Background Toxoplasmic encephalitis (TE) is an opportunistic infection of people living with HIV or other causes of immunosuppression. For decades, the standard of care has been combination therapy with pyrimethamine and sulfadiazine (P-S) or pyrimethamine and clindamycin (P-C). However, a substantial price increase has starkly limited access to pyrimethamine. Consequently, some centers have transitioned to trimethoprim-sulfamethoxazole (TMP-SMX), an inexpensive alternative treatment. We aimed to systematically review the evidence to compare the efficacy and safety of pyrimethamine-containing therapies versus TMP-SMX. Methods We searched for and included randomized controlled trials (RCT) and observational studies of TE treatments, regardless of HIV status. Data for each therapy were pooled by meta-analysis to assess the proportions of patients experiencing clinical and radiologic responses to treatment, all-cause mortality, and discontinuation due to toxicity. Sensitivity analyses limited to RCTs directly compared therapies. Results We identified 6 RCTs/dose-escalation studies and 26 single-arm/observational studies. Pooled proportions of clinical and radiologic response or mortality or were not significantly different between TMP-SMX and pyrimethamine-containing regimens (P > 0.05). Treatment discontinuation due to toxicity was significantly lower in TMP-SMX (7.3%, 95%CI 4.7-11.4, I2 = 0.0%) versus P-S (30.5%, 95%CI 27.1-34.2, I2 = 0.0%, P < 0.01) or P-C (13.7%, 95%CI 9.8-18.8, I2 = 32.0%, P = 0.031). These results were consistent in analyses restricted to RCT data. Limitations Identified studies only included persons living with HIV and most predated modern antiretroviral treatment. Conclusions TMP-SMX appears to be as effective and safer than the pyrimethamine-containing regimens for TE. These findings support modern RCTs comparing TMP-SMX to P-S or P-C and a revisiting of the guidelines.

中文翻译：

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重新审视现代治疗弓形虫脑炎的证据基础：系统回顾和荟萃分析

背景 弓形虫脑炎 (TE) 是 HIV 感染者或其他免疫抑制原因的机会性感染。几十年来，标准治疗一直是乙胺嘧啶和磺胺嘧啶 (PS) 或乙胺嘧啶和克林霉素 (PC) 的联合治疗。然而，大幅上涨的价格明显限制了乙胺嘧啶的获取。因此，一些中心已经过渡到甲氧苄氨嘧啶-磺胺甲恶唑 (TMP-SMX)，这是一种廉价的替代疗法。我们旨在系统地回顾证据，比较含乙胺嘧啶的疗法与 TMP-SMX 的疗效和安全性。方法 我们搜索并纳入了 TE 治疗的随机对照试验 (RCT) 和观察性研究，无论 HIV 状态如何。通过荟萃分析汇总每种疗法的数据，以评估对治疗有临床和放射学反应的患者比例、全因死亡率和因毒性而停药。敏感性分析仅限于直接比较治疗的随机对照试验。结果 我们确定了 6 项随机对照试验/剂量递增研究和 26 项单臂/观察性研究。TMP-SMX 和含乙胺嘧啶的方案之间临床和放射学反应或死亡率的汇总比例没有显着差异 (P > 0.05)。TMP-SMX (7.3%, 95%CI 4.7-11.4, I2 = 0.0%) 与 PS (30.5%, 95%CI 27.1-34.2, I2 = 0.0%, P < 0.01) ) 或 PC (13.7%, 95%CI 9.8-18.8, I2 = 32.0%, P = 0.031)。这些结果在仅限于 RCT 数据的分析中是一致的。局限性确定的研究仅包括艾滋病毒感染者和最早的现代抗逆转录病毒治疗。结论 TMP-SMX 似乎与含乙胺嘧啶的 TE 方案一样有效且安全。这些发现支持现代随机对照试验将 TMP-SMX 与 PS 或 PC 进行比较，并重新审视指南。