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

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1 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) 19 th International Workshop on Co-morbidities and Adverse Drug Reactions in HIV Milan, Italy October 23, 2017

2 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 HIVpopulations 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.

3 High Frequency of Falls Among Middle-Aged HIV+ and HIV- Women in the WIHS (N=1250 HIV+ and 566 HIV- Women) 50% 45% 40% 35% 30% 25% 20% 15% 10% 5% 0% 41% 42% 18% 16% 25% 24% 38% 45% Any Fall Single Fall 2+ Fall Fall with injury Sharma A, et al. Antiviral Therapy % 6% Fall with fracture HIV+ HIV-

4 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

5 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

6 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- )

7 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 exhaustion 4. Unintentional weight loss ( 10 lb within 6 months) 5. Low physical activity *Defined by lowest quintile of HIV- women Fried LP, et al. The journals of gerontology Series A, Biological sciences and medical sciences. 2001

8 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

9 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:

10 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

11 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

12 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 HIVwomen 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

13 Participant Characteristics HIV + (N=729) HIV- (N=326) P value Age at index visit, years, median (IQR) 42 (36-48) 39 (31-46) < Education level high school or greater 473 (65%) 209 (64%) 0.83 Annual Income $12,000/yr 385 (54%) 188 (59%) 0.10 Race 0.54 White 124 (17%) 47 (14%) Black 493 (68%) 230 (71%) Hispanic/Other 112 (15%) 49 (15%) Marijuana use Never 212 (29%) 77 (24%) Past 392 (54%) 162 (50%) Current 125 (17%) 87 (27%) Hepatitis C Virus infection 148 (20%) 49 (15%) Diabetes Mellitus 102 (14%) 46 (14%) 0.95 Hypertension 223 (31%) 96 (29%) 0.71 Renal dysfunction (egfr <60) 37 (5%) 3 (0.9%) Depressive symptoms (modified CESD 15) 255 (35%) 103 (32%) 0.28 Peripheral neuropathy 119 (16%) 21 (6%) < Obesity ( 30kg/m 2 ) 274 (38%) 151 (47%) Number of current CNS active medication types (70%) 270 (83%) (18%) 28 (9%) 2 65 (9%) 17 (5%) 3 23 (3%) 11 (3%)

14 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 (91%) 630 (86%) (14%) 30 (9%) Components of Frailty Index Slow gait 160 (25%) 66 (22%) 0.32 Reduced grip strength 178 (28%) 57 (19%) Physical exhaustion 210 (29%) 64 (20%) Unintentional weight loss 101 (14%) 23 (7%) Low physical activity 168 (23%) 66 (21%) 0.33

15 Characteristics Associated with Single and Recurrent Falls No 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) < Race < 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%) Smoking status Never (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 < Never (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/m 2 ) (N =425) 244 (57%) 63 (15%) 118 (28%) 0.03 Hepatitis C Virus positive (N=197) 91 (46%) 36 (18%) 70 (36%) < Peripheral neuropathy (N=140) 54 (39%) 28 (20%) 58 (41%) < Hypertension (N=319) 161 (50%) 58 (18%) 100 (31%) <0.0001

16 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 < 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%) < Unintentional weight loss (N=124) 49 (40%) 28 (23%) 47 (38%) < Low physical activity (N=234) 116 (50%) 35 (15%) 83 (35%) <0.0001

17 Frailty Score and Other Factors Associated with Falls Adjusted Odds Ratio Single (vs. 0) Falls 95% CI P value Adjusted Odds Ratio Recurrent (vs. 0-1) Falls 95% CI P value HIV Positive Frailty Age (per 10 years) <.0001 Race (ref=white) Black Hispanic/Other Income $12,000/yr Marijuana use (ref=never) Former Current Hypertension Neuropathy Obesity CNS active medication classes used Adjusted for study site

18 Frailty Components Associated with Falls Adjusted Odds Ratio Single (vs. 0) Falls 95% CI P value Adjusted Odds Ratio Recurrent (vs. 0-1) Falls 95% CI P value HIV Positive Slow gait Physical exhaustion Unintentional weight loss Age (per 10 years) Race (ref=white) Black Hispanic/Other Income $12,000/yr Marijuana use (ref=never) Former Current Hypertension Neuropathy CNS active medication classes

19 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

20 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

21 Acknowledgements Primary WIHS funding by NIAID NIAMS K23AR (AS) NIAID R01 AI (MTY) WIHS staff and participants