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乌干达一个高危队列中感染艾滋病毒女性病毒学未抑制后出现高水平获得性艾滋病毒耐药性

High Levels of Acquired HIV Drug Resistance Following Virological Nonsuppression in HIV-Infected Women from a High-Risk Cohort in Uganda.

作者信息

Segujja Farouk, Omooja Jonah, Lunkuse Sandra, Nanyonjo Maria, Nabirye Stella E, Nassolo Faridah, Bugembe Daniel L, Bbosa Nicholas, Kateete David P, Ssenyonga William, Mayanja Yunia, Nsubuga Rebecca N, Seeley Janet, Kaleebu Pontiano, Ssemwanga Deogratius

机构信息

Medical Research Council (MRC)/Uganda Virus Research Institute (UVRI) and London School of Hygiene and Tropical Medicine (LSHTM) Uganda Research Unit, Entebbe, Uganda.

Department of Medical Microbiology, College of Health Sciences, Makerere University, Kampala, Uganda.

出版信息

AIDS Res Hum Retroviruses. 2020 Sep;36(9):782-791. doi: 10.1089/AID.2019.0279. Epub 2020 Jun 25.

Abstract

HIV drug resistance (HIVDR) is of increasing health concern, especially among key populations. We investigated the prevalence of virological suppression (VS), prevalence and correlates of HIVDR in HIV-infected women, enrolled in a high-risk cohort. We enrolled 267 women initiated on first-line antiretroviral therapy (ART) between 2015 and 2018. Participants' plasma samples were analyzed for HIV RNA viral load (VL) and genotypic resistance testing was performed on those with VL nonsuppression (defined as VL ≥1,000 copies/mL). We used the Stanford HIVDR database-algorithm to assess HIVDR mutations and logistic regression to assess risk factors for VL nonsuppression and HIVDR. We observed an overall VS prevalence of 76.0% (203/267) and detected respective acquired drug resistance prevalence to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTIs) of 81.3% [confidence interval (CI) 67.4-91.1] and 45.8% (CI 31.4-60.8) among the 48 successfully genotyped VL nonsuppressors. NNRTI mutations were observed in 81.3% (39/48) of the genotyped participants and 45.8% (22/48) had both NRTI and NNRTI mutations. The mutation K103N was detected in 62.5% (30/48) of participants, 41.7% (20/48) had M184V/I, 14.6% had K65R, and 12.5% (6/48) had thymidine analog mutations (TAMs). None of the analyzed potential risk factors, including age and duration on ART, was significantly correlated with VL nonsuppression or HIVDR. Although high levels of NNRTI mutations support the transition to dolutegravir, the presence of NRTI mutations, especially TAMs, may compromise dolutegravir-based regimens or other second-line ART options. The moderate VS prevalence and high HIVDR prevalence therefore call for timely ART switching and intensive adherence counseling.

摘要

艾滋病毒耐药性(HIVDR)日益引起人们对健康的关注,尤其是在关键人群中。我们调查了参与一项高危队列研究的HIV感染女性中病毒学抑制(VS)的流行率、HIVDR的流行率及其相关因素。我们纳入了2015年至2018年间开始接受一线抗逆转录病毒治疗(ART)的267名女性。对参与者的血浆样本进行HIV RNA病毒载量(VL)分析,并对VL未被抑制者(定义为VL≥1000拷贝/毫升)进行基因型耐药性检测。我们使用斯坦福HIVDR数据库算法评估HIVDR突变,并使用逻辑回归评估VL未被抑制和HIVDR的危险因素。我们观察到总体VS流行率为76.0%(203/267),在48例成功进行基因分型的VL未被抑制者中,对非核苷类逆转录酶抑制剂(NNRTIs)和核苷类逆转录酶抑制剂(NRTIs)的获得性耐药率分别为81.3%[置信区间(CI)67.4 - 91.1]和45.8%(CI 31.4 - 60.8)。在进行基因分型的参与者中,81.3%(39/48)观察到NNRTI突变,45.8%(22/48)同时存在NRTI和NNRTI突变。在62.5%(30/48)的参与者中检测到K103N突变,41.7%(20/48)有M184V/I突变,14.6%有K65R突变,12.5%(6/48)有胸苷类似物突变(TAMs)。分析的所有潜在危险因素,包括年龄和ART疗程,均与VL未被抑制或HIVDR无显著相关性。尽管高水平的NNRTI突变支持向多替拉韦的转换,但NRTI突变的存在,尤其是TAMs,可能会影响基于多替拉韦的治疗方案或其他二线ART选择。因此,中等水平的VS流行率和较高的HIVDR流行率需要及时更换ART方案并加强依从性咨询。

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