The ANRS-IPERGAY trial consisted in providing sexual activity-based antiretroviral prophylaxis for HIV prevention (PrEP) with a package of prevention tools (counselling, condoms, HIV and sexually transmitted infections' screening) to highly exposed HIV-negative men who have sex with men (MSM). Few data exist concerning the patient-physician relationship in the particular context of PrEP, where physicians discuss sexual behaviours with MSM who are not classic patients, in that consultation is for prevention purposes, not for illness. This study took place during the open-label extension of ANRS-IPERGAY trial when all participants received PrEP. In this qualitative study, we examined how physicians perceived their relationship with participants in the ANRS-IPERGAY trial. Of all 30 physicians involved in the trial who were contacted by email to participate in an interview about their opinions and perceptions of ANRS-IPERGAY 18 volunteered to participate in the current sub-study. We performed a vertical analysis for each interview to identify the extract in each physician's discourse concerning their relationship with MSM participants, and conducted a horizontal analysis to construct the thematic tree and subsequently investigate differences and similitudes between themes. An analysis of all physicians' discourses showed that the participant-physician relationship during the trial could be described through 4 themes: (i) personal experience of the relationship, (ii) trust and non-judgement, (iii) positive relational climate and (iv) influence of physician's characteristics (age, gender, etc.) on relationship. We found that the particular context of PrEP led some physicians to adopt a patient-as-partner approach during consultations rather than a paternalist or hierarchical approach. Indeed, the close follow-up provided by the trial and the active role of patients in their own prevention care trajectory, are more compatible with the patient-as-partner approach. The prescription of PrEP may lead to an evolution in patient-physician relationships and may even modify the professional identity of physicians.