Objective Large inter-individual variability in the pharmacokinetics of rilpivirine and cabotegravir has been reported in the first weeks after starting long-acting injectable (LAI) therapy. Here, we assessed the distribution of rilpivirine and cabotegravir trough concentrations in people with HIV (PWH) on long-term LAI treatment. Methods Adult PWH treated with LAI for at least 32 weeks with an assessment of drug plasma trough concentrations were considered. The proportion of rilpivirine and cabotegravir plasma trough concentrations below four-times the protein-adjusted concentrations required for 90% inhibition of viral replication (4×PA-IC90) was estimated. Results Sixty-seven PWH were identified. LAI treatment duration was 216 ± 80 weeks (range 32–320 weeks). Cabotegravir concentrations were associated with lower inter-individual variability compared with rilpivirine (45% versus 84%; P < 0.05). No differences were found in rilpivirine (160 ± 118 versus 189 ± 81 ng/mL; P = 0.430) and cabotegravir (1758 ± 807 versus 1969 ± 802 ng/mL; P = 0.416) trough concentrations in males (n = 55) versus females (n = 12). A non-significant trend for lower cabotegravir concentrations was found in PWH with a body mass index >30 kg/m2 (n = 9) versus non-obese participants (1916 ± 905 versus 1606 ± 576 ng/mL; P = 0.131). Three out of the 67 PWH had at least one drug concentration <4×PA-IC90: 100% of PWH had undetectable HIV viral load. Conclusions At steady state, optimal systemic exposure of cabotegravir and rilpivirine was found in most PWH; cabotegravir trough concentrations were associated with lower inter-individual variability compared with rilpivirine. The study was not powered to assess the contribution of sex and/or body weight on LAI exposure due to the small number of females and obese PWH included.

中文翻译：

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长期接受长效注射抗逆转录病毒药物治疗的艾滋病毒感染者中利匹韦林和卡博特韦的谷浓度

目的 据报道，在开始长效注射剂 (LAI) 治疗后的最初几周内，利匹韦林和卡博特韦的药代动力学存在较大的个体差异。在此，我们评估了接受长期 LAI 治疗的 HIV 感染者 (PWH) 中利匹韦林和卡博特韦的谷浓度分布。方法 考虑使用 LAI 治疗至少 32 周的成人 PWH，并评估血浆药物谷浓度。估计利匹韦林和卡博特韦血浆谷浓度低于抑制病毒复制 90% 所需的蛋白质调整浓度 (4×PA-IC90) 四倍的比例。结果 确定了 67 名感染者。 LAI 治疗持续时间为 216 ± 80 周（范围 32-320 周）。与利匹韦林相比，卡博特韦浓度与较低的个体间变异相关（45% vs 84%；P < 0.05）。男性 (n = 55) 与男性 (n = 55) 中利匹韦林 (160 ± 118 与 189 ± 81 ng/mL；P = 0.430) 和卡博特韦 (cabotegravir) (1758 ± 807 与 1969 ± 802 ng/mL；P = 0.416) 的谷浓度没有差异。女性（n = 12）。与非肥胖参与者相比，体重指数 > 30 kg/m2 (n = 9) 的 PWH 中卡博特韦浓度较低的趋势不显着（1916 ± 905 与 1606 ± 576 ng/mL；P = 0.131） 。 67名PWH中的3名至少有一种药物浓度＜4×PA-IC90：100％的PWH具有不可检测的HIV病毒载量。结论 在稳定状态下，大多数感染者发现卡博特韦和利匹韦林的最佳全身暴露量；与利匹韦林相比，卡博特韦谷浓度与较低的个体间变异相关。由于纳入的女性和肥胖孕妇人数较少，该研究无法评估性别和/或体重对 LAI 暴露的影响。