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HIV virus hides in the brain
 
 
  August 23, 2010
 
Studies of the spinal fluid of patients given anti-HIV drugs have resulted in new findings suggesting that the brain can act as a hiding place for the HIV virus. Around 10% of patients showed traces of the virus in their spinal fluid but not in their blood -- a larger proportion than previously realised, reveals a thesis from the University of Gothenburg, Sweden.
 
We now have effective anti-HIV drugs that can stop the immune system from being compromised and prevent AIDS. Although these drugs effectively prevent the virus from multiplying, the HIV virus also infects the brain and can cause damage if the infection is not treated.
 
"Antiviral treatment in the brain is complicated by a number of factors, partly because it is surrounded by a protective barrier that affects how well medicines get in," says Arvid Eden, doctor and researcher at the Institute of Biomedicine at the Sahlgrenska Academy. "This means that the brain can act as a reservoir where treatment of the virus may be less effective."
 
The thesis includes a study of 15 patients who had been effectively medicated for several years. 60% of them showed signs of inflammation in their spinal fluid, albeit at lower levels than without treatment.
 
"In another study of around 70 patients who had also received anti-HIV drugs, we found HIV in the spinal fluid of around 10% of the patients, even though the virus was not measurable in the blood, which is a significantly higher proportion than previously realised," explains Eden.
 
The results of both studies would suggest that current HIV treatment cannot entirely suppress the effects of the virus in the brain, although it is not clear whether the residual inflammation or small quantities of virus in the spinal fluid in some of the patients entail a risk of future complications.
 
"In my opinion, we need to take into account the effects in the brain when developing new drugs and treatment strategies for HIV infection," says Eden.
 
HIV, human immunodeficiency virus, belongs to the retrovirus family and takes two forms, HIV-1 and HIV-2, which can be transmitted through blood, semen and other secretions and bodily fluids. In the acute phase, patients suffer from fever, swollen lymph glands and rashes. These symptoms do recede, but AIDS develops after a long period of infection. Attempts to produce an HIV vaccine have been ongoing since the 1980s, but have yet to be successful.
 
Provided by University of Gothenburg (news : web)
 
ABSTRACT
 
Although antiretroviral therapy (ART) can effectively inhibit replication of human immunodeficiency virus type 1 (HIV-1), the virus is able to persist in cellular and anatomical viral reservoirs. Latently infected resting memory CD4+ T-cells are an important cellular reservoir, and the central nervous system (CNS) an important a natomical reservoir for HIV-1 infection. The overall aim of this thesis was to gain greater understanding of HIV-1 persistence, in regards to latent infection as well as the central nervous system.
 
The initial viral decay rate after initiation of ART has been proposed as a measure of relative regimen potency. We compared initial viral decay in subjects treated with three ART regimens, and found that efavirenz-based therapy gave a faster initial viral decay than protease inhibitor (PI) treated subjects. In turn, lopinavir/ritonavir-based therapy gave a faster initial viral decay than atazanavir/ritonavir-based therapy. This may reflect different inherent antiretroviral potency between the treatment regimens.
 
Latently infected CD4+ T-cells constitute a major barrier for the eradication of HIV-1 infection. We investigated if a high dose of intravenous immunoglobulin (IVIG) given in addition to effective ART could reduce the size of the pool of latently infected resting cells, and found a reduction in the pool size in five of seven indivi duals where the latent reservoir was quantifiable. Our findings suggest that the reservoir became accessible through IVIG treatment, and indicate that novel modes of intervention can have an effect on the latent reservoir.
 
Increased levels of intrathecal immune activation are often found in cerebrospinal fluid (CSF) of treated patients despite effective systemic suppression of HIV-1. We investigated intrathecal immune activation, measured as neopterin and IgG-index, in patients with several years of successful therapy, and found that although ART has a substantial effect on lowering viral replication and immune activation in the CSF, a majority of patients still have ongoing intrathecal immune activation despite effective suppression of the virus for extended periods of time.
 
Occasional cases of CSF viral escape have been reported. We investigated the occurrence of CSF viral escape in neuroasymptomatic patients effectively treated with commonly used ART regimens. We found that 7 (10%) of 69 patients had evidence of CSF viral escape, which is more common than previously recognized and may have important implications for future treatment strategies and the use of new drug combinations.
 
 
 
 
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