New findings explain T-cell loss in HIV infection

December 10, 2001

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.
-end-
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.

References:

JA Kovacs et al. Identification of dynamically distinct subpopulations of T lymphocytes that are differentially affected by HIV. Journal of Experimental Medicine 194:1731-41 (2001).

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).

Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov

NIH/National Institute of Allergy and Infectious Diseases

Related HIV Articles from Brightsurf:

BEAT-HIV Delaney collaboratory issues recommendations measuring persistent HIV reservoirs
Spearheaded by Wistar scientists, top worldwide HIV researchers from the BEAT-HIV Martin Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy (BEAT-HIV Collaboratory) compiled the first comprehensive set of recommendations on how to best measure the size of persistent HIV reservoirs during cure-directed clinical studies.

The Lancet HIV: Study suggests a second patient has been cured of HIV
A study of the second HIV patient to undergo successful stem cell transplantation from donors with a HIV-resistant gene, finds that there was no active viral infection in the patient's blood 30 months after they stopped anti-retroviral therapy, according to a case report published in The Lancet HIV journal and presented at CROI (Conference on Retroviruses and Opportunistic Infections).

Children with HIV score below HIV-negative peers in cognitive, motor function tests
Children who acquired HIV in utero or during birth or breastfeeding did not perform as well as their peers who do not have HIV on tests measuring cognitive ability, motor function and attention, according to a report published online today in Clinical Infectious Diseases.

Efforts to end the HIV epidemic must not ignore people already living with HIV
Efforts to prevent new HIV transmissions in the US must be accompanied by addressing HIV-associated comorbidities to improve the health of people already living with HIV, NIH experts assert in the third of a series of JAMA commentaries.

The Lancet HIV: Severe anti-LGBT legislations associated with lower testing and awareness of HIV in African countries
This first systematic review to investigate HIV testing, treatment and viral suppression in men who have sex with men in Africa finds that among the most recent studies (conducted after 2011) only half of men have been tested for HIV in the past 12 months.

The Lancet HIV: Tenfold increase in number of adolescents on HIV treatment in South Africa since 2010, but many still untreated
A new study of more than 700,000 one to 19-year olds being treated for HIV infection suggests a ten-fold increase in the number of adolescents aged 15 to 19 receiving HIV treatment in South Africa, according to results published in The Lancet HIV journal.

Starting HIV treatment in ERs may be key to ending HIV spread worldwide
In a follow-up study conducted in South Africa, Johns Hopkins Medicine researchers say they have evidence that hospital emergency departments (EDs) worldwide may be key strategic settings for curbing the spread of HIV infections in hard-to-reach populations if the EDs jump-start treatment and case management as well as diagnosis of the disease.

NIH HIV experts prioritize research to achieve sustained ART-free HIV remission
Achieving sustained remission of HIV without life-long antiretroviral therapy (ART) is a top HIV research priority, according to a new commentary in JAMA by experts at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The Lancet HIV: PrEP implementation is associated with a rapid decline in new HIV infections
Study from Australia is the first to evaluate a population-level roll-out of pre-exposure prophylaxis (PrEP) in men who have sex with men.

Researchers date 'hibernating' HIV strains, advancing BC's leadership in HIV cure research
Researchers have developed a novel way for dating 'hibernating' HIV strains, in an advancement for HIV cure research.

Read More: HIV News and HIV Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.