Correlates of independent HIV-1 replication in the CNS and of its control by antiretrovirals.
OBJECTIVE
To investigate in detail factors associated with independent replication of HIV-1 in CNS, and to predict its therapeutic control.


METHODS
HIV RNA concentration was measured by PCR in 134 cross-sectional paired plasma and CSF samples from 95 patients infected with HIV-1 with various conditions, and in longitudinal CSF samples from 50 patients on antiretroviral treatment. Monocyte chemotactic protein (MCP)-1 was quantified in CSF by ELISA.


RESULTS
High HIV RNA levels either in plasma or in CSF did not correlate with HIV RNA concentration in the paired biologic sample. A high CSF-to-plasma HIV RNA ratio, suggesting independent viral replication in the CNS, was associated with higher CSF viral load and higher CSF MCP-1 levels. Higher MCP-1 levels in the CSF were also associated with neurologic disorders and were not influenced by the use of highly active antiretroviral therapy (HAART). A higher number of antiretroviral drugs with CSF penetration correlated with a more profound CSF HIV-1 load reduction, independently from the use of HAART alone. Virologic suppression in CSF was predicted by a higher number of CSF-penetrating antiretrovirals and by the baseline CSF viral load, whereas lower baseline CD4 counts and higher MCP-1 levels were associated with increased risk of virologic failure.


CONCLUSIONS
Quantification of HIV RNA in CSF is clinically useful, particularly in patients with neurologic disorders. CSF penetration of antiretrovirals must be considered when choosing treatments, mainly in patients with higher CSF viral loads, advanced disease, and CNS disorders associated with significant macrophage activation.
De Luca
Andrea
A
Istituto di Clinica delle Malattie Infettive, Università Cattolica del S Cuore, Largo Francesco Vito, I-00168 Rome, Italy. andreadeluca@rm.unicatt.it
Ciancio
B C
BC
Larussa
D
D
Murri
R
R
Cingolani
A
A
Rizzo
M G
MG
Giancola
M L
ML
Ammassari
A
A
Ortona
L
L
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D023241:Antiretroviral Therapy, Highly Active / Q000706:statistics & numerical data; D020805:Central Nervous System Viral Diseases / Q000188:drug therapy* / Q000821:virology*; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012367:RNA, Viral / Q000096:biosynthesis / Q000097:blood / Q000134:cerebrospinal fluid; D019562:Viral Load / Q000706:statistics & numerical data; D014779:Virus Replication / Q000187:drug effects*
D012367:RNA, Viral