining behaviors that prevent HIV transmission over a lifetime and the occurrence of nonconsensual sex, the need for a safe and effective vaccine is clear. The primary purpose of this study is to determine the safety and efficacy of a VRC DNA/rAd5 vaccine regimen in healthy, at-risk, circumcised men and MTF transgender persons who have sex with men.

Participants will be randomly assigned to one of two arms. Participants in Arm 1 will receive a recombinant DNA plasmid vaccine injection at study entry and on Days 28 and 56, followed by a recombinant adenoviral serotype vector vaccine injection on Day 168. Participants in Arm 2 will receive placebo injections at study entry and on Days 28, 56, and 168.

Participants who do not become HIV infected will be actively followed for a minimum of 24 months and will continue to be contacted by the study for long-term safety surveillance for a total of 5 years following enrollment. Participants will be contacted annually during the period of long-term safety surveillance.

Participants who are found to be HIV infected prior to receiving their first injection or who receive their first injection but were HIV infected prior to study start will be followed on a modified schedule.

Participants who become HIV infected prior to the primary evaluation time point and primary data analysis will be followed for 18 months post-diagnosis.

At most study visits, participants will undergo a physical exam and blood draw. At select visits, participants meeting certain criteria will have the option to undergo a rectal secretion collection and/or semen collection.