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Based on interviews with HIV-positive gay men recently diagnosed with acute hepatitis C, the HEPAIG-quali study demonstrates that sexual practices and drug use are closely intertwined with each other, in order to experience an ultimate aim of sexual pleasure, including unprotected sex. For these men, the use of various psychoactive and stimulant substances (illicit or not) contributes to their bodily endurance and performance, as well as to their overall well-being. These “chemical pleasures”, which they are not ready to give up, take place in the post-AIDS context of medicine and treatments, which promote an ideal subject inspired by self-responsibility and personal discipline, and within a moral pattern stigmatizing drug abuse and addiction. As a consequence, health interventions should be adjusted to their identity and needs as HIV-positive gay men, and promote sexual risk reduction including drug use.