PDF(Pubmed)
Abstract：
The timing of the establishment of the HIV latent viral reservoir (LVR) is of particular interest, as there is evidence that proviruses are preferentially archived at the time of antiretroviral therapy (ART) initiation. Quantitative viral outgrowth assays (QVOAs) were performed using Peripheral Blood Mononuclear Cells (PBMC) collected from Ugandans living with HIV who were virally suppressed on ART for >1 year, had known seroconversion windows, and at least two archived ART-naïve plasma samples. QVOA outgrowth populations and pre-ART plasma samples were deep sequenced for the pol and gp41 genes. The bayroot program was used to estimate the date that each outgrowth virus was incorporated into the reservoir. Bayroot was also applied to previously published data from a South African cohort. In the Ugandan cohort (n = 11), 87.9 per cent pre-ART and 56.3 per cent viral outgrowth sequences were unique. Integration dates were estimated to be relatively evenly distributed throughout viremia in 9/11 participants. In contrast, sequences from the South African cohort (n = 9) were more commonly estimated to have entered the LVR close to ART initiation, as previously reported. Timing of LVR establishment is variable between populations and potentially viral subtypes, which could limit the effectiveness of interventions that target the LVR only at ART initiation.
摘要：
建立HIV潜伏病毒库（LVR）的时机特别令人感兴趣，因为有证据表明，在开始抗逆转录病毒治疗（ART）时优先存档。定量病毒生长测定（QVOAs）是使用从感染HIV的乌干达人收集的外周血单核细胞（PBMC）进行的，这些人在ART中受到病毒抑制>1年，有已知的血清转换窗口，和至少两个存档的ART-初始血浆样品。QVOA生长种群和ART前血浆样品对pol和gp41基因进行了深度测序。Bayroot程序用于估计每种生长病毒掺入水库的日期。Bayroot也应用于南非队列先前发表的数据。在乌干达队列中（n=11），87.9%的ART前和56.3%的病毒生长序列是独特的。估计整合日期在9/11参与者的病毒血症中分布相对均匀。相比之下,来自南非队列（n=9）的序列更常见的估计是在ART开始时进入LVR，如先前报道。LVR建立的时间在人群和潜在的病毒亚型之间是可变的，这可能会限制仅在ART开始时针对LVR的干预措施的有效性。
