Analysis of an ACTG study population showed that cardiovascular disease (CVD) risk factors associated with neurocognitive impairment (NCI) differ between older women and men with HIV . Older age and diabetes predicted NCI in women, while physical activity and longer antiretroviral therapy (ART) protected women from NCI. Among these variables, only older age predicted NCI in men.
Research consistently links CVD with NCI in people with HIV, noted AIDS Clinical Trials Group (ACTG) investigators who conducted this study. Cardiometabolic risk clearly differs between women and men, yet studies of CVD risk and NCI in HIV populations do not distinguish between women and men (and often involve only men). An ACTG team designed this analysis to compare cardiometabolic risk associated with NCI in women versus men.
The study involved older people with HIV who began ART in a randomized ACTG trial then entered the longitudinal ACTG A5322 protocol dubbed HAILO, for HIV, Aging and Immune Function Long-Term Observational study. HAILO participants were eligible for this analysis if they completed a brief neurocognitive screen on entering HAILO. A scoring system that adjusts for age, sex, education, and race/ethnicity allowed researchers to determine who had NCI, defined as at least 1 standard deviation (SD) below the mean on 2 or more tests or at least 2 SD below the mean on 1 or more tests. ACTG researchers used separate logistic regression models to assess links between cardiometabolic risk and NCI in women and in men.
Of the 988 study participants, 195 (20%) were women. Women and men were similar in average age (51 and 52), average nadir CD4 count (209 and 204), and proportions with a viral load below 40 copies (89% and 91%) or who used antidepressants (23% and 21%). But women differed from men in race (22% versus 56% white, 52% versus 25% black, P < 0.001), proportion with only a high school education or less (61% versus 32%, P < 0.001), ART duration (median 7.6 versus 8.3 years, P = 0.02), and average CD4 count (747 versus 639, P < 0.001).
Women differed from men (if not always significantly) in prevalence of several CVD variables: antihypertensive use (42% versus 35%, P = 0.06), diabetes (16% versus 12%, P = 0.08), prior myocardial infarction (1% versus 4%, P = 0.01), 3 or more days of physical activity weekly (43% versus 55%, P = 0.005), and current and prior smoking (29% versus 25% current, 26% versus 35% prior, P = 0.09). Certain average lab values and body measures differed significantly between women and men: "good" HDL cholesterol (58 versus 47 mg/dL, P < 0.001), hemoglobin A1c (5.9% versus 5.7%, P = 0.003), body mass index (31 versus 27 kg/m2, P < 0.001), and waist circumference (100 versus 97 cm, P = 0.009).
Multivariate logistic regression identified several cardiometabolic factors linked to higher or lower odds of NCI in women or men. (P values below 0.05 indicate statistical significance; P values below 0.10 indicate trends; variables preceded by a bold D are predictive factors that differ between women and men):
Raised odds of NCI in women:
-- Every 10 years of age: odds ratio [OR] 1.90, P < 0.05
-- Hispanic: OR 6.35, P < 0.05
-- D: Diabetes: OR 2.77, P < 0.10
Lowered odds of NCI in women:
-- D: More physical activity: OR 0.35, P < 0.05
-- D: Every 10-mg/dL higher HDL cholesterol: OR 0.79, P < 0.10
-- D: Every 1-kg/m2 higher body mass index: OR 0.95, P < 0.10
-- D: Ever 1 year of ART duration: OR 0.90, P < 0.10
Raised odds of NCI in men:
-- Hispanic: OR 2.35, P < 0.05
-- D: Antidepressant use: OR 1.60, P < 0.05
-- Every 10 years of age: OR 1.21, P < 0.10
-- D: HCV infection: OR 1.50, P < 0.10
-- D: Every 50-cell higher nadir CD4 count: OR 1.05, P < 0.10
Lowered odds of NCI in men:
-- D: Black: OR 0.64, P < 0.05
-- D: Some college: OR 0.62, P < 0.05
The ACTG investigators concluded that cardiometabolic factors predicting NCI differ between women and men with HIV. For example, more physical activity proved strongly protective against NCI in women but not in men. In contrast, antidepressant use boosted odds of NCI in men but not in women. The researchers believe their findings "suggest that interventions targeting specific risk factors to prevent neurocognitive impairment in people living with HIV may differ between women and men."
1. Chow FC, Wu K, Tassiopoulos K, Berzins B, Robertson K, Taiwo B. Cardiovascular risk factors associated with neurocognitive impairment differ by sex. 25th Conference on Retroviruses and Opportunistic Infections (CROI). March 4-7, 2018. Boston. Abstract 412.