Department of HIV/AIDS, World Health Organization, Geneva, Switzerland.
Department of HIV/AIDS, World Health Organization, Geneva, Switzerland.
Lancet HIV. 2015 Apr;2(4):e137-50. doi: 10.1016/S2352-3018(15)00005-3. Epub 2015 Mar 3.
Co-trimoxazole prophylaxis is used to reduce morbidity and mortality in people with HIV. We systematically reviewed three topics related to co-trimoxazole prophylaxis to update WHO guidelines: initiation, discontinuation, and dose.
We searched PubMed, Embase, WHO Global Index Medicus, and clinical trial registries in November, 2013, for randomised controlled trials and observational studies including co-trimoxazole prophylaxis and a comparator group. Studies were eligible if they reported death, WHO clinical stage 3 or 4 events, admittance to hospital, severe bacterial infections, tuberculosis, pneumonia, diarrhoea, malaria, or treatment-limiting adverse events. Infant mortality, low birthweight, and placental malaria were additional outcomes for the comparison of co-trimoxazole prophylaxis and intermittent preventive treatment for malaria in pregnant women (IPTp). We compared a dose of 480 mg co-trimoxazole once a day with one of 960 mg co-trimoxazole once a day. We used a 10% margin for non-inferiority and equivalence analyses. We used random-effects models for all meta-analyses. This study is registered with PROSPERO, number CRD42014007163.
19 articles, published from 1995 to 2014 and including 35 328 participants, met the inclusion criteria. Co-trimoxazole prophylaxis reduced rates of death (hazard ratio [HR] 0·40, 95% CI 0·26-0·64) when started at CD4 counts of 350 cells per μL or lower with antiretroviral therapy (ART) worldwide. Co-trimoxazole prophylaxis started at higher than 350 cells per μL without ART reduced rates of death (0·50, 0·30-0·83) and malaria (0·25, 0·10-0·57) in Africa. Co-trimoxazole prophylaxis was non-inferior to IPTp with respect to infant mortality (risk difference [RD] -0·05, 95% CI -0·12 to 0·02), low birthweight (0·00, -0·07 to 0·07), and placental malaria (0·00, -0·10 to 0·10). Co-trimoxazole prophylaxis continuation after ART-induced recovery with CD4 counts higher than 350 cells per μL reduced admittances to hospital (HR 0·42, 95% CI 0·22-0·80), pneumonia (0·73, 0·61-0·88), malaria (0·03, 0·01-0·10), and diarrhoea (0·61, 0·48-0·78) in Africa. A dose of 480 mg co-trimoxazole prophylaxis once a day did not reduce treatment-limiting adverse events compared with 960 mg once a day (RD -0·07, 95% CI -0·52 to 0·39).
Co-trimoxazole prophylaxis should be given with ART in people with CD4 counts of 350 cells per μL or lower in low-income and middle-income countries. Co-trimoxazole prophylaxis should be provided irrespective of CD4 count in settings with a high burden of infectious diseases. Pregnant women with HIV in Africa should use co-trimoxazole rather than IPTp to prevent malaria complications in infants. Further research is needed to inform dose optimisation and co-trimoxazole use in the context of expanded ART in different epidemiological settings.
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复方新诺明预防用于降低艾滋病毒感染者的发病率和死亡率。我们系统性地回顾了与复方新诺明预防有关的三个主题，以更新世卫组织的指南：启动、停止和剂量。
我们于 2013 年 11 月检索了 PubMed、Embase、世卫组织全球索引医学、和临床试验登记处，以寻找包括复方新诺明预防和对照组的随机对照试验和观察性研究。如果研究报告了死亡、世卫组织临床 3 或 4 期事件、住院、严重细菌感染、结核病、肺炎、腹泻、疟疾或治疗相关不良事件，则符合入选标准。婴儿死亡率、低出生体重和胎盘疟疾是孕妇复方新诺明预防和间歇性预防治疗疟疾（IPTp）比较的额外结果。我们比较了每天一次服用 480mg 复方新诺明和每天一次服用 960mg 复方新诺明的效果。我们使用了 10%的非劣效性和等效性分析边界。我们使用随机效应模型进行所有的荟萃分析。本研究在 PROSPERO 注册，编号 CRD42014007163。
19 篇文章，发表于 1995 年至 2014 年，包括 35328 名参与者，符合纳入标准。在全世界范围内，当 CD4 计数为每微升 350 个细胞或更低时，开始使用复方新诺明预防治疗与抗逆转录病毒治疗（ART）联合使用时，可降低死亡率（风险比[HR]0·40，95%置信区间 0·26-0·64）。在非洲，当 CD4 计数高于 350 个细胞每微升但未使用 ART 时，开始使用复方新诺明预防治疗可降低死亡率（0·50，0·30-0·83）和疟疾（0·25，0·10-0·57）。在婴儿死亡率（风险差异[RD]-0·05，95%置信区间-0·12 至 0·02）、低出生体重（0·00，-0·07 至 0·07）和胎盘疟疾（0·00，-0·10 至 0·10）方面，复方新诺明预防与 IPTp 相比无差异。ART 诱导 CD4 计数高于每微升 350 个细胞后继续使用复方新诺明预防治疗可降低住院率（HR 0·42，95%置信区间 0·22-0·80）、肺炎（0·73，0·61-0·88）、疟疾（0·03，0·01-0·10）和腹泻（0·61，0·48-0·78）在非洲。每天服用 480mg 复方新诺明预防治疗与每天服用 960mg 相比，不会减少治疗相关不良事件（RD-0·07，95%置信区间-0·52 至 0·39）。
在低收入和中等收入国家，当 CD4 计数为每微升 350 个细胞或更低时，应在使用抗逆转录病毒治疗（ART）的同时使用复方新诺明预防治疗。在传染病负担高的环境中，无论 CD4 计数如何，都应提供复方新诺明预防治疗。在非洲，艾滋病毒孕妇应使用复方新诺明而不是 IPTp 来预防婴儿的疟疾并发症。在不同的流行病学环境中扩大 ART 的背景下，需要进一步研究剂量优化和复方新诺明的使用。
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