Markers of immune activation and viral load in HIV-associated sensory neuropathy.
BACKGROUND
HIV infection is associated with a painful distal sensory polyneuropathy (DSP) that can severely limit the quality of life of affected subjects. The pathogenesis of DSP is unknown, although both HIV proteins and products of immune activation triggered by HIV infection have been implicated.


OBJECTIVE
To assess the association between baseline markers of immune activation and HIV RNA levels (viral load) and time to symptomatic DSP (SDSP).


METHODS
A cohort of 376 subjects, most receiving highly active antiretroviral therapy (HAART), were followed semiannually for up to 48 months. Blood and CSF levels of HIV viral load, monocyte chemotactic protein-1, macrophage colony-stimulating factor (M-CSF), matrix metalloproteinase-2, and tumor necrosis factor-alpha were measured in addition to CD4 lymphocyte cell count.


RESULTS
In subjects without SDSP at baseline (62.5% of the cohort), among the virologic and immunologic markers, only baseline CSF M-CSF levels were associated with time to SDSP (hazard ratio = 2.97, p = 0.05). The Kaplan-Meier estimate of the 1-year incidence of SDSP was 21%, a 15% decrease from that observed in the Dana cohort, a pre-HAART cohort enrolled with the same inclusion/exclusion criteria.


CONCLUSIONS
Highly active retroviral therapy (HAART) has changed the natural history of HIV-associated symptomatic distal sensory polyneuropathy (SDSP), which may explain, in contrast with studies from the pre-HAART era, the lack of association between SDSP and baseline HIV viral load and CD4 cell count.
Schifitto
G
G
Department of Neurology, University of Rochester, 601 Elmwood Ave., Box 673, Rochester, NY 14642, USA. Giovanni.schifitto@ctcc.rochester.edu
McDermott
M P
MP
McArthur
J C
JC
Marder
K
K
Sacktor
N
N
McClernon
D R
DR
Conant
K
K
Cohen
B
B
Epstein
L G
LG
Kieburtz
K
K
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000706:statistics & numerical data; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D018932:Chemokine CCL2 / Q000097:blood / Q000276:immunology; D015331:Cohort Studies; D005260:Female; D005727:Ganglia, Spinal / Q000276:immunology / Q000821:virology; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000821:virology; D006801:Humans; D007107:Immune System / Q000276:immunology* / Q000821:virology; D008137:Longitudinal Studies; D016173:Macrophage Colony-Stimulating Factor / Q000097:blood / Q000276:immunology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood / Q000276:immunology; D008875:Middle Aged; D009475:Neurons, Afferent / Q000276:immunology* / Q000821:virology; D010525:Peripheral Nerves / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D010523:Peripheral Nervous System Diseases / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D019562:Viral Load
D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor; D020778:Matrix Metalloproteinase 2