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

Background. Dyslipidemia and apolipoprotein E4 (APOE 4) 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 lipoprotein 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 4 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 4 genotype with decline (P =. 9). Conclusions. Elevated cholesterol and APOE 4 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.