Frailty Predicts Recurrent but Not Single Falls 10 Years Later in HIV+

and HIV- Women

Anjali Sharma, Deborah Gustafson, Donald R Hoover, Qiuhu Shi, Michael W Plankey, Phyllis C Tien, Kathleen Weber, Michael T Yin:

The Women’s Interagency HIV Study (WIHS)

19th International Workshop on Co-morbidities and Adverse Drug Reactions in HIVMilan, Italy

October 23, 2017

Frailty• Geriatric syndrome characterized by diminished

strength, endurance, and reduced physiologic function

• Associated with adverse outcomes such as falls, fracture, disability, and death in elderly HIV-populations

• Among middle-aged HIV+ populations, frailty predicts:• Mortality among injection drug users• Mortality among women on ART• Frailty three years prior to ART initiation significantly

predicted subsequent AIDS or death among men

Fried LP, et al. The Journals of Gerontology Series, 2001; Ensrud KE, et al. Arch Intern Med 2008; Ensrud KE, et al. The Journals of Gerontology 2007; Piggott DA, et al. PloS One 2013; Gustafson DR, et al. BMJ open 2017; Desquilbet L, et al. The Journals of Gerontology 2011; High KP, et al. JAIDS 2012.

High Frequency of Falls Among Middle-Aged HIV+ and HIV- Women in the WIHS(N=1250 HIV+ and 566 HIV- Women)

41%

16%

25%

38%

6%

42%

18%

24%

45%

6%

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

50%

Any Fall Single Fall 2+ Fall Fall withinjury

Fall withfracture

HIV+HIV-

Sharma A, et al. Antiviral Therapy. 2017

Objectives

• To evaluate whether frailty status predicts risk of falls approximately 10 years later in HIV+ and HIV- women in WIHS

• To evaluate the contribution of individual components of frailty on subsequent risk of falls

Methods: Study Population (WIHS)

• Multicenter prospective cohort study of the progression of HIV infection in U.S. women

• Frailty assessed in 2005

• Falls reported every 6 months starting 2014

WIHS participants with FFI measured in 2005 and 4 falls questionnaires completed approximately 10 years later

2305 women enrolled in WIHS in 2005 (1634HIV+ and 671 HIV-)

2046 completed FFI assessments (1471 HIV+ and 571 HIV-)

283 Deaths, (252 HIV+ and 31#HIV-)661 Lost to follow-up, (424 HIV+ and 193 HIV-)

1146 Enrolled at WIHS visit 43 (794 HIV+ and 352 HIV-)

1055 completed all 4 falls questionnaires(729 HIV+ and 326 HIV- )

Definition of Frailty

• Fried Frailty Index (FFI) was measured in 2005• Frailty defined as presence of 3 or more of 5 :

1. Slow gait (3-4 m timed gait)*2. Reduced grip strength (dominant hand-held

dynamometer)*3. Physical exhaustion4. Unintentional weight loss (≥10 lb within 6 months)5. Low physical activity

*Defined by lowest quintile of HIV- womenFried LP, et al. The journals of gerontology Series A, Biological sciences and medical sciences. 2001

Ascertainment of Falls

• In 2014 (semiannual visit 40), all WIHS participants were asked to report any history of fall within the prior 6 months

• Participants reporting any fall were asked: ▫ If they had either “1” or “2 or more”▫ Whether any of these falls resulted in injury

for which they sought medical attention▫ Whether any of these falls resulted in fracture

Definition of Falls

“an unexpected event, including a slip or trip, in which you lost your balance and landed

on the floor, ground or lower level, or hit an object like a table or chair”

• Participants instructed to exclude▫ Falls that result from a major medical event▫ OR from an overwhelming external hazard

Lamb SE, et al. Prevention of Falls Network E, Outcomes Consensus G. Development of a common outcome data set for fall injury prevention trials: the Prevention of Falls Network Europe consensus. J Am Geriatr Soc 2005;53:1618-22.

