JAIDS: Journal of Acquired Immune Deficiency Syndromes Inflammation Relates to Poorer Complex Motor Performance among Adults Living with HIV on Suppressive Antiretroviral Therapy

: Background: Inflammatory processes have been suggested to underlie early neurologic abnormalities among persons living with HIV (HIV-positive), such as deficits in complex motor function, that are purported to remit with effective antiretroviral treatment (ART). We hypothesized HIV will have negative direct and indirect effects via inflammation on complex motor performance. Methods: The sample consisted of 90 ART-treated virally suppressed HIV-positive and 94 HIV-negative adults, ages 36 to 65 years, with balanced recruiting in each age decade (36-45, 46-55, 56-65). Biomarkers of inflammation (d-dimer, IL-6, MCP-1/CCL2, sCD14, and TNF-a) were measured, and a composite inflammation burden score was calculated. Complex motor performance was evaluated using the Grooved Pegboard Test. Results: The HIV-positive group had worse complex motor performance (p = 0.001; hedge’s g = -0.49) and a higher average inflammation Re: Inflammation relates to poorer HIV suppressive antiretroviral therapy Abstract Background: Inflammatory processes have been suggested to underlie early neurologic abnormalities among persons living with HIV (HIV-positive), such as deficits in complex motor function, that are purported to remit with effective antiretroviral treatment (ART). We hypothesized HIV will have negative direct and indirect effects via inflammation on complex motor performance. Methods: The sample consisted of 90 ART-treated virally suppressed HIV-positive and 94 HIV-negative adults, ages 36 to 65 years, with balanced recruiting in each age decade (36-45, 46-55, 56-65). Biomarkers of inflammation (d-dimer, IL-6, MCP-1/CCL2, sCD14, and TNF-  ) were measured, and a composite inflammation burden score was calculated. Complex motor performance was evaluated using the Grooved Pegboard Test. Results: The HIV-positive group had worse complex motor performance ( p = 0.001; hedge’s g = -0.49) and a higher average inflammation burden composite score ( p < 0.001; hedge’s g = 0.78) than the HIV-negative group. Path analyses indicated that the indirect effect of HIV disease on complex motor performance through inflammation burden was statistically significant, accounting for 15.1% of the effect of HIV on complex motor performance. Conclusion: Although neurologic findings (e.g., deficits in motor speed/dexterity) commonly associated with HIV infection typically remit with ART, our analysis indicates that inflammation plays an important role in worse complex motor skills among HIV-positive adults. Future studies of strategies for managing chronic inflammation in HIV should consider using an inflammation burden composite and examining its effect on complex motor performance. Abstract Abstract Background: Inflammatory processes have been suggested to underlie early neurologic abnormalities among persons living with HIV (HIV-positive), such as deficits in complex motor function, that are purported to remit with effective antiretroviral treatment (ART). We hypothesized HIV will have negative direct and indirect effects via inflammation on complex motor performance. Methods: The sample consisted of 90 ART-treated virally suppressed HIV-positive and 94 HIV-negative adults, ages 36 to 65 years, with balanced recruiting in each age decade (36-45, 46-55, 56-65). Biomarkers of inflammation (d-dimer, IL-6, MCP-1/CCL2, sCD14, and TNF-  ) were measured, and a composite inflammation burden score was calculated. Complex motor performance was evaluated using the Grooved Pegboard Test. Results: The HIV-positive group had worse complex motor performance ( p = 0.001; hedge’s g = -0.49) and a higher average inflammation burden composite score ( p < 0.001; hedge’s g = 0.78) than the HIV-negative group. Path analyses indicated that the indirect effect of HIV disease on complex motor performance through inflammation burden was statistically significant, accounting for 15.1% of the effect of HIV on complex motor performance. Conclusion: Although neurologic findings (e.g., deficits in motor speed/dexterity) commonly associated with HIV infection typically remit with ART, our analysis indicates that inflammation plays an important role in worse complex motor skills among HIV-positive adults. Future studies of strategies for managing chronic inflammation in HIV should consider using an inflammation burden composite and examining its effect on complex motor performance. inflammation burden accounted for 15.1% of the effect of HIV infection on motor performance when controlling for relevant covariates. These results indicate that inflammatory processes may contribute to worse complex motor skills in the context of cART-treated HIV. Our sample consisted of virally suppressed, chronic HIV-positive patients; however, impairment in complex motor skills was still observed among 20% of the HIV-positive sample. This observed impairment rate is consistent with motor impairment rates reported in previous literature e.g., 34 . Some evidence indicates a higher impairment rate in complex motor performance among persons with chronic HIV compared to persons with acute or early HIV infection, 35 which may reflect a history of immunosuppression and/or greater inflammation burden. For example, persons with AIDS performed significantly worse on a fine motor speed test than those without AIDS. 36 Deficits in motor skills may indicate injury to the basal ganglia, which are part of the motor control pathways. 37 The basal ganglia appears to be particularly vulnerable to alterations in BBB permeability, 38,39 immune cellular infiltration, 40 and accumulation of HIV viral RNA. 41 Neuropathological studies have observed higher concentrations of macrophages, microglia, and viral proteins in the basal ganglia. 42 Our path analyses indicate that inflammation burden may play a role in the association between HIV infection and worse complex motor performance. This finding is consistent with previous research demonstrating the detrimental impact of HIV and its proteins on the brain through peripheral and CNS pathways. 10 Monocytes and macrophages are observed to infiltrate the CNS in HIV infection. 10 Elevations in soluble markers of monocyte and cytokine activation, including sCD14, MCP-1/CCL2 and IL-6, have been observed among HIV-positive adults with neurocognitive impairment. 43-45 Expression of MCP-1/CCL2 may contribute to upregulation of HIV-1 replication, thereby contributing to an increased risk of neurocognitive impairment. 46 In addition to inflammation, coagulation imbalance, which includes upregulation of D-dimer, is associated with global neurocognitive functioning among HIV-positive adults. 15 In the current D-dimer in the inflammation