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Impressive Results with Raltegravir in Treatment-Naive HIV Patients

Rates of virologic suppression were similar between raltegravir and efavirenz, but drug-related adverse events were less common with raltegravir.

The approval of raltegravir, the first integrase inhibitor, in 2007 ushered in a new era for managing treatment-experienced patients with HIV infection (JW AIDS Clin Care Oct 22 2007). Clinicians quickly saw that the drug was highly potent, was well tolerated, and greatly enhanced the activity of salvage regimens. For treatment-naive patients, phase II study results for raltegravir were published in 2007, and phase III findings were first presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy, in 2008. Now we have the published results of the phase III trial, which was funded by raltegravir's manufacturer.

In all, 566 treatment-naive patients were randomized to receive either once-daily efavirenz or twice-daily raltegravir, plus matching placebos to ensure blinding. All patients also received fixed-dose tenofovir/FTC. Typical of the treatment-naive population in current practice, about half the participants had CD4 counts 200 cells/ mm³, and about half had viral loads >100,000 copies/mL.

By 48 weeks, 86% of patients in the raltegravir group and 82% of those in the efavirenz group had reached the primary endpoint of a viral load <50 copies/mL, thereby establishing the noninferiority of raltegravir. Treatment responses were consistent across baseline levels of viral load and CD4-cell count.

As in other raltegravir studies, the drug rapidly reduced viral loads — in this trial, significantly faster than efavirenz did. From baseline to week 48, the mean increase in CD4 count was significantly greater with raltegravir than with efavirenz (189 cells/mm³ vs. 163 cells/mm³). Raltegravir recipients also experienced fewer treatment-related adverse effects, including a significantly lower incidence of central nervous system–related events (10%, vs. 18% in the efavirenz group).

Comment: These results, which have been available for nearly a year, have prompted the FDA to approve raltegravir for treatment-naive patients. But will the findings lead clinicians to select raltegravir as initial treatment for HIV infection? An editorialist notes that the drug has much to recommend it: Its impressive virologic and tolerability profile is bolstered by favorable metabolic effects and a virtual lack of drug–drug interactions. Perhaps the biggest arguments against using raltegravir are twice-daily use (no 1-pill-a-day option as with tenofovir/FTC/efavirenz) and the relative newness of the drug and its class (compared with NRTIs, NNRTIs, and PIs). A study of once-daily raltegravir is under way.

— Paul E. Sax, MD

Published in Journal Watch HIV/AIDS Clinical Care August 10, 2009

Citation(s):

Lennox JL et al. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: A multicentre, double-blind randomised controlled trial. Lancet 2009 Aug 3; [e-pub ahead of print]. (http://dx.doi.org/10.1016/S0140-6736(09)60918-1)

Emery S and Winston A. Raltegravir: A new choice in HIV and new chances for research. Lancet 2009 Aug 3; [e-pub ahead of print]. (http://dx.doi.org/10.1016/S0140-6736(09)61392-1)

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