Kagan Ron M, Baxter John D, Kim Taekkyun, Marlowe Elizabeth M
Department of Infectious Diseases, Quest Diagnostics, San Juan Capistrano, California, USA.
Department of Medicine, Cooper Medical School of Rowan University and Cooper University Health Care, Camden, New Jersey, USA.
Open Forum Infect Dis. 2025 Aug 4;12(8):ofaf446. doi: 10.1093/ofid/ofaf446. eCollection 2025 Aug.
Antiretroviral drug resistance limits treatment options for people with human immunodeficiency virus (HIV) 1 and may reduce the effectiveness of preexposure prophylaxis. Novel treatment options with enhanced efficacy and more convenient formulations have become available from 2016 to 2021. Large-scale studies of trends in the prevalences of plasma RNA drug resistance mutations (DRMs) since 2018 are lacking, and there have been no systematic studies of trends in proviral DNA DRMs.
We retrospectively analyzed deidentified HIV-1 plasma RNA and proviral DNA sequences from specimens submitted to a reference laboratory between January 2018 and May 2024. We analyzed the annual prevalence of DRMs with a Stanford HIV Drug Resistance Database score of ≥30 for nucleoside and nonnucleoside reverse-transcriptase inhibitors (NRTIs and NNRTIs), protease inhibitors, and integrase strand transfer inhibitors (INSTIs).
The prevalence of resistance declined for both RNA and DNA sequences. Single-class and dual-class NRTI + NNRTI resistance declined but was higher for DNA (NRTI + NNRTI, declined from 6.1% to 3.5% for RNA and from 12.1% to 7.8% for DNA). Rilpivirine DRMs remained low, with prevalences of 6.3% (RNA) and 10.2% (DNA) in 2024. The doravirine DRM prevalences in 2024 were 2% (RNA) and 2.9% (DNA). INSTI and dual-class NRTI + INSTI resistance also declined, but the prevalence of integrase DRM R263K increased.
Prevalence of NRTI and NNRTI resistance has declined, consistent with increased use of regimens with higher resistance barriers, improved tolerability, and more convenient dosing. Proviral DNA resistance trends were correlated with those for RNA. Continued advances in antiretroviral therapy efficacy, durability, and tolerability may lead to increased rates of virologic suppression and further reduce the incidence of archived resistance mutations in proviral DNA.
抗逆转录病毒药物耐药性限制了人类免疫缺陷病毒1型（HIV-1）感染者的治疗选择，并可能降低暴露前预防的效果。2016年至2021年期间出现了疗效增强且剂型更便捷的新型治疗选择。自2018年以来，缺乏关于血浆RNA耐药性突变（DRM）流行趋势的大规模研究，也没有关于前病毒DNA DRM趋势的系统性研究。
我们回顾性分析了2018年1月至2024年5月提交至一家参考实验室的标本中未识别身份的HIV-1血浆RNA和前病毒DNA序列。我们使用斯坦福HIV耐药数据库评分≥30分析了核苷类和非核苷类逆转录酶抑制剂（NRTIs和NNRTIs）、蛋白酶抑制剂及整合酶链转移抑制剂（INSTIs）的DRM年度流行率。
RNA和DNA序列的耐药率均下降。单类及双类NRTI + NNRTI耐药率下降，但DNA的耐药率更高（NRTI + NNRTI，RNA从6.1%降至3.5%，DNA从12.1%降至7.8%）。利匹韦林DRM仍然较低，2024年的流行率分别为6.3%（RNA）和10.2%（DNA）。2024年多拉韦林DRM的流行率分别为2%（RNA）和2.9%（DNA）。INSTI及双类NRTI + INSTI耐药率也下降，但整合酶DRM R263K的流行率增加。
NRTI和NNRTI耐药率下降，这与具有更高耐药屏障、更好耐受性及更便捷给药方案的使用增加一致。前病毒DNA耐药趋势与RNA的趋势相关。抗逆转录病毒治疗在疗效、持久性和耐受性方面的持续进展可能会提高病毒学抑制率，并进一步降低前病毒DNA中存档耐药突变的发生率。
