Torti Carlo, Quiros-Roldan Eugenia, Regazzi Mario, De Luca Andrea, Mazzotta Francesco, Antinori Andrea, Ladisa Nicoletta, Micheli Valeria, Orani Anna, Patroni Andrea, Villani Paola, Lo Caputo Sergio, Moretti Francesca, Di Giambenedetto Simona, Castelnuovo Filippo, Maggi Paolo, Tinelli Carmine, Carosi Giampiero
Institute for Infectious and Tropical Diseases, Brescia, Italy.
Clin Infect Dis. 2005 Jun 15;40(12):1828-36. doi: 10.1086/429917. Epub 2005 May 12.
It is not well defined whether concentration-controlled intervention (CCI) and rules-based human immunodeficiency virus (HIV) type 1 genotype drug-resistance interpretation (GI) or virtual phenotype drug-resistance interpretation (VPI) may improve the outcome of HIV salvage therapy.
In a prospective, randomized, controlled trial, patients were randomized (on a factorial basis) to change treatment after either GI or VPI, and they then were further randomized to the control arm (no CCI) or the CCI arm. Protease inhibitor (PI) and nonnucleoside reverse-transcriptase inhibitor (NNRTI) trough concentration (Ctrough) values were determined at weeks 1, 4, 12, and 24 of the study.
Among 230 patients, virological benefit (defined by an HIV RNA load of <400 copies/mL at week 24) was not statistically different, either between patients in the GI and VPI arms or between patients in the CCI and control arms. A virological benefit was found for patients in the CCI arm, compared with patients in the control arm, but this benefit was not statistically significant (56.8% vs. 64.3% at week 4 and 63.6% vs. 74% at week 12). Dosage adaptation was possible for only a fraction of patients, because of low rates of treatment adherence or patient refusal to increase dosages. In the logistic regression analysis, independent predictors of virological response at week 24 were a PI Ctrough value and/or an NNRTI Ctrough value in the higher quartiles (or above cutoff levels) and a low number of PIs previously received. Moreover, receipt of a regimen that contained PIs boosted with ritonavir was an independent predictor of virological response.
The present study did not support the routine use of CCI for patients undergoing salvage treatment, probably as a result of existing difficulties associated with its clinical application. However, a higher Ctrough value appeared to be correlated with treatment response. No major differences were found between VPI or GI when they are used together with expert advice for the selection of salvage treatment combinations.
浓度控制干预（CCI）以及基于规则的人类免疫缺陷病毒1型（HIV-1）基因型耐药性解读（GI）或虚拟表型耐药性解读（VPI）是否能改善HIV挽救治疗的结果，目前尚无明确定论。
在一项前瞻性、随机、对照试验中，患者被随机分组（基于析因设计），依据GI或VPI结果更换治疗方案，随后进一步随机分为对照组（无CCI）或CCI组。在研究的第1、4、12和24周测定蛋白酶抑制剂（PI）和非核苷类逆转录酶抑制剂（NNRTI）的谷浓度（Ctrough）值。
在230例患者中，GI组和VPI组患者之间，以及CCI组和对照组患者之间，病毒学获益（定义为第24周时HIV RNA载量<400拷贝/mL）无统计学差异。与对照组患者相比，CCI组患者有病毒学获益，但该获益无统计学意义（第4周时为56.8%对64.3%，第12周时为63.6%对74%）。由于治疗依从性低或患者拒绝增加剂量，仅一小部分患者能够进行剂量调整。在逻辑回归分析中，第24周病毒学应答的独立预测因素为处于较高四分位数（或高于临界水平）的PI Ctrough值和/或NNRTI Ctrough值，以及既往接受的PI数量较少。此外，接受含ritonavir增强的PI方案是病毒学应答的独立预测因素。
本研究不支持对接受挽救治疗的患者常规使用CCI，这可能是由于其临床应用中存在的现有困难所致。然而，较高的Ctrough值似乎与治疗反应相关。当VPI或GI与专家建议一起用于选择挽救治疗组合时，未发现重大差异。
