Discordance between cerebral spinal fluid and plasma HIV replication in patients with neurological symptoms who are receiving suppressive antiretroviral therapy.
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.


METHODS
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.
Canestri
Ana
A
Hôpital Pitié-Salpêtrière, Paris, France. ana.canestri@psl.aphp.fr
Lescure
François-Xavier
FX
Jaureguiberry
Stephane
S
Moulignier
Antoine
A
Amiel
Corinne
C
Marcelin
Anne Geneviève
AG
Peytavin
Gilles
G
Tubiana
Roland
R
Pialoux
Gilles
G
Katlama
Christine
C
D016263:AIDS-Associated Nephropathy / Q000188:drug therapy* / Q000821:virology; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D002555:Cerebrospinal Fluid / Q000821:virology*; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000821:virology*; D012367:RNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid; D019562:Viral Load
D019380:Anti-HIV Agents; D012367:RNA, Viral