Cerebrospinal fluid human immunodeficiency virus viral load in patients with neurosyphilis.
Syphilis is a frequent coinfection with human immunodeficiency virus (HIV). Whereas systemic syphilis infection increases plasma HIV RNA levels (viral load; VL), effects of syphilis on cerebrospinal fluid (CSF) VL are unknown. We hypothesized that intrathecal immune activation in neurosyphilis would selectively increase CSF VL in coinfected patients. In this study, HIV-infected research subjects (N = 225) were categorized into three groups based on serum rapid plasma reagin (RPR), microhemaglutination for Treponema pallidum (MHA-TP) MHA-TP, and CSF VDRL: 23 with neurosyphilis (NS+; reactive serum RPR and MHA-TP and positive CSF VDRL); 42 with systemic syphilis but not neurosyphilis (Syph+; reactive serum RPR and MHA-TP; negative CSF VDRL), and 160 without syphilis (Syph-; nonreactive serum RPR). Plasma and CSF HIV VL were quantified by reverse transcriptase-ploymerase chain reaction (RT-PCR) (Amplicor, Roche) in log(10) copies/ml. To adjust for covariates previously shown to influence CSF HIV VL (i.e., plasma VL, CD4, pleocytosis, and highly active antiretroviral therapy [HAART]), multivariable linear regression was used. Lumbar punctures (LP) done for research purposes diagnosed 23 with neurosyphilis; most (83%) of these reported prior syphilis treatment. Among subjects with detectable plasma VL, CSF VL was highest in NS+, followed by Syph+ and Syph- (P =.006). This relationship was independent of the level of plasma VL or CSF pleocytosis. By contrast, among subjects with undetectable plasma HIV VL, CSF VLs were similar in the three syphilis subgroups (P = .50). Neurosyphilis may amplify intrathecal HIV replication, possibly through immune activation that persists even after syphilis treatment. Because elevated CSF VL is associated with subsequent neurocognitive decline, future studies should evaluate the impact of neurosyphilis on the course of central nervous system (CNS) HIV infection.
de Almeida
Sergio Monteiro
SM
HIV Neurobehavioral Research Center, University of California San Diego, San Diego, USA.
Bhatt
Archana
A
Riggs
Patricia K
PK
Durelle
Janis
J
Lazzaretto
Deborah
D
Marquie-Beck
Jennifer
J
McCutchan
Allen
A
Letendre
Scott
S
Ellis
Ronald
R
D000328:Adult; D000993:Antitreponemal Agents / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000134:cerebrospinal fluid* / Q000150:complications* / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D008875:Middle Aged; D009494:Neurosyphilis / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D012367:RNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid; D014210:Treponema pallidum; D019562:Viral Load; D014779:Virus Replication
D000993:Antitreponemal Agents; D012367:RNA, Viral