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Published in final edited form as:

Behav Med. 2019 ; 45(3): 210–220. doi:10.1080/08964289.2018.1509053.

Psychosocial Correlates of Frailty Among HIV-Infected and HIV-

Uninfected Adults
Anna A. Rubtsova1, María J. Marquine2,6,7, Colin Depp2,6, Marcia Holstad3, Ronald J.
Ellis4,7, Scott Letendre5,7, Dilip V. Jeste2,4,6, David J. Moore2,7
1Department of Behavioral Sciences and Health Education, Emory University Rollins School of
Public Health, Atlanta, GA
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2Department of Psychiatry, University of California, San Diego, CA

3Emory University Nell Hodgson Woodruff School of Nursing, Atlanta, GA
4Department of Neuroscience, University of California, San Diego, CA
5Department of Medicine, University of California, San Diego, CA
6Sam and Rose Stein Institute for Research on Aging, University of California, San Diego, CA
7HIV Neurobehavioral Research Program, University of California, San Diego

Abstract
Frailty is a geriatric condition characterized by increased vulnerability to physical impairments
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and limitations that may lead to disabilities and mortality. Although studies in the general
population suggest that psychosocial factors affect frailty, less is known about whether similar
associations exist among people living with HIV (PLWH). The purpose of this study was to
examine psychosocial correlates of frailty among PLWH and HIV-uninfected adults. Our sample
included 127 adults (51% PLWH) participating in the Multi-Dimensional Successful Aging among
HIV-Infected Adults study at the University of California San Diego (average age 51 years, 80%
male, 53% White). Frailty was assessed via the Fried Frailty Index. Psychosocial variables
significant in bivariate models were included in principal component analysis to generate factor
variables summarizing psychosocial correlates. Multivariate logistic regression models were fit to

Corresponding author: Anna Rubtsova, PhD, MA, MSc, Assistant Research Professor, Department of Behavioral Sciences and
Health Education, Emory University, 1518 Clifton Rd, Atlanta, GA 30322, Phone: 404-727-9729, [email protected]. Alternate
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corresponding author: David J. Moore, PhD, Associate Professor of Psychiatry, University of California, San Diego, HIV
Neurobehavioral Research Program, 220 Dickinson Street, Suite B (8231), San Diego, CA 92103, Phone: 619-543-5093,
[email protected].
Colin A. Depp, Ph.D., Associate Professor, Department of Psychiatry, University of California, San Diego, 9500 Gilman Drive, La
Jolla, CA 92093-0664, Phone: 858-822-4251, [email protected]
Ronald J. Ellis, MD, PhD, Professor of Neurosciences, University of California, San Diego, 200 W. Arbor Drive #8231, San Diego,
CA 92103-8231, Phone: 619-543—3500, [email protected]
Dilip V. Jeste, M.D., Senior Associate Dean for Healthy Aging and Senior Care, Estelle and Edgar Levi Chair in Aging, Distinguished
Professor of Psychiatry and Neurosciences , Director, Sam and Rose Stein Institute for Research on Aging, University of California,
San Diego, 9500 Gilman Drive #0664, San Diego, California 92093, Phone: (858) 534-4020, [email protected]
María J. Marquine, Ph.D., Assistant Professor, Department of Psychiatry, University of California, San Diego, 9500 Gilman Drive, La
Jolla, CA 92093-0664, Phone: 858-534-6748, [email protected]
Marcia McDonnell Holstad, PhD, FNP-BC, FAANP, FAAN, Professor, Marcia Stanhope Professor in Public Health, Nell Hodgson
Woodruff School of Nursing, Emory University, Phone: 404-727-1307, [email protected]
Scott Letendre, M.D., Professor of Medicine and Psychiatry, University of California, San Diego, 220 Dickinson Street, Suite A, San
Diego, California 92103, Phone: 619-543-8080, [email protected]
 Rubtsova et al. Page 2

examine the independent effects of factor variables and their interaction terms with HIV status. In
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bivariate models, frailty was associated with multiple psychosocial variables, e.g. grit, optimism,
personal mastery, social support, emotional support. Factor analysis revealed that psychosocial
variables loaded on two factors – Positive Resources/Outlook and Support by Others. The
multivariate model showed significant main effects of Support by Others and HIV status, and
interactive effects HIV X Positive Resources/Outlook, such that Positive Resources/Outlook was
negatively associated with frailty for PLWH but not for HIV-uninfected individuals. These
analyses indicate that psychosocial factors may be associated with frailty among PLWH. Positive
resources and outlook may play a role in frailty prevention. Future longitudinal studies are needed
to establish causal links.

