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Meta-Analysis Sees Integrase Inhibitors Superior in First-Line Rx

Author: Mark Mascolini

21 February 2013

Meta-analysis of published and presented trials determined that first-line antiretroviral regimens incorporating an integrase inhibitor are virologically superior to other regimens. The analysis did not support switching to an integrase inhibitor from a suppressive protease inhibitor with a high genetic barrier to resistance.

Integrase inhibitors have emerged as potent, relatively safe, and often-prescribed components of antiretroviral regimens for people with or without antiretroviral experience. Dutch researchers planned this meta-analysis to review evidence on virologic and CD4 response to integrase inhibitors in clinical settings.

The researchers screened electronic databases from April 2006 to November 2012 for randomized controlled trials, nonrandomized controlled trials, and cohort studies involving integrase inhibitors. They also hand-searched meeting abstracts for relevant studies.

This analysis yielded 48 unique studies in which antiretroviral-naive or experienced patients took an integrase inhibitor as part of their antiretroviral regimen. Antiretroviral-experienced patients were switching to an integrase inhibitor because of virologic failure or while virologically suppressed. The investigators performed a meta-analysis on 16 studies with a control arm and with comparable outcome measures and indication. In this analysis an odds ratio [OR] of 1.0 or higher indicates no benefit compared with the control regimen.

A modified intention-to-treat (mITT) analysis found integrase inhibitor regimens virologically superior to comparator regimens for first-line therapy (mITT OR 0.71, 95% confidence interval [CI] 0.59 to 0.86). Regimens that combined an integrase inhibitor only with a protease inhibitor did not result in a better virologic outcome than comparator regimens.

Integrase inhibitor regimens were generally virologically superior to other regimens after virologic failure (mITT OR 0.27, 95% CI 0.11 to 0.66). But the analysis did not support switching to an integrase inhibitor from a suppressive protease inhibitor with a high genetic barrier to resistance (mITT OR 1.43, 95% CI 0.89 to 2.31).

The studies analyzed found that the integrase inhibitors raltegravir and elvitegravir have a low genetic barrier to resistance, but dolutegravir does not. CD4-cell responses to integrase inhibitor regimens were similar to responses to other regimens.

The researchers conclude that their meta-analysis “positioned integrase inhibitors as a preferred drug in the setting of treatment-naive [patients] and as [a] beneficial addition in treatment-experienced patients with virological failure, based on virological efficacy.” But the authors called for “careful use of integrase inhibitors when replacing a high genetic barrier protease inhibitor.”

The researchers suggest that prospects for “new single tablet regimens containing elvitegravir or dolutegravir taken in the absence of food restrictions hold promise for broad use in first line regimens.”

Source: Peter Messiaen, Annemarie M. J. Wensing, Axel Fun, Monique Nijhuis, Nele Brusselaers, Linos Vandekerckhove. Clinical use of HIV integrase inhibitors: a systematic review and meta-analysis. PLoS One. 2013; 8: e52562.

Complete article provided by PLoS One, an open-access journal