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HIV, Vascular Risk Factors, and Cognition in the Combination Antiretroviral Therapy Era: A Systematic Review and Meta-Analysis

Published online by Cambridge University Press:  09 November 2020

Elissa C. McIntosh
Department of Psychology, University of Southern California, Los Angeles, CA, USA
Kayla Tureson
Department of Psychology, University of Southern California, Los Angeles, CA, USA
Lindsay J. Rotblatt
Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, USA
Elyse J. Singer
Department of Neurology, UCLA David Geffen School of Medicine, Los Angeles, CA, USA
April D. Thames*
Department of Psychology, University of Southern California, Los Angeles, CA, USA
*Correspondence and reprint requests to: April D. Thames, Ph.D., Associate Professor of Psychology, University of Southern California, 3620 South McClintock Ave., Building/room: SGM 520, Los Angeles, CA 90089-1061, USA. Tel: +1 213 740 4436. E-mail:



Mounting evidence indicates that vascular risk factors (VRFs) are elevated in HIV and play a significant role in the development and persistence of HIV-associated neurocognitive disorder. Given the increased longevity of people living with HIV (PLWH), there is a great need to better elucidate vascular contributions to neurocognitive impairment in HIV. This systematic review and meta-analysis examine relationships between traditional VRFs, cardiovascular disease (CVD), and cognition in PLWH in the combination antiretroviral therapy era.


For the systematic review, 44 studies met inclusion criteria and included data from 14,376 PLWH and 6,043 HIV-seronegative controls. To better quantify the contribution of VRFs to cognitive impairment in HIV, a robust variance estimation meta-analysis (N = 11 studies) was performed and included data from 2139 PLWH.


In the systematic review, cross-sectional and longitudinal studies supported relationships between VRFs, cognitive dysfunction, and decline, particularly in the domains of attention/processing speed, executive functioning, and fine motor skills. The meta-analysis demonstrated VRFs were associated with increased odds of global neurocognitive impairment (odds ratio [OR ]= 2.059, p = .010), which remained significant after adjustment for clinical HIV variables (p = .017). Analyses of individual VRFs demonstrated type 2 diabetes (p = .004), hyperlipidemia (p = .043), current smoking (p = .037), and previous CVD (p = .0005) were significantly associated with global neurocognitive impairment.


VRFs and CVD are associated with worse cognitive performance and decline, and neurocognitive impairment in PLWH. Future studies are needed to examine these relationships in older adults with HIV, and investigate how race/ethnicity, gender, medical comorbidities, and psychosocial factors contribute to VRF-associated cognitive dysfunction in HIV.

Critical Review
Copyright © INS. Published by Cambridge University Press, 2020

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