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  3rd International Workshop on HIV and Aging
November 5-6, 2012
Baltimore, MD
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HIV Neurocognitive Disorder Linked to Frailty in Study of US Gay Men
  3rd International Workshop on HIV and Aging, November 5-6, 2012, Baltimore

Mark Mascolini

Clinically defined frailty independently raised the odds of HIV-associated neurocognitive disorder (HAND) in a study of more than 500 gay men enrolled in the Multicenter AIDS Cohort Study (MACS) [1]. The association held after statistical adjustment for an array of variables that can affect neurocognitive disorder, and it grew stronger when the investigators considered only symptomatic HAND.

Previous research linked frailty (defined by grip strength, walking speed, involuntary weight loss, self-reported exhaustion, and self-reported energy level) with several forms of cognitive impairment in HIV-negative people. Because a possible association had not been evaluated in people with HIV, researchers conducted this retrospective study of more than 500 HIV-positive men who enrolled in the MACS neurocognitive substudy at four US sites from September 2005 to September 2011.

All substudy enrollees received a comprehensive neurocognitive battery, assessments of activities of daily living, and frailty phenotype testing. The investigators defined frailty as a score in the lowest quintile (one fifth) on at least 3 of the 5 frailty assessments defined above. The primary outcome was a diagnosis of HAND (which includes asymptomatic neurocognitive impairment, mild neurocognitive disorder, and HIV-associated dementia) or symptomatic HAND (mild neurocognitive disorder or dementia).

Among 505 study participants, 314 (62.2%) had some form of HAND, while 191 had normal cognitive function. Asymptomatic neurocognitive impairment accounted for 64 cases of HAND (12.7% of the entire group), mild neurocognitive disorder accounted for 185 cases (36.6% of the entire group), and dementia accounted for 65 cases (12.9% of the entire group).

Men with and without HAND did not differ significantly in education, employment, CD4 count, current antiretroviral use (96% in both groups), depression, or current use of marijuana, noninjection drugs, or injection drugs. A significantly higher proportion of men with HAND than without it were black (21% versus 14%, P = 0.05). Men with HAND had a significantly shorter median duration of HIV infection than men without HAND (8 versus 18 years, P = 0.04). Also, a lower proportion of men with than without HAND had a detectable viral load (19.6% versus 29.9%), and that difference approached statistical significance (P = 0.06).

Close to 1 in 10 men met frailty criteria. Statistical analysis adjusted for study site determined that frailty more than doubled the odds of HAND (odds ratio [OR] 2.18, 95% confidence interval [CI] 1.05 to 4.54, P = 0.036) and tripled the odds of symptomatic HAND (OR 2.99, 95% CI 1.49 to 5.96, P = 0.002). Of the 5 frailty components, grip strength correlated most strongly with HAND.

A second statistical analysis factored in study site, age, race, education, employment status, CD4 count, smoking, marijuana use, drug use other than marijuana, injection drug use, and depression (a Beck Depression Inventory score above 16). Again, frailty approximately doubled the odds of HAND (OR 2.2, 95% CI 1.03 to 4.68, P = 0.042), while almost tripling the odds of symptomatic HAND (OR 2.8, 95% CI 1.37 to 5.75, P = 0.005).

Although the researchers cautioned that the "significant overlap" between frailty and HAND requires further study with longitudinal analysis, they proposed their findings "suggest that HAND could contribute to the frailty phenotype in those with HIV." The MACS team suggested that "cognitive screening should be considered for all persons with frailty."

Earlier MACS research determined that having a persistent frailty-like phenotype before starting antiretroviral therapy independently predicted AIDS or death [2]. Another MACS analysis correlated lower CD4 count with a higher prevalence of frailty, independently of antiretroviral use [3].


1. Smith B Skolasky R, Selnes O, et al. Association of HIV-associated neurocognitive disorder with frailty in HIV-1-seropositive men. 3rd International Workshop on HIV and Aging. November 5-6, 2012, Baltimore. Abstract O_04.

2. Desquilbet L, Jacobson LP, Fried LP, et al. A frailty-related phenotype before HAART initiation as an independent risk factor for AIDS or death after HAART among HIV-infected men. J Gerontol A Biol Sci Med Sci. 2011;66:1030-1038. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3156632/.

3. Desquilbet L, Margolick JB, Fried LP, et al. Relationship between a frailty-related phenotype and progressive deterioration of the immune system in HIV-infected men. J Acquir Immune Defic Syndr. 2009;50:299-306. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699396/.