Institut Pasteur du Cambodge, Laboratoire VIH/Hepatites, Phnom Penh, Cambodia.
Infect Genet Evol. 2011 Jan;11(1):38-43. doi: 10.1016/j.meegid.2010.10.014. Epub 2010 Nov 19.
The HIV integrase enzyme is essential for the HIV life cycle as it mediates integration of HIV-1 proviral DNA into the infected cell's genome. Recently, the development of drugs capable of inhibiting integrase has provided major new options for HIV-infected, treatment-experienced patients with multidrug resistant virus, as well treatment-naïve patients. More than 40 amino acid substitutions within integrase have been described as associated mostly with resistance of HIV B-subtypes to currently available integrase inhibitors (INIs). We have analyzed the natural polymorphisms of the integrase coding region in 87 antiretroviral-naïve subjects (32 from Cambodia, 37 from Thailand and 18 from Vietnam) infected with CRF01_AE virus, the predominant HIV-1 strain circulating in Southeast Asia. The 864bp integrase coding region was sequenced using the ANRS consensus sequencing technique from plasma samples, and amino acid results were interpreted for drug resistance according to the ANRS (Updated July 2009, version 18) and Stanford algorithms (Version November 6, 2009). Alignment of the 87 amino acid sequences against the 2004 Los Alamos HIV-1 clade B consensus sequence showed that overall, 119 of 288 (41.3%) amino acid positions presented at least one polymorphism each. Substitutions found in >60% of study subjects occurred at: K14, A21, V31, S39, I72, T112, T124, T125, G134, I135, K136, D167, V201, L234 and S283. Also, new amino acid substitutions of as yet unknown significance were identified: E152K/H, S153F/L, N155I and E157G. None of the known integrase resistance mutations were observed, except E157Q found in one Cambodian subject (1.1%, CI 95% 0.02-6.3%). The clinical impact of this substitution on resistance of B and nonB-viruses to the licensed INI raltegravir is unclear. If this substitution is confirmed to compromise the virologic response to raltegravir, further studies will be needed to better assess the prevalence of this substitution among CRF01_AE virus.
HIV 整合酶是 HIV 生命周期所必需的，因为它介导 HIV-1 前病毒 DNA 整合到受感染细胞的基因组中。最近，能够抑制整合酶的药物的发展为感染 HIV、有多重耐药病毒的治疗经验丰富的患者以及未经治疗的患者提供了新的选择。已经描述了整合酶内 40 多个氨基酸取代，这些取代主要与 HIV B 亚型对现有整合酶抑制剂 (INIs) 的耐药性有关。我们分析了 87 名抗逆转录病毒治疗初治患者（32 名来自柬埔寨，37 名来自泰国，18 名来自越南）的整合酶编码区的天然多态性，这些患者感染了 CRF01_AE 病毒，这是东南亚流行的主要 HIV-1 株。使用 ANRS 共识测序技术从血浆样本中对 864bp 的整合酶编码区进行测序，并根据 ANRS（2009 年 7 月更新，第 18 版）和斯坦福算法（2009 年 11 月 6 日版）对药物耐药性进行解释。将 87 个氨基酸序列与 2004 年 Los Alamos HIV-1 组 B 共识序列进行比对，结果显示，288 个氨基酸位置中，总体上有 119 个（41.3%）位置每个位置至少存在一个多态性。在研究对象中出现>60%的取代发生在：K14、A21、V31、S39、I72、T112、T124、T125、G134、I135、K136、D167、V201、L234 和 S283。此外，还鉴定了新的氨基酸取代，其意义尚不清楚：E152K/H、S153F/L、N155I 和 E157G。除了在一名柬埔寨患者中发现的 E157Q（1.1%，95%CI 0.02-6.3%）外，未观察到已知的整合酶耐药突变。E157Q 对 B 型和非 B 型病毒对许可的 INI raltegravir 的耐药性的临床影响尚不清楚。如果该取代被证实会影响 raltegravir 的病毒学反应，需要进一步研究以更好地评估 CRF01_AE 病毒中该取代的流行率。
