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喀麦隆的治疗前 HIV 耐药性和遗传多样性:对一线治疗方案的影响。

Pre-Treatment HIV Drug Resistance and Genetic Diversity in Cameroon: Implications for First-Line Regimens.

机构信息

Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Messa, Yaoundé P.O. Box 3077, Cameroon.

Faculty of Health Science, University of Buea, Buea P.O. Box 0063, Cameroon.

出版信息

Viruses. 2023 Jun 28;15(7):1458. doi: 10.3390/v15071458.

Abstract

The efficacy of first-line antiretroviral therapy (ART) may be hampered by the presence of HIV drug resistance (HIVDR). We described HIV-1 pre-treatment drug resistance (PDR) patterns, effect of viral clades on PDR, and programmatic implications on first-line regimens in Cameroon. A sentinel surveillance of PDR was conducted from 2014 to 2019. Sequencing of HIV-1 protease and reverse transcriptase was performed, and HIVDR was interpreted using Stanford HIVdb.v.9.4. In total, 379 sequences were obtained from participants (62% female, mean age 36 ± 10 years). The overall PDR rate was 15.0% [95% CI: 11.8-19.0] nationwide, with significant disparity between regions ( = 0.03). NNRTI PDR was highest (12.4%), of which 7.9% had DRMs to EFV/NVP. Two regions had EFV/NVP PDR above the 10% critical threshold, namely the Far North (15%) and East (10.9%). Eighteen viral strains were identified, predominated by CRF02_AG (65.4%), with no influence of genetic diversity PDR occurrence. TDF-3TC-DTG predictive efficacy was superior (98.4%) to TDF-3TC-EFV (92%), < 0.0001. The overall high rate of PDR in Cameroon, not substantially affected by the wide HIV-1 genetic diversity, underscores the poor efficacy of EFV/NVP-based first-line ART nationwide, with major implications in two regions of the country. This supports the need for a rapid transition to NNRTI-sparing regimens, with TDF-3TC-DTG having optimal efficacy at the programmatic level.

摘要

一线抗逆转录病毒疗法 (ART) 的疗效可能因 HIV 耐药性 (HIVDR) 的存在而受到阻碍。我们描述了喀麦隆 HIV-1 治疗前耐药 (PDR) 模式、病毒群系对 PDR 的影响以及一线方案的方案学意义。从 2014 年到 2019 年,进行了 PDR 的哨点监测。对 HIV-1 蛋白酶和逆转录酶进行了测序,并使用斯坦福 HIVdb.v.9.4 解释了 HIVDR。共从参与者中获得了 379 个序列(62%为女性,平均年龄 36±10 岁)。全国范围内的总体 PDR 率为 15.0%[95%CI:11.8-19.0],地区间存在显著差异(=0.03)。NNRTI PDR 最高(12.4%),其中 7.9%有对 EFV/NVP 的耐药突变。有两个地区的 EFV/NVP PDR 超过了 10%的临界阈值,即北部(15%)和东部(10.9%)。鉴定出 18 种病毒株,以 CRF02_AG 为主(65.4%),遗传多样性对 PDR 发生率无影响。TDF-3TC-DTG 的预测疗效(98.4%)优于 TDF-3TC-EFV(92%),<0.0001。喀麦隆总体上较高的 PDR 率,并没有因 HIV-1 广泛的遗传多样性而受到实质性影响,这突显了 EFV/NVP 为基础的一线 ART 在全国范围内的疗效不佳,对该国的两个地区有重大影响。这支持需要迅速过渡到 NNRTI 节省方案,在方案层面上 TDF-3TC-DTG 具有最佳疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2987/10385257/ee0fc1031058/viruses-15-01458-g001.jpg

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