Share this article on:

Increased HLA-DR Expression on Peripheral Blood Monocytes in Subsets of Subjects With Primary HIV Infection Is Associated With Elevated CD4 T-Cell Apoptosis and CD4 T-Cell Depletion

Gascon, Ronnie L.; Narváez, Amy B.; Zhang, Rongzhen; Kahn, James O.; Hecht, Frederick M.; Herndier, Brian G.; McGrath, Michael S.
JAIDS Journal of Acquired Immune Deficiency Syndromes: June 1st, 2002
doi: 10.1097/01.QAI.0000017720.31903.6E
Articles: PDF Only

Whereas T-cell activation parameters of HIV disease have been extensively studied, the activation status of circulating monocytes has received less attention. Sixty-one subjects with primary HIV infection were evaluated by fluorescentactivated cell sorter (FACS) analysis at baseline (pretreatment) for CD4 T-cell count, CD4 T-cell apoptosis, and immune activation. A subset of 15 subjects with marked elevated (3 standard deviations above normal) monocyte DR expression had significantly reduced CD4 T-cell counts at baseline (p < .01) when compared with 46 subjects without monocyte activation. Ten subjects who presented with elevated levels of both CD14/DR, and CD4/CD38, had higher CD4 T-cell apoptosis (p < .001), and lower CD4 T-cell counts (p < .001) and higher baseline plasma HIV RNA (p < .01) than 21 subjects without elevated CD14/DR and CD4/CD38 coexpression. Fifty subjects were subsequently evaluated for immune cell activation over 24 weeks postinitiation of highly active antiretroviral therapy (HAART). A subgroup of 5 subjects who had persistent CD14/DR activation showed continuous depression of CD4 T-cell counts persisting for up to 2 years. The CD4 T-cell counts of this subgroup were significantly lower, at all time points, in comparison to 35 subjects who lacked any persistent expression of monocyte or CD4 T-cell activation (at 24 weeks, p < .002). We conclude that monocyte activation as defined by elevation of CDI4/DR expression correlates to CD4 T-cell depletion in primary HIV infection, and is predictive of a poor CD4 T-cell response to HAART in a subset of patients.

Address correspondence and request for reprints to Ronnie Gascon, UCSF Box 0874, San Francisco General Hospital, Building 80, Ward 84, 995 Potrero Avenue, San Francisco, CA 94110, U.S.A.; e-mail: Rgascon@php.ucsf.edu

This research was supported by National Institutes of Health Grant numbers U101-A141531 (M.S. McGrath, B.G. Hernidier, J.O. Kahn) and R01-MH56840 (M.S. McGrath).

Manuscript received October 3, 2001; accepted March 22, 2002.

© 2002 Lippincott Williams & Wilkins, Inc.