Machouf N, Thomas R, Nguyen V K, Trottier B, Boulassel M R, Wainberg M A, Routy J P
Clinique Médicale L'Actuel, Montreal, Quebec, Canada.
J Med Virol. 2006 May;78(5):608-13. doi: 10.1002/jmv.20582.
Previous studies on patients who develop drug resistant HIV-1 variants have shown that continued use of failing regimens might provide clinical benefit. However, the effect of long-term exposure to drug resistant variants may lead to emergence of compensatory mutations that may jeopardize this effect. In this study, we assess associations among type and number of drug resistant mutations, viral load and disease progression in patients with long-term follow up. Patients with genotypic testing performed at the time of treatment failure were enrolled. Comparison of viral load and CD4 cell count between different resistance groups was performed using analysis of variance. Multiple linear regression analysis was performed to assess the simultaneous effects of the presence of particular mutations and their accumulation on viral load. Data from 475 patients who were followed for a median of 43 months from October 1999 to July 2005 were studied. A "V shape" relationship was observed between the number of mutations and viral load. Specifically, in patients harboring up to five mutations, viral load was reduced by 0.8 log/copies when compared to wild-type variants. However, with more than six mutations viral load progressively increased. Certain reverse transcriptase mutations such as M184V/I, K70R, V108I, and protease mutations such as L33FIV, M84V, and M36I were associated with reduced viral load. Together, these findings suggest that long-term maintenance of a sub-optimal antiretroviral regimen may have deleterious consequences for the patient.
先前针对产生耐药性HIV-1变异体的患者的研究表明，继续使用无效的治疗方案可能会带来临床益处。然而，长期暴露于耐药变异体的影响可能会导致补偿性突变的出现，这可能会危及这种效果。在本研究中，我们评估了长期随访患者中耐药突变的类型和数量、病毒载量与疾病进展之间的关联。纳入了在治疗失败时进行基因分型检测的患者。使用方差分析对不同耐药组之间的病毒载量和CD4细胞计数进行比较。进行多元线性回归分析以评估特定突变的存在及其累积对病毒载量的同时影响。研究了1999年10月至2005年7月期间475例患者的数据，这些患者的中位随访时间为43个月。观察到突变数量与病毒载量之间呈“V形”关系。具体而言，与野生型变异体相比，携带多达五个突变的患者病毒载量降低了0.8 log/拷贝。然而，当突变超过六个时，病毒载量逐渐增加。某些逆转录酶突变，如M184V/I、K70R、V108I，以及蛋白酶突变，如L33FIV、M84V和M36I，与病毒载量降低有关。总之，这些发现表明，长期维持次优抗逆转录病毒治疗方案可能会对患者产生有害后果。
