Antifungal interventions for the primary prevention of cryptococcal disease in adults with HIV

 

Abstract

Background

Cryptococcal disease is an opportunistic infection that causes significant morbidity and mortality in adults with HIV. Primary prophylaxis with antifungal interventions may decrease cryptococcal disease incidence and associated mortality.

Objectives

To assess the efficacy of antifungal interventions for the primary prevention of cryptococcal disease in adults with HIV.

Search methods

We searched the following databases: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), ClinicalTrials.gov, Database of Abstracts of Reviews of Effectiveness (DARE), Latin American and Caribbean Literature on the Health Sciences (LILACS), and the Cochrane Controlled Trials Register (CCTR). We reviewed abstracts from the following relevant conferences: International AIDS Conference, International AIDS Society Conference on HIV Pathogenesis and Treatment, and Conference on Retroviruses and Opportunistic Infections. We searched reference lists for all primary and other pertinent articles identified. We attempted to contact experts in the field, particularly primary authors of included studies, to better ensure completeness of included studies. We also approached pharmaceutical companies for any available and relevant unpublished data. The time period searched was from 1980 to August 2004. We placed no language restrictions on the search.

Key words used include: meningitis, cryptococcal, cryptococcus, cryptococcosis, acquired immunodeficiency syndrome, human immunodeficiency virus, prophylaxis, chemoprevention, antifungal agents, and the Cochrane screen for randomized controlled trials.

Selection criteria

Randomized controlled trials using antifungal interventions for the primary prevention of cryptococcal disease in adults with HIV were selected.

Data collection and analysis

Two reviewers independently assessed trial eligibility and quality. Trial authors, experts, and pharmaceutical companies were contacted for additional and/or missing information. Data were abstracted by two reviewers. Data were pooled, where appropriate, to yield summary estimates.

Main results

Five studies (N=1316) were identified. All study patients had CD4 cell counts <300 cells/µl, and the majority of patients had CD4 cell counts <150 cells/µl. When all five studies are analyzed as a single group (N=1316), the incidence of cryptococcal disease was decreased in those taking primary prophylaxis (RR 0.21, 95% CI 0.09, 0.46) compared to those taking placebo. However, there was no significant difference in overall mortality observed (RR 1.01, 95% CI 0.71, 1.44). When the three studies using itraconazole as the intervention were analyzed together (N=798), the incidence of cryptococcal disease was decreased in those taking itraconazole for primary prophylaxis (RR 0.12, 95% CI 0.03, 0.51) compared to those taking placebo; however, there was no significant difference in overall mortality (RR 1.12, 95% CI 0.70, 1.80). When the two studies using fluconazole as the intervention were analyzed together (N=518), the incidence of cryptococcal disease was decreased in those taking fluconazole for primary prophylaxis (RR 0.25, 95% CI 0.07, 0.87) compared to those taking placebo; however, there was no significant difference in overall mortality (RR 0.59, 95% CI 0.14, 2.62).

Authors' conclusions

Antifungal primary prophylaxis with either itraconazole or fluconazole is effective in reducing the incidence of cryptococcal disease in adults with advanced HIV disease. However, neither of these interventions has a clear effect on overall mortality. Further research is needed to better understand these interventions and the populations in which they may be most effective.

 

Plain language summary

Antifungal interventions for the primary prevention of cryptococcal disease in adults with HIV

Infection with the human immunodeficiency virus (HIV) leads to progressive destruction and weakening of the body's immune system. Patients with advanced HIV disease are vulnerable to various diseases, called opportunistic infections (OIs), which most people with normal immune systems are protected against. One of these OIs, a fungal disease called cryptococcosis, causes meningitis (an inflammation of the membrane surrounding the brain) and pneumonia and is lethal when untreated. This study looked at two medications, itraconazole and fluconazole, which could be taken by patients with advanced HIV disease, to prevent this fungal infection from ever occurring. This study found that both were effective drugs for preventing cryptococcal disease. However, these drugs were not found to be effective in decreasing the overall death rates from HIV. More studies of these medications are needed to further evaluate their cost-effectiveness and benefits in decreasing death rates in groups of patients with HIV.

