背景:吉罗韦西肺孢子菌肺炎(PCP)是HIV感染者(PLWH)中常见的机会性感染,特别是在新的和未经治疗的病例中。有几种方案可用于预防PCP,包括甲氧苄啶-磺胺甲恶唑(TMP-SMX),基于氨苯砜的方案(DBR),雾化戊脒(AP),还有Atovaquone.
目的:通过网络荟萃分析比较PCP预防方案在PLWH中的有效性和安全性。
方法:Embase,MedLine,和中央从成立到2023年6月21日。
方法:比较随机对照试验(RCTs)。
方法:PLWH。
方法:PCP预防方案比较头对头或不治疗/安慰剂。
■用于RCT2的Cochrane偏差风险工具。
■标题/摘要和全文筛选和数据提取由两名独立审阅者一式两份进行。PCP发病率数据,全因死亡率,我们通过网络荟萃分析对因毒性而停药的患者进行汇总和排序.原发性与原发性的亚组分析二级预防,年,并按剂量进行。
结果:共有26项RCT,包括55个治疗组,涉及7516个PLWH。为了预防PCP,TMP-SMX是最有利的药物,优于DBR(风险比[RR]=0.54,95%置信区间[95CI]=0.36-0.83)和AP(RR=0.53,95CI=0.36-0.77)。与未治疗/安慰剂相比,TMP-SMX也是唯一具有死亡率益处的药物(RR=0.79,95CI=0.64-0.98)。然而,TMP-SMX也被列为毒性最强的药物,其停药风险高于DBRs(RR=1.25,95CI=1.01-1.54)和AP(7.20,95CI=5.37-9.66)。在其他方案中,PCP的预防或死亡率没有显着差异。亚组内的研究结果保持一致。
结论:TMP-SMX是PLWH中预防PCP最有效的药物,也是唯一能使患者死亡获益的药物;它应该继续被推荐为一线代理商。需要进一步的研究来确定TMP-SMX的最佳剂量,以最大限度地提高疗效和降低毒性。
BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) is a common opportunistic infection among people living with HIV (PWH), particularly among new and untreated cases. Several regimens are available for the prophylaxis of PCP, including trimethoprim-sulfamethoxazole (TMP-SMX), dapsone-based regimens (DBRs), aerosolized pentamidine (AP), and
atovaquone.
OBJECTIVE: To compare the efficacy and safety of PCP prophylaxis regimens in PWH by network meta-analysis.
METHODS: DATA SOURCES: Embase, MEDLINE, and CENTRAL from inception to June 21, 2023.
METHODS: Comparative randomized controlled trials (RCTs).
METHODS: PWH.
METHODS: Regimens for PCP prophylaxis either compared head-to-head or versus no treatment/placebo.
UNASSIGNED: Cochrane risk-of-bias tool for RCTs 2.
UNASSIGNED: Title or abstract and full-text screening and data extraction were performed in duplicate by two independent reviewers. Data on PCP incidence, all-cause mortality, and discontinuation due to toxicity were pooled and ranked by network meta-analysis. Subgroup analyses of primary versus secondary prophylaxis, by year, and by dosage were performed.
RESULTS: A total of 26 RCTs, comprising 55 treatment arms involving 7516 PWH were included. For the prevention of PCP, TMP-SMX was ranked the most favourable agent and was superior to DBRs (risk ratio [RR] = 0.54; 95% CI, 0.36-0.83) and AP (RR = 0.53; 95% CI, 0.36-0.77). TMP-SMX was also the only agent with a mortality benefit compared with no treatment/placebo (RR = 0.79; 95% CI, 0.64-0.98). However, TMP-SMX was also ranked as the most toxic agent with a greater risk of discontinuation than DBRs (RR = 1.25; 95% CI, 1.01-1.54) and AP (7.20; 95% CI, 5.37-9.66). No significant differences in PCP prevention or mortality were detected among the other regimens. The findings remained consistent within subgroups.
CONCLUSIONS: TMP-SMX is the most effective agent for PCP prophylaxis in PWH and the only agent to confer a mortality benefit; consequently, it should continue to be recommended as the first-line agent. Further studies are necessary to determine the optimal dosing of TMP-SMX to maximize efficacy and minimize toxicity.