肯尼亚接受抗逆转录病毒治疗的HIV-1感染成人停用复方新诺明预防治疗：一项随机非劣效性试验
Cotrimoxazole Prophylaxis Discontinuation among Antiretroviral-Treated HIV-1-Infected Adults in Kenya: A Randomized Non-inferiority Trial.
作者信息
Polyak Christina S, Yuhas Krista, Singa Benson, Khaemba Monica, Walson Judd, Richardson Barbra A, John-Stewart Grace
机构信息
US Military HIV Research Program, Walter Reed Army Institute of Research, Bethesda, Maryland, United States of America.
Department of Medicine, University of Washington, Seattle, Washington, United States of America.
出版信息
PLoS Med. 2016 Jan 5;13(1):e1001934. doi: 10.1371/journal.pmed.1001934. eCollection 2016 Jan.
BACKGROUND
Cotrimoxazole (CTX) prophylaxis is recommended by the World Health Organization (WHO) for HIV-1-infected individuals in settings with high infectious disease prevalence. The WHO 2006 guidelines were developed prior to the scale-up of antiretroviral therapy (ART). The threshold for CTX discontinuation following ART is undefined in resource-limited settings.
METHODS AND FINDINGS
Between 1 February 2012 and 30 September 2013, we conducted an unblinded non-inferiority randomized controlled trial of CTX prophylaxis cessation versus continuation among HIV-1-infected adults on ART for ≥ 18 mo with CD4 count > 350 cells/mm3 in a malaria-endemic region in Kenya. Participants were randomized and followed up at 3-mo intervals for 12 mo. The primary endpoint was a composite of morbidity (malaria, pneumonia, and diarrhea) and mortality. Incidence rate ratios (IRRs) were estimated using Poisson regression. Among 538 ART-treated adults screened, 500 were enrolled and randomized, 250 per arm. Median age was 40 y, 361 (72%) were women, and 442 (88%) reported insecticide-treated bednet use. Combined morbidity/mortality was significantly higher in the CTX discontinuation arm (IRR = 2.27, 95% CI 1.52-3.38; p < 0.001), driven by malaria morbidity. There were 34 cases of malaria, with 33 in the CTX discontinuation arm (IRR = 33.02, 95% CI 4.52-241.02; p = 0.001). Diarrhea and pneumonia rates did not differ significantly between arms (IRR = 1.36, 95% CI 0.82-2.27, and IRR = 1.43, 95% CI 0.54-3.75, respectively). Study limitations include a lack of placebo and a lower incidence of morbidity events than expected.
CONCLUSIONS
CTX discontinuation among ART-treated, immune-reconstituted adults in a malaria-endemic region resulted in increased incidence of malaria but not pneumonia or diarrhea. Malaria endemicity may be the most relevant factor to consider in the decision to stop CTX after ART-induced immune reconstitution in regions with high infectious disease prevalence. These data support the 2014 WHO CTX guidelines.
TRIAL REGISTRATION
ClinicalTrials.gov NCT01425073.
背景
世界卫生组织（WHO）建议在传染病高发地区对感染HIV-1的个体进行复方新诺明（CTX）预防治疗。WHO 2006年的指南是在抗逆转录病毒疗法（ART）扩大规模之前制定的。在资源有限的环境中，ART治疗后停用CTX的阈值尚未明确。
方法与结果
在2012年2月1日至2013年9月30日期间，我们在肯尼亚一个疟疾流行地区对接受ART治疗≥18个月且CD4细胞计数>350个/立方毫米的HIV-1感染成人进行了一项非盲非劣效性随机对照试验，比较CTX预防治疗停药与继续用药的效果。参与者被随机分组，并每3个月随访一次，共随访12个月。主要终点是发病率（疟疾、肺炎和腹泻）和死亡率的综合指标。使用泊松回归估计发病率比（IRR）。在538名接受ART治疗的成人中进行筛查，500名被纳入并随机分组，每组250名。中位年龄为40岁，361名（72%）为女性，442名（88%）报告使用了经杀虫剂处理的蚊帐。CTX停药组的合并发病率/死亡率显著更高（IRR = 2.27，95% CI 1.52 - 3.38；p < 0.001），主要是由于疟疾发病率升高。共有34例疟疾病例，其中33例在CTX停药组（IRR = 33.02，95% CI 4.52 - 241.02；p = 0.001）。两组之间腹泻和肺炎的发生率没有显著差异（IRR分别为1.36，95% CI 0.82 - 2.27和IRR为1.43，95% CI 0.54 - 3.75）。研究的局限性包括缺乏安慰剂组以及发病率事件的发生率低于预期。
结论
在疟疾流行地区，接受ART治疗且免疫重建的成人停用CTX会导致疟疾发病率增加，但肺炎或腹泻发病率未增加。在传染病高发地区，疟疾流行情况可能是ART诱导免疫重建后决定停用CTX时最需要考虑的相关因素。这些数据支持了2014年WHO的CTX指南。
试验注册
ClinicalTrials.gov NCT01425073。
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