IAS: Maraviroc Called Premature for New HIV Patients

SYDNEY, July 25 -- An investigational HIV drug that blocks the virus from entering its target cells "isn't ready for prime time" in the treatment of newly diagnosed patients, a researcher said here.

In a head-to-head trial, the novel entry inhibitor maraviroc "fell just short" of demonstrating noninferiority to non-nucleoside reverse transcriptase inhibitor efavirenz (Sustiva), according to Michael Saag, M.D., of the University of Alabama at Birmingham.

But the CCR5 antagonist had better safety results than efavirenz, which is regarded as a preferred component of the initial therapy, Dr. Saag told a session with late-breaking results at the International AIDS Society meeting here.

There are also some puzzling results -- an unexplained difference between countries in the northern and southern hemispheres -- that will require further study, he said.

The researchers in an international study dubbed MERIT had been hoping to demonstrate that maraviroc was noninferior to efavirenz at rendering the HIV viral load undetectable -- defined as fewer than 50 copies of HIV RNA per milliliter of blood

In the study of 721 patients, 65.3% of maraviroc patients met that standard, compared with 69.3% for efavirenz.

But the results failed to meet the standard for "non-inferiority" -- to be within 10% of efavirenz in the proportion of patients who had undetectable levels of HIV after 48 weeks of therapy.

That's because the lower bound of the 97.5% confidence interval for the difference was minus 10.9%, Dr. Saag said, and fell outside the 10% standard.

For the less stringent standard of 400 copies per milliliter, maraviroc just met the non-inferiority standard, he said.

On the other hand, he said, the drug outperformed efavirenz on other aspects of treatment:

• 13.6% of efavirenz patients dropped out because of adverse events, compared to 4.2% of maraviroc patients.
• 3.3% of efavirenz patients had serious AIDS-defining events, compared with 1.7% for maraviroc.
• 4.4% of efavirenz patients developed a malignancy, compared to 2.8% for maraviroc.
• On average, efavirenz patients saw their CD4 counts rise by 144 cells, compared to 170 for maraviroc.
• Changes in lipids were less dramatic in the maraviroc arm.

For statistical analysis, Dr. Saag said, patients were stratified according to the region of origin -- in the northern or southern hemisphere - and the researchers found that maraviroc was noninferior to efavirenz in the northern hemisphere.

But in the south, Dr. Saag said, 71% of efavirenz patients reached undetectable HIV levels, compared with 62.1% for maraviroc.

The reasons for the difference "still have to be explained," Dr. Saag said, because the researchers finished compiling their data only a month ago.

Among possible explanations, he said, are that differences in the strains of HIV in the regions might have affected the results, that some tests might have been poorly performed, or that patients in the south might have been sicker in the first place.

Despite the results, "maraviroc is still a very important newcomer," commented Stefano Vella, M.D., of the Italian national health institute. Dr. Vella, a former president of the IAS, chaired the late-breaker session.

He said that maraviroc was held to a high standard: It was tested against efavirenz, which is "the best that we have in our hands today." And the 10% non-inferiority benchmark is a higher-than-usual standard.

The drug may still have a role to play in initial therapy for HIV patients, Dr. Vella said.