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  Conference on Retroviruses
and Opportunistic Infections
Seattle, Washington
March 4-7, 2019
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Obesity--but not frailty--predicts
neurocognitive impairment with HIV
  Conference on Retroviruses and Opportunistic Infections (CROI), March 4-7, 2019, Seattle
Mark Mascolini
Obesity and older age predicted development of neurocognitive impairment (NCI) in a 3-year study of 929 US residents with well-controlled HIV infection [1]. Frailty did not emerge as a risk factor for NCI, but the study linked NCI and low physical activity to development of frailty.
Previous work established a cross-sectional link between frailty and NCI in adults with HIV [2]. But whether frailty contributes to NCI, or NCI to frailty, remained unclear. Other research ties obesity and sarcopenia (muscle loss) to frailty in men with HIV [3]. To sort out these overlapping associations, AIDS Clinical Trials Group (ACTG) investigators conducted a new study aiming to identify factors associated development of--or improvement in--NCI over time.
The analysis focused on participants in ACTG A5322 (HAILO), an ongoing prospective cohort study at 32 sites across the United States. People were 40 or older when they enrolled in 2013-2014 and treatment-naive when randomized to an antiretroviral combination in an ACTG trial. Annual exams include neurocognitive and frailty assessments.
The investigators figured summary z scores from standard neurocognitive tests and used them to define NCI (1 or more z scores at least 2 standard deviation [SD] below 0, or 2 or more z scores at least 1 SD below 0). They defined frailty by standard criteria (grip strength, gait speed, weight loss, fatigue, low activity). The ACTG team used logistic regression to explore age-adjusted associations between NCI or frailty and baseline variables.
Among 1035 people enrolled, 929 had 3 years of follow-up. The group had a median age of 51 years, 19% were women, 49% white, 31% black, and 20% Hispanic. Current median CD4 count stood at 631, 92% of participants had an undetectable viral load, and 33% initially used efavirenz. At the baseline visit 145 people (16%) had NCI and 57 (6%) were frail. Among the 145 people with initial NCI, 89 remained impaired and 56 improved. NCI developed in another 57 previously normal people.
Multivariate analysis linked three factors to higher odds of developing NCI: every additional year of age (P = 0.02), overweight versus normal weight (P = 0.05), and obese versus normal weight (P = 0.04). This analysis did not link frailty to new NCI.
Another multivariable analysis identified initial efavirenz use as an independent predictor of improved NCI over 3 years (P = 0.02), an association probably reflecting the 70% of initial efavirenz takers who stopped the sometimes neurotoxic drug during follow-up. Compared with other racial/ethnic groups, Hispanics had lower odds of improved NCI (P = 0.03). Black versus white race had no impact on improving NCI.
A third analysis linked baseline NCI to becoming frail during follow-up (P = 0.02). Two factors protected against becoming frail: physical activity 3 days a week (P = 0.002) and more education (P = 0.001).
The ACTG investigators concluded that obesity and increasing age predict development of NCI over 3 years of follow-up, but frailty does not. On the other hand, NCI predicted development of frailty. The researchers observed that "frailty reflects a vulnerability to stressors (comorbidities, illness)" and "NCI contributes to this burden of stressors."
The investigators explained that NCI and frailty may occur at the same time, but NCI appears to spur development of frailty rather than vice versa. They proposed that people with (1) NCI, (2) overweight or obesity, and (3) low physical activity "may be at the greatest risk for frailty and may benefit most from interventions focused on weight reduction and increased physical activity."
1. Perez J, Andrade A, Ellis RE, et al. Obesity is independently associated with neurocognitive decline in HIV. Conference on Retroviruses and Opportunistic Infections (CROI). March 4-7, 2019. Seattle. Abstract 129.
2. Erlandson KM, Perez J, Abdo M, et al. Frailty, neurocognitive impairment, or both in predicting poor health outcomes among adults living with human immunodeficiency virus. Clin Infect Dis. 2019;68:131-138.
3. Hawkins KL, Zhang L, Ng DK, et al. Abdominal obesity, sarcopenia, and osteoporosis are associated with frailty in men living with and without HIV. AIDS. 2018;32:1257-1266.