8th Conference on Retroviruses and Opportunistic Infections Chicago, IL - February 4 - 8, 2001

Conf Retroviruses Opportunistic Infect 2001 Feb 4-8;8:43 (abstract no. 1)

C. Eggers¹, K. Hertogs², H. J. Stürenburg¹, H. J. Stellbrink¹, and J. Van Lunzen^1
1Univ. Hosp. Hamburg, Germany and ²Virco Labs., Belgium

BACKGROUND: Antiviral treatment must consider the CNS to prevent or treat HIV dementia and to respond to the role of the CNS as a viral reservoir. In most patients HAART leads to a rapid decay of plasma as well as CSF virus. It was suggested that the source of the CSF virus in these patients is outside the CSF spaces.

METHODS: We studied viral decay kinetics in the CSF and plasma in 39 patients with various stages and manifestations of HIV infection, including nine subjects with HIV dementia and three with primary HIV infection. CSF and plasma were collected in parallel prior to and under a new HAART regimen. Approximate viral decay kinetics in the CSF and plasma were represented by the slope of a graph depicting the log viral load over time under HAART. The discordance of the decay kinetics between the compartments was calculated by (slope CSF- slope plasma). Viral drug resistance was tested genotypically and phenotypically (VircoGEN and Antivirogram, Virco Laboratories). Levels of antiviral substances were measured by liquid chromatography and mass spectroscopy.

RESULTS: The discordance of the CSF versus plasma viral response to HAART ranged from -0.10 to 1.40 (25th and 75th percentiles, positive values representing slower CSF viral decay). In three subjects the CSF viral load increased under HAART. Slower CSF viral decay was significantly correlated with the clinical phenotype of symptomatic late HIV infection of the CNS (r = -0.59, p<0.0002, Spearman rank). There was no correlation of a slow CSF response with the number of HAART substances and their ability to penetrate the CSF with CDC stage, CD4 cell count and age. 16 subjects with differing CSF viral decay kinetics but matched with regard to other baseline characteristics were tested for CSF and serum drug levels and for viral drug resistance. Drug levels were no different in both groups, and drug resistance was not found.

CONCLUSIONS: This compartmentalization of viral response to HAART suggests different mechanisms of viral replication in HIV dementia, possibly contribution of CSF virus by chronically infected brain cells of the macrophage lineage.

2001-02-04
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Copyright © 2001 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.