This evidence synthesis focuses on screening for unsuspected human immunodeficiency virus (HIV) using HIV antibody (Ab) tests in non-pregnant adolescents (aged 13 to 18 years old) and adults. The review will be used by the U.S. Preventive Services Task Force (USPSTF) to make recommendations regarding screening in the general adult and adolescent population. An accompanying report will review evidence regarding screening in pregnant women. Since the USPSTF published HIV screening recommendations in 1996, there have been substantial changes in the management and outcomes of chronic HIV infection. Although this report reviews the overall body of evidence regarding screening, it emphasizes recent data regarding the efficacy of highly active antiretroviral therapy (HAART) regimens, the accuracy and acceptability of new test methods, long-term risks of antiretroviral therapy, and the optimal timing of therapy in asymptomatic patients. HIV is an RNA retrovirus of the lentiretrovirus subfamily that was first isolated from a patient with AIDS in 1983. HIV is capable of particularly rapid replication and has a high propensity to mutate. There is significant genetic variation in HIV within individuals as well as populations. These characteristics explain some of the difficulties in developing effective vaccines and treatments. There remains no effective vaccine to prevent HIV infection and no cure for chronic infection. Interventions for HIV-infected patients include antiretroviral therapy, prophylaxis for opportunistic infections, immunizations, Papanicolaou testing, counseling to reduce high-risk behaviors, and routine monitoring and follow-up. HAART, defined as three or more antiretroviral agents used in combination (usually from at least two classes), is the standard of care for antiretroviral therapy.Key questions addressed include: KQ1. Does Screening for HIV Infection in Asymptomatic Adolescents and Adults Reduce Premature Death and Disability or Spread of Disease? KQ2. Can Clinical or Demographic Characteristics (Including Specific Settings) Identify Subgroups of Asymptomatic Adolescents and Adults at Increased Risk for HIV Compared to the General Population? KQ3. What are the Test Characteristics of HIV Antibody Test Strategies? KQ4. What are the Harms (Including Labeling and Anxiety) Associated with Screening? Is Screening Acceptable to Patients? KQ5. How Many Newly Diagnosed HIV-Positive Patients Meet Criteria for Antiretroviral Treatment or Prophylaxis for Opportunistic Infections? How Many Patients Who Meet Criteria for Interventions Receive Them? KQ6. What are the Harms Associated with the Work-Up for HIV Infection? KQ7a. How Effective are Interventions (Antiretroviral Treatment, Counseling on Risky Behaviors, Immunizations, Routine Monitoring and Follow-Up, More Frequent Papanicolaou Testing, or Prophylaxis for Opportunistic Infections) in Improving Clinical Outcomes (Mortality, Functional Status, Quality of Life, Symptoms, Opportunistic Infections, or Transmission Rates)? KQ7b. In Asymptomatic Patients with HIV Infection, Does Immediate Antiretroviral Treatment Result in Improvements in Clinical Outcomes Compared to Delayed Treatment Until Symptomatic? KQ7c. How Well Do Interventions Reduce the Rate of Viremia, Improve CD4 Counts, or Reduce Risky Behaviors? KQ8. What are the Harms Associated with Antiretroviral Therapy? KQ9. Have Improvements in Intermediate Outcomes (CD4 Counts, Viremia, Risky Behaviors) Been Shown to Reduce Premature Death and Disability or Spread of Disease?