在卢旺达接受一线抗逆转录病毒治疗的成年艾滋病毒感染者中获得性艾滋病毒耐药性:一项具有全国代表性的横断面调查。

IF 1.3 4区 医学 Q4 INFECTIOUS DISEASES Antiviral Therapy Pub Date : 2022-06-01 DOI:10.1177/13596535221102690
Gentille Musengimana, Elysee Tuyishime, Athanase Kiromera, Samuel S Malamba, Augustin Mulindabigwi, Madjid R Habimana, Cyprien Baribwira, Muhayimpundu Ribakare, Savio D Habimana, Josh DeVos, Richard C N Mwesigwa, Eugenie Kayirangwa, Jules M Semuhore, Gallican N Rwibasira, Amitabh B Suthar, Eric Remera
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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.</p><p><strong>Results: </strong>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<sup>3</sup> (IQR, 197-484 cells/mm<sup>3</sup>). 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. 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引用次数: 2

摘要

背景:我们评估了卢旺达接受一线抗逆转录病毒治疗(ART)的患者中获得性艾滋病毒耐药性(HIVDR)的患病率及其相关因素。方法:本横断面研究纳入702例接受一线抗逆转录病毒治疗至少6个月,最后病毒载量(VL)结果≥1000拷贝/mL的患者。血浆样本进行VL检测;对未抑制VL的标本进行基因分型,以确定hiv - dr相关突变。数据采用STATA/SE分析。结果:抗逆转录病毒治疗的中位时间为86.4个月(四分位数间距[IQR], 44.8-130.2个月),抗逆转录病毒治疗开始时的中位CD4计数为311个细胞/mm3 (IQR, 197-484个细胞/mm3)。在414例(68.2%)未抑制VL病例中,378例(88.3%)进行了基因分型。HIVDR包括347个(90.4%)非核苷逆转录酶抑制剂- (NNRTI), 291个(75.5%)核苷逆转录酶抑制剂- (NRTI)和13个(3.5%)蛋白酶抑制剂(PI)耐药相关突变。nnrti中最常见的HIVDR突变为K65R(22.7%)、M184V(15.4%)和D67N (9.8%), nnrti中最常见的HIVDR突变为K103N(34.4%)和Y181C/I/V/YC(7%)。获得性HIVDR的独立预测因子包括齐多夫定+拉米夫定+奈韦拉平当前ART方案(校正优势比[aOR], 3.333[95%可信区间(CI): 1.022-10.870];p = 0.046)对NRTI耐药和目前替诺福韦+恩曲他滨+奈韦拉平抗逆转录病毒治疗方案(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)为NNRTI耐药性。曾经切换ART方案的历史与NRTI耐药相关(aOR, 2.53 [95% CI: 1.198-5.356];p = 0.016)和NNRTI耐药性(aOR, 3.23 [95% CI: 1.435-7.278], p = 0.005)。结论:HIV获得性耐药(HIV acquired drug resistant, HIVDR)在VL再抑制失败的患者中发生率较高,与当前抗逆转录病毒治疗方案和曾经转换抗逆转录病毒治疗方案有关。这项研究的结果支持了目前世卫组织的指南,该指南建议基于nnrti方案的患者应基于单一病毒载量测试进行切换,并表明对接受抗逆转录病毒治疗的患者进行全国性的HIV VL监测可以防止长期治疗失败,否则将导致TAMs的积累和所有NRTI在二线抗逆转录病毒治疗中作为主要药物与多替替韦或增强pi联合使用的潜在疗效丧失。
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Acquired HIV drug resistance among adults living with HIV receiving first-line antiretroviral therapy in Rwanda: A cross-sectional nationally representative survey.

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/mm3 (IQR, 197-484 cells/mm3). 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]; p = 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.

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来源期刊
Antiviral Therapy
Antiviral Therapy 医学-病毒学
CiteScore
2.60
自引率
8.30%
发文量
35
审稿时长
4-8 weeks
期刊介绍: Antiviral Therapy (an official publication of the International Society of Antiviral Research) is an international, peer-reviewed journal devoted to publishing articles on the clinical development and use of antiviral agents and vaccines, and the treatment of all viral diseases. Antiviral Therapy is one of the leading journals in virology and infectious diseases. The journal is comprehensive, and publishes articles concerning all clinical aspects of antiviral therapy. It features editorials, original research papers, specially commissioned review articles, letters and book reviews. The journal is aimed at physicians and specialists interested in clinical and basic research.
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