Brindeiro Patrícia A, Brindeiro Rodrigo M, Mortensen Cláudio, Hertogs Kurt, De Vroey Veronique, Rubini Norma P M, Sion Fernando S, De Sá Carlos A M, Machado Deisy M, Succi Regina C M, Tanuri Amilcar
Laboratory of Molecular Virology, Department of Genetics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
J Clin Microbiol. 2002 Dec;40(12):4512-9. doi: 10.1128/JCM.40.12.4512-4519.2002.
The emergence of resistance to antiretroviral drugs is a major obstacle to the successful treatment of human immunodeficiency virus type 1 (HIV-1)-infected patients. In this work, we correlate clinical and virological trends such as viral load (VL) and CD4 counts to genotypic and phenotypic antiretroviral (ARV) resistance profiles of HIV-1 isolates from the B and non-B subtypes found in vertically infected children failing ARV therapy. Plasma samples were collected from 52 vertically HIV-1-infected children failing different ARV therapies. Samples underwent HIV-1 pol sequencing and phenotyping and were clustered into subtypes by phylogenetic analysis. Clinical data from each patient were analyzed together with the resistance (genotypic and phenotypic) data obtained. Thirty-five samples were from subtype B, 10 samples were non-B (subtypes A, C, and F), and 7 were mosaic samples. There was no significant difference concerning treatment data between B and non-B clades. Prevalence of known drug resistance mutations revealed slightly significant differences among B and non-B subtypes: L10I, 21 and 64%, K20R, 13 and 43%, M36I, 34 and 100%, L63P, 76 and 36%, A71V/T, 24 and 0%, and V77I, 32 and 0%, respectively, in the protease (0.0001 </= P </= 0.0886), and D67N, 38 and 8%, K70R, 33 and 0%, R211K, 49 and 85%, and K219Q/E, 31 and 0%, respectively, in the reverse transcriptase (0.0256 </= P </= 0.0704). Significant differences were found only in secondary resistance mutations and did not reflect significant phenotypic variation between clade B and non-B.
对抗逆转录病毒药物产生耐药性是成功治疗人类免疫缺陷病毒1型(HIV-1)感染患者的主要障碍。在本研究中,我们将病毒载量(VL)和CD4细胞计数等临床和病毒学趋势与接受抗逆转录病毒(ARV)治疗失败的垂直感染儿童中发现的B亚型和非B亚型HIV-1分离株的基因型和表型抗逆转录病毒耐药谱进行关联分析。收集了52例接受不同ARV治疗失败的垂直HIV-1感染儿童的血浆样本。样本进行了HIV-1 pol基因测序和表型分析,并通过系统发育分析聚类为不同亚型。将每位患者的临床数据与获得的耐药(基因型和表型)数据一起进行分析。35个样本来自B亚型,10个样本为非B亚型(A、C和F亚型),7个为嵌合样本。B亚型和非B亚型之间的治疗数据无显著差异。已知耐药突变的发生率在B亚型和非B亚型之间显示出轻微的显著差异:蛋白酶中L10I分别为21%和64%、K20R分别为13%和43%、M36I分别为34%和100%、L63P分别为76%和36%、A71V/T分别为24%和0%、V77I分别为32%和0%(0.0001≤P≤0.0886);逆转录酶中D67N分别为38%和8%、K70R分别为33%和0%、R211K分别为49%和85%、K219Q/E分别为31%和0%(0.0256≤P≤0.0704)。仅在次要耐药突变中发现显著差异,并未反映出B亚型和非B亚型之间显著的表型差异。