Cerebrospinal fluid concentrations, viral suppression and biomarkers with long-acting cabotegravir and rilpivirine intramuscular injections

Our aim was to determine cerebrospinal fluid (CSF) and plasma concentrations of cabotegravir and rilpivirine (CAB/RPV) when administered as long-acting (LA) intramuscular injections every four (Q4W) or eight (Q8W) weeks, and to study the effect on viral suppression and CSF biomarkers of inflammation and neuronal injury. We included six adults with HIV receiving LA CAB/RPV Q4W or Q8W. CSF and plasma concentrations of CAB/RPV (15 samples) were analyzed by UHPLC-MS/MS. We also measured CSF and plasma HIV RNA, CSF and serum neopterin, CSF and serum β2-microglubulin, IgG index, albumin ratio, and CSF NfL. Median (range) total plasma cabotegravir concentrations were 1375 (963–2422) ng/mL, and in CSF 3.48 (1.47–7.60 ng/mL). For rilpivirine, concentrations were 93 (40–157) ng/mL and 1.21 (0.55–1.67) ng/mL, respectively. All participants hade CSF and plasma HIV RNA <20 copies/mL on every occasion. There were no significant changes in any of the CSF biomarkers in participants after switching to LA CAB/RPV. The combination of LA CAB/RPV can achieve therapeutic CSF concentrations throughout the dosing intervals and may suppress HIV replication in the CNS. No significant changes in CSF biomarkers of inflammation or neuronal injury were observed, indicating a neutral CNS effect.