氨苯砜-乙胺嘧啶与雾化喷他脒作为HIV感染患者预防卡氏肺孢子虫肺炎和弓形虫病的一线用药比较。PRIO研究组。

Dapsone-pyrimethamine compared with aerosolized pentamidine as primary prophylaxis against Pneumocystis carinii pneumonia and toxoplasmosis in HIV infection. The PRIO Study Group.

作者信息

Girard P M, Landman R, Gaudebout C, Olivares R, Saimot A G, Jelazko P, Gaudebout C, Certain A, Boué F, Bouvet E

机构信息

Institut National de la Santé et de la Recherche Médicale, Unité 13, Paris, France.

出版信息

N Engl J Med. 1993 May 27;328(21):1514-20. doi: 10.1056/NEJM199305273282102.

DOI:10.1056/NEJM199305273282102

PMID:8479488

Abstract

BACKGROUND

Pneumocystis carinii pneumonia and toxoplasmic encephalitis are frequent life-threatening opportunistic infections in patients with human immunodeficiency virus (HIV) infection. Primary prophylaxis against P. carinii pneumonia is now common, but there are few data on regimens for primary prophylaxis against toxoplasmosis.

METHODS

We conducted a randomized trial that compared two prophylactic regimens: dapsone (50 mg per day) plus pyrimethamine (50 mg per week) was compared with aerosolized pentamidine (300 mg per month). The patients had symptomatic HIV infection, no history of P. carinii pneumonia or symptomatic toxoplasmosis, and CD4+ counts below 200 per cubic millimeter (0.2 x 10(9) per liter).

RESULTS

In an intention-to-treat analysis, after a median follow-up of 539 days P. carinii pneumonia developed in 10 patients in each group, whereas toxoplasmosis developed in 32 of 176 patients in the pentamidine group and 19 of 173 patients in the dapsone-pyrimethamine group. Those assigned to pentamidine had a risk of P. carinii pneumonia that was similar to the risk in those assigned to dapsone-pyrimethamine (adjusted relative risk, 1.13; 95 percent confidence interval, 0.44 to 2.92; P = 0.79), but a higher risk of toxoplasmosis (adjusted relative risk, 1.81; 95 percent confidence interval, 1.12 to 2.94; P = 0.02). Among the 262 patients with serologic evidence of past exposure to Toxoplasma gondii, the relative risk of symptomatic toxoplasmosis was 2.37 times higher in those assigned to pentamidine (95 percent confidence interval, 1.3 to 4.4; P = 0.006). More patients discontinued dapsone-pyrimethamine than pentamidine because of toxicity (42 vs. 3; P < 0.001). Survival was similar in the two groups.

CONCLUSIONS

For primary prevention of P. carinii pneumonia, dapsone-pyrimethamine is as effective, though not as well tolerated, as aerosolized pentamidine. Dapsone-pyrimethamine also prevents first episodes of toxoplasmosis.

摘要

背景

卡氏肺孢子虫肺炎和弓形虫性脑炎是人类免疫缺陷病毒（HIV）感染患者常见的危及生命的机会性感染。目前，针对卡氏肺孢子虫肺炎的一级预防较为普遍，但关于弓形虫病一级预防方案的数据较少。

方法

我们进行了一项随机试验，比较两种预防方案：氨苯砜（每日50毫克）加乙胺嘧啶（每周50毫克）与雾化喷他脒（每月300毫克）。患者有症状性HIV感染，无卡氏肺孢子虫肺炎或症状性弓形虫病病史，且CD4 +细胞计数低于每立方毫米200个（0.2×10⁹ /升）。

结果

在意向性分析中，中位随访539天后，每组各有10例患者发生卡氏肺孢子虫肺炎，而喷他脒组176例患者中有32例发生弓形虫病，氨苯砜 - 乙胺嘧啶组173例患者中有19例发生弓形虫病。接受喷他脒治疗的患者发生卡氏肺孢子虫肺炎的风险与接受氨苯砜 - 乙胺嘧啶治疗的患者相似（校正相对风险，1.13；95%置信区间，0.44至2.92；P = 0.79），但发生弓形虫病的风险更高（校正相对风险，1.81；95%置信区间，1.12至2.94；P = 0.02）。在262例有既往感染弓形虫血清学证据的患者中，接受喷他脒治疗的患者发生症状性弓形虫病的相对风险高2.37倍（95%置信区间，1.3至4.4；P = 0.006）。因毒性反应而停用氨苯砜 - 乙胺嘧啶的患者比停用喷他脒的患者更多（42例对3例；P < 0.001）。两组的生存率相似。