我们是否应该在新诊断出人类免疫缺陷病毒的患者中检测基线整合酶耐药？
Should We Be Testing for Baseline Integrase Resistance in Patients Newly Diagnosed With Human Immunodeficiency Virus?
机构信息
Department of Medicine, Brigham and Women's Hospital, Boston, MA.
Harvard Medical School, Boston, Massachusetts.
出版信息
Clin Infect Dis. 2017 Oct 15;65(8):1274-1281. doi: 10.1093/cid/cix542.
BACKGROUND
Current guidelines recommend genotype resistance testing at diagnosis to guide initial selection of antiretroviral therapy (ART). Many standard resistance genotypes exclude testing for resistance to integrase inhibitors ("IR testing"), although this class of drugs is a component of most recommended first-line regimens.
METHODS
We compared the 96-week clinical outcomes and cost-effectiveness of 2 strategies: no IR testing vs IR testing performed at human immunodeficiency virus (HIV) diagnosis. The base case prevalence of transmitted integrase strand transfer inhibitor (INSTI)-resistant (INSTI-R) virus is estimated at 0.1%. With no IR testing, all patients start dolutegravir (DTG)-based ART after genotype; 12-week suppression rates are 90% (INSTI-susceptible [INSTI-S] virus) and 35% (INSTI-R virus). Those not suppressed at 12 weeks undergo IR testing; if diagnosed with INSTI-R virus, they change to ritonavir-boosted darunavir (DRV/r)-based ART. With IR testing, all patients are diagnosed with INSTI-S/INSTI-R virus prior to ART initiation and start DTG- or DRV/r-based regimens, respectively. Costs include IR tests (175 US dollars [USD]) and ART (41100-44900 USD/year). We examined the impact of key parameters in sensitivity analyses.
RESULTS
IR testing resulted in worse clinical outcomes compared to no IR testing and increased costs by 200 USD/person/year. Prevalence of transmitted INSTI-R virus did not affect the favored strategy. No IR testing remained clinically preferred unless DTG suppression of INSTI-R virus was <20% or 96-week DRV/r suppression was >92%. If quality of life was worse with DRV/r- than DTG-based ART, no IR testing was clinically preferred over an even broader range of parameters.
CONCLUSIONS
In patients with newly diagnosed HIV, IR testing is projected to result in worse outcomes and is not cost-effective. Pretreatment assessment for INSTI resistance should not be recommended in treatment guidelines.
背景
目前的指南建议在诊断时进行基因型耐药性检测，以指导初始抗逆转录病毒治疗（ART）的选择。许多标准耐药基因型不包括对整合酶抑制剂耐药性的检测（“IR 检测”），尽管这类药物是大多数推荐的一线治疗方案的组成部分。
方法
我们比较了两种策略的 96 周临床结果和成本效益：不进行 IR 检测与在 HIV 诊断时进行 IR 检测。传播的整合酶链转移抑制剂（INSTI）耐药（INSTI-R）病毒的基础病例流行率估计为 0.1%。不进行 IR 检测时，所有患者在基因型后开始使用多替拉韦（DTG）为基础的 ART；12 周抑制率为 90%（INSTI 敏感[INSTI-S]病毒）和 35%（INSTI-R 病毒）。12 周未抑制的患者进行 IR 检测；如果诊断为 INSTI-R 病毒，他们改用利托那韦增强的达芦那韦（DRV/r）为基础的 ART。进行 IR 检测时，所有患者在开始 ART 前均诊断为 INSTI-S/INSTI-R 病毒，并分别开始使用 DTG 或 DRV/r 为基础的方案。成本包括 IR 检测（175 美元[USD]）和 ART（41100-44900 美元/年）。我们在敏感性分析中检查了关键参数的影响。
结果
与不进行 IR 检测相比，IR 检测导致临床结局恶化，每年每人增加 200 美元的成本。传播的 INSTI-R 病毒的流行率并不影响首选策略。除非 DTG 抑制 INSTI-R 病毒<20%或 96 周 DRV/r 抑制>92%，否则不进行 IR 检测仍然是临床首选。如果 DRV/r 为基础的 ART 比 DTG 为基础的 ART 对生活质量的影响更差，那么即使在更广泛的参数范围内，不进行 IR 检测也是临床首选。
结论
在新诊断的 HIV 患者中，IR 检测预计会导致更差的结果，并且不具有成本效益。不建议在治疗指南中对 INSTI 耐药性进行治疗前评估。
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