Methods: Statistical Analyses• Logistic regression models were fit to determine risk

of single fall (vs. 0) over the 10-year follow-up▫ frailty and HIV status forced in

• Because associations with falls did not vary across visits, all four visits were pooled

• Covariates were measured at frailty visit (index visit)• A multivariable GEE model of independent

prediction of having single fall in the 6 months prior to each of the 4 visits pooled was fit using stepwise selection with SAS default criteria to enter and remain in the model

Methods: Statistical Analyses

• Recurrent falls: one fall at more than one visit, or 2 or more falls at any visit

• Models were fit for prediction of recurrent vs. 0-1 falls

• To evaluate the contribution of individual components of the FFI on 10-year fall risk, we next constructed models in which we allowed individual frailty components to enter using stepwise regression

• Models restricted to HIV+ women evaluated the contribution of measures of HIV disease- and treatment- specific characteristic on fall risk

Results• 729 HIV+ and 326 HIV- women• Median 9 years between the frailty and first falls

assessments• Single fall: 15% of HIV+ women and 18% of HIV-

women• Recurrent falls: 25% of HIV+ women and 21% of

HIV-women (overall p=0.20)• Among HIV+ women:

▫ 38% reported a prior AIDS▫ median CD4+ count was 462 cells/µl▫ 67% reported taking ART▫ 50% had suppressed HIV RNA viral load

Participant Characteristics HIV + (N=729) HIV- (N=326) P value

Age at index visit, years, median (IQR) 42 (36-48) 39 (31-46) <0.0001Education level high school or greater 473 (65%) 209 (64%) 0.83Annual Income ≥$12,000/yr 385 (54%) 188 (59%) 0.10Race 0.54

White 124 (17%) 47 (14%)Black 493 (68%) 230 (71%)Hispanic/Other 112 (15%) 49 (15%)

Marijuana use 0.0012Never 212 (29%) 77 (24%)Past 392 (54%) 162 (50%)Current 125 (17%) 87 (27%)

Hepatitis C Virus infection 148 (20%) 49 (15%) 0.042Diabetes Mellitus 102 (14%) 46 (14%) 0.95Hypertension 223 (31%) 96 (29%) 0.71Renal dysfunction (eGFR <60) 37 (5%) 3 (0.9%) 0.0011Depressive symptoms (modified CESD ≥15) 255 (35%) 103 (32%) 0.28Peripheral neuropathy 119 (16%) 21 (6%) <0.0001Obesity (≥30kg/m2) 274 (38%) 151 (47%) 0.0076Number of current CNS active medication types 0.0001

0 513 (70%) 270 (83%)1 128 (18%) 28 (9%)2 65 (9%) 17 (5%)≥3 23 (3%) 11 (3%)

Frailty and Falls Occurrence Among HIV+ and HIV- Women in WIHS

HIV + (N=729) HIV- (N=326) P value

Fall status during study 0.20

No fall 441 (61%) 200 (61%)

One fall 108 (15%) 59 (18%)

More than one fall 180 (25%) 67 (21%)

Frailty score 0.045

0-2 296 (91%) 630 (86%)

3-5 99 (14%) 30 (9%)

Components of Frailty Index

Slow gait 160 (25%) 66 (22%) 0.32

Reduced grip strength 178 (28%) 57 (19%) 0.0025

Physical exhaustion 210 (29%) 64 (20%) 0.0019

Unintentional weight loss 101 (14%) 23 (7%) 0.0015

Low physical activity 168 (23%) 66 (21%) 0.33

Characteristics Associated with Single and Recurrent FallsNo Fall

(N=641) One Fall(N=167)

Two+ Falls(N=247)

P-value

HIV status 0.20

HIV-uninfected (N=326) 200 (61%) 59 (18%) 67 (21%)

HIV-infected (N=729) 441 (61%) 108 (15%) 180 (25%)

Age, yrs, median (IQR) 40 (33-45) 41 (35-48) 44 (38-50) <0.0001Race <0.0001

African American (N=723) 465 (64%) 90 (12%) 168 (23%)Hispanic/Other (N=161) 90 (56%) 44 (27%) 27 (17%)Caucasian (N=171) 86 (50%) 33 (19%) 52 (30%)

Annual income ≥$12,000 (N=573) 359 (63%) 100 (18%) 114 (20%) 0.005

Smoking status 0.0003Never (N=314) 222 (71%) 41 (13%) 51 (16%)Former (N=249) 137 (55%) 49 (20%) 63 (25%)Current (N=492) 282 (57%) 77 (16%) 133 (27%)

Marijuana use <0.0001Never (N=289) 211 (73%) 33 (11%) 45 (16%)Former (N=554) 319 (58%) 91 (16%) 144 (26%)Current (N=212) 111 (52%) 43 (20%) 58 (27%)

Obesity (BMI ≥30 kg/m2) (N =425) 244 (57%) 63 (15%) 118 (28%) 0.03Hepatitis C Virus positive (N=197) 91 (46%) 36 (18%) 70 (36%) <0.0001Peripheral neuropathy (N=140) 54 (39%) 28 (20%) 58 (41%) <0.0001Hypertension (N=319) 161 (50%) 58 (18%) 100 (31%) <0.0001

