Recent biomedical advances in the field of HIV prevention and treatment, including Pre-Exposure Prophylaxis (PrEP) and Treatment as Prevention (TasP), have shifted meanings of "risk" and "safety" concerning gay and other men who have sex with men's (MSM) sexual practices, particularly around "barebacking" or condomless sex. However, public health research continues to be based on the paradigm that gay men misbehave and misuse technologies such as PrEP and TasP to engage in barebacking. Public health discourses frame MSM as culpable for the effects of HIV technologies, reinforcing dominant (neoliberal) narratives of individual autonomy and risk behaviour. The purpose of this thesis is to challenge these assumptions. By mobilising analytic frameworks from posthumanist performative theories emphasising the active, dynamic, and agentic nature of material and discursive forces, I consider how advances in HIV prevention actively participate in shaping MSM's sexual practices and culture. I examine the impacts of HIV biomedical knowledge and technologies on MSM's conceptualisations of sexual risk, responsibility, morality, and stigma. Drawing on MSM's accounts from online forum posts and in-depth qualitative interviews on the effects of PrEP and TasP, I argue that gay men creatively incorporate harm reduction measures, including biomedical technologies, into their sexual practices, engendering possibilities for condomless sex to become "safer," empowering, and more pleasurable. This study destabilises the conception of condomless sex as always "risky" and "intentional" by recognising that barebacking practices emerge as complex and multiple—simultaneously safe/unsafe, premeditated/unplanned, and rational/irrational. This work enriches social science's contributions to HIV research by developing a theorised account of the complex considerations taken by gay men in assessing risk through the incorporation of HIV knowledge and biotechnologies. I also contribute to a conceptual rethinking of agency and responsibility beyond human subjects in the materialisation of condomless sexual practices, acknowledging the implication of human and nonhuman forces, including HIV science and public health, in producing a wide variety of effects associated with HIV treatment and prevention technologies.