Neurocognitive Deficits Observed in HIV Despite Long-Term Antiretroviral Therapy

Neurocognitive deficits and mood abnormalities were more common among patients with virologically-controlled HIV infection than HIV-negative control patients.

Despite receiving effective antiretroviral therapy (ART) for more than 10 years, patients with HIV infection were found to have neurocognitive deficits, including reduced brain volume and signs of neuronal injury and neuroinflammation. These study results were published in Neurology.

To evaluate the prevalence of neurocognitive impairment among patients with HIV infection, researchers conducted a study using patient data sourced from 2 longitudinal national history studies. Adult patients with HIV infection (n=155) who started ART at least 15 years ago and HIV-negative control patients (n=100) underwent clinical, laboratory, neuropsychologic, and lumbar puncture testing and magnetic resonance imaging (MRI). A control-weighting approach was used to balance age- and sex-based differences between the cohorts. Weighted linear regression was used to assess the effect of HIV infection on neurocognitive, MRI, and cerebrospinal fluid outcomes.

Among HIV-positive and HIV-negative patients included in the analysis, the mean (SD) ages were 53.2 (5.80) and 52.3 (7.41) years, 20.7% and 32.0% were women, 51.6% and 46.0% were White, and 26.5% and 24.0% met criteria for HIV-associated neurocognitive disorder, respectively. Of patients with HIV infection, the mean (SD) durations of disease and ART receipt were 22.8 (5.4) and 20.3 (4.0), respectively, and the median CD4+ count was 619 (450-833) cells/mm3.

These observations have important implications for understanding the neuropathogenesis of HIV infection and for future approaches to treatment.

Cognitive testing results showed that patients with vs without HIV infection scored significantly lower in the domains of motor function (estimate, -3.16; P =.009) and attention/working memory (estimate, -2.74; P =.008). Patients with HIV infection were significantly more likely to have mild depression symptoms, defined as Beck Depression Inventory score greater than 16 (odds ratio [OR], 31.6; 95% CI, 4.4-3300; P =.014). Functional impairment, defined as Patient Assessment of Own Function Inventory score greater than 7 (OR, 3.90; 95% CI, 1.48-12.7; P =.011), and prior alcohol misuse (OR, 3.58; 95% CI, 1.40-11.2; P =.014) were also significantly more likely among HIV-positive patients.

Analysis of cerebrospinal fluid samples showed significantly higher neurofilament light chain (P =.01) and tumor necrosis factor-α (P =.0008) levels among patients with vs without HIV infection.

Data from MRI scans indicated significantly decreased subcortical gray matter volume among patients with vs without HIV infection (least squares mean, 0.0376 vs 0.0391; P <.001). Brain regions responsible for this significant between-group difference in subcortical gray matter included the hippocampus, amygdala, ventral diencephalon, hypothalamus, and putamen (all P <.05).

Limitations of this study include potential survivor bias as only individuals receiving ART for at least 15 years were included in the HIV group.

According to the researchers, “These observations have important implications for understanding the neuropathogenesis of HIV infection and for future approaches to treatment.”

This article originally appeared on Infectious Disease Advisor


McMahan C, Dietrich DK, Horne EF, et al. Neurocognitive dysfunction with neuronal injury in people with HIV on long-duration antiretroviral therapy. Neurology. 2023;10.1212/WNL.0000000000207339. doi:10.1212/WNL.0000000000207339