Patel Atul, Patel Ketan, Patel Niyati, Shah Kinjal, Kumar Ambuj
Infectious Diseases Department, Sterling Hospital, Ahmedabad, 380052, India.
Department of Internal Medicine, Division of Infectious Diseases, USF, Tampa, FL, USA.
J Neurovirol. 2025 Feb;31(1):75-83. doi: 10.1007/s13365-024-01236-5. Epub 2024 Nov 13.
Antiretroviral treatment (ART) effectively suppresses viral loads in both plasma and cerebrospinal fluid (CSF). Patients with discordant plasma and CSF viral loads may experience chronic-progressive or fluctuating neurocognitive dysfunctions. This study examined the incidence of symptomatic CSF viral escape (CSFVE) in patients receiving ART. This retrospective cohort study was conducted between 2000 and 2023. The primary outcome measure was the incidence of symptomatic CSFVE. Nonparametric Mann-Whitney U and Fisher exact/χ 2 tests were applied for continuous and categorical variables, respectively. The cumulative incidence function with Gray's test was used to compare the incidence of CSFVE across the treatment regimens. During the study period, 52 of the 8415 patients were diagnosed with CSFVE. The median duration of HIV diagnosis in patients with CSF VE was 150 (12-288) months, with a median nadir CD4 + T-cell count 96.5 (13-601 cells/L)], and 75% of the patients were on a ritonavir-boosted protease inhibitor (PI/r) regimen. The cumulative incidence of symptomatic CSFVE at a follow-up of 14 years was 1% (95% CI, 0-1%). PI/r (HR 34.73; 95% CI 13.5 to 89.4; p < 0.001) and integrase strand transfer inhibitor (INSTI) (HR 3.42; 95% CI 1.94 to 6.02; p < 0.001) regimens were significantly more likely to be associated with CSFVE than the Non-nucleoside reverse transcriptase inhibitors (NNRTIs) regimens. NNRTIs had the lowest risk of CSFVE compared to the PI/r and INSTI regimens. A rapid and complete recovery is possible with symptomatic CSFVE if it is diagnosed and treated early.
抗逆转录病毒治疗(ART)可有效抑制血浆和脑脊液(CSF)中的病毒载量。血浆和脑脊液病毒载量不一致的患者可能会出现慢性进行性或波动性神经认知功能障碍。本研究调查了接受ART治疗的患者出现有症状脑脊液病毒逃逸(CSFVE)的发生率。这项回顾性队列研究于2000年至2023年期间进行。主要结局指标是有症状CSFVE的发生率。连续变量和分类变量分别采用非参数Mann-Whitney U检验和Fisher精确检验/χ²检验。采用Gray检验的累积发病率函数来比较不同治疗方案中CSFVE的发生率。在研究期间,8415例患者中有52例被诊断为CSFVE。发生CSFVE的患者中,HIV诊断的中位持续时间为150(12 - 288)个月,CD4 + T细胞计数最低点的中位数为96.5(13 - 601个细胞/升),75%的患者采用了利托那韦增强蛋白酶抑制剂(PI/r)方案。随访14年时,有症状CSFVE的累积发生率为1%(95%CI,0 - 1%)。与非核苷类逆转录酶抑制剂(NNRTIs)方案相比,PI/r(HR 34.73;95%CI 13.5至89.4;p < 0.001)和整合酶链转移抑制剂(INSTI)(HR 3.42;95%CI 1.94至6.02;p < 0.001)方案与CSFVE的关联可能性显著更高。与PI/r和INSTI方案相比,NNRTIs发生CSFVE的风险最低。如果有症状的CSFVE能早期诊断并治疗,有可能实现快速完全康复。