Centre for HIV and STIs, National Institute for Communicable Diseases of The National Health Laboratory Services, Johannesburg, Gauteng, South Africa.
School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Gauteng, South Africa.
PLoS One. 2020 Jun 18;15(6):e0234937. doi: 10.1371/journal.pone.0234937. eCollection 2020.
We have previously reported on HIV-1 infected patients who fail anti-retroviral therapy but manage to re-suppress without a regimen change despite harbouring major drug resistance mutations. Here we explore phenotypic drug resistance in such patients in order to better understand this phenomenon. Patients (n = 71) failing a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen, but who subsequently re-suppressed on the same regimen, were assessed for HIV-1 genotypic drug resistance through Sanger sequencing. A subset (n = 23) of these samples, as well as genotypically matched samples from patients who did not re-suppress (n = 19), were further assessed for phenotypic drug resistance in an in vitro single cycle assay. Half of the patients (n = 36/71, 51%) harboured genotypic drug resistance, with M184V (n = 18/36, 50%) and K103N (n = 16/36, 44%) being the most prevalent mutations. No significant difference in the median time to re-suppression (31-39 weeks) were observed for either group (p = 0.41). However, re-suppressors with mutant virus rebounded significantly earlier than those with wild-type virus (16 vs. 33 weeks; p = 0.014). Similar phenotypic drug resistance profiles were observed between patients who re-suppressed and patients who failed to re-suppress. While most remained susceptible to stavudine (d4T) and zidovudine (AZT), both groups showed a reduced susceptibility to 3TC and NNRTIs. HIV- 1 infected patients on an NNRTI-based regimen can achieve viral re-suppression on the same regimen despite harbouring viruses with genotypic and phenotypic drug resistance. However, re-suppression was less durable in those with resistance, reinforcing the importance of appropriate regimen choices, ongoing viral load monitoring and adherence counselling.
我们之前曾报道过一些 HIV-1 感染患者，他们在抗逆转录病毒治疗失败后，尽管携带主要耐药突变，但仍能在不改变治疗方案的情况下重新抑制病毒。在这里，我们探索了这种患者的表型耐药性，以便更好地理解这种现象。对 71 名基于非核苷类逆转录酶抑制剂（NNRTI）的治疗方案失败但随后在相同方案下重新抑制的患者进行 HIV-1 基因型耐药性评估，通过 Sanger 测序。对这些样本中的一部分（n=23）以及未重新抑制的患者的基因型匹配样本（n=19）进行进一步评估，以在体外单周期测定中评估表型耐药性。一半的患者（n=71，51%）携带基因型耐药性，最常见的突变是 M184V（n=18/36，50%）和 K103N（n=16/36，44%）。两组患者的中位时间到重新抑制（31-39 周）无显著差异（p=0.41）。然而，携带突变病毒的重新抑制者病毒反弹明显早于携带野生型病毒的患者（16 周 vs. 33 周；p=0.014）。重新抑制者和未重新抑制者之间观察到相似的表型耐药性谱。虽然大多数患者对司他夫定（d4T）和齐多夫定（AZT）仍保持敏感，但两组对拉米夫定（3TC）和 NNRTIs 的敏感性均降低。尽管携带基因型和表型耐药性，但接受基于 NNRTI 的治疗方案的 HIV-1 感染患者仍能在相同方案下实现病毒重新抑制。然而，携带耐药性的患者重新抑制的持久性较差，这强调了适当的方案选择、持续的病毒载量监测和依从性咨询的重要性。
