Risk populations for HIV infections tend to neglect condom use, making alternative preventive approaches necessary. Accordingly, we modelled the risk of sexual HIV transmission for condom use vs. use of rapid diagnostic test (RDT) systems with subsequent exclusion of potential sexual partners with a correctly or falsely positive test from unprotected sex with and without the use of HIV pre-exposure prophylaxis (PrEP) in a bio-statistical approach. We combined a previously described model of transmission risk for HIV-exposed individuals with a newly suggested model of risk of HIV exposure for sexually active HIV-negative individuals. The model was adapted for several stages of infection and different strategies of HIV infection prevention.HIV prevention with RDTs can reduce the transmission risk by up to 97% compared with having sex without any prevention and up to 80% compared with condom use. Nevertheless, RDT-based prevention strategies demonstrate a lack of protection in several stages of infection; in particular, RNA-based RDT systems may fail under treatment. RDT-based pre-screening of potential sex partners prior to unprotected sexual contacts substantially reduces HIV transmission risk. Combination of different prevention strategies is advisable for high-risk groups.