Gutiérrez Félix, Fernández-González Marta, Ledesma Christian, Losada-Echeberría María, Barrajón-Catalán Enrique, García-Abellán Javier, De Stefano Daria, López Leandro, Bello-Perez Melissa, Padilla Sergio, Masiá Mar
Infectious Diseases Unit, Hospital General Universitario de Elche, Elche, Spain.
Department of Clinical Medicine, Universidad Miguel Hernández, Alicante, Spain.
Clin Infect Dis. 2025 Apr 30;80(4):842-853. doi: 10.1093/cid/ciae475.
This study aimed to investigate factors contributing to non-sustained viral suppression, including intermittent viremia and persistent low-level viremia, during cabotegravir (CAB) plus rilpivirine (RPV) long-acting (LA) injectable therapy, with a focus on pharmacokinetics (PK).
A prospective cohort study was conducted on people with human immunodeficiency virus (HIV, PWH) transitioning from stable oral antiretroviral therapy (ART) to bimonthly CAB + RPV LA. Standardized follow-up included close monitoring through blood sampling for plasma human immunodeficiency virus type 1 (HIV-1) viral load (VL) and multiple plasma drug concentrations measurements to analyze the connection between PK parameters and virologic outcomes.
Among 173 patients with a median (interquartile range [IQR]) follow-up of 11.1(7.1-13.2) months and 789 pre-dose measurements, 38.7% experienced VL ≥ 20 copies/mL, and 16.2% had levels ≥50 copies/mL. Intermittent viremia occurred in 34.7% of patients, and persistent low-level viremia in 4%. Virological failure developed in 2 cases. Predictors of non-sustained viral suppression included VL at HIV diagnosis (adjusted hazard ratio [AHR]: 1.49 per log10 VL, 95% confidence interval [CI]: 1.04-2.12, P = .027), detectable viremia on oral ART (AHR: 2.45, 95% CI: 1.29-4.65, P = .006), and the level of viral suppression at transition (AHR: 0.38, 95% CI: .19-.75, P = .004). We found a significant association between low trough concentrations of CAB and RPV and episodes of detectable viremia exceeding 50 copies/mL. However, none of the assessed PK covariates predicted non-sustained viral suppression in multivariable models.
Non-sustained viral suppression in PWH transitioning from stable oral ART to CAB + RPV LA was linked to preexisting factors before transition. Higher VL pre-ART and incomplete suppression on oral therapy increased the risk, independent of PK parameters.
本研究旨在调查在卡博特韦（CAB）加rilpivirine（RPV）长效（LA）注射治疗期间导致病毒抑制未持续的因素，包括间歇性病毒血症和持续性低水平病毒血症，重点关注药代动力学（PK）。
对从稳定的口服抗逆转录病毒疗法（ART）过渡到每两个月一次CAB + RPV LA的人类免疫缺陷病毒（HIV）感染者（PWH）进行了一项前瞻性队列研究。标准化随访包括通过血液采样密切监测血浆1型人类免疫缺陷病毒（HIV-1）病毒载量（VL）以及多次测量血浆药物浓度，以分析PK参数与病毒学结果之间的联系。
在173例患者中，中位（四分位间距[IQR]）随访时间为11.1（7.1 - 13.2）个月，进行了789次给药前测量，38.7%的患者病毒载量≥20拷贝/mL，16.2%的患者病毒载量≥50拷贝/mL。34.7%的患者出现间歇性病毒血症，4%的患者出现持续性低水平病毒血症。2例发生病毒学失败。病毒抑制未持续的预测因素包括HIV诊断时的病毒载量（调整后的风险比[AHR]：每log10病毒载量为1.49，95%置信区间[CI]：1.04 - 2.12，P = 0.027）、口服ART时可检测到的病毒血症（AHR：2.45，95% CI：1.29 - 4.65，P = 0.006）以及过渡时的病毒抑制水平（AHR：0.38，95% CI：0.19 - 0.75，P = 0.004）。我们发现CAB和RPV的低谷浓度与超过50拷贝/mL的可检测病毒血症发作之间存在显著关联。然而，在多变量模型中，没有一个评估的PK协变量能够预测病毒抑制未持续。
从稳定的口服ART过渡到CAB + RPV LA的PWH中，病毒抑制未持续与过渡前的既有因素有关。ART前较高的病毒载量和口服治疗时不完全抑制增加了风险，与PK参数无关。
