Lan Yun, Ling Xuemei, Deng Xizi, Lin Yaqing, Li Junbin, Li Liya, He Ruiying, Cai Weiping, Li Feng, Li Linghua, Hu Fengyu
Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, 510440, People's Republic of China.
Guangdong Center for Diagnosis and Treatment of AIDS, Guangzhou, 510060, People's Republic of China.
Infect Drug Resist. 2023 Jul 31;16:4953-4964. doi: 10.2147/IDR.S419610. eCollection 2023.
Antiretroviral therapy (ART) efficiently reduces the morbidities and mortalities caused by HIV-1 infection and prevents the HIV epidemic. However, virologic failure (VF) occurs in some patients receiving ART experience, especially increases in those patients with intermittent or persistent low-level viremia (LLV). The presence of drug resistance mutations (DRMs) in LLV was a strong predictor of subsequent VF. The data on drug resistance (DR) or DRMs for HIV-1 infections at low-level viral load (LLVL) are limited in China.
To monitor the prevalence of HIV-1 drug resistance and to evaluate the risk factors associated with drug resistance in LLVL HIV-1 infections during ART in Guangdong, China.
Plasma samples with LLVL during ART in Guangdong Province between Jan 2011 and Dec 2022 were subjected to a modified reverse-transcription PCR with a pre-step of virus concentration by ultracentrifugation before extraction and the Sanger sequencing. Then, the genotypic resistance test was performed and DR was analyzed by the Stanford HIVDB program. Finally, DR-associated factors were identified by logistic regression analysis.
We found that CRF01_AE (53.57%) and CRF07_BC (25.07%) were the dominant HIV-1 genotypes in LLVL in Guangdong between 2011 and 2022 but that the percentage of CRF01_AE showed a trend of decrease over time. M46 (1.49%), M184 (30.91%), and K103 (21.46%) were the dominant PI-, NRTI-, and NNRTI-associated mutations, respectively. The total DR rate was 47.06%. Specifically, PI (3.71%) showed a significantly lower DR rate than NNRTI (40.74%) and NRTI (34.14%). Duration of ART, initial ART regimen, ethnicity, and WHO clinical stages were associated with DR.
The drug resistance rate among the LLVL during ART in Guangdong, China is high. The risk factors associated with HIV drug resistance should be seriously considered for better control.
抗逆转录病毒疗法（ART）能有效降低HIV-1感染所致的发病率和死亡率，并预防HIV流行。然而，接受ART治疗的部分患者会出现病毒学失败（VF），尤其是间歇性或持续性低水平病毒血症（LLV）患者的VF发生率更高。LLV中耐药突变（DRM）的存在是后续VF的有力预测指标。在中国，关于低水平病毒载量（LLVL）的HIV-1感染的耐药性（DR）或DRM的数据有限。
监测中国广东接受ART治疗的LLVL HIV-1感染者中HIV-1耐药性的流行情况，并评估与耐药性相关的危险因素。
对2011年1月至2022年12月期间广东接受ART治疗的LLVL血浆样本进行改良逆转录PCR检测，提取前通过超速离心进行病毒浓缩预处理，然后进行桑格测序。接着，进行基因型耐药性检测，并通过斯坦福HIV数据库程序分析DR。最后，通过逻辑回归分析确定与DR相关的因素。
我们发现，CRF01_AE（53.57%）和CRF07_BC（25.07%）是2011年至2022年广东LLVL中主要的HIV-1基因型，但CRF01_AE的百分比呈随时间下降趋势。M46（1.49%）、M184（30.91%）和K103（21.46%）分别是主要的蛋白酶抑制剂（PI）、核苷类逆转录酶抑制剂（NRTI）和非核苷类逆转录酶抑制剂（NNRTI）相关突变。总耐药率为47.06%。具体而言，PI（3.71%）的耐药率显著低于NNRTI（40.74%）和NRTI（34.14%）。ART疗程、初始ART方案、种族和世界卫生组织临床分期与DR相关。
中国广东接受ART治疗的LLVL患者中的耐药率较高。为了更好地控制，应认真考虑与HIV耐药性相关的危险因素。
