A combination drug of abacavir-lamivudine-zidovudine (Trizivir®) for treating HIV infection and AIDS

 

Abstract

Background

The human immunodeficiency virus (HIV) has become one of the greatest challenges to global public health. In 2007 UNAIDS estimated that 33.2 million people were living with HIV. Currently recommended regimens for initiating HIV treatment consist of either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or ritonvair-boosted protease inhibitor (PI) combined with two nucleoside reverse transcriptase inhibitors (NRTIs); however, there may be some patients for whom NNRTIs and PIs may not be appropriate.

Objectives

The aim of this review was to evaluate the effects of Trizivir®, a fixed-dose combination of three NRTIs (abacavir-lamivudine-zidovudine) for initial treatment of HIV infection.

Search methods

In February 2008, we searched the Cochrane Library, PubMed, EMBASE, AIDSearch and GATEWAY and checked reference lists of identified articles. In May 2009, we repeated the search in PubMed and the Cochrane Library.

Selection criteria

We selected randomized controlled trials (RCTs) with a minimum follow-up time of six months which compared Trizivir® with either a PI- or NNRTI-based therapy among antiretroviral-naive HIV-infected patients aged at least 13 years.

Data collection and analysis

Three authors independently extracted data. We calculated the relative risk (RR) or mean difference (as appropriate) for each outcome with its 95% confidence interval (CI) and conducted meta-analysis using the random-effects method because of significant statistical heterogeneity (P<0.1).

Main results

We identified nine potentially eligible RCTs, three of which met our inclusion criteria. One trial compared Trizivir® to efavirenz (an NNRTI) plus two or three NRTIs; the second trial compared Trizivir® to a treatment based on the PI nelfinavir; and the third compared Trizivir® to atazanavir (a PI) plus two NRTIs. Overall, there was no significant difference in the incidence of virological failure between participants on Trizivir® and those on PI-based or NNRTI-based therapy (three trials, N=1687; RR 1.14, 95% CI 0.56 to 2.32). However, there was significant heterogeneity between the results of the three trials (heterogeneity P=0.009, I²=79%), with a significant increase in virological failure for Trizivir® compared to efavirenz (N=1147; RR 1.93, 95% CI 1.46 to 2.55) but no difference between Trizivir® and PIs (two trials, N=540; RR 0.82, 95% CI 0.50 to 1.36). We found no significant differences between Trizivir® and either the PI or NNRTI on CD4+ cell counts (standardized mean difference -0.01, 95% CI -0.11 to 0.09, heterogeneity P=0.59, I²=0%), severe adverse events (RR 1.41, 95% CI 0.61 to 3.25, heterogeneity P=0.03, I²=73%) and hypersensitivity reactions (RR 4.04, 95% CI 0.41 to 40.02, heterogeneity P=0.03, I²=72%). Only the studies involving PIs reported the effect of the treatment regimens on the lipid profile. One study found that at 96 weeks, the mean increase in total cholesterol from baseline was significantly lower with Trizivir® than with nelfinavir, but there were no significant differences with triglyceride levels. The second study found the fasting lipid profile to be comparable in both the Trizivir® and atazanavir arms at 48 weeks.

Authors' conclusions

Our findings indicate that Trizivir® remains a viable option for initiating antiretroviral therapy, especially in HIV-infected patients with pre-existing hyperlipidaemia and those who do not tolerate ritonavir.

 

Plain language summary

Trizivir® for treating HIV infection and AIDS

The primary objective of this review was to evaluate the antiviral efficacy of co-formulated zidovudine-lamivudine-abacavir (Trizivir^®) for initial treatment of HIV infection. The secondary objectives were to evaluate the safety and tolerability of the triple drug combination. We identified nine potentially eligible studies, three of which met our inclusion criteria. Our findings indicate that Trizivir® remains a viable option for initiating antiretroviral therapy, especially in HIV-infected patients with pre-existing hyperlipidaemia and those who do not tolerate ritonavir.

