PMID- 15596754
OWN - NLM
STAT- MEDLINE
DCOM- 20050804
LR  - 20190514
IS  - 1526-632X (Electronic)
IS  - 0028-3878 (Linking)
VI  - 63
IP  - 11
DP  - 2004 Dec 14
TI  - Evaluation of HIV RNA and markers of immune activation as predictors of 
      HIV-associated dementia.
PG  - 2084-90
AB  - 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. CONCLUSION: 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.
FAU - Sevigny, J J
AU  - Sevigny JJ
AD  - Columbia University and The Taub Institute, New York, NY 10032, USA.
FAU - Albert, S M
AU  - Albert SM
FAU - McDermott, M P
AU  - McDermott MP
FAU - McArthur, J C
AU  - McArthur JC
FAU - Sacktor, N
AU  - Sacktor N
FAU - Conant, K
AU  - Conant K
FAU - Schifitto, G
AU  - Schifitto G
FAU - Selnes, O A
AU  - Selnes OA
FAU - Stern, Y
AU  - Stern Y
FAU - McClernon, D R
AU  - McClernon DR
FAU - Palumbo, D
AU  - Palumbo D
FAU - Kieburtz, K
AU  - Kieburtz K
FAU - Riggs, G
AU  - Riggs G
FAU - Cohen, B
AU  - Cohen B
FAU - Epstein, L G
AU  - Epstein LG
FAU - Marder, K
AU  - Marder K
LA  - eng
GR  - NS049465/NS/NINDS NIH HHS/United States
GR  - NS26643/NS/NINDS NIH HHS/United States
GR  - NS36519/NS/NINDS NIH HHS/United States
GR  - NS44807/NS/NINDS NIH HHS/United States
GR  - RR00044/RR/NCRR NIH HHS/United States
GR  - RR00522/RR/NCRR NIH HHS/United States
GR  - RR00645/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Biomarkers)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (RNA, Viral)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 81627-83-0 (Macrophage Colony-Stimulating Factor)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
SB  - IM
MH  - AIDS Dementia Complex/blood/cerebrospinal fluid/*epidemiology/immunology
MH  - Adult
MH  - Affect
MH  - Anti-HIV Agents/therapeutic use
MH  - *Antiretroviral Therapy, Highly Active
MH  - Biomarkers
MH  - CD4 Lymphocyte Count
MH  - Chemokine CCL2/analysis/blood/cerebrospinal fluid
MH  - Cognition
MH  - Cohort Studies
MH  - Cytokines/*blood
MH  - Female
MH  - HIV Infections/blood/cerebrospinal fluid/drug therapy/immunology/psychology
MH  - HIV-1/*isolation & purification
MH  - Humans
MH  - Incidence
MH  - Intelligence Tests
MH  - Karnofsky Performance Status
MH  - Life Tables
MH  - Macrophage Colony-Stimulating Factor/analysis/blood/cerebrospinal fluid
MH  - Male
MH  - Matrix Metalloproteinase 2/analysis/blood/cerebrospinal fluid
MH  - Middle Aged
MH  - Models, Immunological
MH  - Neurologic Examination
MH  - Neuropsychological Tests
MH  - Predictive Value of Tests
MH  - Proportional Hazards Models
MH  - RNA, Viral/*analysis/blood/cerebrospinal fluid
MH  - Tumor Necrosis Factor-alpha/analysis/cerebrospinal fluid
MH  - *Viral Load
EDAT- 2004/12/15 09:00
MHDA- 2005/08/05 09:00
CRDT- 2004/12/15 09:00
PHST- 2004/12/15 09:00 [pubmed]
PHST- 2005/08/05 09:00 [medline]
PHST- 2004/12/15 09:00 [entrez]
AID - 63/11/2084 [pii]
AID - 10.1212/01.wnl.0000145763.68284.15 [doi]
PST - ppublish
SO  - Neurology. 2004 Dec 14;63(11):2084-90. doi: 10.1212/01.wnl.0000145763.68284.15.