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

Abstract

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 clinico-neurovirological 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 RT-PCR or PCR in 148 HAART-era brain specimens. Comparison to HAND, HIVE and MGNE and correlation with neuropsychological (NP) test scores were done using one-way ANOVA with Tukey-Kramer and Spearman’s tests respectively. Results Brain HIV RNA was higher in subjects with HAND plus HIVE vs without HAND (delta = 2.48 log10 units, n = 27 vs 36, p < 0.001). In HAND without HIVE or MGNE, brain HIV RNA was not significantly different vs 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). Conclusion 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; while on HAART these patients could obtain added NP improvement by further reducing brain HIV. Patients not in those groups are less certain to obtain added NP benefit.

Characterization of neuropathology in the HIV-1 transgenic rat at different ages

“…The current study concurs with this suggestion, since in more recent publications examining the neuropathology in treated HIV+ patients, the classic signs of inflammation damage such as multinucleated giant cells and HIV encephalitis were lacking. Those results suggested alternative causes for the progressive neurodegeneration in this patient group (Everall et al, 2009, Gelman et al, 2013) and exposure to viral protein is one of those suggested causes (Shin and Thayer, 2013, Silverstein et al, 2012, Yadav and Collman, 2009). The subcortical pattern of neuronal damage that we see in our animals is also reminiscent of HIV damage in the post ART era (Kumar et al, 2009, Kumar et al, 2011).…”

Effects of alpha-tocopherol associated with lovastatin on brain tissue and memory function in SHRSPs

“…In turn, the control group showed a decrease in the number of hippocampal cells, and histopathologically glial nodules and vessel proliferation were detected. Glial nodules may be associated with an inflammatory process and responsible for provoking learning and memory impairment [34,35].…”

Emergence of CD4 Independence Envelopes and Astrocyte Infection in R5 Simian-Human Immunodeficiency Virus Model of Encephalitis

“…Lentiviral neuroinvasion involves the recruitment of infected monocytes/macrophages and/or T cells to the central nervous system (CNS) from circulation, with activation and productive infection of resident microglia and a more restricted/latent infection of astrocytes (4)(5)(6)(7)(8)(9). HIV-1 infection of mononuclear phagocytes in the CNS has been suggested to be the critical driving force of HIV-induced encephalitis (HIVE), as well as HAND (10,11). Infected cells in the brain release neurotoxic viral and host inflammatory proteins that result in neuronal injury and death (6,12).…”