IAS: Raltegravir Effective in New HIV Patients

SYDNEY, July 24 -- The novel integrase inhibitor raltegravir was as effective initial therapy as the standard treatment, a researcher said here.

The drug also had fewer side effects than efavirenz (Sustiva), according to Martin Markowitz, M.D., of the Aaron Diamond AIDS Research Center in New York.

Those findings come from a 48-week study of four doses of the drug head-to-head with efavirenz, which is regarded as the standard of care for patients who are beginning HIV treatment, Dr. Markowitz told attendees at the International AIDS Society meeting.

Raltegravir has been generating interest since clinical trials of the drug began in patients with a long treatment history. (See Investigational Integrase Inhibitor Hits HIV Hard)

And early data from this trial, presented at the 2006 World AIDS Conference in Toronto, also piqued the interest of clinicians looking for new ways to begin therapy for HIV patients.

The researchers enrolled 198 treatment-nave patients and randomized them in a blinded fashion to one of four doses of raltegravir -- 100, 200, 400, and 600 milligrams twice a day -- or to 600 milligrams a day of efavirenz.

Dr. Markowitz said the 48-week data from this Protocol 004 study are essentially the same as those reported in Toronto earlier -- both efavirenz and raltegravir effectively reduce a patient's HIV viral load, but raltegravir does it faster.

Regardless of the study dose, it took only about four weeks for about 90% of patients to reach a viral load of less than 400 copies of HIV RNA per milliliter of blood, he said.

In contrast, patients on efavirenz took between eight and 12 weeks to reach the same level.

That said, Dr. Markowitz noted, there was no difference in the proportions of patients who reached low levels of HIV by the end of the study.

Also, the proportion of patients who experienced treatment failure -- defined as non-response or a rebound in viral load -- was 3% for both raltegravir and efavirenz.

The major difference between the drugs, he said, was in the side effects, with raltegravir being "more benign." There were no dose-related toxicities.

The most common side effects were nausea, dizziness, and headache, which were similar in both arms. The raltegravir group had fewer neuropsychiatric adverse events.

Raltegravir also appears to be neutral with respect to changes in lipids, Dr. Markowitz said.

In an interesting sidelight on the same study, John Murray, Ph.D., of the University of New South Wales, reported that the rapid decline in HIV viral load caused by raltegravir is causing researchers to re-think their understanding of how the virus responds to anti-retroviral drugs.

Treatment usually results in a rapid first-phase decline in viral load, he said, followed by a slower second-phase decline. That second phase had been thought to be the result of long-lived HIV-infected cells dying and not being replaced because of the medication.

But if that's the case, he said, raltegravir -- which blocks HIV from getting into the host genome in the first place -- should not be associated with a more rapid decline than other HIV medications.

Yet, Dr. Murray said, levels of HIV RNA in raltegravir patients appear to be some 70% lower at the beginning of the second phase than they are in patients treated with efavirenz.

The drug has been shown to be "great for patients with resistant virus" and will probably be approved soon for those very sick patients, said Jose Ramon Arribas, M.D. of La Paz Hospital in Madrid, who chaired the session.

"We will continue to use it for those patients," he said, "but this drug has the potential to go to earlier lines of therapy."