Sabin Caroline A, Wilkins Ed, Murphy Maurice, Fisher Martin, de Ruiter Annemiek, Easterbrook Philippa J, Leen Clifford, Vlahakis Emmanuel, Cane Patricia A, Li Xu, Pillay Deenan
Department of Primary Care and Population Sciences, Royal Free and University College Medical School, London, UK.
Antivir Ther. 2003 Aug;8(4):301-8.
We have undertaken a study of virological responses to amprenavir-containing antiretroviral regimens, during the expanded access programme within the UK. Ninety-five HIV-1-infected patients were included for which virological and immunological follow-up was available for 75, and baseline drug resistance data available for 51. These were highly drug-experienced patients, having previously received a median of nine antiviral drugs, within all available classes. Eighty-eight percent of patients had a virological response to the new regimen, with a median maximal decline of 1.45 log10 copies/ml, and 34% of patients reached <400 copies/ml on treatment. Although 68% of patients with resistance data had protease inhibitor resistance mutations, only 10% patients had key amprenavir resistance mutations, and virological response was predicted by the number of active drugs utilized in the amprenavir-containing regimen, as determined by the baseline genotypic resistance test. Other independent predictors of viral load decline were a higher baseline viral load and fewer previous antiviral drugs. We conclude that amprenavir can contribute to antiviral efficacy in salvage regimens, and that resistance testing may help to optimize its use in this scenario. New formulations of amprenavir, together with boosted regimens, may enhance the activity in the presence of protease inhibitor-resistant virus.
我们在英国的扩大准入项目期间,开展了一项关于含安普那韦抗逆转录病毒治疗方案的病毒学反应的研究。纳入了95例HIV-1感染患者,其中75例有病毒学和免疫学随访数据,51例有基线耐药数据。这些患者均有丰富的用药经验,之前平均接受过9种所有可用类别的抗病毒药物治疗。88%的患者对新方案有病毒学反应,最大下降中位数为1.45 log10拷贝/毫升,34%的患者在治疗时病毒载量降至<400拷贝/毫升。虽然68%有耐药数据的患者存在蛋白酶抑制剂耐药突变,但只有10%的患者有关键的安普那韦耐药突变,并且含安普那韦治疗方案中使用的有效药物数量可预测病毒学反应,这由基线基因型耐药检测确定。病毒载量下降的其他独立预测因素是较高的基线病毒载量和较少的既往抗病毒药物使用史。我们得出结论,安普那韦可在挽救治疗方案中发挥抗病毒疗效,耐药检测可能有助于在这种情况下优化其使用。安普那韦的新剂型以及强化治疗方案,可能会增强在存在蛋白酶抑制剂耐药病毒时的活性。