Examining the Role of Genetics in Determining the Immune Response to an HIV Vaccine in HIV-Uninfected Adult Twins

Inclusion Criteria: * Pairs of MZ and DZ twins who shared common childhood environments * If born male, participant must be fully circumcised (as documented at screening examination). Circumcision must have been performed at least 90 days prior to first vaccination and surgical site must be fully healed. * Access to a participating HIV Vaccine Trials Network (HVTN) clinical research site (CRS) and willing to be followed for the duration of the study * Assessment of understanding, including the completion of a questionnaire before the first vaccination and demonstration of understanding for all questionnaire items answered incorrectly * Willing to receive HIV test results * Willing to discuss HIV infection risks, amenable to HIV risk reduction counseling, committed to maintaining behavior consistent with low risk HIV exposure through the last required study visit, and willing to continue annual follow-up contact after the final study visit for a total of 5 years after study entry * In good general health, as shown by medical history, physical exam, and screening laboratory tests * Assessed by the clinic staff as having a "low risk" for HIV infection on the basis of sexual behaviors in the 12 months before study entry. More information on this criterion can be found in the protocol. * Ad5 nAb titer less than 1:18 * Hemoglobin greater than or equal to 11.3 g/dL for participants who were born female, and greater than or equal to 13.0 g/dL for participants who were born male * White blood cell count between 3,300 to 12,000 cells/mm\^3 * Total lymphocyte count greater than or equal to 800 cells/mm\^3 * Remaining differential either within site's normal range or with site physician approval * Platelet level between 125,000 to 550,000/mm\^3 * Alanine aminotransferase (ALT) less than or equal to 2.5 times the site's upper limit of normal * Negative HIV-1 and -2 blood test * Negative Hepatitis B surface antigen (HBsAg) * Negative anti-Hepatitis C virus antibodies (anti-HCV), or negative HCV polymerase chain reaction (PCR) if the anti-HCV test is positive * Participants who were born female must have a negative pregnancy test result before the first study vaccination * Agree not to participate in any other study requiring blood draws more than 10 mLs total or additional investigational drugs 56 days before study entry or during the study * Participants who were born female must agree to use an effective form of contraception from at least 21 days before study entry until the last study visit. More information on this criterion can be found in the protocol. * Participants who were born female must agree not to seek pregnancy through alternative methods (e.g., artificial insemination, in vitro fertilization) until after the last study visit Exclusion Criteria: * Excessive daily alcohol use, frequent binge drinking, chronic marijuana abuse, or use of any other illicit drugs in the 12 months before study entry * History of newly acquired syphilis, gonorrhea, non-gonococcal urethritis, herpes simplex virus type 2, chlamydia, pelvic inflammatory disease (PID), trichomonas, mucopurulent cervicitis, epididymitis, proctitis, lymphogranuloma venereum, chancroid, or hepatitis B in the 12 months before study entry * Received HIV vaccines in a prior HIV vaccine trial * Immunosuppressive medications received within 168 days before the first study vaccination * Blood products received within 120 days before the first study vaccination * Immunoglobulin received within 60 days before the first study vaccination * Live attenuated vaccines received within 30 days before the first study vaccination or scheduled within 14 days after injection * Investigational research agents received within 30 days before the first study vaccination * Intent to participate in another investigational drug study * Any vaccines that are not live attenuated vaccines or allergy treatment with antigen injections received within 14 days before the first study vaccination * Current anti-tuberculosis preventive therapy or treatment * Clinically significant medical condition, abnormal physical examination findings, abnormal laboratory results, or past medical history that may affect current health * Any medical, psychiatric, occupational, or other condition that would interfere with participation in the study * Serious adverse reactions to vaccines, including anaphylaxis and related symptoms (e.g., hives, respiratory difficulty, angioedema, abdominal pain). A person who had an adverse reaction to the pertussis vaccine as a child is not excluded. * Autoimmune disease or immunodeficiency * Active syphilis infection * Asthma, other than mild, well-controlled asthma. More information on this criterion can be found in the protocol. * Type 1 or type 2 diabetes mellitus, including cases controlled with diet alone. People with a history of isolated gestational diabetes are not excluded. * Surgical removal of the thyroid or thyroid disease requiring medication during the 12 months before study entry * History of hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema * Idiopathic urticaria within the 2 years before study entry * High blood pressure that is not well controlled OR blood pressure of 150/100 mm Hg or greater at study entry. More information on this criterion can be found in the protocol. * Bleeding disorder (e.g., factor deficiency, coagulopathy, platelet disorder requiring special precautions) * Cancer. People with surgically removed cancer that, in the opinion of the investigator, is unlikely to recur are not excluded. * Seizure disorder. People with a history of seizures who have not required medications or had a seizure within the 3 years before study entry are not excluded. * Absence of the spleen * Psychiatric condition that makes study compliance difficult (e.g., people with psychoses in the 3 years before study entry, ongoing risk for suicide, history of suicide attempt in the 3 years before study entry) * Pregnant or breastfeeding