蛋白酶抑制剂单药治疗与联合抗逆转录病毒维持治疗的效果比较：一项荟萃分析。

Effectiveness of protease inhibitor monotherapy versus combination antiretroviral maintenance therapy: a meta-analysis.

机构信息

Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland.

出版信息

PLoS One. 2011;6(7):e22003. doi: 10.1371/journal.pone.0022003. Epub 2011 Jul 19.

BACKGROUND

The unparalleled success of combination antiretroviral therapy (cART) is based on the combination of three drugs from two classes. There is insufficient evidence whether simplification to ritonavir boosted protease inhibitor (PI/r) monotherapy in virologically suppressed HIV-infected patients is effective and safe to reduce cART side effects and costs.

METHODS

We systematically searched Medline, Embase, the Cochrane Library, conference proceedings and trial registries to identify all randomised controlled trials comparing PI/r monotherapy to cART in suppressed patients. We calculated in an intention to treat (loss-of follow-up, discontinuation of assigned drugs equals failure) and per-protocol analysis (exclusion of protocol violators following randomisation) and based on three different definitions for virological failure pooled risk ratios for remaining virologically suppressed.

FINDINGS

We identified 10 trials comparing 3 different PIs with cART based on a PI/r plus 2 reverse transcriptase inhibitors in 1189 patients. With the most conservative approach (viral load <50 copies/ml on two consecutive measurements), the risk ratios for viral suppression at 48 weeks of PI/r monotherapy compared to cART were in the ITT analysis 0.94 8 (95% CI 0.89 to 1.00) p = 0.06; risk difference -0.06 (95%CI -0.11 to 0) p = 0.05, p for heterogeneity = 0.08, I(2) = 43.1%) and in the PP analysis 0.93 ((95%CI 0.90 to 0.97) p<0.001; risk difference -0.07 (95%CI -0.10 to -0.03) p<0.001, p for heterogeneity = 0.44, I(2) = 0%). Reintroduction of cART in 44 patients with virological failure led in 93% to de-novo viral suppression.

INTERPRETATION

Virologically well suppressed HIV-infected patients have a lower chance to maintain viral suppression when switching from cART to PI/r monotherapy. Failing patients achieve high rates of de-novo viral suppression following reintroduction of reverse transcriptase inhibitors.

背景

联合抗逆转录病毒疗法（cART）的空前成功基于两种药物类别的三种药物的联合使用。尚无足够证据表明，在病毒学抑制的 HIV 感染患者中，简化为利托那韦增强蛋白酶抑制剂（PI/r）单药治疗是否能有效且安全地减少 cART 的副作用和降低成本。

方法

我们系统地检索了 Medline、Embase、Cochrane 图书馆、会议记录和试验登记处，以确定所有比较 PI/r 单药治疗与抑制患者 cART 的随机对照试验。我们在意向治疗（随访丢失、停用分配药物等于失败）和按方案分析（根据随机分组排除方案违反者）中进行了计算，并基于三种不同的病毒学失败定义，汇总了剩余病毒学抑制的风险比。

结果

我们确定了 10 项试验，这些试验比较了 3 种不同的 PI，基于 1189 名患者的 PI/r 加 2 种逆转录酶抑制剂，在最保守的方法（连续两次测量病毒载量<50 拷贝/ml）中，PI/r 单药治疗与 cART 相比，48 周时病毒抑制的风险比在 ITT 分析中为 0.948（95%CI 0.89 至 1.00），p=0.06；风险差异-0.06（95%CI-0.11 至 0），p=0.05，异质性 p=0.08，I²=43.1%）和按方案分析中为 0.93（95%CI 0.90 至 0.97），p<0.001；风险差异-0.07（95%CI-0.10 至-0.03），p<0.001，异质性 p=0.44，I²=0%）。在 44 例病毒学失败的患者中重新引入 cART，93%的患者实现了病毒学抑制的重新建立。