Antiretroviral pre-exposure prophylaxis (PrEP) for preventing HIV in high-risk individuals

  • Review
  • Intervention

Authors


Abstract

Background

Twenty-five years into the global HIV/AIDS epidemic, infection rates remain alarmingly high, with over 4 million people becoming infected every year. There is a need for HIV prevention strategies that are more effective. Oral antiretroviral pre-exposure prophylaxis (PrEP) in high-risk individuals may be a reliable tool in preventing the transmission of HIV.

Objectives

To evaluate the risk reduction and side effects of antiretroviral chemoprophylaxis in preventing HIV infection in high-risk individuals

Search methods

We conducted electronic searches of MEDLINE (1980 through June 2008); the Cochrane Central Register of Controlled Trials (March 2008); EMBASE (June 2008); and AIDSearch (June 2008). We also searched the WHO International Clinical Trials Registry Platform in June 2008 for ongoing or prospective trials.

Selection criteria

Randomized controlled trials that evaluated the effects of any antiretroviral agent in preventing HIV infection in high-risk individuals

Data collection and analysis

Data concerning outcomes, details of the interventions, and other study characteristics were extracted by two independent authors using a standardized data extraction form. The information gathered from each included trial were location of the trial, date, publication status, demographics of participants (e.g. age, gender, risk behaviour), exposure modality, type of antiretroviral drug used, duration of drug use, and outcomes. Relative risk with a 95% confidence interval (CI) was used as the measure of effect. Only one trial met our inclusion criteria, so we did not perform a meta-analysis.

Main results

One randomised controlled trial met the criteria for the review, although it was not completed as planned. The trial did not have the statistical power to answer questions about the efficacy of antiretroviral PrEP for HIV prevention in the assessed risk group.

Authors' conclusions

Presently there is no reliable evidence to support the use of any antiretroviral agent for HIV chemoprophylaxis.The value of chemoprophylaxis for HIV prevention cannot be assessed on the basis of the included trial. The result was not statistically significant and, moreover, the trial was not completed as planned; therefore, the use of antiretroviral agents for HIV chemoprophylaxis cannot be recommended at present. To assess the value of antiretroviral agents for HIV chemoprophylaxis, we advocate well-conducted trials with the statistical power to answer questions about PrEP efficacy and safety in various populations and risk groups. These trials also should evaluate other important issues of concern, such as drug safety, adherence, drug resistance, and the effect of PrEP on risk behaviour.

摘要

背景

對於高風險族群以抗反轉錄病毒(Antiretroviral)藥物做為接觸前預防人類免疫缺乏病毒(HIV)感染

25年以來,在人類免疫缺乏病毒/愛滋病(HIV/AIDS)盛行區域,病毒感染率始終很驚人地維持在高水平,每年有四百萬人變成帶原者. 因此,我們需要有效的HIV感染預防策略.暴露病毒前預防性投予口服抗反轉錄病毒藥物對於HIV的傳播也許是個可靠的方式.

目標

為了評估預防性投予抗反轉錄病毒藥物對HIV感染高風險族群的風險減少程度及藥物副作用

搜尋策略

我們用電腦搜尋包含MEDLINE (1980 through June 2008); the Cochrane Central Register of Controlled Trials (March 2008); EMBASE (June 2008); and AIDSearch (June 2008). 我們也搜尋 WHO International Clinical Trials Registry Platform in June 2008 for ongoing, 或前瞻性的試驗。

選擇標準

藉由隨機對照試驗(Randomized controlled trials) 來評估抗反轉錄病毒藥物在對於高危險族群預防HIV感染之效用.

資料收集與分析

詳細的治療措施,和其他研究的特點是由兩個獨立作者採用一個標準化的數據提取形式所取得。所收集的資料包括試驗進行的地點,日期,出版狀況,參與者的人口學因素(如年齡,性別,危險的行為),曝露的方式,抗反轉錄病毒藥物使用的類型,藥物使用時間,和結果。相對風險(relative risk)及95%信賴區間(95% confidence interval (CI))被用來作為效果的衡量。只有一個實驗符合我們的收案標準,所以我們沒有進行 metaanalysis。

主要結論

隨機對照試驗雖然它沒有如預定的計劃完成但仍符合納入研究的準則.這個試驗沒有統計學的有力證據去證明對於高風險族群以抗反轉錄病(Antiretroviral)藥物做為接觸前預防HIV感染是否有效.

作者結論

到目前為止仍然沒有可靠的證據去支持任何抗反轉錄病毒藥物的投予對於HIV感染預防的成效. HIV的預防的價值不能只靠這個試驗. 研究結果沒有統計學上的差異, 這個試驗也不是完全照計畫實行. 因此抗反轉錄病毒藥物對於HIV感染的預防現在還不被建議.為評估抗反轉錄病毒藥物對HIV感染的預防功效,我們主張有統計檢定力的良好設計試驗來回答不同族群和危險因子的族群於曝露HIV前預防用藥的有效性和安全性。這些試驗也應評估其他重要的問題,如藥物的安全,藥物遵從性,抗藥性,和預防用藥對高風險行為的影響。

翻譯人

本摘要由臺北榮民總醫院王克帆翻譯。

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

總結

對於高風險族群以抗反轉錄病毒藥物做為接觸前預防HIV感染:本次試驗評估抗反轉錄病毒接觸前預防,以防止高風險群的HIV感染。我們選取了10個試驗:8個正在進行和2個完成。2個已完成的實驗中只有1個符合我們納入的標準。這試驗因為其中2個試驗中心提早結束,所已此納入試驗未能按計劃完成。結果發現,每日口服使用tenofovir disoproxil fumarate (TDF)的無HIV感染的婦女是不會增加不良反應事件。TDF對減少感染HIV風險的有效性無法評估得出結論,因為試驗中HIV感染者的人數太少。然而試驗結果提供進一步的臨床試驗來衡量口服抗反轉錄病毒藥物作為預防免受愛滋病毒感染的一個理由。作為一種新的辦法來預防HIV感染,預防性使TDF或任何其他抗反轉錄病毒藥物目前不被建議。目前需要更大的臨床試驗來確定在具不同危險因子的族群預防性使用藥物預防HIV感染的有效性及安全性。

Plain language summary

Antiretroviral pre-exposure prophylaxis (PrEP) for preventing HIV in high-risk individuals

This review evaluated the effects of antiretroviral pre-exposure prophylaxis (PrEP) for preventing HIV infection in high-risk individuals. We identified 10 trials: eight ongoing or planned and two completed. Only one of the two completed trials met the criteria for this review. The included trial was not completed as planned because two of the trial centres were closed prematurely. It was found that daily oral use of tenofovir disoproxil fumarate (TDF) in HIV-uninfected women was not associated with increased adverse events. The effectiveness of TDF in reducing the risk of acquiring HIV could not be evaluated conclusively because of the small number of HIV infections observed during the trial. The result, however, provides a rationale for further clinical trials to measure the value of oral antiretroviral drugs as prophylaxis against HIV infection. As a new approach to HIV prevention, prophylactic use of TDF or any other antiretroviral drug cannot be recommended at present. Larger clinical trials are needed to determine the effectiveness and safety of using any drug for pre-exposure prophylaxis against HIV infection in various risk groups.