White matter structure alterations in HIV-1-infected men with sustained suppression of viraemia on treatment

Objective: Cognitive impairment is highly prevalent in HIV-1-infected (HIV) patients, despite adequate suppression of viral replication by combination antiretroviral therapy (cART). Cerebral white matter structure alterations are often associated with cognitive impairment and have commonly been reported in the natural course of HIV infection. However, the existence of these alterations in adequately treated HIVpatients remains unknown, as well as its possible association with cognitive impairment. Design: We used diffusion tensor imaging (DTI) to investigate whether white matter structure alterations exist in HIV patients with sustained suppressed viral replication on cART, and if such alterations are related to HIV-associated cognitive deficits. Methods: We compared 100 aviraemic HIV men on cART with 70 HIV-uninfected, otherwise comparable men. Clinical and neuropsychological assessments were performed. From DTI data, white matter fractional anisotropy and mean diffusion were calculated. Subsequently, tract-based spatial statistics (TBSS) was performed, with and without masking out white matter lesions. Results: HIV patients showed diffuse white matter structure alterations as compared with HIV-uninfected controls, observed as widespread decreased fractional anisotropy and an increasedmean diffusion. Thesewhitematter structure alterations were associated with the number of years spent with a CD4 cell count below 500 cells/ml, but not with HIV-associated cognitive deficits. Conclusion: Cerebral white matter structure alterations are found in middle-aged HIV men with sustained suppression of viraemia on cART, and may result from periods with immune deficiency when viral toxicity and host-inflammatory responses were at their peak. These white matter structure alterations were not associated with the observed subtle HIV-associated cognitive deficits.