HIV-1亚型和抗逆转录病毒疗法对蛋白酶和逆转录酶基因型的影响：一项全球合作的结果

Impact of HIV-1 subtype and antiretroviral therapy on protease and reverse transcriptase genotype: results of a global collaboration.

作者信息

Kantor Rami, Katzenstein David A, Efron Brad, Carvalho Ana Patricia, Wynhoven Brian, Cane Patricia, Clarke John, Sirivichayakul Sunee, Soares Marcelo A, Snoeck Joke, Pillay Candice, Rudich Hagit, Rodrigues Rosangela, Holguin Africa, Ariyoshi Koya, Bouzas Maria Belen, Cahn Pedro, Sugiura Wataru, Soriano Vincent, Brigido Luis F, Grossman Zehava, Morris Lynn, Vandamme Anne-Mieke, Tanuri Amilcar, Phanuphak Praphan, Weber Jonathan N, Pillay Deenan, Harrigan P Richard, Camacho Ricardo, Schapiro Jonathan M, Shafer Robert W

机构信息

Division of Infectious Disease and Center for AIDS Research, Stanford University, Stanford, California, USA.

出版信息

PLoS Med. 2005 Apr;2(4):e112. doi: 10.1371/journal.pmed.0020112. Epub 2005 Apr 26.

BACKGROUND

The genetic differences among HIV-1 subtypes may be critical to clinical management and drug resistance surveillance as antiretroviral treatment is expanded to regions of the world where diverse non-subtype-B viruses predominate.

METHODS AND FINDINGS

To assess the impact of HIV-1 subtype and antiretroviral treatment on the distribution of mutations in protease and reverse transcriptase, a binomial response model using subtype and treatment as explanatory variables was used to analyze a large compiled dataset of non-subtype-B HIV-1 sequences. Non-subtype-B sequences from 3,686 persons with well characterized antiretroviral treatment histories were analyzed in comparison to subtype B sequences from 4,769 persons. The non-subtype-B sequences included 461 with subtype A, 1,185 with C, 331 with D, 245 with F, 293 with G, 513 with CRF01_AE, and 618 with CRF02_AG. Each of the 55 known subtype B drug-resistance mutations occurred in at least one non-B isolate, and 44 (80%) of these mutations were significantly associated with antiretroviral treatment in at least one non-B subtype. Conversely, of 67 mutations found to be associated with antiretroviral therapy in at least one non-B subtype, 61 were also associated with antiretroviral therapy in subtype B isolates.

CONCLUSION

Global surveillance and genotypic assessment of drug resistance should focus primarily on the known subtype B drug-resistance mutations.

背景

随着抗逆转录病毒治疗扩展到世界上以多种非B亚型病毒为主的地区，HIV-1亚型之间的基因差异对于临床管理和耐药性监测可能至关重要。

方法与结果

为评估HIV-1亚型和抗逆转录病毒治疗对蛋白酶和逆转录酶突变分布的影响，使用以亚型和治疗为解释变量的二项反应模型分析了一个大量汇编的非B亚型HIV-1序列数据集。将3686名有明确抗逆转录病毒治疗史的人的非B亚型序列与4769名患者的B亚型序列进行了比较分析。非B亚型序列包括461例A亚型、1185例C亚型、331例D亚型、245例F亚型、293例G亚型、513例CRF01_AE亚型和618例CRF02_AG亚型。55种已知的B亚型耐药突变中的每一种都至少在一个非B亚型分离株中出现，其中44种（80%）突变在至少一种非B亚型中与抗逆转录病毒治疗显著相关。相反，在至少一种非B亚型中发现与抗逆转录病毒治疗相关的67种突变中，有61种在B亚型分离株中也与抗逆转录病毒治疗相关。