INTRODUCTION: Long-acting and extended delivery (LAED) regimens for HIV treatment and prevention offer unique benefits to expand uptake, effective use and adherence. To date, research has focused on basic and clinical science around the safety and efficacy of these products. This commentary outlines opportunities in HIV prevention and treatment programmes, both for the health system and clients, that could be addressed through the inclusion of LAED regimens and the vital role of differentiated service delivery (DSD) in ensuring efficient and equitable access. DISCUSSION: The realities and challenges within HIV treatment and prevention programmes are different. Globally, more than 28 million people are accessing HIV treatment-the vast majority on a daily fixed-dose combination oral pill that is largely available, affordable and well-tolerated. Many people collect extended refills outside of health facilities with clinical consultations once or twice a year. Conversely, uptake of daily oral pre-exposure prophylaxis (PrEP) has consistently missed global targets due to limited access with high individual cost and lack of choice contributing to substantial unmet PrEP need. Recent trends in demedicalization, simplification, additional method options and DSD for PrEP have led to accelerated uptake as its availability has become more aligned with user preferences. How people currently receive HIV treatment and prevention services and their barriers to adherence must be considered for the introduction of LAED regimens to achieve the expected improvements in access and outcomes. Important considerations include the building blocks of DSD: who (provider), where (location), when (frequency) and what (package of services). Ideally, all LAED regimens will leverage DSD models that emphasize access at the community level and self-management. For treatment, LAED regimens may address challenges with adherence but their delivery should provide clear advantages over existing oral products to be scaled. For prevention, LAED regimens expand a potential PrEP user's choice of methods, but like other methods, need to be delivered in a manner that can facilitate frequent re-initiation. CONCLUSIONS: To ensure that innovative LAED HIV treatment and prevention products reach those who most stand to benefit, service delivery and client considerations during development, trial and early implementation are critical.