Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
J Infect Dis. 2022 Sep 21;226(6):1057-1068. doi: 10.1093/infdis/jiac100.
HIV-1 replication capacity (RC) of transmitted/founder viruses may influence the further course of HIV-1 infection.
RCs of 355 whole-genome primary HIV-1 isolates derived from samples acquired during acute and recent primary HIV-1 infection (PHI) were determined using a novel high-throughput infection assay in primary cells. The RCs were used to elucidate potential factors that could be associated with RC during PHI.
Increased RC was found to be associated with increased set point viral load (VL), and significant differences in RCs among 13 different HIV-1 subtypes were discerned. Notably, we observed an increase in RCs for primary HIV-1 isolates of HIV-1 subtype B over a 17-year period. Associations were not observed between RC and CD4 count at sample date of RC measurement, CD4 recovery after initiation of antiretroviral treatment, CD4 decline in untreated individuals, and acute retroviral syndrome severity scores.
These findings highlight that RCs of primary HIV-1 isolates acquired during the acute and recent phase of infection are more associated with viral factors, that is set point VL, than with host factors. Furthermore, we observed a temporal increase in RC for HIV-1 subtype B viruses over a period of 17 years.
NCT00537966.
传播/原始病毒的 HIV-1 复制能力(RC)可能影响 HIV-1 感染的进一步进程。
使用新型高通量原发性细胞感染测定法,测定了 355 株源于急性和近期原发性 HIV-1 感染(PHI)样本的原发性 HIV-1 全基因组分离物的 RC。利用 RC 来阐明与 PHI 期间 RC 相关的潜在因素。
发现 RC 增加与设定点病毒载量(VL)增加有关,并且在 13 种不同的 HIV-1 亚型之间也可以辨别出 RC 的显著差异。值得注意的是,我们观察到 HIV-1 亚型 B 的原发性 HIV-1 分离物的 RC 在 17 年内有所增加。在 RC 测量样本日期时,RC 与 CD4 计数、抗逆转录病毒治疗开始后 CD4 恢复、未治疗个体的 CD4 下降以及急性逆转录病毒综合征严重程度评分之间未观察到相关性。
这些发现强调了在感染的急性和近期阶段获得的原发性 HIV-1 分离物的 RC 更与病毒因素(即设定点 VL)相关,而与宿主因素无关。此外,我们观察到在 17 年的时间内 HIV-1 亚型 B 病毒的 RC 呈时间性增加。
NCT00537966。