Masiá Mar, Fernández-González Marta, Ledesma Christian, Losada-Echeberría Maria, Gonzalo-Jiménez Nieves, Mascarell Paula, García-Abellán Javier, López Leandro, Bello-Pérez Melissa, Padilla Sergio, Gutiérrez Felix
Infectious Diseases Unit, Hospital General Universitario de Elche, Elche, Spain.
Department of Clinical Medicine, Universidad Miguel Hernández, San Juan de Alicante, Spain.
J Infect Dis. 2025 Apr 15;231(4):e792-e802. doi: 10.1093/infdis/jiaf117.
The impact of long-acting injectable cabotegravir plus rilpivirine (CAB/RPV) on rectal human immunodeficiency virus 1 (HIV-1) RNA dynamics and the factors associated with viral shedding remain poorly understood.
This prospective study evaluated HIV-1 RNA dynamics by analyzing sequential paired plasma and rectal fluid samples from virologically suppressed individuals who transitioned from oral antiretroviral therapy (ART) to every-2-month CAB/RPV (preceded or not by oral lead-in), over a 9-month follow-up period. RPV trough concentrations were measured in 384 rectal samples.
In total, 597 plasma and 561 rectal samples from 90 participants were analyzed. HIV-1 RNA >50 (>1.69 log10) copies/swab was detected in 14.7% (59/401) of rectal samples (42.2% of participants) during intramuscular CAB/RPV, and in 17.5% (28/160) of rectal samples (29% of participants) during oral ART. Median detectable rectal HIV-1 RNA level during intramuscular ART was 362 (range, 133-2216) copies/swab. The frequency and quantity of rectal shedding did not differ between groups with/without oral lead-in. No correlation was observed between rectal shedding and detectable plasma HIV-1 RNA. Median rectal RPV concentration was 3.07 (quartile 1-quartile 3, 2.83-3.35) log10 ng/swab, 1.6-fold above the 90% maximum effective concentration (EC90) for rectal tissue, and did not correlate with rectal HIV-1 RNA levels. Rectal shedding was associated with plasma pre-ART HIV-1 RNA >5 log10 in multivariate Cox regression, but was unrelated to established predictors of virological failure with CAB/RPV.
Rectal HIV-1 shedding is common during bimonthly intramuscular CAB/RPV treatment and is also observed with oral ART. Shedding was independent of concurrent plasma HIV-1 RNA and rectal RPV concentrations, and was associated with pre-ART viral load.
长效注射用卡博特韦加rilpivirine（CAB/RPV）对直肠人免疫缺陷病毒1（HIV-1）RNA动态变化的影响以及与病毒脱落相关的因素仍知之甚少。
这项前瞻性研究通过分析从口服抗逆转录病毒疗法（ART）转换为每两个月一次CAB/RPV（有无口服导入期）的病毒学抑制个体的连续配对血浆和直肠液样本，评估HIV-1 RNA动态变化，随访期为9个月。在384份直肠样本中测量了RPV谷浓度。
总共分析了来自90名参与者的597份血浆样本和561份直肠样本。在肌肉注射CAB/RPV期间，14.7%（59/401）的直肠样本（42.2%的参与者）检测到HIV-1 RNA>50（>1.69 log10）拷贝/拭子，在口服ART期间，17.5%（28/160）的直肠样本（29%的参与者）检测到该情况。肌肉注射ART期间可检测到的直肠HIV-1 RNA水平中位数为362（范围为133 - 2216）拷贝/拭子。有无口服导入期的组间直肠脱落频率和数量无差异。未观察到直肠脱落与可检测到的血浆HIV-1 RNA之间存在相关性。直肠RPV浓度中位数为3.07（四分位数1 - 四分位数3，2.83 - 3.35）log10 ng/拭子，比直肠组织的90%最大有效浓度（EC90）高1.6倍，且与直肠HIV-1 RNA水平无关。在多变量Cox回归中，直肠脱落与ART前血浆HIV-1 RNA>5 log10相关，但与CAB/RPV病毒学失败的既定预测因素无关。
在每两个月一次的肌肉注射CAB/RPV治疗期间，直肠HIV-1脱落很常见，口服ART时也会出现。脱落与同时期的血浆HIV-1 RNA和直肠RPV浓度无关，且与ART前病毒载量相关。
