One in eight of the 1.2 million Americans living with human immunodeficiency virus (HIV) are unaware of their positive status, and untested individuals are responsible for most new infections. As a result, testing is the most cost-effective HIV prevention strategy and must be accelerated when opportunities are presented. Web searches for HIV spiked around actor Charlie Sheen’s HIV-positive disclosure. However, it is unknown whether Sheen’s disclosure impacted offline behaviors like HIV testing. The goal of this study was to determine if Sheen’s HIV disclosure was a record-setting HIV prevention event and determine if Web searches presage increases in testing allowing for rapid detection and reaction in the future. Sales of OraQuick rapid in-home HIV test kits in the USA were monitored weekly from April 12, 2014, to April 16, 2016, alongside Web searches including the terms “test,” “tests,” or “testing” and “HIV” as accessed from Google Trends. Changes in OraQuick sales around Sheen’s disclosure and prediction models using Web searches were assessed. OraQuick sales rose 95% (95% CI, 75–117; p < 0.001) of the week of Sheen’s disclosure and remained elevated for 4 more weeks (p < 0.05). In total, there were 8225 more sales than expected around Sheen’s disclosure, surpassing World AIDS Day by a factor of about 7. Moreover, Web searches mirrored OraQuick sales trends (r = 0.79), demonstrating their ability to presage increases in testing. The “Charlie Sheen effect” represents an important opportunity for a public health response, and in the future, Web searches can be used to detect and act on more opportunities to foster prevention behaviors.