By Liz Highleyman

It is well established that HIV is present in the brains of HIV positive individuals, but studies looking at how antiretroviral therapy impacts central nervous system HIV levels have yielded mixed results. Only a limited number of antiretroviral agents penetrate the blood-brain barrier to reach the brain and spinal cord.

As reported in the December 15, 2006 Journal of Infectious Diseases, researchers characterized the effects of partially suppressive antiretroviral therapy on levels of HIV RNA in the cerebrospinal fluid (CSF) and CSF inflammation.

This cross-sectional analysis included 139 HIV positive subjects without active neurological disease, categorized as being on successful therapy (plasma HIV RNA </= 500 copies/mL), experiencing treatment failure (plasma HIV RNA > 500 copies/mL), or not receiving therapy. A control group consisted of 48 HIV negative individuals. The investigators used an ultra-sensitive assay to measure CSF and plasma HIV RNA with a lower limit of quantification of 2.5 copies/mL.

Results

• Of the 47 subjects on successful therapy, CSF HIV RNA levels were < 2.5 copies/mL in 34 (72%).

• Only 1 patient had a CSF viral load > 500 copies/mL.

• Although plasma HIV RNA levels were similar in 35 patients on failing therapy and 57 subjects not receiving therapy (P = 0.84), CSF viral loads were at least 10-fold lower in subjects on failing therapy (P < 0.0001).
• This disproportionate effect of treatment on CSF HIV RNA levels was observed across the range of plasma viral load levels.

• The effect was not explained by differences in levels of drug-resistant virus in plasma and CSF.

• Antiretroviral therapy reduced intrathecal CSF inflammation in both treated groups.

• While untreated subjects had CSF pleocytosis (unusual cell proliferation), CSF from patients on either successful or failing therapy did not differ from HIV negative control subjects.

Conclusion

In conclusion, the researchers wrote, "In our cohort, antiretroviral therapy had a greater effect on HIV-1 RNA levels in CSF than in plasma and reduced intrathecal inflammation, even in the presence of drug resistance."

These data indicate that loss of HIV suppression was less common in CSF compared with plasma, even in patients on failing therapy.

"To the extent that CSF findings do reflect viral events in the brain, these observations provide some optimism regarding the treatment and prevention of AIDS dementia complex, even in the face of systemic treatment failure," the authors wrote.

"This response is the opposite of that predicted on the basis of the limitations of treating infection within an isolated tissue compartment," lead author Serena Spudich from the University of California at San Francisco told Reuters Health.
01/16/07

References

S Spudich, N Lollo, T Liegler, and others. Treatment Benefit on Cerebrospinal Fluid HIV-1 Levels in the Setting of Systemic Virological Suppression and Failure. Journal of Infectious Diseases 194(12): 1686-1696. December 15, 2006.

J C McArthur and S L Letendre. Is the Glass Three-Quarters Full or One-Quarter Empty? Journal of Infectious Diseases 194(12): 1628-1631. December 15, 2006.