Solas Caroline, Colson Philippe, Ravaux Isabelle, Poizot-Martin Isabelle, Moreau Jacques, Lacarelle Bruno, Tamalet Catherine
Laboratoire de Pharmacocinétique, Hôpital Universitaire de La Timone, Marseille, France.
J Acquir Immune Defic Syndr. 2008 Jun 1;48(2):177-80. doi: 10.1097/QAI.0b013e318164226a.
To evaluate the predictive value of the genotypic inhibitory quotient (GIQ) on the atazanavir response in treatment-experienced HIV-1-infected patients.
Thirty-six patients receiving an atazanavir-containing regimen were enrolled in the study. Atazanavir plasma concentrations were measured at month (M) 1, and genotype was performed at baseline. Virologic response was defined as a viral load <400 copies/mL or a decrease > or =1 log10.
The median numbers (range) of previous regimens, baseline protease inhibitors, and atazanavir resistance mutations were 8 (0 to 20), 3 (0 to 15), and 1 (0 to 10), respectively. The atazanavir-GIQ was associated with virologic response at M6, with a median value (range) of 365 (50 to 1172) in responder patients compared with 126 (23 to 1126) in nonresponders (P = 0.05). The cutoff value estimated for the atazanavir-GIQ was 183 (receiver operating characteristic curve test: 60% specificity, 74% sensitivity). Virologic response was achieved in 74% of patients with an atazanavir-GIQ >183 compared with only 26% of patients with an atazanavir-GIQ <183 (P = 0.02). Neither the number of mutations nor the atazanavir trough concentration was predictive of the virologic response.
In pretreated patients, the atazanavir-GIQ might be useful to predict early virologic response and allow the determination of the target atazanavir trough concentration required to achieve virologic response and overcome drug resistance emergence in a given patient.
评估基因型抑制商(GIQ)对接受过治疗的HIV-1感染患者阿扎那韦治疗反应的预测价值。
36例接受含阿扎那韦治疗方案的患者纳入本研究。在第1个月(M1)测定阿扎那韦血浆浓度,并在基线时进行基因分型。病毒学反应定义为病毒载量<400拷贝/mL或下降≥1 log10。
既往治疗方案、基线蛋白酶抑制剂及阿扎那韦耐药突变的中位数(范围)分别为8(0至20)、3(0至15)和1(0至10)。阿扎那韦-GIQ与M6时的病毒学反应相关,反应者患者的中位数(范围)为365(5至1172),无反应者为126(23至1126)(P = 0.05)。阿扎那韦-GIQ的估计临界值为183(受试者工作特征曲线检验:特异性60%,敏感性74%)。阿扎那韦-GIQ>183的患者中有74%实现了病毒学反应,而阿扎那韦-GIQ<183的患者中只有26%(P = 0.02)。突变数量和阿扎那韦谷浓度均不能预测病毒学反应。
在经治患者中,阿扎那韦-GIQ可能有助于预测早期病毒学反应,并有助于确定在特定患者中实现病毒学反应并克服耐药性出现所需的阿扎那韦目标谷浓度。