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Higher CMV Antibody Linked to Lower CD4 Nadir and Worse Neurocognitive Function
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19th Conference on Retroviruses and Opportunistic Infections, March 5-8, 2012, Seattle
Results "also support that earlier initiation of ART may reduce CMV-associated complications and that CMV screening--and perhaps even treatment--might benefit aging people living with HIV disease."
Mark Mascolini
Higher cytomegalovirus (CMV) antibody levels were associated with worse global neurocognitive function in a study of 138 people with HIV, particularly during effective antiretroviral therapy (ART) [1]. The findings add to evidence that "periodic CMV reactivation might cause immune activation and nervous system injury," say Scott Letendre and CHARTER Group colleagues.
Cross-sectional studies demonstrate that CMV infection influences age-associated changes in adaptive immune status. Such CMV-related immune changes may pose a risk to people surviving to older ages with HIV infection, Letendre and colleagues proposed. They noted that antiretroviral-treated people have higher levels of CMV-specific CD8 cells than untreated people [2] and suggested that these higher CD8 levels could boost the risk of cerebrovascular disease because CMV-specific T-cell responses have been linked to thicker carotid artery intima media [3].
The CHARTER team planned this study to explore the hypothesis "that periodic CMV reactivation leads to worse neurocognitive functioning." This cross-sectional analysis involved 138 HIV-positive CHARTER cohort members who had matched cerebrospinal fluid (CSF), plasma, and serum samples and no comorbidities severe enough to account for neurocognitive impairment. The researchers measured CMV IgG concentrations in serum and CMV DNA in CSF and plasma. All study participants completed a comprehensive battery of neuropsychological tests. The investigators summarized test results as a global deficit score ranging from 0 to 5 with 5 indicating the worst impairment.
Most study participants (81%) were men, two thirds were taking ART, and 51% had no AIDS diagnosis. Median age stood at 43 years, and 58% of study participants had global neurocognitive impairment. CMV IgG levels ranged from 5.2 to 46.1 U/mL (median 24.1). Eighteen people (13%) had detectable CMV DNA in plasma, and 2 (1.4%) had detectable CMV DNA in CSF. Among people with detectable CMV DNA in plasma, levels ranged from 0.58 to 180 copies/mL (median 3.2).
Higher CMV IgG levels were associated with:
-- Older age: r = 0.23, P = 0.006
-- Lower nadir CD4 count: r(2) = 0.19, P < 0.0001
-- ART use: tau = 3.0, P = 0.004
-- Worse global deficit score: r = 0.17, P = 0.04
Among participants not taking ART, higher CMV IgG levels were also associated with higher HIV RNA in CSF: r(2) = 0.13, P = 0.04. People with AIDS were twice as likely as those without AIDS to have detectable CMV DNA in plasma (RR 2.1, P = 0.097), and people with detectable HIV RNA in plasma were 30% more likely to have detectable CMV DNA in plasma (RR 1.3, P = 0.054). CMV antibody levels were also associated with an array of immune activation markers in CSF.
A worse global deficit score was associated with higher CMV IgG, more comorbid conditions, and an interaction between CMV IgG levels and plasma HIV RNA (r(2) = 0.09, P = 0.02). Further analysis showed that higher CMV IgG was associated with a worse global deficit score only in the 41 study participants with undetectable HIV RNA in plasma (r = 0.39, P = 0.01). Everyone in this subgroup with CMV IgG levels of 34.5 U/mL or higher had neurocognitive impairment.
Letendre and colleagues proposed that "together, these findings support that periodic CMV reactivation might cause immune activation and nervous system injury" in people with HIV. They suggested the results "also support that earlier initiation of ART may reduce CMV-associated complications and that CMV screening--and perhaps even treatment--might benefit aging people living with HIV disease."
References
1. Letendre S, Bharti A, Perez Valero I, et al. Higher cytomegalovirus antibody concentrations are associated with older age, lower nadir CD4+ cell counts, and worse global neurocognitive functioning in people with HIV disease. 19th Conference on Retroviruses and Opportunistic Infections. March 5-8, 2012. Seattle. Abstract 466. http://www.retroconference.org/2012b/PDFs/466.pdf.
2. Naeger DM, Martin JN, Sinclair E, et al. Cytomegalovirus-specific T cells persist at very high levels during long-term antiretroviral treatment of HIV disease. PLoS One. 2010;5(1):e8886. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0008886.
3. Hsue P, Hunt PW, Sinclair E, et al. Increased carotid intima-media thickness in HIV patients is associated with increased cytomegalovirus-specific T-cell responses. AIDS. 2006;20:2275-2283. http://www.ncbi.nlm.nih.gov/pubmed/17117013.
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