Background: Despite effective combination antiretroviral therapy (ART), neurocognitive impairment (NCI) remains prevalent in persons living with HIV (PLWH). The contribution of cardiovascular comorbidities to NCI may increase as PLWH age. We investigated the association of cardiovascular risk factors with prevalent NCI in a prospective cohort of older PLWH at entry into the AIDS Clinical Trials Group A5322 study.
Methods: Participants who underwent a brief neurocognitive screen (Trailmaking Tests A and B, HVLT-R, Digit Symbol) at entry into A5322 were eligible. Primary outcomes were overall cognitive performance summarized by mean z-scores of the 4 tests (NPZ-4) and presence of NCI, defined as ­>1 SD below the mean on 2 or more tests or >2 SD below the mean on 1 test. We used linear and logistic regression models to determine the association between cardiovascular risk and the primary outcomes.
Results: Of 988 participants (30% black, 21% Hispanic/Latino, 20% women), mean age was 52 years and education 14 years. Median ART duration was 8 years, mean CD4 count 661 cells/mm3, and 90% of participants had viral load < 40 copies/mL. Current smoking (26%), statin (27%) and anti-hypertensive (36%) use were common, while stroke (2%), myocardial infarction (3%) and injection drug use (< 1%) were uncommon. Mean LDL and HDL cholesterol were 109 and 49 mg/dL, respectively, and systolic blood pressure was 126 mmHg. 180 participants (18%) had NCI. In demographics and education-adjusted models, higher HDL was associated with better NPZ-4 (+0.04, p=0.040) and lower odds (OR 0.88, p=0.043) of NCI per 10 mg/dL higher HDL, as was statin use (+0.15 NPZ-4, p=0.037). An association between smoking and worse NPZ-4 (-0.15, p=0.053) became non-significant after controlling for anti-depressant use and hepatitis C. In a multivariable model including factors significant at p< 0.10 in demographics and education-adjusted analyses, older age, female sex, Hispanic/Latino ethnicity, high school education or less, and anti-depressant use were associated with worse NPZ-4. Longer ART duration and higher HDL were associated with better NPZ-4.
Conclusions: Among older PLWH with well-controlled cardiovascular risk factors, higher HDL was associated with better cognition. Investigation into the impact of modifying HDL cholesterol on cognition in PLWH is merited.