Association of FFI and Frailty Components with Single and Recurrent Falls

No Fall (N=641)

One Fall(N=167)

Two+ Falls(N=247)

P-value

Frailty Status <0.0001

Non-frail (FFI score 0-2), (N=926) 587 (66%) 148 (17%) 191 (22%)

Frail (FFI score 3-5), (N=129) 54 (42%) 19 (15%) 56 (43%)

Components of Frailty Index

Slow gait (N=226) 127 (56%) 29 (13%) 70 (31%) 0.01

Reduced grip strength (N=235) 133 (57%) 48 (20%) 54 (23%) 0.04

Physical exhaustion (N=274) 127 (46%) 38 (14%) 109 (40%) <0.0001

Unintentional weight loss (N=124) 49 (40%) 28 (23%) 47 (38%) <0.0001

Low physical activity (N=234) 116 (50%) 35 (15%) 83 (35%) <0.0001

Frailty Score and Other Factors Associated with Falls Single (vs. 0) Falls Recurrent (vs. 0-1) Falls

Adjusted Odds Ratio

95% CI P value Adjusted Odds Ratio

95% CI P value

HIV Positive 0.85 0.58 - 1.27 0.43 0.93 0.65 - 1.34 0.71

Frailty 0.93 0.50 - 1.75 0.83 1.66 1.06 - 2.61 0.03

Age (per 10 years) - - - 1.44 1.20 - 1.74 <.0001

Race (ref=White)

Black 0.52 0.32 - 0.86 0.01 0.74 0.49 - 1.14 0.17

Hispanic/Other 1.45 0.81 - 2.62 0.21 0.42 0.23 - 0.76 0.004

Income ≥$12,000/yr - - - 0.61 0.44 - 0.84 0.003

Marijuana use (ref=never)

Former 1.71 1.06 - 2.74 0.03 - -

Current 2.43 1.38 - 4.25 0.002 - -

Hypertension 1.72 1.15 - 2.57 0.009 - -

Neuropathy 2.02 1.17 - 3.49 0.01 1.93 1.26 - 2.95 0.003

Obesity - - 1.46 1.06 - 2.02 0.02

CNS active medication classes used - - 1.42 1.17 - 1.73 0.0004

Adjusted for study site

Frailty Components Associated with FallsSingle (vs. 0) Falls Recurrent (vs. 0-1) Falls

Adjusted Odds Ratio

95% CI P value Adjusted Odds Ratio

95% CI P value

HIV Positive 0.90 0.59-1.39 0.64 0.79 0.54-1.16 0.23

Slow gait - - - 1.50 1.01- 2.22 0.04

Physical exhaustion - - - 1.66 1.13 -2.46 0.01

Unintentional weight loss 2.31 1.28- 4.17 0.005 - -

Age (per 10 years) - - - 1.41 1.16- 1.71 0.0006

Race (ref=White)

Black 0.45 0.27-0.77 0.003 0.71 0.45-1.13 0.14

Hispanic/Other 1.15 0.61-2.16 0.67 0.42 0.22-0.79 0.007

Income ≥$12,000/yr - - - 0.62 0.44 -0.89 0.0085

Marijuana use (ref=never)

Former 1.65 0.99 -2.75 0.06 - - -

Current 2.20 1.20-4.01 0.01 - - -

Hypertension 1.63 1.05- 2.52 0.03 - - -

Neuropathy 1.89 1.05- 3.30 0.04 1.99 1.27- 3.11 0.0016

CNS active medication classes - - - 1.35 1.09 -1.67 0.0067

Summary• Among middle aged HIV+ and HIV- women, frailty

independently predicted recurrent falls 10 years later

• FFI components (exhaustion and slow gait) predicted greater risk of recurrent falls

• Frailty did not predict single falls 10 years later▫ unintentional weight loss predicted single falls

• Frequent occurrence of falls in the WIHS cohort• Neither HIV serostatus, nor HIV disease or treatment

related factors were associated with falls

Conclusions• As HIV+ women continue to age, early frailty

assessment is an important tool to identify women at risk of falling

• Fall prevention strategy for HIV+ women

• Importance of examining the construct of geriatric syndromes even at younger ages, particularly in relation to chronic HIV disease, which has been implicated in accelerated aging

Acknowledgements• Primary WIHS funding by NIAID• NIAMS K23AR06199301 (AS)• NIAID R01 AI095089 (MTY)• WIHS staff and participants