Asociacion Civil Impacta Salud y Educacion, Lima, Perú.
University of Washington, Seattle, Washington, USA.
Clin Infect Dis. 2021 Mar 15;72(6):1042-1050. doi: 10.1093/cid/ciaa167.
In addition to demonstrated public health benefits on reducing transmission, it remains unclear how early antiretroviral therapy (ART) must be started after acquisition of human immunodeficiency virus (HIV) to maximize individual benefits.
We conducted an open-label randomized clinical study in Lima, Peru among adult men who have sex with men and transgender women with acute (HIV-antibody negative/HIV-1 RNA positive) or recent (confirmed negative HIV-antibody or RNA test within 3 months) HIV infection, who were randomized to start ART immediately versus defer by 24 weeks. We evaluated outcomes by treatment arm and immunologic markers by days since estimated date of detectible infection (EDDI).
Of 216 participants, 105 were assigned to immediate arm and 111 to deferred arm (median age 26.8 years, 37% with acute HIV). The incidence of non-ART-related adverse events was lower in immediate versus deferred arm (83 vs 123/100 person-years, IRR 0.67 (95% confidence interval [CI] .47, .95; P = .02), the difference dominated by fewer infections in those treated immediately. After 24 weeks of ART, between-group differences in CD4/CD8 cell ratio lessened (P = .09 overall), but differences between those initiating ART ≤ 30 days from EDDI (median 1.03, interquartile range [IQR] 0.84, 1.37), and those initiating > 90 days (0.88, IQR 0.61, 1.11) remained, P = .02. Principal components analysis of 20 immune biomarkers demonstrated distinct patterns between those starting ART > 90 days from EDDI versus those starting within 30 or 90 days (both P < .001).
To our knowledge, this is the only evaluation of randomized ART initiation during primary HIV and provides evidence to explicitly consider acute HIV in World Health Organization recommendations for universal ART.
NCT01815580.
除了已证实的减少传播的公共卫生效益外，人们仍不清楚在获得人类免疫缺陷病毒 (HIV) 后，为了使个体获益最大化，抗逆转录病毒治疗 (ART) 必须多早开始。
我们在秘鲁利马开展了一项针对急性 (HIV 抗体阴性/HIV-1 RNA 阳性) 或近期 (3 个月内 HIV 抗体或 RNA 检测确证阴性) HIV 感染者的开放性随机临床试验，这些感染者为男男性行为者和跨性别女性，他们被随机分为立即开始 ART 组和延迟 24 周开始 ART 组。我们根据治疗组评估了结局，并根据自估计可检测感染日期 (EDDI) 的天数评估了免疫标志物。
在 216 名参与者中，105 名被分配到立即治疗组，111 名被分配到延迟治疗组（中位年龄 26.8 岁，37%为急性 HIV）。与延迟治疗组相比，立即治疗组非 ART 相关不良事件发生率较低（83 比 123/100 人年，IRR 0.67（95%CI 0.47，0.95；P=0.02），差异主要是由于立即治疗组的感染减少。在开始 ART 治疗 24 周后，两组间 CD4/CD8 细胞比值的差异缩小（总体 P=0.09），但在 EDDI 后≤30 天开始 ART（中位 1.03，四分位距 [IQR] 0.84，1.37）和 EDDI 后>90 天开始 ART（0.88，IQR 0.61，1.11）的两组间差异仍存在，P=0.02。对 20 个免疫生物标志物的主成分分析表明，EDDI 后>90 天开始 ART 与 EDDI 后 30 天或 90 天内开始 ART 的两组之间存在明显差异（均 P<0.001）。
据我们所知，这是唯一一项在原发性 HIV 中评估随机 ART 起始的研究，为世界卫生组织关于普遍 ART 的建议中明确考虑急性 HIV 提供了证据。
NCT01815580。
