Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Inserm UMR-S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Université Pierre et Marie Curie, Paris, France.
J Antimicrob Chemother. 2017 Oct 1;72(10):2862-2868. doi: 10.1093/jac/dkx247.
The natural clinical and immunological courses following HIV seroconversion with CXCR4-tropic or dual-mixed (X4/DM) viruses are controversial. We compared spontaneous immunological outcome in patients harbouring an X4/DM virus at the time of seroconversion with those harbouring a CCR5-tropic (R5) virus.
Data were included from patients participating in CASCADE, a large cohort collaboration of HIV seroconverters, with ≥2 years of follow-up since seroconversion. The HIV envelope gene was sequenced from frozen plasma samples collected at enrolment, and HIV tropism was determined using Geno2Pheno (false-positive rate 10%). The spontaneous CD4 T cell evolution was compared by modelling CD4 kinetics using linear mixed-effects models with random intercept and random slope.
A total of 1387 patients were eligible. Median time between seroconversion and enrolment was 1 month (range 0-3). At enrolment, 202 of 1387 (15%) harboured an X4/DM-tropic virus. CD4 decrease slopes were not significantly different according to HIV-1 tropism during the first 30 months after seroconversion. No marked change in these results was found after adjusting for age, year of seroconversion and baseline HIV viral load. Time to antiretroviral treatment initiation was not statistically different between patients harbouring an R5 (20.76 months) and those harbouring an X4/DM-tropic virus (22.86 months, logrank test P = 0.32). Conclusions: In this large cohort collaboration, 15% of the patients harboured an X4/DM virus close to HIV seroconversion. Patients harbouring X4/DM-tropic viruses close to seroconversion did not have an increased risk of disease progression, estimated by the decline in CD4 T cell count or time to combined ART initiation.
HIV 血清转换后，伴随 CXCR4 嗜性或双重混合（X4/DM）病毒的自然临床和免疫过程存在争议。我们比较了在血清转换时携带 X4/DM 病毒的患者与携带 CCR5 嗜性（R5）病毒的患者的自发免疫结果。
数据来自参与大型队列合作的 HIV 血清转换者 CASCADE 中的患者，自血清转换以来，随访时间至少为 2 年。从纳入时采集的冷冻血浆样本中对 HIV 包膜基因进行测序，并使用 Geno2Pheno 确定 HIV 嗜性（假阳性率为 10%）。通过使用具有随机截距和随机斜率的线性混合效应模型对 CD4 动力学进行建模，比较自发 CD4 T 细胞的演变。
共纳入 1387 例患者。血清转换和纳入之间的中位时间为 1 个月（范围 0-3）。在纳入时，1387 例中有 202 例（15%）携带 X4/DM 嗜性病毒。在血清转换后 30 个月内，根据 HIV-1 嗜性，CD4 下降斜率没有显著差异。调整年龄、血清转换年份和基线 HIV 病毒载量后，这些结果没有明显变化。开始抗逆转录病毒治疗的时间在携带 R5 病毒（20.76 个月）和携带 X4/DM 嗜性病毒的患者之间没有统计学差异（22.86 个月，对数秩检验 P=0.32）。
在这项大型队列合作中，15%的患者在接近 HIV 血清转换时携带 X4/DM 病毒。在血清转换时携带 X4/DM 嗜性病毒的患者，通过 CD4 T 细胞计数下降或联合 ART 开始时间来估计，没有增加疾病进展的风险。
