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在塞内加尔一个分散式城市艾滋病病毒诊所,在检测即治疗政策实施之前,接受一线抗逆转录病毒治疗至少12个月的成年患者中,艾滋病病毒-1病毒学高失败率和耐药情况。

High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat.

作者信息

Ekollo Mbange Aristid, Malick Diouara Abou Abdallah, Diop-Ndiaye Halimatou, Diaw Diouf Ndèye Aminata, Ngom-Ngueye Ndèye Fatou, Ndiaye Touré Kine, Dieng Ahmed, Lô Seynabou, Fall Mamadou, Fon Mbacham Wilfred, Mboup Souleymane, Touré-Kane Coumba

机构信息

The Institute for Health Research, Epidemiological Surveillance and Training (IRESSEF), Diamniadio, Senegal.

The Biotechnology Center and Department of Biochemistry, University of Yaoundé I, Yaoundé, Cameroon.

出版信息

Infect Dis (Auckl). 2021 May 10;14:11786337211014503. doi: 10.1177/11786337211014503. eCollection 2021.

Abstract

BACKGROUND

The feasibility of antiretroviral therapy (ART) monitoring remains problematic in decentralized HIV clinic settings of sub-Saharan Africa. We assessed the rates and correlates of HIV-1 virological failure (VF) and drug resistance (DR) in 2 pre-test-and-treat urban clinic settings of Senegal.

METHODS

Consenting HIV-1-infected adults (⩾18 years) receiving first-line ART for ⩾12 months were cross-sectionally enrolled between January and March 2015, at the referral outpatient treatment center of Dakar (n = 151) and decentralized regional hospital of Saint-Louis (n = 127). In the 12 months preceding plasma specimens' collection patients at Saint-Louis had no viral load (VL) testing. Significant predictors of VF (VL ⩾ 1000 copies/ml) and DR (clinically relevant mutations) were determined using binomial logistic regression in R software.

RESULTS

Of the 278 adults on EFV-/NVP-based regimens, 32 (11.5% [95%CI: 8.0-15.9]) experienced VF. Failing and non-failing patients had comparable median time [interquartile] on ART (69.5 [23.0-89.5] vs 64.0 [34.0-99.0] months;  = .46, Mann-Whitney -test). Of the 27 viraemic isolates successfully genotyped, 20 (74.1%) carried DR mutations; most frequent were M184VI (55.6%), K103N (37.1%), thymidine analog mutations (29.6%), Y181CY (22.2%). The pattern of mutations did not always correspond to the ongoing treatment. The adjusted odds of VF was significantly associated with the decentralized clinic site ( < .001) and CD4 < 350 cells/mm ( < .006). Strong correlates of DR also included Saint-Louis ( < .009), CD4 < 350 cells/mm ( <. 001), and nevirapine-based therapies (comparator: efavirenz-based therapies;  < .027). In stratification analyses by site, higher rate of VF at Saint-Louis (20.5% [95%CI: 13.8-28.5] vs 4.0% [95%CI: 1.5-8.5] in Dakar) was associated with nevirapine-based therapies (OR = 3.34 [1.07-11.75],  = .038), self-reported missing doses (OR = 3.30 [1.13-10.24],  = .029), and medical appointments (OR = 2.91 [1.05-8.47],  = .039) in the last 1 and 12 months(s), respectively. The higher rate of DR at Saint-Louis (12.9% [95%CI: 7.6-20.1] vs 2.7% [95%CI: 0.7-6.7] in Dakar) was associated with nevirapine-based therapies (OR = 5.13 [1.12-37.35],  = .035).

CONCLUSION

At decentralized urban settings, there is need for enhanced virological monitoring and adherence support. HIV programs in Senegal should intensify early HIV diagnosis for effective test-and-treat. These interventions, in addition to the superiority of efavirenz-based therapies provide a favorable framework for transitioning to the recommended potent drug dolutegravir, thereby ensuring its long-term use.

摘要

背景

在撒哈拉以南非洲地区分散的艾滋病诊所环境中,抗逆转录病毒疗法(ART)监测的可行性仍然存在问题。我们评估了塞内加尔两个城市预检并治疗诊所环境中HIV-1病毒学失败(VF)和耐药性(DR)的发生率及相关因素。

方法

2015年1月至3月,在达喀尔的转诊门诊治疗中心(n = 151)和圣路易的分散区域医院(n = 127),对同意参加研究的接受一线抗逆转录病毒治疗至少12个月的HIV-1感染成人(≥18岁)进行横断面研究。在圣路易,血浆标本采集前12个月内患者未进行病毒载量(VL)检测。使用R软件中的二项逻辑回归确定病毒学失败(VL≥1000拷贝/ml)和耐药性(临床相关突变)的显著预测因素。

结果

在278名接受基于依非韦伦/奈韦拉平方案治疗的成人中,32名(11.5%[95%CI:8.0 - 15.9])经历了病毒学失败。失败和未失败患者接受抗逆转录病毒治疗的中位时间[四分位间距]相当(69.5[23.0 - 89.5]个月对64.0[34.0 - 99.0]个月;P = 0.46,曼-惠特尼U检验)。在成功进行基因分型的27份病毒血症分离株中,20份(74.1%)携带耐药突变;最常见的是M184VI(55.6%)、K103N(37.1%)、胸苷类似物突变(29.6%)、Y181CY(22.2%)。突变模式并不总是与正在进行的治疗相对应。病毒学失败的校正比值与分散诊所地点(P < 0.001)和CD4 < 350细胞/mm³(P < 0.006)显著相关。耐药的强相关因素还包括圣路易(P < 0.009)、CD4 < 350细胞/mm³(P < 0.001)以及基于奈韦拉平的治疗方案(对照:基于依非韦伦的治疗方案;P < 0.027)。在按地点分层分析中,圣路易较高的病毒学失败率(20.5%[95%CI:13.8 - 28.5]对达喀尔的4.0%[95%CI:1.5 - 8.5])与基于奈韦拉平的治疗方案(OR = 3.34[1.07 - 11.75],P = 0.038)、自我报告的漏服剂量(OR = 3.30[1.13 - 10.24],P = 0.029)以及过去1个月和12个月内的医疗预约(OR = 2.91[1.05 - 8.47],P = 0.039)分别相关。圣路易较高的耐药率(12.9%[95%CI:7.6 - 20.1]对达喀尔的2.7%[95%CI:0.7 - 6.7])与基于奈韦拉平的治疗方案(OR = 5.13[1.12 - 37.35],P = 0.035)相关。

结论

在分散的城市环境中,需要加强病毒学监测和依从性支持。塞内加尔的艾滋病项目应加强早期艾滋病诊断以实现有效的检测和治疗。这些干预措施以及基于依非韦伦治疗方案的优势为过渡到推荐的强效药物多替拉韦提供了有利框架,从而确保其长期使用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a96/8120520/7442b0e090cd/10.1177_11786337211014503-fig1.jpg

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