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NEUROLOGY 2009;72:992-998
© 2009 American Academy of Neurology

HIV DNA and cognition in a Thai longitudinal HAART initiation cohort

The SEARCH 001 Cohort Study

V. G. Valcour, MD, B. T. Shiramizu, MD, P. Sithinamsuwan, MD, S. Nidhinandana, MD, S. Ratto-Kim, PhD, J. Ananworanich, MD, PhD, U. Siangphoe, MS, J. H. Kim, MD, M. de Souza, PhD, V. Degruttola, PhD, R. H. Paul, PhD, C. M. Shikuma, MD For the Southeast Asia Research Collaboration with the University of Hawaii (SEARCH) 001 protocol team

From the Hawaii AIDS Clinical Research Program (V.G.V., B.T.S., S.R.-K., J.A., J.H.K., C.M.S.), John A. Burns School of Medicine, University of Hawaii, Honolulu; Memory and Aging Center (V.G.V.), Department of Neurology, University of California, San Francisco; Division of Neurology (P.S., S.N.), Department of Medicine, Phramongkutklao Hospital, Bangkok; Department of Retrovirology (S.R.-K., J.H.K., M.d.S.), Armed Forces Research Institute of Medical Sciences, Bangkok; Southeast Asia Research Collaboration with Hawaii (J.A., U.S.), Bangkok, Thailand; Department of Biostatistics (V.D.), Harvard School of Public Health, Boston, MA; and Department of Psychology (R.H.P.), Division of Behavioral Neuroscience, University of Missouri, St. Louis.

Address correspondence and reprint requests to Dr. Victor Valcour, Hawaii AIDS Clinical Research Program, c/o Cecilia Shikuma, Young 5th Floor, Leahi Hospital, 3675 Kilauea Avenue, Honolulu, HI 96816 Vvalcour{at}hawaii.edu

Objectives: The extent to which highly active antiretroviral therapy (HAART) era cognitive disorders are due to active processes, incomplete clearance of reservoirs, or comorbidities is controversial. This study aimed to determine if immunologic and virologic factors influence cognition after first-time HAART in Thai individuals with HIV-associated dementia (HAD) and Thai individuals without HAD (non-HAD).

Methods: Variables were captured longitudinally to determine factors predictive of degree of cognitive recovery after first-time HAART. Neuropsychological data were compared to those of 230 HIV-negative Thai controls.

Results: HIV RNA and CD4 lymphocyte counts were not predictive of HAD cross-sectionally or degree of cognitive improvement longitudinally. In contrast, baseline and longitudinal HIV DNA isolated from monocytes correlated to cognitive performance irrespective of plasma HIV RNA and CD4 lymphocyte counts pre-HAART (p < 0.001) and at 48 weeks post HAART (p < 0.001). Levels exceeding 3.5 log10 copies HIV DNA/106 monocyte at baseline distinguished all HAD and non-HAD cases (p < 0.001). At 48 weeks, monocyte HIV DNA was below the level of detection of our assay (10 copies/106 cells) in 15/15 non-HAD compared to only 4/12 HAD cases, despite undetectable plasma HIV RNA in 26/27 cases. Baseline monocyte HIV DNA predicted 48-week cognitive performance on a composite score, independently of concurrent monocyte HIV DNA and CD4 count (p < 0.001).

Conclusions: Monocyte HIV DNA level correlates to cognitive performance before highly active antiretroviral therapy (HAART) and 48 weeks after HAART in this cohort and baseline monocyte HIV DNA may predict 48-week cognitive performance. These findings raise the possibility that short-term incomplete cognitive recovery with HAART may represent an active process related to this peripheral reservoir.

Abbreviations: ARV = antiretroviral; CI = confidence interval; CRF = circulating recombinant form; GDS = global deficit score; HAART = highly active antiretroviral therapy; HAD = HIV-associated dementia; IHDS = International HIV Dementia Scale; IQR = interquartile range; NCI = neurocognitive impairment; PBMC = peripheral blood mononuclear cell; TDI = Thai Depression Inventory score.

Supplemental data at www.neurology.org

Supported by NIH R21MH072388, R01NS053345, and K23MH65857. The antiretrovirals were provided via standard clinical care through the Thai Ministry of Public Health Antiretroviral Treatment Program.

Disclosure: Dr. Valcour is a consultant for GlaxoSmithKline.

The opinions expressed herein are those of the authors and do not represent the views of the Department of the Army or the Department of Defense.

Received July 25, 2008. Accepted in final form December 8, 2008.




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