Lipid Profiles and APOE4 Allele Impact Midlife Cognitive Decline in HIV-Infected Men on Antiretroviral Therapy

• Published in: Clinical infectious diseases Vol. 63; no. 8; pp. 1130 - 1139
• Main Authors: Mukerji, Shibani S., Locascio, Joseph J., Misra, Vikas, Lorenz, David R., Holman, Alex, Dutta, Anupriya, Penugonda, Sudhir, Wolinsky, Steven M., Gabuzda, Dana
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 15.10.2016
• Subjects: Age Factors; Aged; Alleles; Antiretroviral Therapy, Highly Active; Apolipoprotein E4 - genetics; Apolipoproteins; Biomarkers; Cognitive Dysfunction - blood; Cognitive Dysfunction - diagnosis; Cognitive Dysfunction - etiology; Disease Susceptibility; Female; Follow-Up Studies; Genotype; Genotype & phenotype; HIV; HIV Infections - complications; HIV Infections - drug therapy; HIV Infections - genetics; HIV/AIDS; Human immunodeficiency virus; Humans; Lentivirus; Lipids; Lipids - blood; Male; Mental Status and Dementia Tests; Middle Aged; Retroviridae; Risk Factors; Sociodemographics; HIV-1; cholesterol; APOE; aging; cognitive decline
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/ciw495

Background. Dyslipidemia and apolipoprotein E4 (APOE ε4) allele are risk factors for age-related cognitive decline, but how these risks are modified by human immunodeficiency virus (HIV) infection is unclear. Methods. In a longitudinal nested study from the Multicenter AIDS Cohort Study, 273 HIV type 1–infected (HIV+) men aged 50–65 years with baseline HIV RNA <400 copies/mL and on continuous antiretroviral therapy (ART) in ≥95% of follow-up visits were matched by sociodemographic variables to 516 HIV-uninfected (HIV−) controls. The association between lipid markers (total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density liproprotein cholesterol [HDL-C], and triglycerides), APOE genotype, and cognitive decline in HIV infection was examined using mixed-effects models. Results. The median baseline age of participants was 51, 81% were white, and 89% had education >12 years. HIV+ men had similar baseline total cholesterol and LDL-C, but lower HDL-C and higher triglycerides than controls (P < .001). Higher total cholesterol and LDL-C were associated with faster rates of cognitive decline (P < .01), whereas higher HDL-C attenuated decline (P = .02) in HIV+ men. In HIV+ men with elevated cholesterol, statin use was associated with a slower estimated rate of decline (P = .02). APOE ε4 genotype accelerated cognitive decline in HIV+ but not HIV− men (P = .01), with trajectories diverging from HIV− ε4 carriers after age 50. Total cholesterol levels did not modify the association of ε4 genotype with decline (P = .9). Conclusions. Elevated cholesterol and APOE ε4 genotype are independent risk factors for cognitive decline in ART-adherent HIV+ men aged >50 years. Treatment of dyslipidemia may be an effective strategy to reduce cognitive decline in older HIV+ individuals.