Hatano Hiroyu, Delwart Eric L, Norris Philip J, Lee Tzong-Hae, Dunn-Williams Joan, Hunt Peter W, Hoh Rebecca, Stramer Susan L, Linnen Jeffrey M, McCune Joseph M, Martin Jeffrey N, Busch Michael P, Deeks Steven G
San Francisco General Hospital, Building 80, Ward 84, 995 Potrero Avenue, San Francisco, CA 94110, USA.
J Virol. 2009 Jan;83(1):329-35. doi: 10.1128/JVI.01763-08. Epub 2008 Oct 22.
A subset of antiretroviral-untreated, human immunodeficiency virus (HIV)-infected individuals are able to maintain undetectable plasma HIV RNA levels in the absence of antiretroviral therapy. These "elite" controllers are of high interest as they may provide novel insights regarding host mechanisms of virus control. The degree to which these individuals have residual plasma viremia has not been well defined. We performed a longitudinal study of 46 elite controllers, defined as HIV-seropositive, antiretroviral-untreated individuals with plasma HIV RNA levels of <50 to 75 copies/ml. The median duration of HIV diagnosis was 13 years, the median baseline CD4(+) T-cell count was 753 cells/mm(3), and the median duration of follow-up was 16 months. Plasma and cellular HIV RNA levels were measured using the transcription-mediated amplification (TMA) assay (estimated limit of detection of <3.5 copies RNA/ml). A total of 1,117 TMA assays were performed (median of five time points/subject and four replicates/time point). All but one subject had detectable plasma HIV RNA on at least one time point, and 15 (33%) subjects had detectable RNA at all time points. The majority of controllers also had detectable cell-associated RNA and proviral DNA. A mixed-effect linear model showed no strong evidence of change in plasma RNA levels over time. In conclusion, the vast majority (98%) of elite controllers had measurable plasma HIV RNA, often at levels higher than that observed in antiretroviral-treated patients. This confirms the failure to eradicate the virus, even in these unique individuals who are able to reduce plasma viremia to very low levels without antiretroviral therapy.
在未接受抗逆转录病毒治疗的情况下，有一部分感染人类免疫缺陷病毒（HIV）的个体能够维持血浆HIV RNA水平检测不到。这些“精英”控制者备受关注，因为他们可能为病毒控制的宿主机制提供新的见解。这些个体残留血浆病毒血症的程度尚未明确界定。我们对46名精英控制者进行了一项纵向研究，这些精英控制者定义为HIV血清学阳性、未接受抗逆转录病毒治疗且血浆HIV RNA水平<50至75拷贝/毫升的个体。HIV诊断的中位持续时间为13年，基线CD4(+) T细胞计数的中位数为753个细胞/立方毫米，随访的中位持续时间为16个月。使用转录介导扩增（TMA）检测法测量血浆和细胞HIV RNA水平（估计检测下限<3.5拷贝RNA/毫升）。总共进行了1117次TMA检测（每位受试者中位数为5个时间点，每个时间点4次重复检测）。除一名受试者外，所有受试者至少在一个时间点检测到血浆HIV RNA，15名（33%）受试者在所有时间点均检测到RNA。大多数控制者还检测到细胞相关RNA和前病毒DNA。混合效应线性模型显示没有强有力的证据表明血浆RNA水平随时间变化。总之，绝大多数（98%）精英控制者血浆HIV RNA可测量，其水平通常高于接受抗逆转录病毒治疗患者中观察到的水平。这证实即使在这些无需抗逆转录病毒治疗就能将血浆病毒血症降至极低水平的独特个体中，也未能根除病毒。
