Aug. 7, 2008 A Johns Hopkins expert in HIV and how the AIDS virus hides in the body says antiretroviral drugs have stopped HIV from replicating, the first of three key steps needed to rid people of the virus.
In an address to be delivered Aug. 6 at the XVII International Conference on AIDS, taking place in Mexico City, infectious disease specialist Robert Siliciano, M.D., Ph.D., says current drug-combination therapies can stop HIV in its tracks, with some combos suppressing its ability to make copies to less than one in a billion.
But, he says, progress is still needed in identifying where viral reservoirs persist and in finding ways to eliminate these HIV hiding places.
Indeed, it was Siliciano's team at Hopkins in 1995 that confirmed the existence of these reservoirs in immune system CD4 memory T-cells - those left behind, after an initial infection, to fight recurrences. The CD4s concentrate in the lymph nodes and spleen. Siliciano suggests that other as yet unverified viral pools could exist, citing previous studies at Johns Hopkins that, in 2006, identified adult stem cells and progenitor cells as potential hideaways for HIV.
According to Siliciano, a professor at the Johns Hopkins University School of Medicine and a Howard Hughes Medical Institute investigator, laboratory models that mimic HIV infection in these reservoir cells are key to finding drugs that can eliminate them.
"We know now that HIV can be stopped," says Siliciano. "Our next steps are to go after these reservoirs of HIV. And although much work needs to be done to find and eliminate them, infected people who have access to antiretroviral drugs and who take them as prescribed stand a good chance of leading normal lives."
Siliciano points out that if antiretroviral drugs can be made more accessible, affordable and less toxic, then infected people who take the drugs correctly will not develop AIDS.
Included in Siliciano's presentation are recent data from his team and researchers at the National Cancer Institute and the University of Pittsburgh, which shows that adding a fourth, more potent anti-HIV drug to existing antiviral combinations does not further suppress the number of HIV viral copies in the blood.
"Adding more drugs to current regimens will not further reduce the amount of virus in the blood," says Siliciano. "We have already reached rock bottom in using drugs to stop HIV from replicating. The trace amounts of virus that remain are coming from viral reservoirs, not active replication of the virus."
In 15 HIV-positive study participants already using highly active antiretroviral therapy, or HAART, to suppress the virus, researchers added either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor. They found no greater suppression in viral blood levels than seen before the fourth drug was added.
Hundreds of thousands of the more than 1 million Americans infected with HIV are currently using HAART, a combination usually of three of 25 potent antiviral medications. And these drugs almost eliminate the amount of virus in the blood, lowering the number to fewer than 50 copies per cubic milliliter of blood.
Siliciano also describes the progress of four laboratory models for testing HIV reservoirs, including one developed at Johns Hopkins, in identifying all viral reservoirs, and in penetrating them with antiretroviral drugs.
There are more than 33 million people in the world living with HIV, including an estimated 950,000 in the United States and 23,000 in the state of Maryland.
Funding for the latest study was provided by the Howard Hughes Medical Institute; the National Institute of Allergy and Infectious Diseases, a member of the National Institutes of Health (NIH); and the Doris Duke Charitable Foundation.
Presentation title: HIV Persistence in HAART: Re-evaluating Prospects for Eradication.
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