Contacts: Ashley Haase, Microbiology Department, (612) 624-4442
Winston Cavert, Microbiology Department, (612) 624-9130
Deane Morrison, University News Service, (612) 624-2346, [email protected]
HIV triple therapy dramatically cuts virus levels in lymph tissue reservoir as well as blood cells, u of minnesota study finds A regimen of three anti-HIV drugs reduces amounts of virus stored in lymph tissue by 99.9 percent after six months, according to a study led by University of Minnesota researchers. The triple therapy was already known to drive virus in the blood to near-undetectable levels, but the new study shows similar results against virus stored in tonsils, a lymphoid tissue that acts as a reservoir for HIV.
The study will appear in Friday's issue of Science. Led by virologist Dr. Winston Cavert, the researchers counted HIV viral particles using a technique developed by Dr. Ashley Haase, head of the University of Minnesota microbiology department. The technique allows scientists to visually locate and count HIV-infected immune cells and copies of viral RNA contained in particles in tonsilar tissue. (HIV infects immune cells known as CD4s [or T helper cells] and forces them to produce new viral particles. HIV is stored in particles on the outer surfaces of tonsil cells known as follicular dendritic cells, or FDCs. FDCs normally serve as a depot for substances, HIV included, that trigger an immune response.)
The researchers measured the virus in tonsil tissue from 10 previously untreated HIV-positive adults who underwent therapy with three drugs: the protease inhibitor ritonavir and the reverse transcriptase inhibitors zidovudine and lamivudine. The researchers found that in the early days of treatment, about half of infected CD4s that were producing new virus disappeared in only 0.9 day. That is, the half-life of HIV-infected CD4 cells was 0.9 day. Similarly, it took only 1.7 days to clear half the viral particles from FDCs. After three weeks, the rate of disappearance slowed but still continued at a strong pace. In most patients, some viral RNA remained detectable after six months, but in one patient, viral RNA dropped to undetectable levels. However, cautioned Cavert, the virus can also exist in latent form as DNA--made from the RNA blueprint that constitutes the core of the virus--and even the patient in whom HIV RNA had disappeared had at least some residual viral DNA.
"This confirms our hopes that reductions of HIV in blood are occurring throughout the body," said Cavert. "It shows that the drug gets into lymph tissue and that production of the HIV virus in cells in lymph tissue is nearly shut off.
"We believe that by greatly decreasing the amount of virus in the body, aggressive treatment will slow the rate of devastation to the immune system, particularly to the CD4 cells that are the target of HIV," said Cavert. "The next question we hope to answer is whether lowering the burden of HIV virus will allow the immune system to begin recovering." Until the body's response to the reduction in virus is known, the full therapeutic implications for AIDS patients remain unclear, he said.
Other investigators in the study were Katherine Staskus, Stephen Wietgrefe, Mary Zupancic, Kristin Gebhard, Zhi-Qiang Zhang and Ashley Haase of the University of Minnesota microbiology department; Daan Notermans, Jaap Goudsmit and Sven Danner of the University of Amsterdam, the Netherlands; Keith Henry of St. Paul-Ramsey Medical Center in St. Paul, Minn.; Roger Mills of Abbott Laboratories, Abbott Park, Ill.; and Hugh McDade of Glaxo Wellcome Research and Development, Greenford, England.
Recent developments in AIDS/HIV research at the university will be the focus of the second International Center for Antiviral Research and Epidemiology (ICARE) symposium, starting at 9 a.m. Thursday, May 8, in the University Ballroom, Radisson Hotel Metrodome, Minneapolis.
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