Evaluation of HIV RNA and markers of immune activation as predictors of HIV-associated dementia.
OBJECTIVE
To evaluate whether baseline levels of plasma and CSF HIV RNA, tumor necrosis factor alpha (TNFalpha), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-2 (MMP-2), or macrophage colony stimulating factor (M-CSF) are predictors of incident HIV-associated dementia (HIVD) in a cohort with advanced HIV infection.


METHODS
A total of 203 nondemented subjects with CD4 lymphocyte counts less than 200/muL, or <300/microL but with cognitive impairment, underwent semiannual neurologic, cognitive, functional, and laboratory assessments. HIVD and minor cognitive motor disorder (MCMD) were defined using American Academy of Neurology criteria. The cumulative incidence of HIVD was estimated using Kaplan-Meier curves. Cox proportional hazards regression models were used to examine the associations between biologic variables and time to HIVD, adjusting for age, sex, years of education, duration of HIV infection, type of antiretroviral use, premorbid IQ score, and presence of MCMD.


RESULTS
After a median follow-up time of 20.7 months, 74 (36%) subjects reached the HIVD endpoint. The dementia was mild in 70% of cases. The cumulative incidence of HIVD was 20% at 1 year and 33% at 2 years. Highly active antiretroviral therapy (HAART) was used by 73% of subjects at baseline. A plasma HIV RNA level was undetectable in 23% of subjects and a CSF HIV RNA level was undetectable in 48% of subjects. In adjusted analyses, neither plasma nor CSF HIV RNA levels (log10) were associated with time to HIVD; log10 levels of plasma TNFalpha (HR 3.07, p = 0.03) and CSF MCP-1 (HR = 3.36, p = 0.06) tended to be associated with time to HIVD.


CONCLUSIONS
The lack of association between baseline plasma and CSF HIV RNA levels and incident dementia suggests highly active antiretroviral therapy may be affecting CNS viral dynamics, leading to lower HIV RNA levels, and therefore weakening the utility of baseline HIV RNA levels as predictors of HIV-associated dementia.
Sevigny
J J
JJ
Columbia University and The Taub Institute, New York, NY 10032, USA.
Albert
S M
SM
McDermott
M P
MP
McArthur
J C
JC
Sacktor
N
N
Conant
K
K
Schifitto
G
G
Selnes
O A
OA
Stern
Y
Y
McClernon
D R
DR
Palumbo
D
D
Kieburtz
K
K
Riggs
G
G
Cohen
B
B
Epstein
L G
LG
Marder
K
K
D015526:AIDS Dementia Complex / Q000097:blood / Q000134:cerebrospinal fluid / Q000453:epidemiology* / Q000276:immunology; D000328:Adult; D000339:Affect; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers; D018791:CD4 Lymphocyte Count; D018932:Chemokine CCL2 / Q000032:analysis / Q000097:blood / Q000134:cerebrospinal fluid; D003071:Cognition; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000276:immunology / Q000523:psychology; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D015994:Incidence; D007361:Intelligence Tests; D017567:Karnofsky Performance Status; D015993:Life Tables; D016173:Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000097:blood / Q000134:cerebrospinal fluid; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000097:blood / Q000134:cerebrospinal fluid; D008875:Middle Aged; D018448:Models, Immunological; D009460:Neurologic Examination; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012367:RNA, Viral / Q000032:analysis* / Q000097:blood / Q000134:cerebrospinal fluid; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000134:cerebrospinal fluid; D019562:Viral Load
D019380:Anti-HIV Agents; D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor; D020778:Matrix Metalloproteinase 2