Two New Classes of Drugs Found To Control Viral Loads Among HIV-Positive People Who Have Developed Drug Resistance, Studies Say

Two new classes of antiretroviral drugs, called CCR5 and integrase inhibitors, have been found to control the viral loads of HIV-positive people who have developed drug resistance, according to studies presented Tuesday at the 14th Annual Conference on Retroviruses and Opportunistic Infections in Los Angeles, the Los Angeles Times reports (Chong, Los Angeles Times, 2/28). An estimated 40,000 HIV-positive people in the U.S. have developed resistance to available antiretrovirals and rely on a complex and changing combination of available drugs (Kaiser Daily HIV/AIDS Report, 1/2). According to the New York Times, the two new antiretrovirals if approved would represent the first new classes of HIV/AIDS drugs since 2003. They also would be the first new classes of oral antiretrovirals in 10 years. One drug, developed by Pfizer and called maraviroc, works by blocking a protein, called CCR5, on human immune system cells that HIV uses as a portal to enter and infect the cell. Pfizer has applied for FDA approval to market the drug, and an FDA advisory panel announced last week that it will meet on April 24 to examine the safety and efficacy of the drug. Pfizer plans to offer the drug with a test developed by Monogram Biosciences that determines if people likely will respond to the treatment, the Times reports (Altman/Pollack, New York Times, 2/28). The other antiretroviral, developed by Merck and called raltegravir, was formerly known as MK-0518. The drug works by blocking an HIV enzyme called integrase, the San Francisco Chronicle reports (Russell, San Francisco Chronicle, 2/28). Integrase is one of the three enzymes necessary for HIV to replicate in the body, and integrase inhibitors would stop HIV from inserting its genes into uninfected DNA. The other two enzymes necessary for viral replication -- reverse transcriptase and protease -- already are targeted by a variety of antiretrovirals (Kaiser Daily HIV/AIDS Report, 8/18/06). Merck has announced that it will apply for FDA approval in the second quarter of 2007 (New York Times, 2/28).

Studies

• Raltegravir: David Cooper of the University of New South Wales in Australia and Roy Steigbigel of State University of New York-Stony Brook on Tuesday at the conference reported on two studies funded by Merck involving about 700 HIV-positive people, two-thirds of whom received raltegravir in addition to their regular antiretroviral regimens, the Los Angeles Times reports (Los Angeles Times, 2/28). Participants in the two Phase III studies had developed resistance to at least one drug in each of the three classes of anitretrovirals (New York Times, 2/28). The study found that viral loads in about 62% of the participants receiving raltegravir decreased to undetectable levels after 16 weeks, compared with 35% of those who received the standard drugs alone (Los Angeles Times, 2/28). The researchers also found that 80% of participants who received raltegravir had a decrease in viral loads to a level that is considered manageable (San Francisco Chronicle, 2/28).
  

• Maraviroc: Howard Mayer of Pfizer on Tuesday reported on two studies that involved 1,049 HIV-positive people, 840 of whom received maraviroc in combination with their regular drug regimens, while the rest received a placebo and their regular antiretroviral regimens (Los Angeles Times, 2/28). The study participants had developed resistance to the three classes of antiretrovirals, according to the New York Times. The study found that after 24 weeks of a 48-week study, more than 40% of the participants who received maraviroc had undetectable viral loads (New York Times, 2/28). The researchers also found that 60% of participants who received maraviroc experienced a decrease in viral loads to manageable levels (San Francisco Chronicle, 2/28).
  

Reaction
This is "a pivotal moment" for HIV-positive people who have developed resistance to most antiretrovirals, Eric Daar, chief of HIV medicine at Harbor-UCLA Medical Center, said. He added that given the problems associated with providing treatment to people who have developed drug resistance, the study's findings present "the opportunity for a new life." John Mellors of the University of Pittsburgh said, "This is really a remarkable development in the field." John Bartlett -- an epidemiologist at Johns Hopkins University who was not involved with the studies -- said, "The big question now is how will these drugs be used in practice. If they become first-line drugs, that could mean a paradigm shift" (Los Angeles Times, 2/28). Some experts said that they are slightly cautious about maraviroc, in part because the drug targets a human protein and not a viral one and could have unknown, long-term side effects, according to the New York Times (New York Times, 2/28). In addition, fewer than half of the 40,000 HIV-positive people in the U.S. who have developed drug resistance might benefit from maraviroc, according to the Wall Street Journal. Most HIV-positive people on long-term treatment have HIV strains that enter through a different portal, called CRCX4, which is unaffected by the drug, according to Steven Deeks of the University of California-San Francisco (Chase/Goldstein, Wall Street Journal, 2/28). Merck and Pfizer have said that they are conducting studies to test the drugs for use as initial treatments. Neither company has said how much the drugs will cost (New York Times, 2/28).