Puerta de Hierro University Hospital, Majadahonda, Madrid, Spain.
Hospital de Poniente, Almería, Spain.
J Antimicrob Chemother. 2017 Jul 1;72(7):2083-2088. doi: 10.1093/jac/dkx090.
A broader extent of amino acid substitutions in the integrase of HIV-2 compared with HIV-1 might enable greater cross-resistance between raltegravir and dolutegravir in HIV-2 infection. Few studies have examined the virological response to dolutegravir in HIV-2 patients that failed raltegravir.
All patients recorded in the HIV-2 Spanish cohort were examined. The integrase coding region was sequenced in viraemic patients. Changes associated with resistance to raltegravir and dolutegravir in HIV-1 were recorded.
From 319 HIV-2-infected patients recorded in the HIV-2 Spanish cohort, 53 integrase sequences from 30 individuals were obtained (20 raltegravir naive and 10 raltegravir experienced). Only one secondary mutation (E138A) was found in one of the 20 raltegravir-naive HIV-2 patients. For raltegravir-experienced individuals, the resistance mutation profile in 9 of 10 viraemic patients was as follows: N155H + A153G/S (four); Y143G + A153S (two); Q148R + G140A/S (two); and Y143C + Q91R (one). Of note, all patients with Y143G and N155H developed a rare non-polymorphic mutation at codon 153. Rescue therapy with dolutegravir was given to 5 of these 10 patients. After >6 months on dolutegravir therapy, three patients with baseline N155H experienced viral rebound. In two of them N155H was replaced by Q148K/R and in another by G118R.
A wide repertoire of resistance mutations in the integrase gene occur in HIV-2-infected patients failing on raltegravir. Although dolutegravir may allow successful rescue in most HIV-2 raltegravir failures, we report and characterize three cases of dolutegravir resistance in HIV-2 patients, emerging variants Q148K and Q148R and a novel change G118R.
与 HIV-1 相比，HIV-2 整合酶的氨基酸取代范围更广，这可能使 HIV-2 感染中拉替拉韦和多替拉韦之间的交叉耐药性更大。很少有研究检查过拉替拉韦失败的 HIV-2 患者对多替拉韦的病毒学反应。
检查了记录在 HIV-2 西班牙队列中的所有患者。对病毒血症患者进行了整合酶编码区测序。记录了与 HIV-1 中拉替拉韦和多替拉韦耐药相关的变化。
从记录在 HIV-2 西班牙队列中的 319 名 HIV-2 感染患者中，获得了 30 名个体的 53 个整合酶序列（20 名拉替拉韦初治和 10 名拉替拉韦经验）。在 20 名拉替拉韦初治的 HIV-2 患者中，仅在一名患者中发现了一个次要突变（E138A）。对于拉替拉韦经验丰富的个体，10 名病毒血症患者的耐药突变谱如下：N155H+A153G/S（4 例）；Y143G+A153S（2 例）；Q148R+G140A/S（2 例）；Y143C+Q91R（1 例）。值得注意的是，所有 Y143G 和 N155H 患者均在密码子 153 处发生罕见的非多态性突变。对这 10 名患者中的 5 名给予了多替拉韦挽救治疗。在多替拉韦治疗 >6 个月后，基线时 N155H 的 3 名患者出现病毒反弹。其中 2 名患者的 N155H 被 Q148K/R 取代，另一名患者的 N155H 被 G118R 取代。
拉替拉韦耐药的 HIV-2 感染患者中整合酶基因发生了广泛的耐药突变。尽管多替拉韦可能允许大多数 HIV-2 拉替拉韦失败的患者成功挽救，但我们报告并描述了 3 例 HIV-2 患者的多替拉韦耐药情况，出现了 Q148K 和 Q148R 变体以及新的 G118R 变化。