 

摘要

背景

抗黴菌的介入在HIV感染病患初級預防隱球菌疾病

隱球菌疾病是一種是伺機性感染，它可以在HIV感染病患身上造成顯著的發病率與致死率。所以抗黴菌介入的初級預防可以減少隱球菌病的發生率與可能相關的致死率。

目標

抗黴菌的介入在HIV感染患初級預防隱球菌疾病的效率

搜尋策略

我們研究以下的資料庫: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), ClinicalTrials.gov, Database of Abstracts of Reviews of Effectiveness (DARE), Latin American and Caribbean Literature on the Health Sciences (LILACS), and the Cochrane Controlled Trials Register (CCTR)。我們回顧以下有意義性會談的摘要:國際愛滋病會議,國際愛滋病病理與治療會議，和反轉錄病毒與伺機性感染的會議。我們研究所有主要與其他有關的文章。我們試圖去聯絡這方面的專家，尤其是這些研究的第一作者，來更能確認這些文章的完整性。我們也去接洽藥商公司看是否有任何有意義的未發表資料。尋找的資料主要是從1980到2004年8月。資料沒有語言的限制。關鍵字包括有: 腦膜炎、隱球菌的、隱球菌、隱球菌病、後天免疫缺乏症候群、人類免疫缺乏病毒、預防、化學預防、抗黴菌藥物、和考科藍篩檢隨機對照實驗。

選擇標準

有關抗黴菌的介入在HIV感染患者初級預防隱球菌疾病的隨機對照實驗。

資料收集與分析

兩位評論人個別地評估實驗的合格性和品質。還會因為額外的資料或遺失的資料而再去聯絡實驗的作者、專家、和藥商公司。他們還會收集資料，做成適當的摘要。

主要結論

5個資料庫(N = 1316)被擷取。 所有的病人的CD4 cell 量小於300 cells/μl, 還有大多數的病人的CD4 cell 量小於150。當這5個資料庫當作單一個族群來分析時, 有做初期預防的比安慰劑對照組，隱球菌病的發生率有降低的現象(RR 0.21, 95% CI 0.09, 0.46)。 然而, 死亡率上則無顯著的差異(RR 1.01, 95% CI 0.71, 1.44)。當其中有3個研究(N = 798)使用itraconazole 作為初級預防,可以發現隱球菌病的發生率比安慰劑對照組還小(RR 0.12, 95% CI 0.03, 0.51)。當另外兩個研究(N = 518)使用fluconazole 作為初級預防,可以發現隱球菌病的發生率比安慰劑對照組還小(RR 0.25, 95% CI 0.07, 0.87)。然而, 在這些研究,總死亡率是沒有顯著的差異(RR 0.59, 95% CI 0.14, 2.62)。

作者結論

抗黴菌初級預防無論是使用itraconazole或是fluconazole，在減少HIV病人罹患隱球菌病的發生率上是有效的。然而不管是哪一個藥物對總死亡率都沒有明顯的效果。 還需要更進一步的研究來了解哪些藥物針對哪些族群是最有效果的。

翻譯人

本摘要由臺北榮民總醫院李美慧翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

感染人類免疫缺乏病毒(HIV)可以造成身體免疫系統漸進性的破壞與損弱。 病人若處於HIV感染後期，易得到大多正常有免疫系統人可抵抗的病，也就是易有伺機性感染(OIs)。 其中一種伺機性感染，叫做隱球菌病，是一種黴菌感染，容易引起腦膜炎(腦部周圍包膜發炎)和肺炎，若無治療易致死。 這篇研究在研究兩種藥物, itraconazole和fluconazole， HIV病人用來作預防黴菌感染的發生。 這篇研究發現兩種藥物對預防隱球菌病很有效果。 然而，在HIV上,兩種藥物對減少死亡率都沒有效果。 所以還需要有關這些藥的研究來評估在減少HIV病人死亡率的經濟效益。