Schneider M M, Hoepelman A I, Eeftinck Schattenkerk J K, Nielsen T L, van der Graaf Y, Frissen J P, van der Ende I M, Kolsters A F, Borleffs J C
Department of Internal Medicine, University Hospital Utrecht, The Netherlands.
N Engl J Med. 1992 Dec 24;327(26):1836-41. doi: 10.1056/NEJM199212243272603.
Primary prophylaxis against Pneumocystis carinii pneumonia (PCP) is recommended for patients with human immunodeficiency virus (HIV) infection if their CD4 cell counts are below 200 per cubic millimeter (0.2 x 10(9) per liter). Either aerosolized pentamidine or trimethoprim-sulfamethoxazole (co-trimoxazole) is commonly prescribed for prophylaxis, but the relative efficacy and toxicity of these agents are unknown.
We conducted a multicenter trial involving 215 HIV-infected patients with no history of PCP but with CD4 cell counts below 200 per cubic millimeter. The patients were randomly assigned to one of three regimens: aerosolized pentamidine once a month, 480 mg of trimethoprim-sulfamethoxazole once a day (80 mg of trimethoprim and 400 mg of sulfamethoxazole), or 960 mg of trimethoprim-sulfamethoxazole once a day (160 mg and 800 mg, respectively). The cumulative incidence of PCP was estimated by Kaplan-Meier survival analysis.
After a mean follow-up of 264 days, 6 of the 71 patients in the pentamidine group had a confirmed first episode of PCP (11 percent), whereas none of the 142 patients in the two trimethoprim-sulfamethoxazole groups had PCP (P = 0.002). However, adverse events that required discontinuation of the medication were much more frequent in the trimethoprim-sulfamethoxazole groups (17 and 18 patients) than in the pentamidine group (2 patients). The adverse reactions occurred significantly sooner in the group given 960 mg of trimethoprim-sulfamethoxazole than in the group given 480 mg (mean time, 16 vs. 57 days; P = 0.02).
For patients with HIV infection, trimethoprim-sulfamethoxazole taken once a day is more effective as primary prophylaxis against PCP than aerosolized pentamidine administered once a month, although adverse drug reactions are more frequent with trimethoprim-sulfamethoxazole.
对于人类免疫缺陷病毒（HIV）感染且CD4细胞计数低于每立方毫米200个（每升0.2×10⁹个）的患者，推荐进行卡氏肺孢子虫肺炎（PCP）的一级预防。雾化喷他脒或甲氧苄啶 - 磺胺甲恶唑（复方新诺明）通常被用于预防，但这些药物的相对疗效和毒性尚不清楚。
我们开展了一项多中心试验，纳入215例无PCP病史但CD4细胞计数低于每立方毫米200个的HIV感染患者。患者被随机分配至三种治疗方案之一：每月雾化喷他脒一次；每日服用480毫克甲氧苄啶 - 磺胺甲恶唑（80毫克甲氧苄啶和400毫克磺胺甲恶唑）；或每日服用960毫克甲氧苄啶 - 磺胺甲恶唑（分别为160毫克和800毫克）。采用Kaplan - Meier生存分析估计PCP的累积发病率。
平均随访264天后，喷他脒组71例患者中有6例确诊首次发生PCP（11%），而两个甲氧苄啶 - 磺胺甲恶唑组的142例患者均未发生PCP（P = 0.002）。然而，需要停药的不良事件在甲氧苄啶 - 磺胺甲恶唑组（分别为17例和18例患者）比喷他脒组（2例患者）更为频繁。服用960毫克甲氧苄啶 - 磺胺甲恶唑组的不良反应发生时间显著早于服用480毫克组（平均时间分别为16天和57天；P = 0.02）。
对于HIV感染患者，每日服用一次甲氧苄啶 - 磺胺甲恶唑作为PCP的一级预防比每月雾化喷他脒更有效，尽管甲氧苄啶 - 磺胺甲恶唑的药物不良反应更频繁。
