Within a population already at high risk of HIV, gay and bisexual men (GBM) who use drugs, particularly methamphetamine, to enhance sexual pleasure (chemsex) have previously been identified as being at higher risk of HIV compared to their non-drugs-for-sex peers. HIV pre-exposure prophylaxis (PrEP) has had a substantial impact on HIV prevention globally. This questions whether GBM who engage in chemsex remain at risk of HIV in the context of PrEP. This research explores ongoing HIV risk behaviours among men who engage in chemsex in the context of the availability of PrEP. This thesis comprises six projects. The first project described the implementation of a cohort management system that I designed to automate data collection for this project. In 2014, baseline prevalence of methamphetamine use was high, as was concurrent use of erectile dysfunction medication (EDM) and gamma-hydroxybutyrate (GHB). The second and third projects examined EDM and GHB separately. Prior to the widespread availability of PrEP in Australia, use of these drugs was strongly associated with HIV risk behaviours. The fourth project was conducted in 2017 and measured incidence of PrEP initiation among GBM in the cohort, and identified factors associated with PrEP initiation. Many GBM who had reported high-risk behaviours subsequently initiated PrEP, but a large proportion of GBM at high-risk of HIV did not initiate PrEP. The fifth project demonstrated a change in HIV prevention among GBM who engage in chemsex. Prevalence of PrEP use among GBM who engage in chemsex increased dramatically between 2014 and 2017. With methamphetamine use consistently linked to HIV infection, the sixth project investigated the relationship between its use and HIV risk behaviours, specifically in the current context of HIV biomedical prevention. GBM who were previously considered at highest risk of infection are more likely to use PrEP to mitigate against the HIV risk in 2018. PrEP as an HIV prevention strategy is changing the trajectory of the HIV epidemic among GBM in Australia. This thesis demonstrates a shift in epidemiology away from the previously highest risk practices due to the incorporation of PrEP into the regimens of GBM who engage in chemsex.