Neurovirological Correlation With HIV-Associated Neurocognitive Disorders and Encephalitis in a HAART-Era Cohort

Gelman, Benjamin B. MD, PhD*; Lisinicchia, Joshua G. BS*; Morgello, Susan MD; Masliah, Eliezer MD, PhD; Commins, Deborah MD, PhD§; Achim, Cristian L. MD, PhD; Fox, Howard S. MD, PhD; Kolson, Dennis L. MD, PhD; Grant, Igor MD; Singer, Elyse MD#; Yiannoutsos, Constantin T. PhD**; Sherman, Seth PhD††; Gensler, Gary MS††; Moore, David J. PhD; Chen, Tiansheng MD*; Soukup, Vicki M. PhD*

JAIDS Journal of Acquired Immune Deficiency Syndromes: 15 April 2013 - Volume 62 - Issue 5 - p 487–495
doi: 10.1097/QAI.0b013e31827f1bdb
Basic and Translational Science

Objective: Replicating HIV-1 in the brain is present in HIV encephalitis (HIVE) and microglial nodule encephalitis (MGNE) and is putatively linked with HIV-associated neurocognitive disorders (HAND). A cliniconeurovirological correlation was conducted to elucidate the relationship between brain viral load and clinical phenotype.

Subjects and assays: HIV gag/pol RNA and DNA copies were quantified with reverse transcriptase-polymerase chain reaction or polymerase chain reaction in 148 HAART-era brain specimens. Comparison with HAND, HIVE, and MGNE and correlation with neuropsychological (NP) test scores were done using one-way ANOVA with Tukey-Kramer and Spearman tests, respectively.

Results: Brain HIV RNA was higher in subjects with HAND plus HIVE versus without HAND (delta = 2.48 log10 units, n = 27 versus 36, P < 0.001). In HAND without HIVE or MGNE, brain HIV RNA was not significantly different versus without HAND (P = 0.314). Worse NP scores correlated significantly with higher HIV RNA and interferon responses in brain specimens (P < 0.001) but not with HIV RNA levels in premortem blood plasma (n = 114) or cerebrospinal fluid (n = 104). In subjects with MGNE, brain HIV RNA was slightly higher versus without MGNE (P < 0.01) and much lower versus with HIVE (P < 0.001).

Conclusions: Brain HIV RNA and to a lesser extent HIV DNA are correlated with worse NP performance in the 6 months before death. Linkage occurs primarily in patients with HIVE and MGNE, and these patients could obtain added NP improvement by further reducing brain HIV while on HAART. Patients not in those groups are less certain to obtain added NP benefit.

*Texas NeuroAIDS Research Center and Department of Pathology, University of Texas Medical Branch, Galveston, TX

Manhattan HIV Brain Bank and Department of Neurology, Mount Sinai Medical Center, New York, NY

California NeuroAIDS Tissue Network, University of California, San Diego, La Jolla, CA

§Department of Pathology, University of Southern California, Los Angeles, CA

Department of Pharmacology and Experimental Neuroscience, University of Nebraska, Omaha, NE

Department of Neurology, University of Pennsylvania, Philadelphia, PA

#National Neurological AIDS Bank and Department of Neurology, University of California, Los Angeles, Los Angeles, CA

**Department of Biostatistics, Indiana University, Indianapolis, IN

††The EMMES Corporation, Rockville, MD.

Correspondence to: Benjamin B. Gelman, MD, PhD, Department of Pathology, University of Texas Medical Branch Route 0609, 3.118 Keiller Building, Galveston, TX 77555-0609 (e-mail: bgelman@utmb.edu).

The study was made possible in part due to the human specimen resources that were made available by the National NeuroAIDS Tissue Consortium (NNTC). The NNTC is supported by grants from the U.S. National Institutes of Health including U01 MH083507 and R24NS045091 (B.B.G., J.G.L., T.C., V.M.S.), U01 MH083506 and R24 MH059745 (I.G., E.M., C.L.A., D.J.M.), U01 MH083501 and R24 MH059724 (S.M.), U01 5U01MH083500 and R24 NS038841 (E.J.S. and D.C.), and U01 MH083545 and N01MH32002 (C.Y., G.G., S.S.) Additional support was provided by R01 MH79886 and R01 NS072005 (B.B.G., J.G.L., T.C., V.M.S., D.L.K.). For the remaining authors, no conflicts of interest were disclosed.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.jaids.com).

Received July 31, 2012

Accepted November 20, 2012

© 2013 Lippincott Williams & Wilkins, Inc.