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New Antiretroviral Agent, Enfuvirtide, Shows Promise In Treating Multidrug-Resistant HIV-1 Infection

Treatment with enfuvirtide, a new antiretroviral agent, provided significant viral suppression and immunological benefit for patients with multidrug-resistant HIV-1 infection, according to data from two similar phase 3 studies conducted in North and South America, Europe, and Australia.

Enfuvirtide is a synthetic, 36-amino-acid peptide that binds to the first heptad-repeat region of envelope glycoprotein 41 of HIV-1. In the study, it was well tolerated and reduced the plasma viral load in HIV-1 infected patients previously treated with multiple antiretroviral medications.

Dr. Jacob P. Lalezari of Quest Clinical Research in San Francisco, California, United States, and colleagues analysed data from patients over 16 years of age previously treated for at least 6 months at sites in the United States, Canada, Mexico, and Brazil. The patients had received 3 classes of antiretroviral drugs (including at least 2 protease inhibitors) and/or were resistant to these drugs, and had at least 5000 copies of HIV-1 RNA per millilitre of plasma.

A total of 501 patients were randomised (2:1 ratio) to 24-weeks of treatment with 90 mg enfuvirtide by subcutaneous injection twice daily plus their optimised background regimen of 3 to 5 antiretroviral medications, or their background regimen alone.

At week 24, the least-squares mean change from baseline in the plasma HIV-1 RNA level in the intent-to-treat population, significantly favoured the enfuvirtide group, researchers report. The enfuvirtide group showed a decrease of 1.696 log to the base of 10 copies per millilitre compared with a decrease of 0.764 log to the base of 10 in controls.

The enfuvirtide group also showed a significantly greater mean increase from baseline in the CD4+ cell count (76.2 cells per cubic millimetre) than the control group (32.1 cells per cubic millimetre).

In a second study, conducted at sites in France, Spain, Belgium, Germany, Australia, the United Kingdom, Switzerland, the Netherlands, Sweden and Italy, Dr. Adriano Lazzarin at San Raffaele Vita-Salute University in Milan and colleagues analysed data from a similar group of 512 patients who had undergone at least 3 months of treatment. The patients had received at least 1 drug from each of the 3 classes of antiretroviral medications and/or were resistant to each class and had at least 5000 copies of HIV-1 RNA per millilitre of plasma.

This patient population was also randomised to receive either their optimised background regimen of antiretroviral medications alone or their antiretroviral medications plus 90 mg enfuvirtide.

At 24 weeks, this intent-to-treat population also showed a significant difference in favour of the enfuvirtide group from baseline to the least-squares mean change in plasma HIV-1 RNA level. The researchers report a decrease of 1.429 log to the base of 10 copies per millilitre in the enfuvirtide group versus a decrease of 0.648 log to the base of 10 copies per millilitre in controls.

The mean CD4+ cell count was significantly greater in the enfuvirtide group (65.5 cells per cubic millimetre) versus controls (38.0 cells per cubic millimetre).

The researchers of both studies report that, except for local injection-site reactions with enfuvirtide, the safety and tolerability seen in patients in the treatment group was similar to controls. Combined results from both studies, which offers data from longer exposure to enfuvirtide, show a higher rate of pneumonia in the treatment groups compared with controls as well as a higher incidence of eosinophilia in enfuvirtide treated patients even after adjustment for the duration of exposure.

The results of these to concomitant studies, the researchers conclude, indicate that the addition of enfuvirtide to an optimised antiretroviral regimen provided significant benefits to patients who had previously received multiple antiretroviral medications and had multidrug-resistant HIV-1 infection.


Related Link: Enfuvirtide, an HIV-1 Fusion Inhibitor, for Drug-Resistant HIV Infection in North and South America (NEJM 2003;348:2175-2185)
NEJM 2003;348:2186-2195. "Efficacy of enfuvirtide in patients infected with drug-resistant HIV-1 in Europe and Australia"

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