Normandie Univ, UNIROUEN, EA2656, GRAM 2.0, CHU de Rouen, Laboratoire de Virologie associé au CNR du VIH, F-76000, Rouen, France.
IAME, UMR 1137, INSERM, Université Paris Diderot, Sorbonne Paris Cité, AP-HP, Laboratoire de Virologie, Hôpital Bichat, AP-HP, Paris, France.
J Antimicrob Chemother. 2021 Aug 12;76(9):2306-2309. doi: 10.1093/jac/dkab196.
HIV-1 group O (HIV-1/O) is one of the four HIV-1 groups and is endemic in Cameroon, representing 1% of HIV-1 infections in the population. Around 50% of the strains of this group naturally show a mutation (Y181C) providing them with resistance to NNRTIs and making therapeutic management more difficult. Today, the WHO recommends the use of integrase strand transfer inhibitors (INSTIs) as first-line treatment. Bictegravir and cabotegravir are the two most recent INSTIs. Because of the genetic polymorphism of HIV-1/O, studies are required to evaluate their phenotypic susceptibility to these two drugs.
We performed a phenotypic study on a large panel including 41 HIV-1/O clinical isolates and other rare non-group M HIV-1 (2 HIV-1/N and 1 HIV-1/P) to evaluate in vitro susceptibility to bictegravir and cabotegravir.
The results showed an overall susceptibility of non-group M strains to the two drugs compared with HIV-1 group M. There was no difference between the mean (min-max) IC50 of HIV-1/M [1.86 (0.93-4.12) and 5.24 (1.76-12.41) nM for bictegravir and cabotegravir, respectively] and HIV-1/non-M [2.17 (0.03-9.47) and 4.88 (0.02-15.64) nM for bictegravir and cabotegravir, respectively]. However, we found a significant difference between IC50 values for bictegravir and cabotegravir in the whole panel (P value < 0.001).
This study has shown encouraging results regarding the clinical use of these drugs in HIV-1/non-M-infected patients, which will need to be confirmed with clinical data.
HIV-1 组 O（HIV-1/O）是 HIV-1 的四个组之一，在喀麦隆流行，占人群中 HIV-1 感染的 1%。该组的约 50%的毒株自然存在突变（Y181C），使它们对 NNRTIs 产生耐药性，使治疗管理更加困难。如今，世界卫生组织（WHO）建议将整合酶链转移抑制剂（INSTIs）作为一线治疗药物。比克替拉韦和卡博替拉韦是最近的两种 INSTIs。由于 HIV-1/O 的遗传多态性，需要进行研究以评估这两种药物对它们的表型敏感性。
我们对包括 41 例 HIV-1/O 临床分离株和其他罕见的非 M 组 HIV-1（2 例 HIV-1/N 和 1 例 HIV-1/P）在内的大型面板进行了表型研究，以评估对比克替拉韦和卡博替拉韦的体外敏感性。
结果显示，与 HIV-1 组 M 相比，非 M 组毒株对这两种药物的总体敏感性较高。HIV-1/M 的平均（最小-最大）IC50 无差异[比克替拉韦和卡博替拉韦分别为 1.86（0.93-4.12）和 5.24（1.76-12.41）nM]和 HIV-1/非-M[比克替拉韦和卡博替拉韦分别为 2.17（0.03-9.47）和 4.88（0.02-15.64）nM]。然而，我们发现整个面板中比克替拉韦和卡博替拉韦的 IC50 值存在显著差异（P 值<0.001）。
这项研究对于 HIV-1/非-M 感染患者使用这些药物的临床应用显示出令人鼓舞的结果，这需要通过临床数据来证实。
