Despite the life-preserving benefits of antiretroviral therapy (ART), some people living with HIV (PLHIV) delay, decline or diverge from recommended treatment while paradoxically being willing to use potentially dangerous substances, such as recreational drugs (RD) and complementary medicines (CM). During 2016 and 2017, interviews were conducted with 40 PLHIV, in Australia to understand drivers underpinning treatment decisions. While many believed ART to be effective, they expressed concerns about long-term effects, frustration over perceived lack of autonomy in treatment decisions and financial, emotional and physical burdens of HIV care. In contrast, they ascribed a sense of self-control over the use of RD and CM, along with multiple professed benefits. The perceived burden of ART emerged as a motivator for deviating from recommended treatment, while positive views towards RD and CM appear to justify use. This study may serve as guidance for the development of future strategies to address barriers to treatment uptake and adherence and subsequently health outcomes for PLHIV in Australia and elsewhere.