van der Ende M E, Guillon C, Boers P H, Ly T D, Gruters R A, Osterhaus A D, Schutten M
Department of Internal Medicine, University Hospital Centre Rotterdam, Rotterdam, The Netherlands.
J Acquir Immune Defic Syndr. 2000 Sep 1;25(1):11-8. doi: 10.1097/00042560-200009010-00002.
To study phenotypic and genotypic resistance of HIV-2 against nucleoside reverse transcriptase inhibitors (NRTI).
Biologic HIV-2 clones were generated from 3 patients before and after initiation of antiretroviral therapy with zidovudine (AZT) in patient RH2-7, AZT and didanosine (ddI) in patient PH2-1, and after addition of lamivudine (3TC) to AZT monotherapy in patient RH2-5. The sensitivity to NRTI of the virus clones, as defined by the 50% inhibitory concentration (IC(50)), was determined in vitro. The predicted amino acid sequences of the reverse transcriptase proteins from these clones were determined.
Comparing the sensitivity of the biologic HIV-2 clones obtained after start of therapy with those from antiviral naive patients, resistance had developed to AZT (patients RH2-7 and RH2-5) and 3TC (patient PH2-1 and RH2-5). No resistance to AZT was observed in the biologic clone from PH2-1 obtained after start of therapy. The resistant clones from RH2-5 and PH2-1, but not RH2-7, contained amino acid mutations at positions where HIV-1 has been shown to mutate after AZT and 3TC treatment.
Phenotypic resistance of HIV-2 to nucleoside analogues, which developed in HIV-2-infected patients treated with NRTIs, was associated with genotypic changes. Some of the mutations at amino acid positions in the HIV-2 reverse transcriptase gene corresponded with those involved in HIV-1 resistance, although no conventional mutations associated with resistance to AZT were observed.
研究HIV - 2对核苷类逆转录酶抑制剂（NRTI）的表型和基因型耐药性。
从3例患者中产生生物HIV - 2克隆。在患者RH2 - 7中，在开始使用齐多夫定（AZT）抗逆转录病毒治疗之前和之后；在患者PH2 - 1中，在开始使用AZT和去羟肌苷（ddI）抗逆转录病毒治疗之前和之后；在患者RH2 - 5中，在AZT单药治疗基础上加用拉米夫定（3TC）之前和之后。通过体外测定病毒克隆对NRTI的敏感性（以50%抑制浓度（IC(50)）定义）。确定这些克隆的逆转录酶蛋白的预测氨基酸序列。
将治疗开始后获得的生物HIV - 2克隆与抗病毒初治患者的克隆的敏感性进行比较，发现对AZT（患者RH2 - 7和RH2 - 5）和3TC（患者PH2 - 1和RH2 - 5）产生了耐药性。在治疗开始后从PH2 - 1获得的生物克隆中未观察到对AZT的耐药性。来自RH2 - 5和PH2 - 1的耐药克隆，但不是RH2 - 7，在HIV - 1经AZT和3TC治疗后已显示发生突变的位置含有氨基酸突变。
在接受NRTIs治疗的HIV - 2感染患者中出现的HIV - 2对核苷类似物的表型耐药性与基因型变化有关。HIV - 2逆转录酶基因中一些氨基酸位置的突变与HIV - 1耐药相关的突变相对应，尽管未观察到与AZT耐药相关的传统突变。
