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Justin C. McArthur, MBBS, MPH; Michael P. McDermott, PhD; Daniel McClernon, BS; Coryse St Hillaire, BS; Kathy Conant, MD; Karen Marder, MD, MPH; Giovanni Schifitto, MD; Ola A. Selnes, PhD; Ned Sacktor, MD; Yaakov Stern, PhD; Steve M. Albert, PhD; Karl Kieburtz, MD, MPH; Joy A. deMarcaida, MD; Bruce Cohen, MD; Leon G. Epstein, MD

Arch Neurol. 2004;61:1687-1696.

Background  Before the introduction of combination antiretroviral therapy (CART), neurological disease correlated with cerebrospinal fluid (CSF) levels of human immunodeficiency virus (HIV) RNA.

Objective  To investigate the relationships among HIV RNA levels, immune activation markers, and neurological status in patients receiving CART.

Design  Multicenter cohort study.

Setting  Academic neurology departments.

Patients  A total of 371 patients unselected for neurological complaints and with CD4 cell counts less than 200/µL or with cognitive symptoms and CD4 cell counts less than 300/µL were enrolled into the Northeastern AIDS Dementia cohort in 1998-2002. Diagnoses of HIV-associated dementia (HIV-D) and minor cognitive-motor disorder (MCMD) were obtained with a computerized algorithm. Plasma and CSF levels of HIV RNA, monocyte chemotactic protein 1, macrophage colony-stimulating factor, and tumor necrosis factor were quantified.

Results  The mean ± SD age was 41.5 ± 7.2 years, and the mean ± SD educational level was 12.3 ± 2.2 years. Seventy percent of the cohort was black, and 30% were women. The mean ± SD CD4 cell count was 136.8 ± 87.9/µL, and CART was used in 71%. Twenty-nine percent of the patients were unimpaired (n = 106), 36% had MCMD (n = 133), and 35% had HIV-D (n = 128). Mean log₁₀ CSF HIV RNA copies per milliliter was 2.6 ± 0.8, with no differences among the neurological groups, even after adjustments for baseline CD4 cell counts and antiretroviral therapy. Cerebrospinal fluid HIV RNA was undetectable in 47% of unimpaired, 46% of MCMD, and 43% of HIV-D patients (P = .91). Plasma levels of monocyte chemotactic protein type 1 and tumor necrosis factor correlated weakly with HIV RNA levels but did not distinguish those with neurological deficits.

Conclusions  In contrast to observations in individuals not treated with CART, we found no relationshipbetween CSF markers and neurological status in this CART-using cohort with advanced HIV/AIDS. This was not explicable by demographic differences or plasma virological control. CART may substantially attenuate the degree of central nervous system HIV infection and immune activation, and in CART users, CSF HIV RNA and immune activation markers may fail to discriminate milder degrees of HIV-D and MCMD.

Author Affiliations: Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Md (Drs McArthur, Conant, Selnes, and Sacktor and Ms St Hillaire); Departments of Neurology (Drs McDermott, Schifitto, Kieburtz, and deMarcaida) and Biostatistics (Dr McDermott), University of Rochester, Rochester, NY; GlaxoSmithKline, Research Triangle Park, NC (MrMcClernon); Gertrude H. Sergievsky Center and Taub Institute for Research on Alzheimer’s Disease and the Aging Brain (Drs Marder, Stern, and Albert) and Mailman School of Public Health, (Dr Albert), Columbia University, New York, NY; Department of Neurology, Northwestern University, Chicago, Ill (Dr Cohen); and Division of Pediatric Neurology, Children’s Memorial Hospital, Chicago (Dr Epstein).

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