The prevention strategies can effectively block the spread of Coronavirus disease (Coronavirus disease 19; COVID-19), and at the same time may indirectly reduce or increase the risk behaviors and factors of Human Immunodeficiency Virus (HIV) and sexually transmitted comorbidities. The main purpose of this research is to apply the Protection Motivation Theory (PMT) as the framework to analyze COVID-19 prevention knowledge, COVID-19 prevention intentions and anxiety level, and COVID-19 prevention behavior and HIV risk behavior and risk factors of people living with HIV/AIDS (PLWHA) and HIV high-risk groups. The cross-sectional research method was adopted, and the subjects included the northern, central, southern, and eastern regions of Taiwan.About 1100 PLWHA and 1100 high-risk groups will be recruited. The information of recruitment will be disseminated through the AIDS designated medical institutions and related institutions, and social media, Snowball recruitment of interviewees will also be used. After completing the online questionnaire, the structural equation modeling (SEM) will be applied to test the good of fit of the theory model and to explain the structural relationship between COVID-19 prevention knowledge, attitudes, behaviors and HIV risk factors. The relationship with the above variables and stigma also been discussed. In addition to verifying the theories proposition of PMT, the research results also contribute to the prevention and treatment of HIV high-risk groups, and provide important references for prevention strategies for susceptible groups during the epidemic of emerging infectious diseases in the future.