Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
AIDS. 2012 Jul 31;26(12):1483-90. doi: 10.1097/QAD.0b013e3283553638.
Identification of HIV infection in exposed infants facilitates early therapy, which may limit viral reservoirs that maintain HIV infection under HAART.
The dynamics of the resting CD4 T-cell latent HIV reservoir was determined over the first 2 years of life in 17 HIV-infected infants initiating lopinavir/ritonavir-based HAART at a median age of 8.1 weeks and achieving adequate suppression of plasma viral load by 24 weeks.
The resting CD4 T-cell latent HIV reservoir was detected in 12 of 14 (86%) infants tested at 24 weeks of HAART [median frequency 1.88 infectious units per million (IUPM); range <0.22 to 81.7), and remained measurable (median IUPM = 0.32; range <0.22 to 3.25) in six of 10 (60%) children retested at 96 weeks. The reservoir declined, from 24 to 96 weeks of HAART, at an estimated mean rate of 0.028 log10 IUPM/month, corresponding to a half-life of 11 months (95% confidence interval 6-30 months]. A strong relationship was found between the frequency of latently infected CD4 T cells at 96 weeks of HAART and time to first undetectable plasma viral load (Spearman r = 0.91, P < 0.001).
Although the resting CD4 T-cell latent reservoir remains detectable over the first 2 years of HAART in a substantial proportion of infants, its size is associated with time to first undetectable viral load. To minimize HIV reservoirs in infants, rapid curtailment of viremia may limit HIV reservoirs and should be a therapeutic goal of early HAART in infants.
鉴定暴露婴儿中的 HIV 感染有助于早期治疗,这可能会限制 HIV 感染在高效抗逆转录病毒治疗(HAART)下维持的病毒库。
17 名感染 HIV 的婴儿在 8.1 周的中位年龄开始接受洛匹那韦/利托那韦为基础的 HAART,并在 24 周时实现了足够的血浆病毒载量抑制,我们在这些婴儿生命的头 2 年内确定了静息 CD4 T 细胞潜伏 HIV 库的动态。
在接受 HAART 24 周时,对 14 名婴儿中的 12 名(86%)进行了检测,结果检测到静息 CD4 T 细胞潜伏 HIV 库[中位数频率为每百万个 CD4 T 细胞中有 1.88 个感染性单位(IUPM);范围为<0.22 至 81.7],在接受 96 周复查的 10 名婴儿中的 6 名(60%)中仍可测量(中位数 IUPM=0.32;范围为<0.22 至 3.25)。从 24 周到 96 周的 HAART,库的下降速度估计为平均每月 0.028 log10 IUPM,半衰期为 11 个月(95%置信区间为 6-30 个月)。在 HAART 96 周时,潜伏感染的 CD4 T 细胞频率与首次不可检测的血浆病毒载量之间存在很强的关系(Spearman r=0.91,P<0.001)。
尽管在相当一部分婴儿中,静息 CD4 T 细胞潜伏库在 HAART 的头 2 年内仍可检测到,但它的大小与首次不可检测的病毒载量之间存在关联。为了使婴儿的 HIV 库最小化,迅速减少病毒血症可能会限制 HIV 库,这应该成为婴儿早期 HAART 的治疗目标。