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应用前病毒 DNA 基因型耐药检测优化多重耐药 HIV-1 经治患者的抗逆转录病毒治疗。

Optimizing Antiretroviral Therapy in Heavily ART-Experienced Patients with Multi-Class Resistant HIV-1 Using Proviral DNA Genotypic Resistance Testing.

机构信息

Division of Infectious Diseases, Department I of Internal Medicine, Medical Faculty and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany.

Department Ib of Internal Medicine, Bundeswehrzentralkrankenhaus Koblenz, Rübenacher Straße 170, 56072 Koblenz, Germany.

出版信息

Viruses. 2023 Jun 27;15(7):1444. doi: 10.3390/v15071444.

DOI:10.3390/v15071444
PMID:37515133
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10384096/
Abstract

Resistance to multiple antiretroviral drugs among people living with HIV (PLWH) can result in a high pill burden, causing toxicity and drug interactions. Thus, the goal is to simplify treatment regimens while maintaining effectiveness. However, former resistance analysis data may not be current or complete. The use of proviral DNA genotyping may assist in selecting appropriate treatment options. A retrospective study was carried out on individuals belonging to the Cologne HIV cohort with a resistance history to two or more antiretroviral (ARV) classes and on non-standard antiretroviral therapy (ART). Patients required former viral RNA and a recent proviral DNA resistance test to be available prior to the switch to ART. Potential discrepancies between resistance test results obtained through RNA and proviral DNA methods and the consequent virological and clinical outcomes following ART adjustments were analyzed. Out of 1250 patients, 35 were eligible for inclusion in this study. The median length of known HIV infection was 27 years, and the median duration of ART was 22 years. Of the 35 participants, 16 had received all five ARV classes. Based on proviral DNA genotyping results, ART was simplified in 17 patients. At the last follow-up examination after changing therapy, 15 patients had HIV RNA <50 copies/mL (median 202 days, range 21-636). The mean number of pills per day decreased from eight to three, and the median intake frequency decreased from two to one time/day (ranges 1-2). Our study supports the use of proviral DNA genotyping as a safe strategy for switching to simplified ART regimens. However, the lack of extensive research on the advantages of proviral DNA genotyping makes it challenging to fully assess its benefits in terms of treatment selection.

摘要

HIV 感染者(PLWH)对多种抗逆转录病毒药物的耐药性可能导致较高的药物负担,引起毒性和药物相互作用。因此,目标是简化治疗方案,同时保持疗效。然而,以前的耐药性分析数据可能不是最新的或完整的。前病毒 DNA 基因分型的使用可能有助于选择合适的治疗方案。对曾接受两种或两种以上抗逆转录病毒(ARV)类药物和非标准抗逆转录病毒治疗(ART)的科隆 HIV 队列个体进行了一项回顾性研究。在开始 ART 之前,患者需要以前的病毒 RNA 和最近的前病毒 DNA 耐药性测试。分析了通过 RNA 和前病毒 DNA 方法获得的耐药性测试结果之间的潜在差异以及随后 ART 调整后的病毒学和临床结果。在 1250 名患者中,有 35 名符合纳入本研究的条件。已知 HIV 感染的中位时间为 27 年,ART 的中位时间为 22 年。在 35 名参与者中,有 16 名接受了所有五种 ARV 类药物。根据前病毒 DNA 基因分型结果,17 名患者简化了 ART。在改变治疗后的最后一次随访检查时,15 名患者的 HIV RNA <50 拷贝/ml(中位数 202 天,范围 21-636)。每天服用的药丸数量从 8 片减少到 3 片,每日服用频率中位数从 2 次减少到 1 次(范围 1-2)。我们的研究支持使用前病毒 DNA 基因分型作为简化 ART 方案的安全策略。然而,由于缺乏对前病毒 DNA 基因分型优势的广泛研究,因此难以全面评估其在治疗选择方面的益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42c1/10384096/9a66a51c5852/viruses-15-01444-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42c1/10384096/029d7584f42e/viruses-15-01444-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42c1/10384096/0350ec583d95/viruses-15-01444-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42c1/10384096/c9305bba418c/viruses-15-01444-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42c1/10384096/9a66a51c5852/viruses-15-01444-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42c1/10384096/029d7584f42e/viruses-15-01444-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42c1/10384096/0350ec583d95/viruses-15-01444-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42c1/10384096/c9305bba418c/viruses-15-01444-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42c1/10384096/9a66a51c5852/viruses-15-01444-g004.jpg

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