Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Européen Georges Pompidou, Laboratoire de Virologie, France.
AIDS. 2010 Mar 27;24(6):867-73. doi: 10.1097/QAD.0b013e3283367796.
Integrase positions 148 and 155 represent main determinants of resistance to integrase inhibitors. We assessed the prevalence of minority variants harboring such mutations in integrase-naive HIV-infected patients.
Two groups of patients were studied: 40 heavily antiretroviral-experienced patients, initiating a raltegravir-based therapy and 51 antiretroviral-naive patients. Allele-specific real-time PCR (AS-PCR) systems, developed for Q148H, Q148R and N155H mutations, were performed at baseline for antiretroviral-experienced patients. Samples from antiretroviral-naive patients were tested with the Q148R AS-PCR assay.
The limits of detection of AS-PCR systems were 0.10, 0.10 and 0.05% for Q148H, Q148R and N155H mutations, respectively. AS-PCR systems were successful in 79 of 91 samples. In antiretroviral-experienced patients, Q148R minority variants were frequently detected (26/32 patients, 81%) at low-level frequency (median = 0.40%), whereas no minority variants exhibiting Q148H or N155H mutation were found. Twenty-four of 26 patients exhibiting Q148R variants were virological responders but four of them displayed a delayed virological response occurring between W18 and W36. Two patients exhibited virological failure under raltegravir, both harboring Q148R minority variants at baseline. However, we did not find any association between the presence of Q148R minority variants and an increased risk of virological failure. Q148R minority variants were also found in 86% of antiretroviral-naive patients, a prevalence significantly higher than that of K103N minority variants (26%).
Q148R variants were frequently detected, always at low-level, in antiretroviral-experienced and naive patients. Although their presence was not consistently associated with virological failure, their impact on long-term viral suppression needs to be further investigated.
整合酶位置 148 和 155 是对整合酶抑制剂耐药的主要决定因素。我们评估了整合酶初治的 HIV 感染者中携带这些突变的少数变异体的流行率。
研究了两组患者：40 例接受过大量抗逆转录病毒治疗的患者，开始接受拉替拉韦治疗；51 例初治患者。在接受过抗逆转录病毒治疗的患者中，使用针对 Q148H、Q148R 和 N155H 突变的等位基因特异性实时 PCR（AS-PCR）系统在基线时进行检测。初治患者的样本使用 Q148R AS-PCR 检测。
AS-PCR 系统的检测下限分别为 Q148H、Q148R 和 N155H 突变的 0.10%、0.10%和 0.05%。79 例样本中的 79 例（79/91） AS-PCR 系统检测成功。在接受过抗逆转录病毒治疗的患者中，Q148R 少数变异体频繁检出（32 例中的 26 例，81%），频率较低（中位数=0.40%），但未发现 Q148H 或 N155H 突变的少数变异体。26 例存在 Q148R 变异体的患者中有 24 例为病毒学应答者，但其中 4 例在 W18 和 W36 之间出现了延迟的病毒学应答。2 例接受拉替拉韦治疗的患者发生病毒学失败，均在基线时存在 Q148R 少数变异体。然而，我们没有发现 Q148R 少数变异体的存在与病毒学失败风险增加之间存在任何关联。在初治患者中，Q148R 少数变异体的检出率也高达 86%，明显高于 K103N 少数变异体（26%）。
在接受过抗逆转录病毒治疗和初治的患者中，Q148R 变异体频繁检出，且总是处于低水平。尽管其存在并不总是与病毒学失败相关，但需要进一步研究其对长期病毒抑制的影响。
