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Less Inflammation Tied to Lower Frailty Progression, Greater Frailty Recovery
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Conference on Retroviruses and Opportunistic Infections (CROI), February 13-16, 2017, Seattle
" Less inflammation (calculated by an inflammatory index score*) lowered odds of progression to frailty ….The Hopkins investigators propose that clinicians and people with HIV can prevent frailty progression or promote recovery from frailty through several measures: (1) reducing chronic inflammation [from Jules: exercise, diet], (2) preventing or reducing chronic comorbid diseases, (3) modulating economic factors (education, employment), and (4) pursuing early and consistent antiretroviral therapy to attain virologic suppression, avoid a low CD4 nadir, and avoid progression to AIDS."
Mark Mascolini
Less inflammation (calculated by an inflammatory index score*) lowered odds of progression to frailty in an 800-person analysis of the HIV+/HIV- ALIVE cohort [1]. A lower inflammation score boosted chances of recovery from frailty to nonfrail or robust status in this Baltimore group with a drug-injecting history.
Although people with HIV are living longer, most analyses show them still lagging the general population in life expectancy. Shorter survival particularly affects minority populations and drug injectors. Research charts growing frailty rates in HIV populations, and much general-population research links frailty to mortality, new or worsening chronic disease, and disability.
The Fried criteria offer one standard definition of frailty [2]. These criteria consider 5 factors: weight loss, weakness (measured by grip strength), exhaustion, slow gait, and low physical activity. A person with 3 or more criteria is considered frail, while 1 or 2 criteria indicate prefrailty and a score of 0 indicates robust status. Johns Hopkins University researchers conducted this frailty analysis in the ALIVE cohort, which has enrolled 1300 HIV-positive and negative adults who are current or prior drug injectors. ALIVE investigators began assessing frailty in 2005.
The Hopkins team already determined that HIV-positive ALIVE members are 66% more likely to be frail than HIV-negative members and that frailty predicts death [3]. They also found that frailty predicts hospital admission in HIV-positive people independently of HIV disease stage or comorbidity [4]. They note that frailty is a dynamic state in which people can cycle between robust status, prefrailty, and frailty. They conducted the new ALIVE study to identify epidemiologic and biologic factors that drive these transitions.
The analysis involved 1353 ALIVE participants who had 9559 frailty transitions from 2005 through 2013. Adjusted models linked several factors to lower odds of progression from robust to frail or from nonfrail to frail: younger age, employment, absence of depressive symptoms, and fewer comorbid conditions. On the other hand, HIV infection independently raised odds of progression from robust to frail (adjusted odds ratio [aOR] 1.36, 95% confidence interval [CI] 1.14 to 1.61) or from nonfrail to frail (aOR 1.23, 95% CI 1.06 to 1.43).
Some of the same factors independently boosted odds of recovery from frail to nonfrail status or from frail to robust status: younger age, high school education or more, employment, absence of depressive symptoms, and fewer comorbid conditions. In this analysis, HIV positivity lowered chances of recovery from frail to nonfrail status (aOR 0.81, 95% CI 0.70 to 0.94) and recovery from frail to robust status (aOR 0.74, 95% CI 0.62 to 0.87).
Virologic suppression (below 500 copies) and earlier HIV control (determined by lack of prior AIDS or nadir CD4 count above 500) were associated with reduced progression from nonfrail to frail or from robust to frail, and with greater odds of recovery from frail to nonfrail or from frail to robust. For example, compared with people whose CD4 nadir lay below 50 copies, those with a nadir above 500 copies had more than tripled odds of recovery from frail to robust (aOR 3.37, 95% CI 1.17 to 9.71).
Previous work linked heightened inflammation (determined by an inflammatory index score*) to frailty independently of HIV disease stage and comorbidity [5]. The new analysis (adjusted for age, sociodemographics, depressive symptoms, comorbid conditions, and HIV status) tied every 1 standard deviation lower inflammatory index score to lower odds of progression from nonfrail to frail (aOR 0.78, 95% CI 0.65 to 0.92) or progression from robust to frail (aOR 0.70, 95% CI 0.58 to 0.84) and to greater odds of recovery from frail to nonfrail (aOR 1.29, 95% CI 1.08 to 1.53) or from frail to robust (aOR 1.43, 95% CI 1.20 to 1.72).
The Hopkins investigators propose that clinicians and people with HIV can prevent frailty progression or promote recovery from frailty through several measures: (1) reducing chronic inflammation, (2) preventing or reducing chronic comorbid diseases, (3) modulating economic factors (education, employment), and (4) pursuing early and consistent antiretroviral therapy to attain virologic suppression, avoid a low CD4 nadir, and avoid progression to AIDS.
*The score combines interleukin-6 and soluble tumor necrosis factor-alpha receptor-1. See reference 5.
References
1. Piggott DA, Bandeen-Roche K, Mehta SH, et al. Frailty progression and recovery among persons aging with HIV and substance use. Conference on Retroviruses and Opportunistic Infections (CROI), February 13-16, 2017, Seattle. Abstract 133.
2. Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56:M146-M156.
3. Piggott DA, Muzaale AD, Mehta SH, et al. Frailty, HIV infection, and mortality in an aging cohort of injection drug users. PLoS One. 2013;8:e54910.
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0054910
4. Piggott DA, Muzaale AD, Varadhan R, et al. Frailty and cause-specific hospitalization among persons aging with HIV infection and injection drug use. J Gerontol A Biol Sci Med Sci. 2016;Aug 11:pii: glw142. Epub ahead of print.
5. Piggott DA, Varadhan R, Mehta SH, et al. Frailty, inflammation, and mortality among persons aging with HIV infection and injection drug use. J Gerontol A Biol Sci Med Sci. 2015;70:1542-1547. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643614/
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