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Worse Neurocognitive Score Tied to Higher CMV, Longer HIV, Lower BP
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7th International Workshop on HIV and Aging, September 26-27, 2016, Washington, DC
Mark Mascolini
Higher anti-CMV antibody levels, lower systolic blood pressure (BP), and longer HIV duration predicted worse neurocognitive performance in a 138-person analysis of the CHARTER cohort [1].
Nearly all HIV-positive adults also carry CMV, a herpesvirus tied to age-related disorders including cardiovascular disease and cognitive impairment [2]. Researchers from the University of California, San Diego and colleagues from other centers conducted this study to get a better understanding of links between CMV and age, HIV load, and neurocognitive performance.
The study involved 138 adults in the CHARTER Cohort, which monitors neurocognitive performance in people with HIV [3]. Researchers selected participants to vary by CD4 nadir, antiretroviral use, and neurocognitive impairment. No one had a severe neuropsychiatric condition. Participants underwent a comprehensive neuropsychological battery and had anti-CMV IgG concentrations measured in blood serum by enzyme-linked immunosorbent assay.
Study participants had a median age of 43 (interquartile range [IQR] 39 to 49), 19% were women, and 46% were white. Median CD4 count measured 436 (IQR 270 to 634). Two thirds of participants were taking antiretroviral therapy, and they had a median plasma viral load of 4.37 log (about 23,000 copies). People not taking antiretrovirals had a median HIV load around 300 copies.
In this CHARTER group, anti-CMV IgG concentrations in blood ranged from 5.2 to 46.1 U/mL. Older age correlated positively with anti-CMV IgG levels (r = 0.24, P = 0.005), and nadir CD4 count correlated negatively with anti-CMV IgG (r = -0.40, P < 0.0001). Higher anti-CMV IgG correlated positively with HIV load in blood (r = 0.29, P = 0.04). In people with detectable HIV RNA, higher anti-CMV IgG levels in serum correlated with higher HIV load in cerebrospinal fluid (P = 0.04).
Multivariate analysis identified a trend to an association between higher anti-CMV IgG and worse neurocognitive performance (beta = -3.5, P = 0.09). Factors independently associated with worse neurocognitive performance were longer HIV infection duration (beta = -2.7, P = 0.003), white or Hispanic ethnicity (beta = -1.7, P = 0.0006), lower systolic blood pressure (beta = 0.09, P = 0.006), and higher cerebrospinal fluid levels of CCL2, an immunoregulation and inflammation marker [4] (beta = -7.9, P = 0.02).
The researchers concluded that "older age and more advanced past immune suppression are associated with a stronger immune response to CMV, which appears to influence HIV pathogenesis in the brain." They suggested that clinical trials of anti-CMV therapy "should help untangle whether the observed relationships are causal."
References
1. Bharti A, Letendre S, Hanson B, et al. Higher CMV antibody concentrations are associated with older age and worse neurocognitive performance in adults living with HIV disease. 7th International Workshop on HIV and Aging, September 26-27, 2016, Washington, DC. Abstract 8.
2. Vescovini R, Biasini C, Telera AR, et al. Intense antiextracellular adaptive immune response to human cytomegalovirus in very old subjects with impaired health and cognitive and functional status. J Immunol. 2010;184:3242-3249. http://www.jimmunol.org/content/184/6/3242.long
3. Heaton RK, Franklin DR Jr, Deutsch R, et al. Neurocognitive change in the era of HIV combination antiretroviral therapy: the longitudinal CHARTER study. Clin Infect Dis. 2015;60:473-480. http://cid.oxfordjournals.org/content/60/3/473.long
4. National Center for Biotechnology Information. National Library of Medicine. Ccl2 Gene. Chemokine (C-C motif) ligand 2 [Mus musculus (house mouse)]. CCL2, a chemokine protein involved in immunoregulatory and inflammatory processes, is implicated in the pathogenesis of monocytic infiltrate diseases such as atherosclerosis, rheumatoid arthritis, and psoriasis. http://www.ncbi.nlm.nih.gov/gene/20296
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