As the management of HIV changes and demand for HIV health services in primary care settings increases, new approaches to engaging the general practice workforce with HIV medicine are required. This paper reports on qualitative research conducted with 47 clinicians who provide HIV care in general practice settings around Australia, including accredited HIV s100 prescribers as well as other GPs and general practice nurses. Balanced numbers of men and women took part; less than one-quarter were based outside of urban metropolitan settings. The most significant workforce challenges that participants said they faced in providing HIV care in general practice were keeping up with knowledge, navigating low caseload and regional issues, balancing quality care with cost factors, and addressing the persistent social stigma associated with HIV. Strategic responses developed by participants to address these challenges included thinking more creatively about business and caseload planning, pursuing opportunities to share care with specialist clinicians, and challenging prejudiced attitudes amongst patients and colleagues. Understanding and supporting the needs of the general practice workforce in both high and low HIV caseload settings will be essential in ensuring Australia has the capacity to respond to emerging priorities in HIV prevention and care.