CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

654

Association of Trough Concentrations of Cabotegravir and Rilpivirine and HIV-1 RNA Sebastian Noe, Arlette Baxmann, Farhad Schabaz, Ariane von Krosigk, Carmen

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-IC 90 (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-IC 90 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-IC 90 . 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-IC 90 . No demographic or laboratory factors were associated with concentrations below 4x PA-IC 90 (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.

Wiese, Eva Wolf, Celia Jonsson-Oldenbüttel MVZ München am Goetheplatz, Munich, Germany

Background: The relevance of plasma (trough) concentrations of cabotegravir (CAB) and rilpivirine (RPV) with regard to sustained virologic suppression in people with HIV (PWH) on long-acting treatment (LA) is an ongoing matter of debate. We aimed to add to the currently available data by analyzing the association between CAB and RPV trough concentrations and viral suppression in a real-world setting. Methods: Retrospective single-center analysis of clinical routine data from PWH receiving CAB and RPV LA intramuscular every eight weeks. Concentrations of CAB and RPV measured within a week prior to (the planned) application of the next injection were considered for analysis; multiple measurements were allowed per person. People with laboratory signs of intercurrent infections were excluded from the analysis. Lower limits of normal for CAB and RPV were 800 ng/mL and 0.038 µg/mL, respectively. The quantification limit of the essay (HIV-1 RNA <20 cps/mL) was used to define viral suppression. Medians and interquartile ranges were used for descriptive statistics. Mann-Whitney and Fisher’s exact test were used for comparisons of continuous and binary variables between two groups, respectively. α=0.05 was used as level of significance. The use of monocentric clinical routine data did not require ethics approval. Results: Overall, 350 samples from 165 PWH were included. Concentrations for CAB and RPV were 1,460 (1,120; 1,940) ng/mL or 1,160 (879; 1,560) ng/ mL (p=0.009) and 0.073 (0.051; 0.101) µg/mL or 0.064 (0.037; 0.075) µg/mL (p=0.027) for PWH with HIV-1 RNA <20 cps/mL or ≥20 cps/mL, respectively. Proportions of samples with HIV-1 RNA ≥20 cps/mL were 8.2% and 21.9% (p=0.027) among samples with normal and low plasma concentrations of CAB, and 7.9% and 18.8% (p=0.035) among samples with normal and low plasma concentrations of RPV, respectively. Odds ratios for HIV ≥20 copies/mL were 3.1 (1.0; 8.4) and 2.7 (1.0; 6.5) for samples with low concentrations of CAB and RPV, respectively. Conclusions: Our data indicate that low concentrations of CAB and/or RPV are associated with a higher odds of quantifiable viral load (≥ 20 copies/mL) and that, on a population level, lower levels of both drugs are found in people with HIV-1 RNA ≥20 cps/mL. It is unclear if this is also predictive of virologic failure. Based on our findings, however, it warrants further investigation if dosing can be indivualized taking trough concentrations into account.

Poster Abstracts

656

Plasma Concentrations of Lenacapavir in People Living With Multidrug Resistant HIV: Real-Life Study Minh Le 1 , Quentin Le Hingrat 1 , Marc-Antoine Valantin 2 , Claudine Duvivier 3 , Charlotte Charpentier 1 , Sidonie Lambert-Niclot 4 , Anne-Geneviève Marcelin 2 , Valerie Pourcher 2 , Jade Ghosn 1 , Gilles Peytavin 2 1 Hôpital Bichat-Claude-Bernard, Paris, France, 2 Assistance Publique – Hôpitaux de Paris, Paris, France, 3 Necker Hospital, Paris, France, 4 Sorbonne University, Paris, France Background: Lenacapavir (LEN) is a potent first-in-class, long acting, capsid inhibitor recently approved for the treatment of multidrug-resistant HIV, in combination with other antiretroviral agents, in heavily treatment experienced (HTE) people with HIV (PWH). PWH initiated usual or simplified regimen combining oral loading tablets and subcutaneous (SC) dose then SC maintenance dose (927 mg) every 6 months. The objective of this analysis was to describe the plasma concentrations (Cpl) of LEN in HTE adults. Methods: A multicenter, cross-sectional, cohort was conducted from 2020 to 2023. PWH who were receiving LEN containing regimen were enrolled. Basic demographic data were recorded using NADIS database (NCT#02898987). Blood samples were collected during the routine clinic visits between week 2, every each 6 months, and month 24 if available. LEN Cpl were determined by UPLC-MSMS (Waters Acquity) with LOQ<5 ng/mL and interpreted using a cutoff of 15 ng/mL corresponding to 4-fold protein adjusted 95% effective concentration on WT HIV-1. Results are presented as median (IQR).

655

Inter- and Intraindividual Variability of LA CAB/RPV Pharmacokinetics After 1 Year of Continuous Use Shawnalyn W. Sunagawa, Josh P. Havens, Sara H. Bares, Maureen Kubat, Jennifer O'Neill, Elizabeth Lyden, Timothy Mykris, Lee C. Winchester, Sean Avedissian, Anthony T. Podany, Courtney V. Fletcher, Kimberly K. Scarsi University of Nebraska Medical Center, Omaha, NE, USA 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.

CROI 2025 182