重新审视抗逆转录病毒治疗时代非洲成人复方新诺明预防应用：一项随机对照临床试验。
Revisiting Co-trimoxazole Prophylaxis for African Adults in the Era of Antiretroviral Therapy: A Randomized Controlled Clinical Trial.
机构信息
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi.
出版信息
Clin Infect Dis. 2021 Sep 15;73(6):1058-1065. doi: 10.1093/cid/ciab252.
BACKGROUND
Daily co-trimoxazole is recommended for African adults living with human immunodeficiency virus (HIV) irrespective of antiretroviral treatment, immune status, or disease stage. Benefits of continued prophylaxis and whether co-trimoxazole can be stopped following immune reconstitution are unknown.
METHODS
We conducted a randomized controlled trial at 2 sites in Malawi that enrolled adults with HIV with undetectable viral load and CD4 count of >250/mm3 and randomized them to continue daily co-trimoxazole, discontinue daily co-trimoxazole and begin weekly chloroquine, or discontinue daily co-trimoxazole. The primary endpoint was the preventive effect of co-trimoxazole prophylaxis against death or World Health Organization (WHO) HIV/AIDS stage 3-4 events, using Cox proportional hazards modeling, in an intention-to-treat population.
RESULTS
1499 adults were enrolled. The preventive effect of co-trimoxazole on the primary endpoint was 22% (95% CI: -14%-47%; P = .20) versus no prophylaxis and 25% (-10%-48%; P = .14) versus chloroquine. When WHO HIV/AIDS stage 2 events were added to the primary endpoint, preventive effect increased to 31% (3-51%; P = .032) and 32% (4-51%; P = .026), respectively. Co-trimoxazole and chloroquine prophylaxis effectively prevented clinical malaria episodes (3.8 and 3.0, respectively, vs 28/100 person-years; P < .001).
CONCLUSIONS
Malawian adults with HIV who immune reconstituted on ART and continued co-trimoxazole prophylaxis experienced fewer deaths and WHO HIV/AIDS stage 3-4 events compared with prophylaxis discontinuation, although statistical significance was not achieved. Co-trimoxazole prevented a composite of death plus WHO HIV/AIDS stage 2-4 events. Given poor healthcare access and lack of routine viral load monitoring, co-trimoxazole prophylaxis should continue in adults on ART after immune reconstitution in sub-Saharan Africa. Clinical Trials Registration. NCT01650558.
背景
每日复方磺胺甲噁唑被推荐用于非洲艾滋病毒感染者（HIV），无论其是否接受抗逆转录病毒治疗、免疫状态或疾病阶段如何。持续预防的益处以及免疫重建后是否可以停止使用复方磺胺甲噁唑尚不清楚。
方法
我们在马拉维的 2 个地点进行了一项随机对照试验，招募了病毒载量不可检测且 CD4 计数>250/mm3 的 HIV 感染者，并将他们随机分配至继续每日服用复方磺胺甲噁唑、停止每日服用复方磺胺甲噁唑并开始每周服用氯喹或停止每日服用复方磺胺甲噁唑。主要终点是使用 Cox 比例风险模型，在意向治疗人群中，评估复方磺胺甲噁唑预防治疗对死亡或世界卫生组织（WHO）HIV/AIDS 3-4 期事件的预防效果。
结果
共纳入 1499 名成年人。与未进行预防治疗相比，复方磺胺甲噁唑组对主要终点的预防效果为 22%（95%CI：-14%-47%；P=0.20），与氯喹组的预防效果为 25%（-10%-48%；P=0.14）。当将 WHO HIV/AIDS 2 期事件纳入主要终点时，预防效果分别增加至 31%（3-51%；P=0.032）和 32%（4-51%；P=0.026）。复方磺胺甲噁唑和氯喹预防治疗可有效预防临床疟疾发作（分别为 3.8 和 3.0 例/100 人年，P<0.001）。
结论
在撒哈拉以南非洲地区，接受抗逆转录病毒治疗后免疫重建且继续服用复方磺胺甲噁唑的 HIV 感染者与停止预防治疗相比，死亡和 WHO HIV/AIDS 3-4 期事件发生率较低，但未达到统计学意义。复方磺胺甲噁唑预防了死亡和 WHO HIV/AIDS 2-4 期事件的复合终点。鉴于较差的医疗保健获取机会和缺乏常规病毒载量监测，在撒哈拉以南非洲地区，接受抗逆转录病毒治疗后免疫重建的成人应继续使用复方磺胺甲噁唑预防治疗。临床试验注册。NCT01650558。
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