icon-    folder.gif   Conference Reports for NATAP  
  17th CROI
Conference on Retroviruses
and Opportunistic Infections
San Francisco CA
February 16-19, 2010
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No Decrease in Intrathecal Immunoactivation or Residual CSF Viremiaduring Treatment Intensification in Patients on Stable ART
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Reported by Jules Levin
CROI 2010
Aylin Yilmaz1, Lars Hagberg1, Bo Svennerholm2, and Magnus Gisslén1 1Departments of Infectious Diseases and 2Virology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

"Ongoing low-level plasma viremia in suppressed patients measured by sensitive assays may not be due to ongoing viral replication but rather of virus output from stable reservoirs of infection. Activation of latently infected resting CD4 T cells are probably a major source of plasma virus during treatment, but also other reservoirs, such as cells from the CNS may contribute"
Background: ART significantly reduces cerebrospinal fluid (CSF) HIV-1 RNA and detectable residual viremia (2 to 20 copies/mL) is less frequently found in CSF than in blood. However, continuous intrathecal immunoactivation is a common finding also after several years of effective ART. To assess if the residual intrathecal immunoactivation derives from ongoing low-grade viral replication in the CNS or merely reflects other unspecific mechanisms, we conducted a trial of treatment intensification in patients with effective ART.
Methods: Ten patients on ART with plasma HIV RNA <50 copies/mL >18 months were included. All subjects were given treatment intensification for in total 8 weeks; 7 patients were placed on 4 weeks with maraviroc, 3 patients on 4 weeks of lopinavir/r, drugs with good penetration into the CNS, and 4 weeks with enfuvirtide that does not penetrate into the CNS. Subjects were randomized to one of the intensification drugs to start with and were switched to the other after 4 weeks. Lumbar punctures were performed 4 weeks before, at intensification start, at switch-over after 4 weeks, at the end of, and 4 weeks after the intensification period. Analysis of CSF and plasma included HIV RNA (detection limit 2 copies/mL), b2-microglobulin, IgG-index, and CSF WBC count.
Results: The median viral load was 3.9 copies/mL in blood and <2 copies/mL in CSF before intensification. Nine of 10 subjects had increased levels of b2-microglobulin in CSF (median 1.62 mg/L, upper normal limit 1.2) and 5 had signs of intrathecal immunoglobulin production with increased IgG-index (median 0.62 mg/L, UNL 0.63) before treatment intensification. The CSF WBC count was in median 1.8 x 106/L and the peripheral CD4 cell count was 552 x 106/L.
No significant changes were found in markers of intrathecal immunoactivation or HIV-RNA levels in CSF or blood during, or after, the intensification periods.
Conclusions: Irrespective of CNS penetration ability, antiretroviral intensification for 4 + 4 weeks did not decrease the residual intrathecal immunoactivation in patients on stable ART. These results do not support the hypothesis that intrathecal immunoactivation results from ongoing viral replication.