HIV chemoprophylaxis (PrEP/PEP) has emerged as a transformative prevention tool to reduce infection rates and decrease disease burden. However, uptake is low, and efficacy depends upon adherence. To maximize impact, potential barriers to uptake and adherence must be identified and understood. Using univariate and logistic regression analytic methods, we assessed associations among potential barriers to uptake and adherence, including HIV chemoprophylaxis knowledge, negative stereotyped beliefs about people who use it and negative attitudes towards HIV chemoprophylaxis use by relatives among 583 residents of two high HIV prevalence neighborhoods in New York City. About a quarter of respondents knew about HIV chemoprophylaxis and over 50 % endorsed negative stereotyped beliefs about users; yet, approximately two-thirds had positive attitudes toward its use among a male or female relative. Young age, having lesbian or gay friends/family members and low levels of homophobia were associated with not endorsing negative stereotyped beliefs. Negative stereotyped beliefs were not associated with negative attitudes toward HIV chemoprophylaxis use among relatives. Implications for PrEP dissemination are discussed.