Evaluating long-acting injectable HIV treatment: an update on cabotegravir and rilpivirine

Antiretroviral therapy has transformed HIV into a chronic manageable condition; however, lifelong daily oral therapy remains a barrier to adherence and quality of life. Long-acting cabotegravir (CAB) and rilpivirine (RPV) provide the first complete regimen administered by intramuscular injections every 4 or 8 weeks, enabling virologic maintenance without daily pills.

This review summarizes the pharmacological properties of CAB+RPV and the evidence supporting their long-acting use. Phase II (LATTE, LATTE-2) and phase III (FLAIR, ATLAS, ATLAS-2 M, SOLAR) trials demonstrated that CAB+RPV long-acting is non-inferior to oral therapy, showing durable viral suppression. Safety data confirm a favorable profile, with injection site reactions as the most common adverse events, usually mild, transient, and declining over time. Pharmacokinetic and pharmacodynamic studies support sustained inhibitory drug levels.

CAB+RPV represents a paradigm shift in HIV management, offering a valuable alternative for virologically suppressed individuals seeking freedom from daily dosing. Its successful implementation requires careful patient selection, robust systems to support timely injections, and strategies to mitigate pharmacokinetic challenges. Future directions include expanding eligibility to broader populations, optimizing ultra-long-acting formulations, and integrating injectables into differentiated care models to ensure equity of access.