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New Drug Can Expose Dromant HIV


Dromant HIV

Researchers at the University of North Carolina made a discovery that could provide a new treatment option for HIV infection. Vorinostat, a deacetylase inhibitor, used so far in the treatment of lymphoma, has proven to unmask the dormant HIV virus. HIV infected cells are T helper cells or CD4 + cells. After the primary infection, HIV escapes immune defenses and the infection persists in the body. Lymph nodes are the sites where the virus replicates the most. It is during the asymptomatic infection, when the number of T helper cells remains normal. The symptomatic phase is next, and because of the massive replication of the virus, there is constant  decrease in T helper cells. A hallmark of HIV infection  is that the virus hides in some reservoirs, which are not accessible to antiretroviral drugs or immune response. These reservoirs are found in lymphoid organs, central nervous system, etc.. Healing can not occur because the virus is stuck in these reservoirs and can not be destroyed. There are, of course, other mechanisms by which the virus can not be destroyed by drugs, such as genomic variability.

HIV virus

Currently, treatment of HIV  is based on antiretroviral drugs, which are grouped into several classes: viral reverse transcriptase inhibitors, protease inhibitors, fusion inhibitors, and combined drugs. Viral reverse transcriptase inhibitors are divided into nucleoside analogues (NIRT) and nonnucleosides analogues (NNIRT). Combined treatment of HIV drugs can be made of the same class or different classes. The combination of different classes of drugs is called HAART, highly active antiretroviral therapy. HAART lowers viral load rapidly but this rapid response is followed by a slower decline over the next years. However, the disease can not be eradicated because of persistent virus in tissue reservoirs.
The new drug that has proven useful in the treatment of HIV infection, vorinostat, is used for treatment of cutaneous T cell lymphoma. It also appears that vorinostat is effective in treating recurrent glioblastoma multiforme and small cell lung cancer.

According to the study published July 25 in the scientific journal Nature, the administration of vorinostat in patients with HIV increases the levels of HIV RNA in CD4 + T cells, which means that this drug help unmask the virus responsible for persistent infection. After having conducted analyses in 8 patients infected with HIV, the researchers then administered vorinostat to these patients. After these investigations it was found that vorinostat increased levels of HIV RNA 4.5 times in CD4 + T cells. David Margolis, MD, professor of medicine, microbiology and immunology, and epidemiology at the University of North Carolina at Chapel Hill, said that this work is a new strategy to fight against latent HIV infection.