LOS ANGELES, Feb. 28 (UPI) -- Two new drugs appear to give patients who are running out of medical options potent weapons against advanced, resistant infection with the virus that causes AIDS.
"I would not be going out on a limb to say these results are as exciting for experienced patients as were the results of the original trials with combination highly active antiretroviral therapy," said John Mellors, professor of medicine at the University of Pittsburgh.
Mellors moderated a news briefing during which researchers detailed results of phase 3 clinical trials of the new drugs, raltegravir and maraviroc, at the 14th annual Retrovirus Conference in Los Angeles.
Experienced patients with human immunodeficiency virus (HIV) -- the microbe responsible for AIDS -- are infected with virus strains that have developed resistance to almost all classes of drugs designed to fight AIDS.
"We had patients who had no drugs that were still active against HIV," Roy Steigbigel, professor of medicine at the State University of New York Stony Brook Health Sciences Center, told United Press International.
"Yet when these patients were given raltegravir, 61 percent of them were able to reduce viral levels in the blood to undetectable levels," Steigbigel said. "That compared to 5 percent of patients with the same background of drugs who did not receive raltegravir."
Raltegravir is an investigative integrase inhibitor being developed by Merck. In earlier studies, the drug was known as MK-0518.
Integrase is one of the three enzymes of the virus that is required for viral replication. Drugs to inhibit the other enzymes, protease and reverse transcriptase, have already been developed and are basic backbones of multi-drug combinations.
In two phase 3 trials, raltegravir delivered along with the best combination of other drugs available was clearly superior to the best optimized treatment without raltegravir, said David Cooper, director of the National Centre in HIV Epidemiology and Clinical Research in Sydney, Australia.
Overall, Cooper said, 77 percent of the 232 patients in his BENCHMARK-1 trial achieved an undetectable viral load after 16 weeks of treatment, compared with 41 percent of 118 patients who did not receive the experimental drug.
In BENCHMARK-II, Steigbigel said the results mirrored Cooper's trial. He said 77 percent of 230 patients on raltegravir achieved an undetectable virus, compared with 43 percent of 119 patients on the best available care without raltegravir.
Steigbigel said that, when raltegravir was combined with two newly approved agents, the injectable fusion inhibitor enfuvirtide (Fuzeon, also known as T-20) and darunavir (Prezista), "about 98 percent of patients were able to reach undetectable virus levels."
Researchers reporting phase 3 trials of Pfizer's experimental drug maraviroc found similar results in similarly designed trials.
Howard Mayer, executive director of global research and development at Pfizer, said the results of MOTIVATE I and II showed that about 60 percent of 426 patients taking maraviroc were able to lower viral levels to undetectable compared with less than 30 percent of 209 patients on optimized background treatment.
Maraviroc was delivered either once a day or twice a day, with the twice-a-day formulation appearing to have a slightly better result in achieving undetectable levels of virus. Both the regimens, however, were superior to combinations without maraviroc.
Research has determined that undetectable viral levels -- although not a cure -- slows viral replication to the point where the virus has less chance of mutating and developing resistance to the drugs.
Maraviroc is known as a CCR5 inhibitor. CCR5 is one of two receptors used by the virus to help it enter cells, where the virus then begins its replication process.
Mellors said that in order for HIV to enter a cell, it has to go through a doorway. "The virus is like a key to that door, but it requires a receptor, CCR5 or CXCR4, to turn the combination of that lock," he explained. Some individuals have exclusively CCR5 receptors; others have both CCR5 and CXCR4 receptors. In the maraviroc trials, all the patients had CCR5 receptors.
Mellors, in moderating the discussion, noted that the findings seen with maraviroc and raltegravir were similar to the revolutionary results in 1996 at the Retrovirus Conference in Washington in which the first combination therapies were described.
Those studies ushered in the era of effective anti-retroviral therapy that altered the face of the AIDS epidemic in the Western world. Instead of a two-year life expectancy marked by serial bouts of nasty opportunistic infections with uncommon pneumonia and diarrhea, patients who stayed adherent to drug therapy were able to have extended survival.
As good as the results are with maraviroc and raltegravir, Steigbigel told UPI, "We still need to be developing more drugs. This virus always seems to develop resistance to what we throw at it."
The new drugs still require Food and Drug Administration approval before they will be widely available.
