Worse Cognitive Outcomes Associated With CMV Antibodies Following ART for HIV

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Changes in immune response mediated by cytomegalovirus infection may contribute to compromised neurocognitive performance in adults with HIV.
Changes in immune response mediated by cytomegalovirus infection may contribute to compromised neurocognitive performance in adults with HIV.

Patients living with HIV who receive antiretroviral therapy (ART) have a higher concentration of anti-cytomegalovirus (CMV) immunoglobulin G antibody (IgG), according to an article recently published in Clinical Infectious Diseases. Furthermore, researchers found that these higher anti-CMV antibody levels are associated with worse neurocognitive outcomes in those receiving ART compared with their HIV-positive peers not receiving ART  (P =.045).

The researchers examined blood, serum, and cerebrospinal fluid specimens for the presence of anti-CMV antibodies, along with HIV RNA, CMV-specific T-cell counts, and CMV DNA analysis. The samples came from 80 previously identified patients with HIV who had already undergone comprehensive neurocognitive testing. The patients were grouped according to whether they were undergoing suppressive ART at the time of sample collection (n=38) or not undergoing such treatment (n=42).

The researchers found blood plasma concentrations of anti-CMV antibodies to be significantly higher in patients undergoing ART. Study-wide, higher IgG anti-CMV antibodies were also associated with older age (P =.0017), lower nadir CD4+ T-cell count (P <.001), AIDS (P <.001), and higher soluble CD163 (P =.009). Anti-CMV antibodies may therefore be predictive of increased aging and system decline.

Although 7 cognitive domains were tested, linkages across them varied. Higher anti-CMV IgG antibodies were especially associated with worse functioning in 3 neurocognitive domains: delayed recall (β=-0.38, P =.0064), executive functioning (β=-0.36, P =.0019), and working memory (β=-0.30, P =.011).  There were also trends toward worsening performance in 3 other domains (learning (β=-0.25, P =.067), speed of information processing (β=-0.21, P =.078), and verbal fluency (β=-0.24, P =.093)).

This research is significant in that individuals with HIV are at increased risk of contracting CMV, which may lead to immune system decline, increased mortality, and the increased aging sometimes observed in HIV-positive cohorts. While CMV has previously been demonstrated to negatively affect neurocognitive outcomes in older adults, this study also points to a potential link between ART and worse neurocognitive outcomes. 

As individuals with HIV are now living longer, both negative and positive effects of ART may become more significant in clinical presentation. Although the researchers note that this study was limited by small sample size and the lack of an HIV peer cohort, the links found between anti-CMV IgG antibodies, ART, and neurocognitive decline deserve further exploration. Additional research could determine whether the relationships found in this study are causative and give more insight into their specific mechanisms of action.

Reference  

Letendre S, Bharti A, Perez-Valero I, et al; for the CHARTER Group. Higher anti-CMV IgG concentrations are associated with worse neurocognitive performance during suppressive antiretroviral therapy. [published online March 1, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy170

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