Delayed central nervous system virus suppression during highly active antiretroviral therapy is associated with HIV encephalopathy, but not with viral drug resistance or poor central nervous system drug penetration.
OBJECTIVE
HIV-1 encephalopathy (HIVE) is associated with high levels of viral RNA in the central nervous system (CNS). Highly active antiretroviral therapy (HAART) effectively reduces HIV replication in both plasma and cerebrospinal fluid (CSF). Some individuals, however, exhibit delayed CSF HIV RNA suppression in the presence of rapid plasma responses. We investigated the reasons for this discrepancy.


METHODS
CSF and plasma were collected prospectively in paired samples before and once or several times during HAART in 40 HIV-positive subjects. Ten had HIVE and 30 patients were neurologically asymptomatic or had non-HIVE neurological manifestations.


METHODS
The slopes of viral RNA decay during HAART were compared between the compartments. The presence of HIVE was defined by clinical standards and its severity categorized according to the Memorial Sloan Kettering score. CSF and plasma levels of antiretroviral drugs were measured. Viral drug resistance during HAART in CSF and plasma was analysed both genotypically and phenotypically.


RESULTS
Slow CSF viral decay and a high degree of compartmental discordance (slopeCSF/slopeplasma) were both significantly correlated with HIVE (P < 0.00002). There was no correlation of a rapid CSF response with Centers for Disease Control and Prevention stage, CD4 cell count, or with the number of antiretroviral compounds and their known CSF penetration. Slow CSF viral decay was associated with neither low levels of antiretroviral drugs in the CSF or plasma, nor with viral drug resistance.


CONCLUSIONS
None of the treatment-associated variables, but only the presence of HIVE, was associated with delayed virus elimination during HAART in the CSF. This suggests a distinct pattern of viral replication in the CNS in HIVE.
Eggers
Christian
C
Neurological Department, University Hospital Hamburg, Germany. eggers@uke.uni-hamburg.de
Hertogs
Kurt
K
Stürenburg
Hans-Jörg
HJ
van Lunzen
Jan
J
Stellbrink
Hans-Jürgen
HJ
D015526:AIDS Dementia Complex / Q000821:virology*; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid; D019562:Viral Load; D014779:Virus Replication
D019380:Anti-HIV Agents; D012367:RNA, Viral