HIV-1 Molecular Epidemiology Laboratory, Microbiology and Parasitology Department, Hospital Universitario Ramón y Cajal-IRyCIS and CIBERESP, Spain.
George Washington University, Washington, DC, USA.
Clin Microbiol Infect. 2015 Jun;21(6):605.e1-9. doi: 10.1016/j.cmi.2015.02.003. Epub 2015 Feb 11.
Drug resistance mutations compromise the success of antiretroviral treatment in human immunodeficiency virus type 1 (HIV-1)-infected children. We report the virologic and clinical follow-up of the Madrid cohort of perinatally HIV-infected children and adolescents after the selection of triple-class drug-resistant mutations (TC-DRM). We identified patients from the cohort carrying HIV-1 variants with TC-DRM to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors and protease inhibitors according to IAS-USA-2013. We recovered pol sequences or resistance profiles from 2000 to 2011 and clinical-immunologic-virologic data from the moment of TC-DRM detection until December 2013. Viruses harbouring TC-DRM were observed in 48 (9%) of the 534 children and adolescents from 2000 to 2011, rising to 24.4% among those 197 with resistance data. Among them, 95.8% were diagnosed before 2003, 91.7% were Spaniards, 89.6% carried HIV-1-subtype B and 75% received mono/dual therapy as first regimen. The most common TC-DRM present in ≥50% of them were D67NME, T215FVY, M41L and K103N (retrotranscriptase) and L90M (protease). The susceptibility to darunavir, tipranavir, etravirine and rilpivirine was 67.7%, 43.7%, 33.3% and 33.3%, respectively, and all reported high resistance to didanosine, abacavir and nelfinavir. Despite the presence of HIV-1 resistance mutations to the three main antiretroviral families in our paediatric cohort, some drugs maintained their susceptibility, mainly the new protease inhibitors (tipranavir and darunavir) and nonnucleoside reverse transcriptase inhibitors (etravirine and rilpivirine). These data will help to improve the clinical management of HIV-infected children with triple resistance in Spain.
耐药突变会影响人类免疫缺陷病毒 1 型（HIV-1）感染儿童的抗逆转录病毒治疗效果。我们报告了马德里围产期感染 HIV 的儿童和青少年队列的病毒学和临床随访情况，这些儿童和青少年在选择三重耐药突变（TC-DRM）后出现了耐药情况。根据 IAS-USA-2013，我们从队列中鉴定出携带具有核苷逆转录酶抑制剂、非核苷逆转录酶抑制剂和蛋白酶抑制剂 TC-DRM 的 HIV-1 变异体的患者。我们从 2000 年到 2011 年恢复了 pol 序列或耐药谱，从检测到 TC-DRM 到 2013 年 12 月的临床-免疫-病毒学数据。2000 年至 2011 年期间，在 534 名儿童和青少年中观察到携带 TC-DRM 的病毒，在有耐药数据的 197 名儿童和青少年中，这一比例上升至 24.4%。其中，95.8%在 2003 年前被诊断，91.7%为西班牙人，89.6%携带 HIV-1 亚型 B，75%作为首剂方案接受单药/二联治疗。在他们中，≥50%的患者携带 D67NME、T215FVY、M41L 和 K103N（逆转录酶）和 L90M（蛋白酶）等常见 TC-DRM。对达努韦、替拉那韦、依曲韦林和利匹韦林的敏感性分别为 67.7%、43.7%、33.3%和 33.3%，所有报告对阿巴卡韦、司他夫定和奈韦拉平均高度耐药。尽管我们的儿科队列中存在对三种主要抗逆转录病毒药物的 HIV 耐药突变，但一些药物仍保持敏感性，主要是新型蛋白酶抑制剂（替拉那韦和达努韦）和非核苷逆转录酶抑制剂（依曲韦林和利匹韦林）。这些数据将有助于改善西班牙三重耐药感染 HIV 的儿童的临床管理。
