Temporary increase in circulating replication-competent latent HIV-infected resting CD4+ T cells after switch to an integrase inhibitor based antiretroviral regimen.
Temporary increase in circulating replication-competent latent HIV-infected resting CD4+ T cells after switch to an integrase inhibitor based antiretroviral regimen.
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改用基于整合酶抑制剂的抗逆转录病毒治疗方案后，循环中具有复制能力的潜伏 HIV 感染静息 CD4 T 细胞暂时增加。
DOI：
10.1101/2023.05.12.23289896
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Anok,Ag
中科院分区：
文献类型：
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作者：
Ferreira,Roux-Cil;Reynolds,StevenJ;Capoferri,AdamA;Baker,Owen;Brown,ErinE;Klock,Ethan;Miller,Jernelle;Lai,Jun;Saraf,Sharada;Kirby,Charles;Lynch,Briana;Hackman,Jada;Gowanlock,SarahN;Tomusange,Stephen;Jamiru,Samiri;Anok,Ag
HIV治愈的主要障碍是潜伏病毒库（LVR）的存在，这在非洲人群中尚未得到充分研究。从2018年到2019年，乌干达在全国范围内推广了由Dolutegravir （DTG）和两种NRTI组成的抗逆转录病毒治疗方案，取代了之前一种NNRTI和同样两种NRTI的方案。方法采用定量病毒生长法检测2015 - 2020年88例抗逆转录病毒（art）抑制的乌干达HIV感染者诱导复制能力LVR （RC-LVR）的变化。检测出的病毒是否进化。使用贝叶斯模型的三个版本来分析RC-LVR的变化，这些模型估计随时间的衰减率为单一的线性速率（模型a），或者允许在DTG开始时发生变化（模型B&C）。模型A估计RC-LVR变化的斜率为不显著的正增加，这是由于RC-LVR在dtg开始后0-12个月出现暂时峰值（p < 0.005）。模型B和C证实了这一点；例如，模型B估计dtg开始前的衰变显著，半衰期为6.9年，dtg开始后RC-LVR的大小增加了~ 1.7倍。在队列中没有病毒失败或持续进化的证据。这些数据表明，从NNRTI到基于dtg的ART的变化与循环RC-LVR的显着暂时增加有关。美国国立卫生研究院资助（资助1-UM1AI164565）；吉利德艾滋病治愈资助项目（90072171）；加拿大卫生研究所（PJT-155990）；和安大略基因组学-加拿大统计科学研究所。
BackgroundThe principal barrier to an HIV cure is the presence of the latent viral reservoir (LVR), which has been understudied in African populations. From 2018 to 2019, Uganda instituted a nationwide rollout of ART consisting of Dolutegravir (DTG) with two NRTI, which replaced the previous regimen of one NNRTI and the same two NRTI.MethodsChanges in the inducible replication-competent LVR (RC-LVR) of ART-suppressed Ugandans with HIV (n = 88) from 2015 to 2020 were examined using the quantitative viral outgrowth assay. Outgrowth viruses were examined for viral evolution. Changes in the RC-LVR were analyzed using three versions of a Bayesian model that estimated the decay rate over time as a single, linear rate (model A), or allowing for a change at time of DTG initiation (model B&C).FindingsModel A estimated the slope of RC-LVR change as a non-significant positive increase, which was due to a temporary spike in the RC-LVR that occurred 0–12 months post-DTG initiation (p < 0.005). This was confirmed with models B and C; for instance, model B estimated a significant decay pre-DTG initiation with a half-life of 6.9 years, and an ∼1.7-fold increase in the size of the RC-LVR post-DTG initiation. There was no evidence of viral failure or consistent evolution in the cohort.InterpretationThese data suggest that the change from NNRTI- to DTG-based ART is associated with a significant temporary increase in the circulating RC-LVR.FundingSupported by the NIH (grant 1-UM1AI164565); Gilead HIV Cure Grants Program (90072171); Canadian Institutes of Health Research (PJT-155990); and Ontario Genomics-Canadian Statistical Sciences Institute.