Sustained Virologic Suppression After Discontinuation of Long-acting Cabotegravir/Rilpivirine: A Two-case Series Highlighting Unexpected Heterogeneity in Pharmacokinetics and Viral Control.

Long-acting (LA) injectable cabotegravir (CAB) and rilpivirine (RPV) are recommended for maintenance treatment in virologically suppressed people with HIV-1. A key concern with this strategy is the prolonged pharmacokinetic "tail" after treatment discontinuation, during which declining drug concentrations may increase the risk of viral rebound and resistance selection. Current clinical guidance therefore recommends prompt initiation of alternative antiretroviral therapy if injections are interrupted. We report two people with HIV who remained virologically suppressed (HIV-1 RNA <50 copies/mL) for several months after discontinuation of LA CAB/RPV without any documented alternative antiretroviral therapy. The first case involved a 54-year-old man with well-controlled HIV-1 disease who had received 13 CAB/RPV injections over approximately two years before treatment interruption. After missing scheduled visits, he returned to care seven months after his last injection with persistent viral suppression and plasma drug concentrations who had received 13 CAB/RPV injections over approximately two years before treatment interruption, both above commonly used pharmacokinetic target thresholds. The second case involved a 60-year-old woman with advanced HIV-1 infection and metastatic anal cancer who discontinued treatment after three injections. Five months later, HIV-1 RNA remained undetectable despite very low plasma CAB/RPV concentrations, both below commonly used pharmacokinetic target thresholds. The literature reports another similar case of sustained virologic control 18 months after LA CAB/RPV discontinuation despite inadequate adherence on oral antiretroviral treatment. Altogether, these cases underscore the need for further research to better understand the pharmacological and viro-immunological mechanisms underlying this phenomenon.