People living with HIV (PLWH) prescribed with ART are at risk of potential drug–drug interactions (pDDIs) with recreational drugs.

This article describes the pDDIs between ART and chemsex drugs in a cohort of PLWH engaged in chemsex from a tertiary Hospital in Barcelona, Spain, and evaluate their association with unscheduled relevant hospital consultations.

Among 172 participants, we observed 2048 pDDIs. Of these, 23% were orange flag pDDIs and mainly related to boosted ARTs. The IR of the 285 unscheduled relevant episodes in patients with orange flag pDDIs was 64.67 (95% CI 40.07–89.28). The IRR of green flag pDDIs was 1.05 (95% CI 0.60–1.8; p = 0.876).

Despite one in four pDDIs being of moderate severity, no significant increase in the incidence of unscheduled relevant consultations was found. Beyond using non-boosted ART to minimize pDDIs, other factors related to the practice of chemsex must be addressed, to offer a better approach.