Caby F, Schneider L, Blanc C, Soulié C, Tindel M, Peytavin G, Agher R, Valantin M A, Tubiana R, Wirden M, Calvez V, Marcelin A G, Katlama C
Service des Maladies Infectieuses et Tropicales, Groupe Hospitalier Pitié-Salpêtrière, 47/83 Boulevard de l'Hôpital, 75651, Paris Cedex 13, France,
Infection. 2014 Apr;42(2):295-301. doi: 10.1007/s15010-013-0542-8. Epub 2013 Oct 24.
The lack of antiretroviral (ARV) backbone activity associated with raltegravir has been proposed as the main explanation for virological relapse observed in patients with undetectable viraemia who are switched from a ritonavir-boosted protease inhibitor (PI) to raltegravir. However ARV activity remains difficult to assess in this context. The aim of our study was to precisely assess the ARV backbone activity in patients with undetectable viraemia who underwent raltegravir switching strategies and to evaluate the efficacy of such switching strategies based on the genotypic sensitivity score (GSS).
Patients with a plasma human immunodeficiency virus type 1 (HIV-1) RNA level of <50 copies/mL on a stable two ARV-class regimen were enrolled if they switched one of their ARV drugs to raltegravir 400 mg twice daily. The GSS was calculated using a genotyping test performed on the HIV-1 RNA of the last plasma measurement with a HIV-1 RNA level of >50 copies/mL before the switch and on the results of all previous genotyping tests. The primary endpoint was the proportion of patients with a plasma HIV-1 RNA level of <50 copies/mL at week 24.
Fifty-six patients were enrolled in this study. The proportion of patients with a plasma HIV-1 RNA level of <50 copies/mL at week 24 was 92.9 % (range 83.0-97.2 %) in the intent-to-treat analysis and 98.1 % (90.0-99.7 %) in per-protocol analysis. When the backbone was fully active, the proportion was 100.0 % (86.7-100.0 %) at week 24 and week 48 in the per-protocol analysis. We observed a decrease in plasma total cholesterol and triglycerides of -12.7 % (p = 0.005) and -26.5 % (p = 0.001), respectively.
Raltegravir switching strategies are effective when the associated backbone is fully active according to the GSS. In the context of undetectable viraemia, where ARV activity remains difficult to assess, the determination of the GSS requires the entire ARV history of the patient and all previous HIV-RNA genotyping test results.
与拉替拉韦相关的抗逆转录病毒（ARV）主干活性缺乏，被认为是病毒血症检测不到且从利托那韦增强型蛋白酶抑制剂（PI）转换为拉替拉韦的患者出现病毒学复发的主要原因。然而，在这种情况下，ARV活性仍然难以评估。我们研究的目的是精确评估接受拉替拉韦转换策略且病毒血症检测不到的患者的ARV主干活性，并基于基因型敏感性评分（GSS）评估此类转换策略的疗效。
如果患者将其一种ARV药物转换为每日两次400mg拉替拉韦，且在稳定的两种ARV药物联合方案下血浆1型人类免疫缺陷病毒（HIV-1）RNA水平<50拷贝/mL，则纳入研究。使用对转换前最后一次血浆测量中HIV-1 RNA水平>50拷贝/mL的HIV-1 RNA进行的基因分型检测结果以及所有先前基因分型检测的结果来计算GSS。主要终点是第24周时血浆HIV-1 RNA水平<50拷贝/mL的患者比例。
本研究纳入了56例患者。在意向性分析中，第24周时血浆HIV-1 RNA水平<50拷贝/mL的患者比例为92.9%（范围83.0 - 97.2%），符合方案分析中为98.1%（90.0 - 99.7%）。当主干完全有活性时，符合方案分析中第24周和第48周的比例为100.0%（86.7 - 100.0%）。我们观察到血浆总胆固醇和甘油三酯分别下降了-12.7%（p = 0.005）和-26.5%（p = 0.001）。
根据GSS，当相关主干完全有活性时，拉替拉韦转换策略是有效的。在病毒血症检测不到且ARV活性仍然难以评估的情况下，GSS的确定需要患者的整个ARV治疗史以及所有先前的HIV-RNA基因分型检测结果。
