Yan Lei, Henegar Cassidy E, Marconi Vincent C, Gordon Kirsha S, Hicks Charles, Vannappagari Vani, Justice Amy C, Aslan Mihaela
Veterans Affairs (VA) Connecticut Healthcare System Cooperative Studies Program Clinical Epidemiology Research Center (CSP-CERC), 950 Campbell Avenue, West Haven, CT, 06516-2770, USA.
Yale University School of Public Health, New Haven, CT, USA.
AIDS Res Ther. 2024 Dec 21;21(1):96. doi: 10.1186/s12981-024-00681-w.
Real-world data on treatment patterns and clinical outcomes for newer drugs, including integrase strand transfer inhibitors, among older people with human immunodeficiency virus (PWH) are limited.
This cohort study included PWH enrolled in the Veterans Aging Cohort Study (VACS) who were prescribed a standard 3-drug antiretroviral therapy (ART) regimen containing dolutegravir (DTG), bictegravir (BIC), cobicistat boosted elvitegravir (EVG), raltegravir (RAL), or darunavir/ritonavir (DRV) plus 2 nucleoside reverse transcriptase inhibitors between January 1, 2014, and March 31, 2020, and who were ≥50 years at regimen initiation. The association between regimen and virologic effectiveness or discontinuation was assessed using logistic regression models with inverse probability of treatment weights. Pairwise comparisons were made between DTG-based regimen and each of the other 3-drug regimens, stratified by ART experience.
Among 15,702 PWH (across treatment groups, median age 58-62 years; 94-98% male; 5-11% Hispanic; 44-60% Black; 29-42% White), 5,800 received DTG-based regimens, 2,081 BIC-based regimens, 4,159 EVG-based regimens, 1,607 RAL-based regimens, and 2,055 received DRV-based regimens. Among ART-naïve PWH, there were no statistical differences in the odds of virologic suppression, and 6- and 12-month discontinuations were higher in those on DRV. Among ART-experienced PWH, compared to DTG, those on RAL and DRV were less likely to be suppressed at 6 months (RAL vs DTG: aOR 0.64, 95% CI 0.51-0.81; DRV vs DTG: aOR 0.63, 95% CI 0.51-0.76) and those on EVG and DRV were less likely suppressed at 12 months (EVG vs DTG: aOR 0.82, 95% CI 0.68-0.99; DRV vs DTG: aOR 0.64, 95% CI 0.52-0.80). Those on DRV were more likely to have virologic failure within 12 months (aOR 1.96, 95% CI 1.30-2.97). Six- and 12-month discontinuations were higher in those on RAL and DRV, but less likely for BIC-based regimens.
DTG-based regimens demonstrated higher levels of effectiveness and durability compared to DRV- or RAL-based regimens and had similar treatment responses as BIC- and EVG-based regimens among ART-experienced older PWH.
关于新型药物（包括整合酶链转移抑制剂）在老年人类免疫缺陷病毒感染者（PWH）中的治疗模式和临床结局的真实世界数据有限。
这项队列研究纳入了参加退伍军人老龄化队列研究（VACS）的PWH，他们在2014年1月1日至2020年3月31日期间接受了包含多替拉韦（DTG）、比克替拉韦（BIC）、考比司他增强的艾维雷韦（EVG）、拉替拉韦（RAL）或达芦那韦/利托那韦（DRV）加2种核苷类逆转录酶抑制剂的标准三联抗逆转录病毒疗法（ART）方案，且在开始治疗方案时年龄≥50岁。使用具有治疗权重逆概率的逻辑回归模型评估治疗方案与病毒学有效性或停药之间的关联。按ART经验分层，对基于DTG的方案与其他每种三联药物方案进行两两比较。
在15702名PWH中（各治疗组的中位年龄为58 - 62岁；94 - 98%为男性；5 - 11%为西班牙裔；44 - 60%为黑人；29 - 42%为白人），5800人接受基于DTG的方案，2081人接受基于BIC的方案，4159人接受基于EVG的方案，1607人接受基于RAL的方案，2055人接受基于DRV的方案。在初治PWH中，病毒学抑制的几率无统计学差异，接受DRV治疗的患者6个月和12个月停药率更高。在有ART经验的PWH中，与DTG相比，接受RAL和DRV治疗的患者在6个月时病毒学抑制的可能性较小（RAL与DTG相比：调整后比值比[aOR]为0.64，95%置信区间[CI]为0.51 - 0.81；DRV与DTG相比：aOR为0.63，95% CI为0.51 - 0.76），接受EVG和DRV治疗的患者在12个月时病毒学抑制的可能性较小（EVG与DTG相比：aOR为0.82，95% CI为0.68 - 0.99；DRV与DTG相比：aOR为0.64，95% CI为0.52 - 0.80）。接受DRV治疗的患者在12个月内病毒学失败的可能性更大（aOR为1.96，95% CI为1.30 - 2.97）。接受RAL和DRV治疗的患者6个月和12个月停药率更高，但基于BIC的方案停药可能性较小。
在有ART经验的老年PWH中，与基于DRV或RAL的方案相比，基于DTG的方案显示出更高的有效性和持久性，并且与基于BIC和EVG的方案具有相似的治疗反应。