 

摘要

背景

組合藥物(abacavirlamivudinezidovudine) (Trizivir) 用於愛滋病毒感染和愛滋病的治療

人類免疫缺陷病毒 (HIV) 已經成為全球公眾健康的最大挑戰之一。 2007年，聯合國愛滋病規劃署估計有3320萬人感染了愛滋病毒。目前推薦的愛滋病的起始治療，包含非核?逆轉錄抑製劑 (NNRTI) 或ritonvair促進蛋白酵素抑制劑 (PI) 合併兩個核?逆轉錄抑制劑。然而，對某些病人而言，非核?逆轉錄抑製劑與ritonvair促進蛋白酵素抑制劑，可能未必恰當。

目標

此回顧文章目的是評估固定劑量Trizivir (由3種核?逆轉錄抑制劑 abacavir, lamivudine, zidovudine組成的藥物) 用於愛滋病毒感染之起始治療效果。

搜尋策略

2008年2月，我們檢索了Cochrane Library、PubMed、EMBASE、AIDSearch and GATEWAY，並核對相關文章的參考文獻。2009年5月，我們在PubMed和Cochrane Library做第二次的檢索。

選擇標準

我們選擇至少追蹤6個月以上的隨機對照試驗，比較Trizivir與ritonvair促進蛋白酵素抑制劑 (PI) 或非核?逆轉錄抑製劑 (NNRTI) 為基礎的抗逆轉錄病毒療法，對13歲以上，從未接受抗愛滋病毒藥物的療效。

資料收集與分析

三位作者獨立擷取數據。我們計算每個結果的相對危險度或每項結果的平均差異與95%信賴區間，且因為統計的顯著異質性，採用隨機效應的模式進行合併分析 (P < 0.1)。

主要結論

我們確認9個潛在合格的隨機對照試驗，其中3個符合我們的納入標準。第一項試驗比較 Trizivir與efavirenz(1種非核?逆轉錄抑製劑)加兩個或三個核?逆轉錄抑製劑；第二項試驗比較Trizivir與nelfinavir (一種ritonvair促進蛋白酵素抑制劑)；第三項試驗比較Trizivir和atazanavir(1種ritonvair促進蛋白酵素抑制劑)加兩種核?逆轉錄抑製劑。總體而言，比較trizivir和ritonvair促進蛋白酵素抑制劑或非核?逆轉錄抑製劑為治療基礎的療法，病毒學失敗發生率並無顯著差異 (三項試驗，總個案數為1687;RR1.14，95％CI為0.56至2.32)。不過，這三項試驗有顯著異質性的結果 (異質性P值為0.009，I2 = 79％) 與efavirenz相比，trizivir的病毒學失敗有顯著增加(總數為1147;RR1.93，95％CI為1.46至2.55)，但Trizivir和ritonvair促進蛋白酵素抑制劑之間則無差異 (兩項試驗總數為540;RR 0.82，95％CI為 0.50至1.36)。我們發現顯在trizivir和ritonvair促進蛋白酵素抑制劑或非核?逆轉錄抑製劑之間，在各方面無顯著差異，包括 CD4細胞計數(標準平均差−0.01，95％CI為−0.11至0.09，異值性P值0.59，I2 = 0％)、嚴重不良反應度(RR 1.41，95％CI為 0.61至3.25，異值性P值0.03，I2 = 73％)、和過敏反應 (RR 4.04，95％CI為0.41至40.02，異值性P值0.03，I2 = 72％)；只有與ritonvair促進蛋白酵素抑制劑相關之研究，報告其治療對血脂的影響。一項研究發現，在96週時，與nelfinavir相比，trizivir平均增加總膽固醇有顯著下降，但對甘油三酯而言，則無顯著差異。第二項研究發現，在第48週時，空腹血脂在Trizivir和atazanavir是相當的。

作者結論

我們的研究結果指出，對抗逆轉錄病毒的起始療法而言，Trizivir仍然是一個可行的選擇，特別是針對有高血脂症或無法容忍RITONAVIR的愛滋病毒感染的患者。

翻譯人

本摘要由臺北榮民總醫院劉彥宏翻譯。

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

總結

這篇回顧的主要目的是評估Trizivir對愛滋病毒感染之起始治療的療效。次要目的是評估這個組合3種藥物的安全性和耐受性。我們找到9個潛在合格的研究，其中3個符合我們的納入標準。我們的研究結果指出，對抗逆轉錄病毒的起始療法，Trizivir仍是一個可行的選擇，特別是針對有高血脂症或無法容忍RITONAVIR的愛滋病毒感染的患者。