Background
Low plasma concentrations of LA CAB/RPV are associated with increased risk of virologic failure. However, trough LA CAB/RPV demonstrates high interindividual variability (CAB 31%, RPV 35%), and intraindividual variability (CAB 52%, RPV 29%) during the first 12 months of use. We sought to characterize the variability in trough plasma concentrations of CAB and RPV in PWH receiving LA CAB/RPV after 1 year of use.
Methods
We conducted a prospective PK study in virologically suppressed PWH who had received >12 months of continuous LA CAB/RPV (600mg/900mg) given IM every 2 months. All doses were administered by the same 4 nurses. Plasma samples were collected pre-injection at three consecutive visits and CAB/RPV concentrations were quantified via LC-MS/MS. The primary outcomes were inter- and intraindividual CAB and RPV trough concentration variability reported as % coefficient of variation (CV), Fleiss Kappa, and intraclass correlation coefficient (ICC). Secondary outcomes were proportion of participants with CAB or RPV concentrations below 4x PA-IC90 (CAB=664 ng/mL; RPV=48 ng/mL) and associated laboratory or clinical characteristics. We performed descriptive statistics (median; range, unless noted) and compared participants with troughs above vs. below 4x PA-IC90 with Fisher’s exact and Wilcoxon rank sum tests.
Results
Overall, 90 trough samples were obtained from 30 participants receiving LA CAB/RPV for 71 weeks (55-97) at entry. Most participants were male (80%) and White (70%) with a median age of 45 years (IQR 33-59). Geometric mean CAB and RPV concentrations were 1661.3 ng/mL and 83.1 ng/mL, respectively (Figure). Interindividual CV for CAB was 44% (38-44%) and 45.8% (40-49%) for RPV. CAB and RPV Fleiss Kappa was -0.01, indicating poor interindividual agreement. Intraindividual CV for CAB was 26.3% (6-53%) and 32% (10-68%) for RPV. ICC was 0.75 and 0.63 for CAB and RPV, respectively, indicating moderate intraindividual agreement. There were 11 (12%) RPV and 2 (2%) CAB concentrations below 4x PA-IC90. Five participants had 9 HIV-RNA results >20 copies/mL (26-75 copies/mL). All subsequently re-suppressed (HIV-RNA <20 copies/mL) and none had CAB or RPV <4x PA-IC90. No demographic or laboratory factors were associated with concentrations below 4x PA-IC90 (all p>0.05).
Conclusions
After achieving proposed steady state concentrations, inter- and intraindividual variability persists for CAB and RPV. Despite this variability, there was no association between CAB/RPV concentrations and viremia.
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