Pieniazek Danuta, Rayfield Mark, Hu Dale J, Nkengasong John N, Soriano Vincent, Heneine Walid, Zeh Clement, Agwale Simon M, Wambebe Charles, Odama Liliana, Wiktor Stefan Z
HIV and Retrovirology Branch and the Office of the Director, Division of AIDS, STD, and TB Laboratory Research, National Center for Infectious Diseases, Atlanta, Georgia, USA.
AIDS. 2004 Feb 20;18(3):495-502. doi: 10.1097/00002030-200402200-00016.
HIV-1 protease inhibitors (PI) have been used for treating HIV-2-infected persons but little is known about amino acid mutations associated with PI resistance in HIV-2 and whether they are similar to those seen in HIV-1.
To determine the frequency of HIV-1 PI resistance-associated mutations in PI-naive HIV-2-infected individuals.
Using PCR, protease genes were amplified from 76 individuals, directly sequenced, phylogenetically subtyped, and translated into amino acids to analyze PI-associated major and minor mutations.
Of the 76 HIV-2 sequences, 68% belonged to subtype A and 32% to subtype B. All sequences contained at least four codon changes giving substitutions at 10, 30, 32, 36, 46, 47, 71 or 77. The frequency of these mutations was similar in subtype A and B viruses. Two major resistance-conferring mutations, 30N and 46I, were identified in one (1%) and 68 (89%) specimens, respectively. Minor mutations 10V/I, 32I, 36I, 47V, and 71V were predominant (89%-100%), followed by the rare mutation 77I (1%). Of the 76 strains, 89% harbored multiple PI resistance-associated substitutions comprising both the major 46I and minor mutations: 10V/I, 32I, 36I, 46I, 47V, 71V (76%); 10V, 32I, 36I, 46I, 47V (9%); and 10V, 32I, 36I, 46I, 47V 71V, 77I (1.3%), 10V, 32I, 46I, 47V, 71V (1.3%), and 10V, 30N, 32I, 36I, 46I, 47V, 71V (1.3%). The remaining 11% of the sequences had patterns with only minor mutations: 10V, 32I, 36I, 47V, 71V (9%) and 10V, 32I, 36I, 47V (1.3%).
The high frequency of multiple PI-associated substitutions represent natural polymorphisms occurring in HIV-2 strains of subtypes A and B. Phenotypic and clinical studies are needed to determine the relevance of these substitutions.
HIV-1蛋白酶抑制剂（PI）已用于治疗HIV-2感染者，但对于HIV-2中与PI耐药相关的氨基酸突变以及它们是否与HIV-1中的相似，人们了解甚少。
确定初治的HIV-2感染者中与HIV-1 PI耐药相关突变的频率。
使用聚合酶链反应（PCR）从76名个体中扩增蛋白酶基因，直接测序，进行系统发育分型，并翻译成氨基酸以分析与PI相关的主要和次要突变。
在76条HIV-2序列中，68%属于A亚型，32%属于B亚型。所有序列至少包含四个密码子变化，导致在第10、30、32、36、46、47、71或77位发生替换。这些突变在A亚型和B亚型病毒中的频率相似。分别在1份（1%）和68份（89%）标本中鉴定出两种主要的耐药性突变，即30N和46I。次要突变10V/I、32I、36I、47V和71V占主导（89%-100%），其次是罕见突变77I（1%）。在76株病毒中，89%含有多个与PI耐药相关的替换，包括主要的46I和次要突变：10V/I、32I、36I、46I、47V、71V（76%）；10V、32I、36I、46I、47V（9%）；以及10V、32I、36I、46I、47V、71V、77I（1.3%）、10V、32I、46I、47V、71V（1.3%）和10V、30N、32I、36I、46I、47V、71V（1.3%）。其余11%的序列只有次要突变模式：10V、32I、36I、47V、71V（9%）和10V、32I、36I、47V（1.3%）。
多个与PI相关的替换的高频率代表了A亚型和B亚型HIV-2毒株中存在的自然多态性。需要进行表型和临床研究以确定这些替换的相关性。
