From January to July 2017, the West Virginia Department of Health and Human Resources (WV DHHR) identified 10 cases of human immunodeficiency virus (HIV) infection in three counties where HIV diagnoses typically range from six to 13 annually (1). In these counties, the spread of bloodborne pathogens via injection drug use (IDU) is a major public health concern, and risk reduction programs offering syringe services were not available, although they were available in other counties (2,3). As of July 2017, nine of the 10 persons identified were men who have sex with men (MSM), two of whom had reported a prior history of IDU. Coinfections with syphilis (five patients), hepatitis B virus (three), and hepatitis C virus (HCV) (two) were also documented. By September 2017, the sexual or injection contacts named by persons in the investigation expanded the original assessment area to encompass 15 counties, 14 of which were among the nation’s top 220 counties thought to be particularly vulnerable to rapid spread of HIV and HCV infections via IDU (4). The investigated counties share some characteristics with rural Scott County, Indiana, where an HIV outbreak was linked to IDU in 2015 (5), including a high prevalence of drug overdose deaths, prescription opioid sales, and unemployment.