For a number of years, many scientists have believed that HIV depletes its primary target, CD4+ T cells, by blocking new T-cell production. Two independent studies now challenge that point of view, showing that HIV does not block such production but instead accelerates the division of existing T cells. Following the initiation of highly active antiretroviral therapy, or HAART, there is an immediate drop in the rate of T-cell production accompanied by an even greater decrease in the rate of CD4 T-cell death. Thus, the increases in CD4+ T-cell counts seen following HAART are not due to a boost in the production of new T cells. Rather, they are caused by a slowdown in the loss of existing T cells.
"These two studies have come to the same conclusion, namely that the primary cause of the immunodeficiency associated with HIV infection is an increase in the rate of CD4+ T-cell death," notes Anthony S. Fauci, M.D., Director of the National Institute of Allergy and Infectious Diseases, which funded both studies. "This research sheds light on how we might best reduce the decline in those cells in the setting of HIV infection and more effectively treat people with HIV."
David Ho, M.D., a coauthor of one of the studies, adds, "These two papers should put to rest a controversy that has been part of the scientific debate in HIV research for the past decade."
Using different sophisticated methods to directly study the growth and death of individual T cells in people infected with HIV, researchers from NIH and the Aaron Diamond AIDS Research Center at The Rockefeller University independently studied the virus' effects on T-cell dynamics in treated and untreated individuals. In the NIH study, reported today in the Journal of Experimental Medicine online and scheduled for print in the December 17 issue, Joseph Kovacs, M.D., and his colleagues attached chemical tags to dividing cells to monitor the fates of individual T cells in 17 HIV-infected patients before and after the initiation of HAART. Their results showed that high HIV levels did not block T-cell production, but instead caused those cells to multiply and divide more rapidly. When patients were treated with antiretroviral drugs, T-cell proliferation and death both slowed.
Their findings are in agreement with those published recently in the same journal by Dr. Ho, Hiroshi Mohri, M.D., and their colleagues at the Aaron Diamond AIDS Research Center. At the same time as the NIAID team was conducting its study, Drs. Ho and Mohri were using a different technique to monitor and compare T-cell proliferation in seven people with HIV infection before and after HAART therapy and in four uninfected individuals. Their studies found the same effect of HIV infection on T-cell production. They were also able to demonstrate that HIV infection increased T-cell proliferation, again indicating that the loss of CD4+ T cells in the setting of HIV infection is due to an increase in destruction, not a decrease in production.
NIAID is a component of the National Institutes of Health (NIH). NIAID supports basic and applied research to prevent, diagnose, and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, tuberculosis, malaria, autoimmune disorders, asthma and allergies.
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H Mohri et al. Increased turnover of T lymphocytes in HIV-1 infection and its reduction by antiretroviral therapy. Journal of Experimental Medicine 194:1277-87 (2001).