Treatment benefit on cerebrospinal fluid HIV-1 levels in the setting of systemic virological suppression and failure.
OBJECTIVE
To characterize the effect of partially suppressive combination antiretroviral therapy on cerebrospinal fluid (CSF) human immunodeficiency virus (HIV)-1 RNA levels and CSF inflammation.


METHODS
The study was a cross-sectional analysis of 139 HIV-1-infected subjects without active neurological disease, categorized as having successful therapy (plasma HIV-1 RNA level < or =500 copies/mL), having failure of therapy (plasma HIV-1 RNA level >500 copies/mL), or not receiving therapy. The control group consisted of 48 HIV-negative subjects. CSF and plasma HIV-1 RNA assays had a lower limit of quantification of 2.5 copies/mL. Genotypic resistance testing was performed on a subset of subjects.


RESULTS
Of the 47 subjects with successful therapy, CSF HIV-1 RNA levels were <2.5 copies/mL in 34 (72%). Only 1 had an HIV-1 RNA level >500 copies/mL. Although plasma HIV-1 RNA levels were similar in 35 subjects with failed therapy and 57 of those not receiving therapy (P=.84), CSF HIV-1 RNA levels were at least 10-fold lower in subjects with failed therapy (P<.0001). This disproportionate effect of treatment on CSF HIV-1 RNA levels was found across the range of plasma HIV-1 RNA levels and was not explained by differences in levels of drug resistance in plasma or CSF. Therapy reduced CSF inflammation in both treated groups.


CONCLUSIONS
In our cohort, antiretroviral therapy had a greater effect on HIV-1 RNA levels in CSF than in plasma and reduced intrathecal inflammation, even in the presence of drug resistance.
Spudich
Serena
S
Department of Neurology, San Francisco General Hospital, University of California, San Francisco, CA 94110-3518, USA. sspudich@sfgh.ucsf.edu
Lollo
Nicole
N
Liegler
Teri
T
Deeks
Steven G
SG
Price
Richard W
RW
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000134:cerebrospinal fluid* / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007249:Inflammation / Q000134:cerebrospinal fluid; D008297:Male; D012367:RNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid*; D012495:San Francisco; D016896:Treatment Outcome; D019562:Viral Load
D019380:Anti-HIV Agents; D015415:Biomarkers; D012367:RNA, Viral