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传播的 HIV-1 耐药性对一线含两种核苷（酸）逆转录酶抑制剂加整合酶抑制剂或蛋白酶抑制剂的抗逆转录病毒治疗疗效的影响。

Impact of transmitted HIV-1 drug resistance on the efficacy of first-line antiretroviral therapy with two nucleos(t)ide reverse transcriptase inhibitors plus an integrase inhibitor or a protease inhibitor.

机构信息

Department of Medical Biotechnologies, University of Siena, Siena, Italy.

University Division of Infectious Diseases, Hospital Department of Specialized and Internal Medicine, Siena University Hospital, Siena, Italy.

出版信息

J Antimicrob Chemother. 2018 Sep 1;73(9):2480-2484. doi: 10.1093/jac/dky211.

DOI:10.1093/jac/dky211

PMID:29945251

Abstract

OBJECTIVES

To examine the impact of transmitted drug resistance (TDR) on response to first-line regimens with integrase strand transfer inhibitors (INSTIs) or boosted protease inhibitors (bPIs).

METHODS

From an Italian observational database (ARCA) we selected HIV-1-infected drug-naive patients starting two NRTIs and either an INSTI or a bPI, with an available pre-ART resistance genotype. The endpoint was virological failure (VF; plasma HIV-1 RNA >200 copies/mL after week 24). WHO surveillance drug resistance mutations and the Stanford algorithm were used to classify patients into three resistance categories: no TDR (A), TDR but fully-active ART prescribed (B), TDR and at least low-level resistance to one or more prescribed drug (C).

RESULTS

We included 1365 patients with a median follow-up of 96 weeks (IQR 54-110): 1205 (88.3%) starting bPI and 160 (11.7%) INSTI. Prevalence of TDR was 6.1%, 12.5%, 2.6% and 0% for NRTI, NNRTI, bPI and INSTI, respectively. Cumulative Kaplan-Meier estimates for VF at 48 weeks were 11% (95% CI 10.1%-11.9%) for the bPI group and 7.7% (95% CI 5.4%-10%) for the INSTI group. In the INSTI group, cumulative estimates for VF at 48 weeks were 6% (95% CI 4%-8%) in resistance category A, 5% (95% CI 1%-10%) in B and 50% (95% CI 30%-70%) in C (P < 0.001). Resistance category C [versus A, adjusted hazard ratio (aHR) 12.6, 95% CI 3.2-49.8, P < 0.001] and nadir CD4 (+100 cells/mm3, aHR 0.6, 95% CI 0.4-0.9, P = 0.03) predicted VF. In the bPI group, VF rates were not influenced by baseline resistance.

CONCLUSIONS

Our data support the need for NRTI resistance genotyping in patients starting an INSTI-based first-line ART.

摘要

目的

研究传播性耐药（TDR）对整合酶抑制剂（INSTIs）或增效蛋白酶抑制剂（bPIs）一线方案治疗应答的影响。

方法

我们从意大利观察性数据库（ARCA）中选择了开始使用两种核苷逆转录酶抑制剂（NRTIs）加 INSTI 或 bPI 且有可用的 ART 前耐药基因型的 HIV-1 感染的初治药物患者。终点是病毒学失败（VF；治疗 24 周后血浆 HIV-1 RNA>200 拷贝/mL）。我们使用世界卫生组织（WHO）监测耐药突变和斯坦福算法将患者分为三种耐药类别：无 TDR（A）、有 TDR 但有完全有效的 ART 方案（B）和有 TDR 且对一种或多种处方药物有至少低水平耐药（C）。

结果

我们纳入了 1365 例中位随访时间为 96 周（IQR 54-110）的患者：1205 例（88.3%）开始使用 bPI，160 例（11.7%）使用 INSTI。NRTI、NNRTI、bPI 和 INSTI 的 TDR 发生率分别为 6.1%、12.5%、2.6%和 0%。48 周时 bPI 组和 INSTI 组的 VF 累积 Kaplan-Meier 估计值分别为 11%（95%CI 10.1%-11.9%）和 7.7%（95%CI 5.4%-10%）。在 INSTI 组中，48 周时 VF 的累积估计值在耐药类别 A 中为 6%（95%CI 4%-8%），在 B 中为 5%（95%CI 1%-10%），在 C 中为 50%（95%CI 30%-70%）（P<0.001）。耐药类别 C[与 A 相比，调整后的危险比（aHR）为 12.6，95%CI 3.2-49.8，P<0.001]和 CD4 最低点（增加 100 个细胞/mm3，aHR 0.6，95%CI 0.4-0.9，P=0.03）预测了 VF。在 bPI 组中，基线耐药不影响 VF 发生率。