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首页> 外文期刊>AIDS Research and Human Retroviruses >Plasma HIV RNA Decline and Emergence of Drug Resistance Mutations among Patients with Multiple Virologic Failures Receiving Resistance Testing-Guided HAART
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Plasma HIV RNA Decline and Emergence of Drug Resistance Mutations among Patients with Multiple Virologic Failures Receiving Resistance Testing-Guided HAART

机译：接受抗药性试验指导的多病毒学衰竭患者的血浆HIV RNA下降和耐药突变的出现

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Early recognition of virologic failure in patients with extensive drug resistance receiving salvage-HAART is essential to avoid exposure to subinhibitory regimens. We studied plasma viral load (PVL) decline and rates of drug-resistance mutation (DRM) accumulation in such patients. A prospective, 48 week study of 38 heavily pretreated patients receiving genotypic resistance testing (GRT)-guided HAART was conducted. The rate of PVL decline was studied by weekly PVL determinations. To assess DRM accumulation, serial GRTs were performed in all nonresponders (never reaching PVL <50 or two PVLs >50 copies/ml after suppression). Over 48 weeks, 10 patients (26%) were nonresponders. Receiving less then two fully active drugs and having an elevated number of PI and NRTI mutations at baseline were strongly associated with virologic failure. There was no evidence of a difference in the change from baseline PVL to week 1 and 2 between responders and nonresponders. By contrast, PVL reductions from week 2 to week 3 and thereafter were significantly greater for responders (p < 0.01). Among nonresponders, the incidence rates per patient-month (95% CI) of emergent DRM were 0.67 (0.13–1.20), 0.40 (0.00–0.74), and 0.37 (0.00–0.75) at weeks 4, 8, and 24, respectively. Having limited baseline resistance, receiving at least two fully active drugs, and showing constant PVL reductions from week 2 to week 3 and thereafter were predictive of virologic response. In contrast, early changes in PVL levels were not. Virologic failure was associated with detection of emergent DRMs. Virologic rebound in patients on salvage-HAART should be addressed aggressively
机译：对具有广泛耐药性且接受挽救-HAART的患者进行病毒学衰竭的早期识别对于避免暴露于亚抑制方案至关重要。我们研究了这类患者的血浆病毒载量（PVL）下降和耐药突变（DRM）积累的速率。进行了一项前瞻性，为期48周的研究，对接受基因型耐药性测试（GRT）指导的HAART的38例经过大量预处理的患者进行了研究。通过每周一次的PVL测定研究PVL下降的速率。为了评估DRM积累，在所有无反应者中进行了连续GRT（抑制后从未达到PVL <50或两次达到PVLs> 50拷贝/ ml）。在48周内，有10位患者（26％）无反应。接受少于两种全活性药物并在基线时具有升高的PI和NRTI突变数量与病毒学衰竭密切相关。没有证据表明应答者和非应答者从基线PVL到第1周和第2周的变化没有差异。相比之下，响应者从第2周到第3周及其后的PVL降低幅度更大（p <0.01）。在无反应者中，在第4、8和24周时，急诊DRM的每个患者每月（95％CI）发生率分别为0.67（0.13-1.20），0.40（0.00-0.74）和0.37（0.00-0.75）。 。基线抵抗力有限，至少要接受两种完全活性药物，并且从第2周到第3周以及此后显示出持续的PVL降低，可以预测病毒学应答。相反，PVL水平没有早期变化。病毒学衰竭与紧急DRM的检测有关。抢救性HAART患者的病毒学反弹应积极处理

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