Chiappini Elena, Galli Luisa, Zazzi Maurizio, de Martino Maurizio
Division of Paediatrics and Infectious Diseases, Department of Paediatrics, University of Florence, Florence, Italy.
J Med Virol. 2003 Aug;70(4):506-12. doi: 10.1002/jmv.10424.
Relationships between human immunodeficiency virus-type-1 (HIV-1) drug-resistant mutants and immunological recovery were investigated after 12-week antiretroviral therapy in 43 children infected perinatally with virological failure. Twenty-two children received highly active antiretroviral therapy (HAART) and 21 received double therapy with reverse transcriptase inhibitors. At baseline, no difference in reverse transcriptase or protease inhibitors resistant mutants was present among the groups. After 12 weeks, the two groups were similar regarding proportion of children with reverse transcriptase resistant mutants. Sixteen (73%) HAART-treated children, but no child receiving double therapy had HIV-1 with primary resistance mutations to protease inhibitors. Secondary protease mutations were found in all HAART-treated and in 17/21 (81%) children receiving double therapy. The mutation numbers in reverse transcriptase or protease genes were significantly higher after HAART than after double therapy. Nevertheless, 12 (55%) of HAART-treated children (but no child receiving double therapy) showed immunological recovery. The frequency and number of mutations were similar in HAART-treated children with or without immunological recovery both at baseline and after 12 weeks. The findings suggest, immunological recovery notwithstanding, virological failure is independent of drug-resistant mutations and consequent possible changes in viral fitness.
对43例围产期感染且病毒学治疗失败的儿童进行12周抗逆转录病毒治疗后,研究了人类免疫缺陷病毒1型(HIV-1)耐药突变体与免疫恢复之间的关系。22名儿童接受了高效抗逆转录病毒治疗(HAART),21名儿童接受了逆转录酶抑制剂双重治疗。基线时,各组之间逆转录酶或蛋白酶抑制剂耐药突变体无差异。12周后,两组中具有逆转录酶耐药突变体的儿童比例相似。16名(73%)接受HAART治疗的儿童,但接受双重治疗的儿童中没有发现对蛋白酶抑制剂具有原发性耐药突变的HIV-1。在所有接受HAART治疗的儿童以及17/21名(81%)接受双重治疗的儿童中均发现了继发性蛋白酶突变。HAART治疗后逆转录酶或蛋白酶基因中的突变数量显著高于双重治疗后。然而,12名(55%)接受HAART治疗的儿童(但接受双重治疗的儿童中没有)出现了免疫恢复。在基线和12周后,有或没有免疫恢复的接受HAART治疗的儿童中,突变的频率和数量相似。研究结果表明,尽管有免疫恢复,但病毒学治疗失败与耐药突变以及随之而来的病毒适应性可能变化无关。