Treatment of latent tuberculosis infection in HIV infected persons

 

Abstract

Background

Individuals with human immunodeficiency virus (HIV) infection are at an increased risk of developing active tuberculosis (TB). It is known that treatment of latent TB infection (LTBI), also referred to as TB preventive therapy or chemoprophylaxis, helps to prevent progression to active disease in HIV negative populations. However, the extent and magnitude of protection (if any) associated with preventive therapy in those infected with HIV should be quantified. This present study is an update of the original review.

Objectives

To determine the effectiveness of TB preventive therapy in reducing the risk of active tuberculosis and death in HIV-infected persons.

Search methods

This review was updated using the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, AIDSLINE, AIDSTRIALS, AIDSearch, NLM Gateway and AIDSDRUGS (publication date from 01 July 2002 to 04 April 2008). We also scanned reference lists of articles and contacted authors and other researchers in the field in an attempt to identify additional studies that may be eligible for inclusion in this review.

Selection criteria

We included randomized controlled trials in which HIV positive individuals were randomly allocated to TB preventive therapy or placebo, or to alternative TB preventive therapy regimens. Participants could be tuberculin skin test positive or negative, but without active tuberculosis.

Data collection and analysis

Three reviewers independently applied the study selection criteria, assessed study quality and extracted data. Effects were assessed using relative risk for dichotomous data and mean differences for continuous data.

Main results

12 trials were included with a total of 8578 randomized participants. TB preventive therapy (any anti-TB drug) versus placebo was associated with a lower incidence of active TB (RR 0.68, 95% CI 0.54 to 0.85). This benefit was more pronounced in individuals with a positive tuberculin skin test (RR 0.38, 95% CI 0.25 to 0.57) than in those who had a negative test (RR 0.89, 95% CI 0.64 to 1.24). Efficacy was similar for all regimens (regardless of drug type, frequency or duration of treatment). However, compared to INH monotherapy, short-course multi-drug regimens were much more likely to require discontinuation of treatment due to adverse effects. Although there was reduction in mortality with INH monotherapy versus placebo among individuals with a positive tuberculin skin test (RR 0.74, 95% CI 0.55 to 1.00) and with INH plus rifampicin versus placebo regardless of tuberculin skin test status (RR 0.69, 95% CI 0.50 to 0.95), overall, there was no evidence that TB preventive therapy versus placebo reduced all-cause mortality (RR 0.94, 95% CI 0.85 to 1.05).

Authors' conclusions

Treatment of latent tuberculosis infection reduces the risk of active TB in HIV positive individuals especially in those with a positive tuberculin skin test. The choice of regimen will depend on factors such as availability, cost, adverse effects, adherence and drug resistance. Future studies should assess these aspects. In addition, trials evaluating the long-term effects of anti-tuberculosis chemoprophylaxis, the optimal duration of TB preventive therapy, the influence of level of immunocompromise on effectiveness and combination of anti-tuberculosis chemoprophylaxis with antiretroviral therapy are needed.

 

Plain language summary

Treatment of latent tuberculosis (TB) with isoniazid in people infected with HIV reduces their risk of developing active TB

Most people infected with tuberculosis (TB) never get TB symptoms. This is called latent TB. People infected with HIV/AIDS are at increased risk of getting TB and about 30% of people with HIV who have latent TB will eventually get active TB. This results in an increase in the risk of earlier death. This update of the review of available clinical trials found that the risk of developing active TB was reduced when people infected with both HIV and TB used isoniazid. Isoniazid for latent TB is usually taken for six to 12 months, but more research is still needed to show optimal duration of treatment, the best treatment regime for people with HIV, and especially the best regimen in combination with HIV drugs.

 

摘要

背景

治療患有人類免疫缺乏病毒(HIV)感染病人的潛伏性結核病

患有HIV感染的病人有比較高的風險產生活動性結核病。對潛伏性結核病(LTBI)進行治療,或稱之為預防治療或是化學治療預防(chemoprophylaxis)可以有效避免HIV陰性病人的潛伏性結核病進行成活動性結核病。然而,在HIV陽性病人,預防治療所提供保護的程度及強度則還有待量化。

目標

決定結核病預防治療在降低HIV感染病人產生活動性結核病的風險及死亡的效果。

搜尋策略

本篇文獻回顧使用以下資料庫進行更新： the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, AIDSLINE, AIDSTRIALS, AIDSearch, NLM Gateway 及AIDSDRUGS (出刊日期自2002年7月1日到2008年4月4日)。我們也掃描了文章的參考文獻清單並且連絡作者及其他本領域的研究人員，嘗試找出合乎本回顧條件的額外研究。

選擇標準

所收納進來的試驗必須是HIV(+)的病人隨機的分成結核病預防治療組及安慰劑組或是替代性結核病治療藥物組。所收納的成員可以是結核菌素皮膚試驗陽性或是陰性的病人,但是必須沒有活動性結核病。

資料收集與分析

兩個審查者獨立的應用試驗選擇準則,評估試驗品質及數據採集.其成效的評估分成:針對分叉數據(dichotomous data)以相對危險(relative risk)評估。針對連續數據(continuous data)則以平均差(mean difference)評估。

主要結論

有11個試驗被收納進來,總共有8130個隨機參與者。相對於安慰劑組,預防治療組(任何抗結核藥物)有著較低的活動性結核病發生率(相對危險(RR) 0.64, 95%信賴區間(95% CI) 0.51 to 0.81)。相對於結核菌素皮膚測試陰性的病人,這個好處相對於在結核菌素皮膚測試陽性的病人更為明顯。(相對危險(RR) 0.83, 95%信賴區間(95% CI) 0.58 to 1.18)。有限的資料顯示出,預防治療的抗結核效果會隨著時間慢慢降低。所有治療方針的效果都是相似的。然而,相對於INH的單一藥物治療,短期的多重藥物治療顯得更為容易因為副作用的產生而中途終止。總體而言,雖然結核菌素皮膚測試陽性的病人有著較低的總死亡率趨勢(相對危險(RR) 0.80, 95%信賴區間(95% CI) 0.63 to 1.02),但是並沒有任何證據顯示出預防治療組相對於安慰劑組可以降低總死亡率(相對危險(RR) 0.95, 95%信賴區間(95%) CI 0.85 to 1.06)。

作者結論

治療潛伏性肺結核感染(LTBI)可以降低HIV(+)且結核菌素皮膚測試陽性的病人發展成活動性結核病的風險。治療方針的選擇端賴於花費,副作用,服藥順從性,及抗藥性來決定。未來的研究應該對這幾方面進行評估。此外,對於結核病預防藥物的長期效果以及免疫不全病人對於預防效果的影響則需要進一步的試驗來評估。

翻譯人

本摘要由臺北榮民總醫院李霖昆翻譯。

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

總結

以INH治療HIV(+)病人的潛伏性結核病可以減少他們發展成活動性結核病的風險。而這些HIV(+)的病人獲得結核病的風險其實是比較高的,導致早期死亡。大部分感染結核病的病人都沒有症狀。此稱為潛伏性結核病。大約30%有潛伏性結核病的病人最終會發展成活動性結核病。而這些試驗發現同時帶有HIV及結核病的病人以INH治療可以減少活動性結核病的產生。針對潛伏性結核病的治療, INH的療程通常是6∼12個月,不過仍需要更多的研究去訂出最佳的治療方針。