Laboratoire de Virologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Bichat-Claude Bernard, HUPNVS, Université Paris Diderot, Paris 7, PRES Sorbonne Paris Cité, EA4409, Paris, France.
PLoS One. 2013;8(1):e54381. doi: 10.1371/journal.pone.0054381. Epub 2013 Jan 18.
To describe the prevalence of the L76V protease inhibitors resistance-associated mutation (PI-RAM) in relation with patients' characteristics and protease genotypic background in HIV-1 B- and "non-B"-infected patients.
Frequency of the L76V mutation between 1998 and 2010 was surveyed in the laboratory database of 3 clinical centers. Major PI-RAMs were identified according to the IAS-USA list. Fisher's and Wilcoxon tests were used to compare variables.
Among the overall 29,643 sequences analyzed, the prevalence of L76V was 1.50%, while was 5.42% in PI-resistant viruses. Since 2008 the prevalence of L76V was higher in "non-B"-infected than in B-infected patients each year. Median time since diagnosis of HIV-1 infection and median time under antiretroviral-based regimen were both shorter in "non-B"- than in B-infected patients (8 vs 11 years, P<0.0001; and 7 vs 8 years, P = 0.004). In addition, "non-B"-infected patients had been pre-exposed to a lower number of PI (2 vs 3, P = 0.016). The L76V was also associated with a lower number of major PI-RAMs in "non-B" vs B samples (3 vs 4, P = 0.0001), and thus it was more frequent found as single major PI-RAM in "non-B" vs B subtype (10% vs 2%, P = 0.014).
We showed an impact of viral subtype on the selection of the L76V major PI-RAM with a higher prevalence in "non-B" subtypes observed since 2008. In addition, in "non-B"-infected patients this mutation appeared more rapidly and was associated with less PI-RAM.
描述 HIV-1 B 型和“非 B”型感染者中 L76V 蛋白酶抑制剂耐药相关突变（PI-RAM）与患者特征和蛋白酶基因型背景的相关性。
在三个临床中心的实验室数据库中调查了 1998 年至 2010 年间 L76V 突变的频率。根据 IAS-USA 列表确定主要 PI-RAMs。使用 Fisher 和 Wilcoxon 检验比较变量。
在分析的 29643 条序列中，L76V 的流行率为 1.50%，而在耐药病毒中为 5.42%。自 2008 年以来，“非 B”型感染者中 L76V 的流行率每年均高于 B 型感染者。HIV-1 感染诊断后中位时间和抗逆转录病毒治疗方案中位时间在“非 B”型感染者中均短于 B 型感染者（8 年 vs 11 年，P<0.0001；7 年 vs 8 年，P=0.004）。此外，“非 B”型感染者之前接触的 PI 数量较少（2 个 vs 3 个，P=0.016）。L76V 也与“非 B”型样本中较少的主要 PI-RAMs 相关（3 个 vs 4 个，P=0.0001），因此，“非 B”型感染者中 L76V 更常见为单一主要 PI-RAM（10% vs 2%，P=0.014）。
我们发现病毒亚型对 L76V 主要 PI-RAM 的选择有影响，自 2008 年以来，“非 B”亚型中观察到 L76V 主要 PI-RAM 的流行率更高。此外，在“非 B”型感染者中，该突变出现更快，且与较少的 PI-RAM 相关。
