Wind-Rotolo Megan, Durand Christine, Cranmer Lisa, Reid Alison, Martinson Neil, Doherty Meg, Jilek Benjamin L, Kagaayi Joseph, Kizza Allan, Pillay Visva, Laeyendecker Oliver, Reynolds Steven J, Eshleman Susan H, Lau Bryan, Ray Stuart C, Siliciano Janet D, Quinn Thomas C, Siliciano Robert F
Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
J Infect Dis. 2009 May 1;199(9):1301-9. doi: 10.1086/597759.
Intrapartum single-dose nevirapine decreases mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) but promotes nevirapine resistance. Although resistant viruses fade to undetectable levels in plasma, they may persist as stably integrated proviruses within the latent reservoir in resting CD4(+) T cells, potentially complicating future treatment.
Blood samples were collected from 60 women from South Africa and Uganda >6 months after they had received single-dose nevirapine. To selectively analyze the stable latent form of HIV-1, resting CD4(+) T cells were isolated and activated in the presence of reverse-transcriptase inhibitors and integrase inhibitors, which allows for the specific isolation of viruses produced by cells with stably integrated proviral DNA. These viruses were then analyzed for nevirapine resistance.
Although only a small number of latently infected cells were present in each blood sample (mean, 162 cells), nevirapine resistance mutations (K103N and G190A) were detected in the latent reservoir of 4 (8%) of 50 evaluable women.
A single dose of nevirapine can establish antiretroviral resistance within the latent reservoir. This results in a potentially lifelong risk of reemergence of nevirapine-resistant virus and highlights the need for strategies to prevent transmission that do not compromise successful future treatment.
产时单剂量奈韦拉平可降低人类免疫缺陷病毒1型（HIV-1）的母婴传播，但会促进奈韦拉平耐药性。尽管耐药病毒在血浆中降至检测不到的水平，但它们可能作为稳定整合的前病毒持续存在于静息CD4(+) T细胞的潜伏库中，这可能会使未来的治疗复杂化。
从南非和乌干达的60名妇女中采集血样，这些妇女在接受单剂量奈韦拉平治疗6个月后。为了选择性分析HIV-1的稳定潜伏形式，分离静息CD4(+) T细胞并在逆转录酶抑制剂和整合酶抑制剂存在的情况下进行激活，这允许特异性分离由具有稳定整合的前病毒DNA的细胞产生的病毒。然后对这些病毒进行奈韦拉平耐药性分析。
尽管每个血样中仅存在少量潜伏感染细胞（平均162个细胞），但在50名可评估妇女中的4名（8%）的潜伏库中检测到奈韦拉平耐药突变（K103N和G190A）。
单剂量奈韦拉平可在潜伏库中产生抗逆转录病毒耐药性。这导致奈韦拉平耐药病毒重新出现的潜在终身风险，并突出了需要采取不影响未来成功治疗的预防传播策略。
