Occurrence of HIV-1 reverse transcriptase gene mutation at codon 215 in HIV-infected infants
Occurrence of HIV-1 reverse transcriptase gene mutation at codon 215 in HIV-infected infants
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DOI：
10.1016/s1386-6532(01)00178-0
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发表时间：
2001-08-01
影响因子：
8.8
通讯作者：
Charbonneau, T
中科院分区：
文献类型：
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作者：
Kamkamidze, G;Sullivan, T;Charbonneau, T
背景：核苷类逆转录酶抑制剂齐多夫定（ZDV）降低母婴传播HIV感染。然而，在怀孕期间接受ZDV治疗的母亲中，仍有相当大比例传播病毒。与其他因素一起，ZDV预防失败可能是由于母体感染ZDV耐药菌株及其随后的垂直传播。目的：本研究的目的是调查HIV-1感染婴儿密码子215突变的发生及其与临床状态和病毒学参数的关系。研究设计：该队列由49名HIV-1感染婴儿组成。从全血中分离出单个核细胞DNA，作为定性DNA PCR和密码子215测定（巢式PCR）的输入DNA。采用Roche Amplicor (TM) Monitor检测血浆中HIV-1病毒载量（RNA PCR）。结果：49株病毒中有12株（24.5%）存在密码子215突变。1992年至1994年出生的婴儿（6.3%）与1998年至1999年出生的婴儿（33.3%）相比有显著差异。此外，在1998-1999年出生的婴儿中，在密码子215处的齐多夫定耐药突变的频率有增加的趋势，这与母体齐多夫定治疗的增加相对应。14名低病毒载量（< 750,000 c/ml）婴儿中有2名（14.3%）检测到野生型和突变型HIV-1毒株的混合物，而19名HIV-1 RNA浓度极高的婴儿中有9名（47.4%）检测到HIV-1 RNA浓度（750,000 c/ml）。在33名接受检测的婴儿中，只有两名出现了HIV症状，而且在这两名婴儿中都检测到了野生型和突变型HIV- 1病毒株的混合物。在这两个婴儿中，病毒载量为750000c /ml。结论：本研究表明，1998-1999年出生的婴儿中ZDV耐药菌株的总体频率明显高于1992 - 1994年出生的婴儿样本。到1998年，已知感染艾滋病毒的母亲的护理标准是使用ZDV的单一疗法或使用包括ZDV在内的各种抗逆转录病毒药物的联合疗法。虽然ZDV耐药在限制旨在阻断艾滋病毒垂直传播的治疗有效性方面的确切作用仍有待确定，但很明显，艾滋病毒耐药菌株在包括婴儿在内的所有类型的艾滋病毒感染中发生的频率更高。(C) 2001 Elsevier Science B.V.版权所有
Background: The nucleoside reverse transcriptase inhibitor Zidovudine (ZDV) decreases mother to child transmission of HIV infection. Nevertheless, significant proportions of mothers who are treated during pregnancy with ZDV still transmit the virus. Along with other factors, failure of ZDV prophylaxis may be due to maternal infection with ZDV-resistant strains and their consequent vertical transmission. Objectives: The purpose of the study was to investigate the occurrence of mutations at codon 215 in HIV-1 infected infants and its association with clinical status and virological parameters. Study design: The cohort consisted of 49 HIV-1 infected infants. Mononuclear cell DNA was isolated from whole blood and served as the input DNA for both a qualitative DNA PCR and the codon 215 assay (nested PCR). HIV-1 viral load (RNA PCR) was measured in plasma by the Roche Amplicor (TM) Monitor assay. Results: Twelve of the 49 (24.5%) demonstrated viral strains with mutation at codon 215. A significant difference was found in infants born between 1992 and 1994 (6.3%) compared to those born in 1998-1999 (33.3%). Furthermore, in those infants born in 1998-1999, there was a trend toward an increase in the frequency of zidovudine resistant mutations at codon 215 corresponding to an increase in maternal zidovudine treatment. The mixture of wild and mutant HIV-1 strains was detected in two of 14 infants (14.3%) with a low viral load ( < 750 000 c/ml) compared to nine of 19 (47.4%) infants with extremely high levels of HIV-1 RNA concentration ( > 750 000 c/ml). Only two of 33 tested infants were HIV symptomatic and in both, a mixture of wild and mutant HIV-I strains was detected. In both infants, the viral load was > 750000 c/ml. Conclusions: This study showed that the overall frequency of ZDV resistant strains in infants born in 1998-1999 was significantly higher than that found in infant samples from 1992 to 1994. By 1998, the standard of care for mothers known to be infected with HIV was treatment with either monotherapy using ZDV or combined therapy using a variety of antiretroviral agents including ZDV. Although the exact role of ZDV resistance in limiting the effectiveness of therapies aimed at blocking vertical transmission of HIV remains to be defined, it is clear that drug resistant strains of HIV are occurring more frequently in all types of HIV infection, including infants. (C) 2001 Elsevier Science B.V. All rights reserved.