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MACS Frailty - HIV-1 Infection Is Associated With an Earlier
Occurrence of a Phenotype Related to Frailty
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Loic Desquilbet,1 Lisa P. Jacobson,1 Linda P. Fried,2,3 John P. Phair,4 Beth D. Jamieson,5
Marcy Holloway,6 and Joseph B. Margolick,7 for the Multicenter AIDS Cohort Study
HIV infection was strongly associated with FRP prevalence. Compared to HIV-uninfected men of similar age, ethnicity and education, HIV-infected men were more likely to have the FRP for all durations of infection: for ≤4 years, the adjusted odds ratio (OR) was 3.38, with 95% confidence interval (CI), 1.25-9.11, and for 4.01-8 years and 8.01-12 years the corresponding figures were (OR = 12.95, 95% CI, 6.60-25.40) and (OR = 14.68, 95% CI, 7.60-28.35), respectively. The FRP prevalence for 55-year-old men infected with HIV for ≤4 years (3.4%; 95% CI, 1.3-8.6) was similar to that of uninfected men ≥65 years old (3.4%; 95% CI, 1.5-7.6).
Of the 245 seroconverters, 34 (13.9%) manifested the FRP at least once, as opposed to only 28 (1.5%) of the 1905 HIV-uninfected individuals during the same time period (p <.01); in all, the FRP was reported at 50 HIV-positive person-visits and 32 HIV-negative person-visits. We examined whether the FRP was more likely to occur among individuals with comorbidities of cancers and neurological disorders, ascertained according to the standardized MACS protocol. History of a cancer was more frequent among person-visits with FRP than among those free of FRP, in both HIV seropositives (22.0% vs 6.3%; p <.01) and HIV seronegatives (6.3% vs 1.6%; p =.04). Similar results were observed for neurological disorders for both HIV-positive person-visits (38.0% vs 6.8%; p <.01) and HIV-negative person-visits (9.4% vs 1.8%; p <.01).
In a multivariate model including age, ethnicity, and educational level (Table 3, Model 1), HIV-infected men were more likely than were uninfected men to manifest physical shrinking (odds ratio [OR] = 12.80), exhaustion (OR = 3.02), slowness (OR = 3.94), low physical activity level (OR = 3.40), and the aggregate FRP (OR = 10.97).
The risk of exhibiting the FRP increased with duration of HIV infection, after adjusting for age, ethnicity, and education (Table 4 and Figure 2a). Older and college-educated men were more likely to manifest the FRP, although the association with education was of borderline significance.
Figure 2. Adjusted prevalence of having a frailty-related phenotype according to age and presence and duration of HIV infection, for fixed values of ethnicity (white non-Hispanic) and educational level (college), among HIV-seronegative and -seroconverted men in the Multicenter AIDS Cohort Study (MACS) between April 1994 and January 1, 1996 when (a) all person-visits were included and (b) excluding person-visits occurring later than 6 months before the first AIDS-defining illness. The ratio of the areas (and middle vertical length) of any two shaded polygons equals the ratio of the two corresponding prevalences written in their centers. For example the area corresponding to a prevalence of 1.7% is equal in a and b, and is the equivalent of half the area corresponding to a prevalence of 3.4%. See reference (52) for
further details.
In a multivariate model including age, ethnicity, and educational level (Table 3, Model 1), HIV-infected men were more likely than were uninfected men to manifest physical shrinking (odds ratio [OR] . 12.80), exhaustion (OR . 3.02), slowness (OR . 3.94), low physical activity level (OR . 3.40), and the aggregate FRP (OR . 10.97).
In this study, both HIV infection and AIDS were predictors of frailty-like manifestations, and the duration of HIV infection was associated with the likelihood of these manifestations. The observed increases of FRP with low CD4 T-cell count and high HIV viral load, two biomarkers of HIV disease progression, suggest a common underlying biology between frailty and HIV disease. However, the presence of the FRP was far from automatic in men with HIV or AIDS. Finally, in this study, HIV infection for 4
years appeared to confer a rate of FRP comparable to that of HIV-uninfected men 10 years older, and this rate was further
increased by 2- to 3-fold for men infected . 4 years and an additional 2-fold for men with AIDS.
In additional adjusted models, we found that the prevalence of the FRP was not affected by behavioral practices
at enrollment in the cohort such as being a former smoker (OR . 1.21; 95% CI, 0.54-2.75; p . .64) or a current smoker (OR . 1.56; 95% CI, 0.87-2.85; p. .14) compared to a nonsmoker, or use (compared to non-use) of hash/ marijuana (OR. 0.85; 95% CI, 0.47-1.53; p. .59), poppers (OR. 0.81; 95% CI, 0.44-1.48; p. .49), or cocaine (OR. 1.23; 95% CI, 0.68-2.24; p . .49). Adjustments for these behavioral practices did not affect the estimates of the association between the FRP and duration of HIV
infection.
Duration of HIV infection remained strongly associated with FRP, as did age (Table 4 and Figure 2b); education was of borderline significance. Further supporting the distinction between AIDS and the FRP, we found that of the 34 AIDS cases occurring during the study period, 23 (68%) did not exhibit the FRP during the study period. Of the 32% who did exhibit the FRP during the
study period, 3 (9%) had an FRP prior to their first AIDS diagnosis (all within 6 months prior to the diagnosis) and 8 (23%) exhibited the FRP after their AIDS diagnosis.
In this study, both HIV infection and AIDS were predictors of frailty-like manifestations, and the duration of HIV infection was associated with the likelihood of these manifestations. The observed increases of FRP with low CD4 T-cell count and high HIV viral load, two biomarkers of HIV disease progression, suggest a common underlying biology between frailty and HIV disease. However, the presence of the FRP was far from automatic in men with HIV or AIDS. Finally, in this study, HIV infection for ≤4 years appeared to confer a rate of FRP comparable to that of HIV-uninfected men 10 years older, and this rate was further increased by 2- to 3-fold for men infected > 4 years and an additional 2-fold for men with AIDS.
Abstract
Background. Older healthy and HIV-infected adults exhibit physiological similarities. Frailty is a clinical syndrome associated with aging that identifies a subset of older adults at high risk of mortality and other outcomes. We investigated whether HIV infection increases the prevalence of a frailty-related phenotype (FRP) that approximates a clinical definition of frailty.
Methods. We first defined the FRP and assessed its prevalence among HIV-uninfected men followed in the Multicenter AIDS Cohort Study (MACS) between 1994 and 2004. Using repeated measurements logistic regression models, we then assessed the association between FRP and HIV infection before the era of highly active antiretroviral therapies, adjusting for covariates among HIV-uninfected (N = 1905) and incident HIV cases (N = 245).
Results. HIV infection was strongly associated with FRP prevalence. Compared to HIV-uninfected men of similar age, ethnicity and education, HIV-infected men were more likely to have the FRP for all durations of infection: for ≤4 years, the adjusted odds ratio (OR) was 3.38, with 95% confidence interval (CI), 1.25-9.11, and for 4.01-8 years and 8.01-12 years the corresponding figures were (OR = 12.95, 95% CI, 6.60-25.40) and (OR = 14.68, 95% CI, 7.60-28.35), respectively. The FRP prevalence for 55-year-old men infected with HIV for ≤4 years (3.4%; 95% CI, 1.3-8.6) was similar to that of uninfected men ≥65 years old (3.4%; 95% CI, 1.5-7.6).
Conclusion. In this cohort, HIV infection was associated with an earlier occurrence of a phenotype that resembles the phenotype of frailty in older adults without HIV infection. Studies of frailty in the setting of HIV infection may help to clarify the biological mechanism of frailty.
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