Targeted therapies may prevent neurocognitive worsening in HIV

Anti-inflammatories and antidepressants may help prevent neurocognitive worsening among people with HIV, according to findings presented at the American Neurological Association annual meeting.

“Even among those who are virally suppressed on antiretroviral therapy, impairment persists and is associated with adverse outcomes,” Ronald J. Ellis, MD, PhD, of the departments of neurosciences and psychiatry at the University of California, San Diego, said during a virtual presentation. “A number of mechanisms have been proposed as underlying this, including persistent inflammation, oxidative stress and altered amyloid processing. Depression in people with HIV is closely related to inflammation; however, there have been no studies of these mechanisms in predicting long-term neurocognitive decline.”

Ellis and colleagues aimed to evaluate how depressed mood, persistent inflammation, oxidative stress and altered amyloid processing, all of which are common among people with HIV, are associated with neurocognitive worsening in a 12-year period. They analyzed data of 191 people with HIV (average age at follow-up, 56 years) at six U.S. sites. Specifically, they used immunoassay to quantify biomarkers in participants’ blood and assess inflammation, oxidative stress and altered amyloid processing. They used the Beck Depression Inventory-II (BDI-II) to assess depressed mood severity at entry. Further, researchers used summary regression-based change score method to examine neurocognitive decline for 12 years. Via factor analysis, they reduced dimensionality of biomarkers.

According to the study abstract, 113 participants did not have depression, 27 had mild depression, four had moderate depression and 47 had severe depression. Those whose depressed mood was worse at entry had more neurocognitive decline. Analysis identified three biomarker factors: loading on plasma interleukin-6 (factor one), soluble tumor necrosis factor receptor – type II (factor two) and soluble CD40 ligand (sCD40L).

Participants with higher factor one, which reflected worse systemic inflammation at baseline, had more significant decline in global neurocognition at 12 years, according to the study abstract. Neurocognitive decline did not appear related to other biomarkers/factors. Further, it was not significantly linked to demographics, nadir and current CD4, viral suppression or neurocognitive confound status, such as head injury or learning disability. Multivariable regression showed BDI-II and factor one both contributed independently to neurocognitive decline, and the researchers noted this interaction was not significant.

“If these relationships are indeed causal, then it's possible that targeted therapies, such as anti-inflammatories and antidepressants, could prevent future neurocognitive worsening,” Ellis said during the presentation. “The longitudinal design is consistent, but not definitive proof, of forward causation. A limitation is that there are unobserved factors that could determine both inflammation, depression and neurocognitive decline together.”