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抗逆转录病毒治疗依从性、病毒载量升高以及妊娠时开始治疗的人类免疫缺陷病毒感染妇女的耐药突变:巢式病例对照研究。

Antiretroviral Adherence, Elevated Viral Load, and Drug Resistance Mutations in Human Immunodeficiency Virus-infected Women Initiating Treatment in Pregnancy: A Nested Case-control Study.

机构信息

Division of Epidemiology and Biostatistics, University of Cape Town, South Africa.

Centre for Infectious Diseases Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, South Africa.

出版信息

Clin Infect Dis. 2020 Jan 16;70(3):501-508. doi: 10.1093/cid/ciz209.

Abstract

BACKGROUND

Elevated viral load (VL) early after antiretroviral therapy (ART) initiation appears frequently in pregnant and postpartum women living with human immunodeficiency virus; however the relative contributions of pre-ART drug resistance mutations (DRMs) vs nonadherence in the etiology of elevated VL are unknown.

METHODS

Within a cohort of women initiating ART during pregnancy in Cape Town, South Africa, we compared women with elevated VL after initial suppression (cases, n = 80) incidence-density matched to women who maintained suppression over time (controls, n = 87). Groups were compared on pre-ART DRMs and detection of antiretrovirals in stored plasma.

RESULTS

The prevalence of pre-ART DRMs was 10% in cases and 5% in controls (adjusted odds ratio [aOR], 1.53 [95% confidence interval {CI}, .4-5.9]); all mutations were to nonnucleoside reverse transcriptase inhibitors. At the time of elevated VL, 19% of cases had antiretrovirals detected in plasma, compared with 87% of controls who were suppressed at a matched time point (aOR, 131.43 [95% CI, 32.8-527.4]). Based on these findings, we estimate that <10% of all elevated VL in the cohort may be attributable to pre-ART DRMs vs >90% attributable to ART nonadherence.

CONCLUSIONS

DRMs account for a small proportion of all elevated VL among women occurring in the 12 months after ART initiation during pregnancy in this setting, with nonadherence appearing to drive most episodes of elevated VL. Alongside the drive for access to more robust antiretroviral agents in resource-limited settings, there is an ongoing need for effective strategies to support ART adherence in this patient population.

摘要

背景

在开始抗逆转录病毒治疗(ART)后早期,艾滋病毒感染者孕妇和产后妇女的病毒载量(VL)升高现象较为常见;然而,尚不清楚导致 VL 升高的原因是 ART 前耐药相关突变(DRMs)还是不依从治疗。

方法

在南非开普敦的一项孕妇开始 ART 的队列研究中,我们将初始抑制后 VL 升高的女性(病例,n = 80)与随时间维持抑制的女性(对照,n = 87)进行了比较。比较了两组的 ART 前 DRMs 以及在储存血浆中检测到的抗逆转录病毒药物。

结果

病例组的 ART 前 DRMs 患病率为 10%,对照组为 5%(校正比值比 [aOR],1.53 [95%置信区间 {CI},.4-5.9]);所有突变均为非核苷类逆转录酶抑制剂。在 VL 升高时,19%的病例在血浆中检测到抗逆转录病毒药物,而在匹配时间点抑制的对照者中为 87%(aOR,131.43 [95% CI,32.8-527.4])。根据这些发现,我们估计在该队列中,VL 升高的所有病例中,仅有不到 10%可能归因于 ART 前 DRMs,而超过 90%可能归因于 ART 不依从。

结论

在这一背景下,在妊娠期间开始 ART 后的 12 个月内,DRMs 仅占所有 VL 升高的一小部分,而不依从治疗似乎是大多数 VL 升高的原因。在资源有限的环境中,除了努力获得更有效的抗逆转录病毒药物外,还需要继续制定有效的策略来支持这一患者群体的 ART 依从性。

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