Aung Su, Novitsky Vlad, Steingrimsson Jon, Gillani Fizza S, Howison Mark, Nagel Katherine, Solomon Matthew, Bertrand Thomas, Bhattarai Lila, Fulton John, Bandy Utpala, Kantor Rami
Department of Medicine, University of California, San Francisco.
Department of Medicine, Brown University.
J Infect Dis. 2024 Dec 16;230(6):1422-1433. doi: 10.1093/infdis/jiae344.
Human immunodeficiency virus type 1 (HIV-1) acquired drug resistance (ADR) compromises antiretroviral therapy (ART).
We aggregated all HIV-1 protease-reverse transcriptase-integrase sequences over 2004-2021 at the largest HIV center in Rhode Island and evaluated ADR extent, trends, and impact using Stanford Database tools. Trends were measured with Mann-Kendall statistic, and multivariable regressions evaluated resistance predictors.
Sequences were available for 914 ART-experienced persons. Overall ADR to any drug decreased from 77% to 49% (-0.66 Mann-Kendall statistic); nucleoside reverse transcriptase inhibitors 65% to 32%, nonnucleoside reverse transcriptase inhibitors 53% to 43%, and protease inhibitors 28% to 7% (2004-2021), and integrase strand transfer inhibitors 16% to 13% (2017-2021). Multiclass resistance decreased from 44% to 12% (2-class) and 12% to 6% (3-class). In 2021, 94% had at least one 3-drug or 2-drug one-pill-once-daily (OPOD) option. Males and those exposed to more ART regimens were more likely to have ≥2-class resistance, and higher regimen exposure was also associated with fewer OPOD options.
Comprehensive analyses within a densely-sampled HIV epidemic over 2004-2021 demonstrated decreasing ADR. Continued ADR monitoring is important to maintain ART success, particularly with rising INSTI use in all lines of therapy and 2-drug and long-acting formulations.
1型人类免疫缺陷病毒（HIV-1）获得性耐药（ADR）会影响抗逆转录病毒疗法（ART）。
我们汇总了罗德岛最大的HIV中心2004年至2021年期间所有的HIV-1蛋白酶-逆转录酶-整合酶序列，并使用斯坦福数据库工具评估ADR的程度、趋势及影响。趋势采用曼-肯德尔统计量进行测量，多变量回归分析评估耐药预测因素。
有914名有ART治疗经验的患者的序列数据可用。对任何药物的总体ADR从77%降至49%（曼-肯德尔统计量为-0.66）；核苷类逆转录酶抑制剂从65%降至32%，非核苷类逆转录酶抑制剂从53%降至43%，蛋白酶抑制剂从28%降至7%（2004年至2021年），整合酶链转移抑制剂从16%降至13%（2017年至2021年）。多类耐药从44%降至12%（2类）和12%降至6%（3类）。2021年，94%的患者至少有一种每日一次单一片剂（OPOD）的三联或二联药物方案。男性以及接受更多ART方案的患者更有可能出现≥2类耐药，且更高的方案暴露量也与更少的OPOD方案相关。
对2004年至2021年期间密集抽样的HIV流行情况进行的综合分析表明ADR在下降。持续进行ADR监测对于维持ART的成功很重要，特别是在所有治疗线中整合酶链转移抑制剂（INSTI）的使用增加以及二联药物和长效制剂使用增加的情况下。
