Department of Biomedical and Molecular Sciences and Public Health, Queen's University, Kingston, Ontario, Canada.
CIHR Canadian HIV Trials Network (CIHR-CTN), Vancouver, British Columbia, Canada.
PLoS One. 2022 Jul 14;17(7):e0270590. doi: 10.1371/journal.pone.0270590. eCollection 2022.
Although micronutrient and antioxidant supplementation are widely used by persons with human immunodeficiency virus (HIV), a therapeutic role beyond recommended daily allowances (RDA) remains unproven. An oral high-dose micronutrient and antioxidant supplement (Treatment) was compared to an RDA supplement (Control) for time to progressive immunodeficiency or initiation of antiretroviral therapy (ART) in people living with HIV (PLWH).
This study was a randomized, double-blind, placebo-controlled multicenter clinical trial. PLWH were recruited from Canadian HIV Trials Network sites, and followed quarterly for two years. Eligible participants were asymptomatic, antiretroviral treatment (ART)-naïve, HIV-seropositive adults with a CD4 T lymphocyte count (CD4 count) between 375-750 cells/μL. Participants were randomly allocated 1:1 to receive Treatment or Control supplements. The primary outcome was a composite of time-to-first of confirmed CD4 count below 350 cells/μL, initiation of ART, AIDS-defining illness or death. Primary analysis was by intention-to-treat. Secondary outcomes included CD4 count trajectory from baseline to ART initiation or two years. A Data and Safety Monitoring Board reviewed the study for safety, recruitment and protocol adherence every six months.
Of 171 enrolled participants: 66 (38.6%) experienced a primary outcome: 27 reached a CD4 count below 350 cells/μL, and 57 started ART. There was no significant difference in time-to-first outcome between groups (Hazard Ratio = 1.05; 95%CI: 0.65, 1.70), or in time to any component outcome. Using intent-to-treat censoring, mean annualized rates of CD4 count decline were -42.703 cells/μL and -79.763 cells/μL for Treatment and Control groups, with no statistical difference in the mean change between groups (-37.06 cells/μL/52 weeks, 95%CI: (-93.59, 19.47); p = 0.1993). Accrual was stopped at 171 of the 212 intended participants after an interim analysis for futility, although participant follow-up was completed.
In ART-naïve PLWH, high-dose antioxidant, micronutrient supplementation compared to RDA supplementation had no significant effect on disease progression or ART initiation.
ClinicalTrials.gov Identifier: NCT00798772.
尽管有人体免疫缺陷病毒（HIV）感染者广泛使用微量营养素和抗氧化剂补充剂，但超出推荐日摄入量（RDA）的治疗作用仍未得到证实。一种口服高剂量微量营养素和抗氧化剂补充剂（治疗组）与 RDA 补充剂（对照组）在 HIV 感染者（PLWH）中进行了比较，以观察其在进展性免疫缺陷或开始抗逆转录病毒治疗（ART）方面的效果。
这是一项随机、双盲、安慰剂对照的多中心临床试验。PLWH 是从加拿大艾滋病毒试验网络站点招募的，并每季度随访两年。合格的参与者是无症状、未接受过抗逆转录病毒治疗（ART）、HIV 阳性、CD4 淋巴细胞计数（CD4 计数）在 375-750 个细胞/μL 之间的成年人。参与者以 1:1 的比例随机分配接受治疗或对照补充剂。主要结局是首次确认 CD4 计数低于 350 个细胞/μL、开始接受 ART、艾滋病定义性疾病或死亡的复合事件。主要分析采用意向治疗。次要结局包括从基线到开始 ART 或两年时的 CD4 计数轨迹。一个数据和安全监测委员会每六个月审查一次研究的安全性、招募情况和协议依从性。
在 171 名入组的参与者中：66 人（38.6%）出现了主要结局：27 人 CD4 计数降至 350 个细胞/μL 以下，57 人开始接受 ART。两组之间首次结局的时间无显著差异（风险比=1.05；95%CI：0.65，1.70），也没有任何组成部分结局的时间差异。采用意向治疗 censoring，治疗组和对照组的 CD4 计数每年下降平均速率分别为-42.703 个细胞/μL 和-79.763 个细胞/μL，两组间的平均变化无统计学差异（-37.06 个细胞/μL/52 周，95%CI：-93.59，19.47；p=0.1993）。尽管参与者的随访已经完成，但在中期分析显示无效后，停止了对 212 名预期参与者中的 171 名的入组。
在未经 ART 治疗的 PLWH 中，与 RDA 补充剂相比，高剂量抗氧化剂、微量营养素补充剂对疾病进展或 ART 开始没有显著影响。
ClinicalTrials.gov 标识符：NCT00798772。
