Neurocognition may decline more with age among people living with HIV (PLWH) compared to uninfected persons. The factors related to this decline are not well understood in the current antiretroviral therapy (ART) era.
AIDS Clinical Trials Group (ACTG) A5322 (HAILO) is an observational cohort study of PLWH ≥ 40 years old, on ART. Participants undergo annual assessments for neurocognitive impairment (NCI), with NCI defined by ≥1 z-score ≥2 SD below 0 or ≥2 z-scores ≥1 SD below 0 on Trailmaking A and B and the Wechsler Adult Intelligence Scale-Revised Digit Symbol tests. Obesity was defined as body mass index (BMI) >30 kg/m², overweight as 25-30 kg/m², normal weight as 18.5-25 kg/m², and underweight < 18.5 kg/m². Participants who developed NCI during the first 3 years were compared to persons who maintained normal neurocognition. We used logistic regression to assess the age-adjusted associations between NCI and baseline covariates including sex, race, alcohol use, BMI, waist circumference, nadir CD4, history of AIDS defining illness, hemoglobin A1C. Only covariates with a p-value < 0.1 from age-adjusted analysis were included in the multivariable models.
Of 929 participants, 81% were male, 31% Black, and 20% Hispanic. Median age was 51 years (IQR 46-56). Most individuals (92%) had undetectable plasma HIV RNA with median CD4 count 631 cells/mm³ (IQR 458-840) at study entry. At study entry, 16% had NCI, 29% were obese, and 40% were overweight. Over 3 years, 6% of participants developed NCI while 78% remained unimpaired. In multivariable models, increasing age (OR 1.04; 95% CI 1.00, 1.08; p=0.04), and having an obese (OR 2.45; 1.05, 5.70; p=0.04) or overweight BMI (OR 2.21; 1.00, 4.91; p=0.05) vs normal BMI were associated with increasing prevalence of NCI compared to those who remained unimpaired.
Both greater age and obesity were independently associated with worsening cognitive function. These results extend previous work demonstrating a higher risk of NCI among obese PLWH by showing that obese individuals are also at greater risk of subsequently transitioning from unimpaired to impaired neurocognition.