Long-acting cabotegravir and rilpivirine for the treatment of people with HIV: current landscape and challenges ahead.

Long-acting injectable cabotegravir plus rilpivirine (LAI CAB + RPV) represents an important advance in HIV treatment, offering an alternative to daily oral antiretroviral therapy (ART) for people with HIV (PWH) who are virologically suppressed. This narrative review aims to (i) evaluate the effectiveness and safety of LAI CAB + RPV in real-world clinical practice; (ii) assess outcomes in key subgroups, including women, older adults, people with elevated BMI, transgender people, and those with adherence challenges; and (iii) discuss practical and implementation considerations relevant to routine care. We synthesized the most up-to-date evidence from peer-reviewed publications and major international HIV conferences. Recent real-world cohort studies consistently report high rates of virological suppression (typically >90%) and low rates of confirmed virological failure, even in diverse populations and those with complex social or medical needs. Injection site reactions are common but rarely lead to discontinuation, and overall tolerability is high. Evidence suggests that LAI CAB + RPV can be successfully implemented in clinical practice, including among individuals with a history of non-adherence, provided that appropriate support systems are in place. However, current data are limited by short follow-up periods and relatively small sample sizes, especially in underrepresented groups such as women, older adults, people with high BMI, or transgender people. Further research is needed to clarify long-term outcomes and optimize patient selection. In summary, LAI CAB + RPV is a promising and well-tolerated option for maintaining virological suppression in routine care, with the potential to address important unmet needs across a broad spectrum of PWH. Ongoing studies will help define its optimal use and long-term benefits in real-world settings.