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卢旺达接受一线抗逆转录病毒治疗的 HIV 感染者中成年人获得性 HIV 耐药性:一项全国代表性横断面调查。

Acquired HIV drug resistance among adults living with HIV receiving first-line antiretroviral therapy in Rwanda: A cross-sectional nationally representative survey.

机构信息

Ministry of Health, 1242Rwanda Biomedical Center, HIV/AIDs, STIs and OBBI Division, Kigali City, Rwanda.

U.S. Centers for Disease Control and Prevention, Center for Global Health, Division of Global HIV & TB, Rwanda.

出版信息

Antivir Ther. 2022 Jun;27(3):13596535221102690. doi: 10.1177/13596535221102690.

Abstract

BACKGROUND

We assessed the prevalence of acquired HIV drug resistance (HIVDR) and associated factors among patients receiving first-line antiretroviral therapy (ART) in Rwanda.

METHODS

This cross-sectional study included 702 patients receiving first-line ART for at least 6 months with last viral load (VL) results ≥1000 copies/mL. Blood plasma samples were subjected to VL testing; specimens with unsuppressed VL were genotyped to identify HIVDR-associated mutations. Data were analysed using STATA/SE.

RESULTS

Median time on ART was 86.4 months (interquartile range [IQR], 44.8-130.2 months), and median CD4 count at ART initiation was 311 cells/mm (IQR, 197-484 cells/mm). Of 414 (68.2%) samples with unsuppressed VL, 378 (88.3%) were genotyped. HIVDR included 347 (90.4%) non-nucleoside reverse transcriptase inhibitor- (NNRTI), 291 (75.5%) nucleoside reverse transcriptase inhibitor- (NRTI) and 13 (3.5%) protease inhibitor (PI) resistance-associated mutations. The most common HIVDR mutations were K65R (22.7%), M184V (15.4%) and D67N (9.8%) for NRTIs and K103N (34.4%) and Y181C/I/V/YC (7%) for NNRTIs. Independent predictors of acquired HIVDR included current ART regimen of zidovudine + lamivudine + nevirapine (adjusted odds ratio [aOR], 3.333 [95% confidence interval (CI): 1.022-10.870]; p = 0.046) for NRTI resistance and current ART regimen of tenofovir + emtricitabine + nevirapine (aOR, 0.148 [95% CI: 0.028-0.779]; p = 0.025), zidovudine + lamivudine + efavirenz (aOR, 0.105 [95% CI: 0.016-0.693]; p = 0.020) and zidovudine + lamivudine + nevirapine (aOR, 0.259 [95% CI: 0.084-0.793]; p = 0.019) for NNRTI resistance. History of ever switching ART regimen was associated with NRTI resistance (aOR, 2.53 [95% CI: 1.198-5.356]; = 0.016) and NNRTI resistance (aOR, 3.23 [95% CI: 1.435-7.278], p = 0.005).

CONCLUSION

The prevalence of acquired HIV drug resistance (HIVDR) was high among patient failing to re-suppress VL and was associated with current ART regimen and ever switching ART regimen. The findings of this study support the current WHO guidelines recommending that patients on an NNRTI-based regimen should be switched based on a single viral load test and suggests that national HIV VL monitoring of patients receiving ART has prevented long-term treatment failure that would result in the accumulation of TAMs and potential loss of efficacy of all NRTI used in second-line ART as the backbone in combination with either dolutegravir or boosted PIs.

摘要

背景

我们评估了在卢旺达接受一线抗逆转录病毒治疗(ART)的患者中获得性 HIV 耐药(HIVDR)的流行率及其相关因素。

方法

本横断面研究纳入了至少接受了 6 个月一线 ART 治疗且最后一次病毒载量(VL)结果≥1000 拷贝/mL 的 702 名患者。采集血血浆样本进行 VL 检测;未抑制 VL 的标本进行基因型检测,以确定与 HIVDR 相关的突变。使用 STATA/SE 进行数据分析。

结果

ART 中位时间为 86.4 个月(四分位距 [IQR],44.8-130.2 个月),ART 起始时 CD4 计数的中位数为 311 个细胞/mm(IQR,197-484 个细胞/mm)。在 414 份(68.2%)未抑制 VL 的样本中,378 份(88.3%)进行了基因型检测。HIVDR 包括 347 例(90.4%)非核苷类逆转录酶抑制剂(NNRTI)耐药、291 例(75.5%)核苷类逆转录酶抑制剂(NRTI)耐药和 13 例(3.5%)蛋白酶抑制剂(PI)耐药相关突变。最常见的 HIVDR 突变包括 NRTI 中的 K65R(22.7%)、M184V(15.4%)和 D67N(9.8%),NNRTI 中的 K103N(34.4%)和 Y181C/I/V/YC(7%)。获得性 HIVDR 的独立预测因素包括当前的齐多夫定+拉米夫定+奈韦拉平(调整后的优势比 [aOR],3.333 [95%置信区间(CI):1.022-10.870];p = 0.046)的 NRTI 耐药和当前的替诺福韦+恩曲他滨+奈韦拉平(aOR,0.148 [95%CI:0.028-0.779];p = 0.025)、齐多夫定+拉米夫定+依非韦伦(aOR,0.105 [95%CI:0.016-0.693];p = 0.020)和齐多夫定+拉米夫定+奈韦拉平(aOR,0.259 [95%CI:0.084-0.793];p = 0.019)的 NNRTI 耐药。曾经转换过 ART 方案与 NRTI 耐药(aOR,2.53 [95%CI:1.198-5.356]; = 0.016)和 NNRTI 耐药(aOR,3.23 [95%CI:1.435-7.278],p = 0.005)相关。

结论

未能再次抑制 VL 的患者中获得性 HIV 耐药(HIVDR)的流行率很高,与当前的 ART 方案和曾经转换过 ART 方案有关。本研究的结果支持当前的世卫组织指南,该指南建议基于 NNRTI 的方案的患者应根据单次病毒载量检测进行转换,并表明在接受 ART 的患者中进行国家 HIV VL 监测已防止了长期治疗失败,这将导致 TAMs 的积累和潜在地丧失所有 NRTI 的疗效,这些 NRTI 作为二线 ART 的骨干,与多替拉韦或增效 PI 联合使用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5655/9263597/352f63583945/nihms-1812025-f0001.jpg

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