Journal Article

Discordance Between Cerebral Spinal Fluid and Plasma HIV Replication in Patients with Neurological Symptoms Who Are Receiving Suppressive Antiretroviral Therapy

Ana Canestri, Franæois-Xavier Lescure, Stephane Jaureguiberry, Antoine Moulignier, Corinne Amiel, AnneGeneviève Marcelin, Gilles Peytavin, Roland Tubiana, Gilles Pialoux and Christine Katlama

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 50, issue 5, pages 773-778
Published in print March 2010 | ISSN: 1058-4838
Published online March 2010 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/650538
Discordance Between Cerebral Spinal Fluid and Plasma HIV Replication in Patients with Neurological Symptoms Who Are Receiving Suppressive Antiretroviral Therapy

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Objective. We report data on 11 patients with neurological symptoms and human immunodeficiency virus (HIV) cerebrospinal fluid (CSF) viremia contrasting with suppressed plasma HIV RNA during receipt of combined antiretroviral therapy.

Design. We retrospectively identified instances of central nervous system (CNS) symptoms in patients who had been receiving stable combination antiretroviral therapy. Discordance between plasma and CSF HIV RNA levels was defined by any detectable CSF HIV RNA level >200 copies/mL while plasma levels were <50 copies/mL or by a CSF HIV RNA level that was ⩾1 log greater than the plasma HIV RNA level.

Results. Eleven patients had experienced acute or subacute neurological symptoms. All but one patient had CSF pleocytosis and/or elevated protein levels. The median CSF HIV RNA level was 880 copies/mL (range, 558–12,885 copies/mL). Patients had been receiving stable combination antiretroviral therapy for a median of 13 months (range, 10–32 months). Eight of 11 patients had a plasma HIV RNA level <50 copies/mL, and 3 had plasma HIV RNA blips with their CSF HIV RNA level >1 log higher than their plasma HIV RNA level. Resistance-associated mutations were detected in 7 of 8 CSF HIV RNA genotypic strains. The median number of resistance-associated mutations was 6 (range, 2–8) to nucleoside reverse-transcriptase inhibitors and 3 (range, 1–9) to protease inhibitors. One patient had a virus harboring nonnucleoside reverse-transcriptase inhibitor mutations. The median central nervous system penetration-effectiveness (CPE) rank was 2 (range, 1–3), and 5 patients had a CPE ⩽1.5. After antiretroviral therapy optimization based on genotypes and CPE, all patients clinically improved, with normalization of CSF.

Conclusions. Despite successful suppression of plasma viremia with antiretroviral therapy, HIV may replicate in CSF, with development of CSF HIV resistance resulting in acute or subacute neurological manifestations.

Journal Article.  3710 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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