This report updates an evidence synthesis commissioned by the U.S. Preventive Services Task Force (USPSTF) and completed in March 2005, 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. This brief update was requested by the USPSTF to determine whether there is sufficient new evidence to justify revision of recommendations based on the 2005 evidence synthesis. A key reason for this update is the release in September 2006 of revised Centers for Disease Control and Prevention (CDC) recommendations advising routine voluntary HIV screening of most U.S. adolescents and adults. The 2005 USPSTF recommendations differ from the revised CDC recommendations in that they do not recommend for or against routine screening non-pregnant adults and adolescents who do not report risk factors and are not in high-prevalence (greater than 1%) or other high-risk settings. Staff at the CDC have indicated that the agency's expanded screening recommendations are based primarily on new evidence as to the effects of HIV screening on transmission risk. This report focuses on new or "breakthrough" evidence that could affect the 2005 USPSTF recommendations regarding routine screening of low- or average-risk adults and adolescents. This update reviews new evidence on HIV screening not included in the 2005 evidence synthesis. It focuses on evidence in non-pregnant, adults and adolescents who do not report risk factors and are evaluated in lower-prevalence (less than 1%), low-risk clinical settings (referred to in this report as 'low-risk' persons), because this is the population for which the USPSTF and the 2006 CDC recommendations are discordant. In the 2005 evidence review, we identified several key areas where additional evidence could strengthen the case for screening in low-risk populations. These include gaps in the research regarding uncertainties about the acceptability of routine voluntary screening in low-risk persons; the yield of targeted versus universal screening and optimal methods of risk assessment in low-risk settings; the impact on test uptake and follow-up of abbreviated or streamlined counseling methods and newer testing or sampling methods; and the effects of screening on HIV transmission rates. We therefore focused on studies that could help fill in these gaps. We also evaluated new evidence on the cost-effectiveness of routine HIV screening and studies on the frequency of testing.