Anton Peter A, Mitsuyasu Ronald T, Deeks Steven G, Scadden David T, Wagner Bridget, Huang Christine, Macken Catherine, Richman Douglas D, Christopherson Cindy, Borellini Flavia, Lazar Richard, Hege Kristen M
University of California, Los Angeles, the San Francisco General Hospital, San Francisco, California, USA.
AIDS. 2003 Jan 3;17(1):53-63. doi: 10.1097/00002030-200301030-00008.
To determine the levels of residual HIV DNA and RNA in blood and gut reservoirs in aviremic patients, assess correlations among compartmental measurements of HIV burden, and evaluate association with clinical parameters.
Cross-sectional analysis of baseline data only, on 40 patients enrolled in phase II study evaluating efficacy of autologous gene-modified CD4+ and CD8+ T cells. All patients were on stable antiretroviral regimen with undetectable plasma HIV RNA (< 50 copies/ml).
Measurements repeatedly performed over 8-12 weeks pre-intervention: blood HIV DNA, analysis of rectal mucosa-associated lymphoid tissue for both HIV RNA and HIV DNA, and quantitative co-culture of HIV from CD8-depleted peripheral blood mononuclear cells (PBMC).
Quantifiable levels of HIV detected in compartments despite undetectable levels of plasma HIV RNA: HIV co-culture of PBMC (88%), blood HIV DNA (95%), rectal biopsy HIV DNA (95%), rectal biopsy HIV RNA (65%). A significant correlation existed among various measures of HIV burden (HIV co-culture, blood HIV DNA, rectal biopsy HIV RNA and DNA) but not between assays and clinical parameters [duration of highly active antiretroviral therapy (HAART), type of HAART]. All assays had comparable or less variability than in plasma viral load assays; HIV co-culture had the highest coefficient of variability whereas the blood HIV DNA assay had the lowest and was considered the most reliable assay.
The data support safety, feasibility and high compliance of quantifying reservoirs of residual HIV in treated subjects with undetectable plasma HIV RNA. Lack of correlation between levels of HIV in residual reservoirs and duration of HAART suggests treatment-mediated viral suppression alone does not lead to reproducible decay in HIV reservoirs.
确定病毒血症患者血液和肠道储存库中残留的HIV DNA和RNA水平，评估HIV负荷各部分测量值之间的相关性，并评估与临床参数的关联。
仅对40名参与评估自体基因修饰CD4+和CD8+ T细胞疗效的II期研究的患者的基线数据进行横断面分析。所有患者均接受稳定的抗逆转录病毒治疗方案，血浆HIV RNA检测不到（<50拷贝/ml）。
在干预前8-12周内重复进行测量：血液HIV DNA、直肠黏膜相关淋巴组织的HIV RNA和HIV DNA分析，以及从CD8细胞耗竭的外周血单核细胞（PBMC）中定量共培养HIV。
尽管血浆HIV RNA水平检测不到，但在各部分仍检测到可量化的HIV水平：PBMC的HIV共培养（88%）、血液HIV DNA（95%）、直肠活检HIV DNA（95%）、直肠活检HIV RNA（65%）。HIV负荷的各种测量值（HIV共培养、血液HIV DNA、直肠活检HIV RNA和DNA）之间存在显著相关性，但检测方法与临床参数[高效抗逆转录病毒治疗（HAART）的持续时间、HAART的类型]之间无显著相关性。所有检测方法的变异性均与血浆病毒载量检测相当或更低；HIV共培养的变异系数最高，而血液HIV DNA检测的变异系数最低，被认为是最可靠的检测方法。
数据支持在血浆HIV RNA检测不到的接受治疗的受试者中量化残留HIV储存库的安全性、可行性和高依从性。残留储存库中HIV水平与HAART持续时间之间缺乏相关性表明，仅治疗介导的病毒抑制不会导致HIV储存库出现可重复的衰减。
