Noble S, Goa K L
Adis International Limited, Mairangi Bay, Auckland, New Zealand.
Drugs. 2000 Dec;60(6):1383-410. doi: 10.2165/00003495-200060060-00012.
The virological/immunological efficacy of amprenavir-containing combination regimens has been evaluated in a small number of clinical trials in patients with HIV infection. Amprenavir plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) was more effective than 2 NRTIs (in treatment-naive patients) or amprenavir monotherapy (in treatment-naive or -experienced patients) in double-blind trials. In the only direct comparison with another protease inhibitor as part of triple therapy, amprenavir was less effective than indinavir in treatment-experienced (protease inhibitor-naive) patients. Amprenavir was as effective as other protease inhibitors when given with abacavir in a small nonblind trial. Amprenavir is generally well tolerated (most events are mild or moderate). GI disturbance and rash are the principal treatment-limiting effects. Preclinical data suggest that amprenavir may have a low potential for metabolic disturbances (e.g. lipodystrophy, fat redistribution); such effects have been infrequent in patients treated to date, but longer term experience is needed. 150V is the major HIV protease substitution associated with amprenavir resistance; this mutation is not seen in isolates from patients receiving other available protease inhibitors. Amprenavir-resistant isolates evaluated to date showed no significant cross-resistance to most other protease inhibitors, although some cross-resistance to ritonavir was noted. Many isolates from patients previously treated with other protease inhibitors are susceptible to amprenavir. Amprenavir offers the convenience of twice-daily administration with no food-timing or fluid restrictions, but this may be offset by the large number and size of the capsules. However, pharmacokinetic data support the use of co-administration of amprenavir and ritonavir at reduced dosages, thereby allowing a reduction in the number of amprenavir capsules.
Amprenavir-containing combination regimens have shown virological efficacy, and have generally been well tolerated, in patients with HIV infection (primarily treatment-naive or protease inhibitor-naive). The limited number of studies available and the absence of well controlled comparisons with other triple therapies limits the conclusions that can be drawn at present. The clinical value of amprenavir for patients with isolates which are resistant to other protease inhibitors but sensitive to amprenavir, and in treatment-experienced patients in general, requires further investigation. Further evaluation of the amprenavir/ritonavir combination is awaited with interest. Like other members of its class, amprenavir has a particular profile of tolerability, resistance and administration characteristics which should be carefully considered in relation to the needs of individual patients.
含安普那韦的联合治疗方案的病毒学/免疫学疗效已在少数针对HIV感染患者的临床试验中进行了评估。在双盲试验中，安普那韦加2种核苷类逆转录酶抑制剂（NRTIs）比2种NRTIs（在初治患者中）或安普那韦单药治疗（在初治或经治患者中）更有效。在与另一种蛋白酶抑制剂作为三联疗法一部分的唯一直接比较中，在经治（未用过蛋白酶抑制剂）患者中，安普那韦的疗效低于茚地那韦。在一项小型非盲试验中，安普那韦与阿巴卡韦联用时与其他蛋白酶抑制剂效果相当。安普那韦一般耐受性良好（大多数事件为轻度或中度）。胃肠道不适和皮疹是主要的限制治疗的效应。临床前数据表明安普那韦可能导致代谢紊乱（如脂肪营养不良、脂肪重新分布）的可能性较低；迄今为止在接受治疗的患者中此类效应并不常见，但仍需要长期经验。150V是与安普那韦耐药相关的主要HIV蛋白酶替代突变；在接受其他现有蛋白酶抑制剂治疗的患者分离株中未发现这种突变。迄今为止评估的对安普那韦耐药的分离株对大多数其他蛋白酶抑制剂无明显交叉耐药性，尽管注意到对利托那韦有一些交叉耐药性。许多先前接受过其他蛋白酶抑制剂治疗的患者的分离株对安普那韦敏感。安普那韦具有每日两次给药的便利性，无需考虑进食时间或液体限制，但这可能被胶囊的数量和大小所抵消。然而，药代动力学数据支持以降低剂量联合使用安普那韦和利托那韦，从而减少安普那韦胶囊的数量。
含安普那韦的联合治疗方案在HIV感染患者（主要是初治或未用过蛋白酶抑制剂的患者）中已显示出病毒学疗效，且一般耐受性良好。现有研究数量有限，且缺乏与其他三联疗法的良好对照比较，限制了目前可得出的结论。安普那韦对于对其他蛋白酶抑制剂耐药但对安普那韦敏感的分离株患者以及一般经治患者的临床价值需要进一步研究。人们期待着对安普那韦/利托那韦联合治疗进行进一步评估。与该类中的其他药物一样，安普那韦具有特定的耐受性、耐药性和给药特征，应根据个体患者的需求仔细考虑。