Keywords
Successful aging; AIDS; grit; optimism; social support
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Introduction
Even though advances in antiretroviral therapy (ART) contribute to increasing longevity,1
aging people living with HIV (PLWH) experience greater morbidity and age-related
complications than otherwise comparable HIV-uninfected adults.2,3 One of the geriatric
syndromes that may be exacerbated by HIV infection is frailty, defined as a state of
vulnerability that puts an individual at increased risk of adverse clinical outcomes when
faced with internal or external stressors.4–7 A recent study among participants in the Multi-
Center AIDS Cohort Study (MACS) found 12% frailty prevalence among HIV-infected men
versus 9% among HIV-uninfected men (median age 53.8, IQR=47.6, 61.3).8 Similarly,
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frailty prevalence among women participating in the Women’s Interagency HIV Study
(WIHS) was 17% among the HIV-infected and 10% among the HIV-uninfected (average age
39 years).5,9 Moreover, studies suggest that PLWH experience earlier onset and higher
prevalence of frailty when compared to their HIV-uninfected counterparts.2,6,9–11 Research
among PLWH shows that frailty is associated with increased likelihood of falls,12,13
hospitalizations,14 disability,15 and mortality.7,16 Given the increased frailty prevalence and
its adverse effects among PLWH, it is important to understand factors associated with frailty
in this population.

To date, little is known about psychosocial correlates of frailty among PLWH. The existing
research has mostly focused on biomedical and sociodemographic predictors and correlates
of frailty. Thus, the presence of frailty in the era of combination ART (cART) was found to
be associated, though somewhat inconsistently, with greater age, female gender, lower
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education, non-Hispanic Black ethnicity, and low annual income by both cross-sectional and
longitudinal studies.6,17,18 Other frailty predictors include HIV disease characteristics, such
as low CD4 cell count or AIDS diagnosis,5,19,20 as well as the presence of inflammatory
markers (e.g., c-reactive protein),2 and medical comorbidities, such as psychiatric disease,
neurocognitive impairment, chronic kidney disease, hypertension, and diabetes mellitus.5,6
Additionally, research examined the effects of several lifestyle risk factors on frailty among

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PLWH, including protective effects of physical activity and low to moderate drinking, and
detrimental effects of smoking and drug use.5,17,18
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Even though many predictors and correlates of frailty have been identified, relatively little is
known about psychosocial factors associated with frailty among PLWH. Research among
those without HIV shows that frailty may be connected to multiple psychosocial factors,
such as wellbeing, positive affect, perceived control, resilience, social support, and
emotional support.21–26 For example, a recent cross-sectional study by Freitag and
Schmidt24 examined multiple psychosocial correlates of frailty in a sample of community-
dwelling older adults and found that higher frailty was associated with greater depressive
symptomatology and lower resilience. Importantly, a number of longitudinal observational
studies revealed that increases in frailty observed at study follow-up were associated with
greater baseline levels of negative affect27 and depressive symptomatology25,28,29 as well as
lower baseline levels of positive affect,22 personal mastery,30 and perceived social support.25
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Therefore, the overall goal of this study is to assess the association between multiple
psychosocial factors and the frailty phenotype as measured by the Fried Frailty Index (FFI)
among PLWH. The FFI classifies individuals into three categories – robust, pre-frail, and
frail – based on the criteria of weakness, slowness, physical exhaustion, low physical
activity, and unintended weight loss.31 More specifically, the purpose of this research was
among PLWH and HIV-uninfected adults: 1) to assess psychosocial correlates of frailty; 2)
to explore whether psychosocial variables associated with frailty have an underlying
structure such that they can be reduced to several summary factor variables, and 3) to
evaluate whether the effects of psychosocial variables on frailty differ by HIV status. Based
on research in the general population reviewed above, we hypothesize that frailty will be
associated with: 1) higher levels of negative psychosocial factors, such as stress and
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depression, and 2) lower levels of positive psychosocial factors, such as grit and optimism.
In the view of studies suggesting that aging PLWH are more likely to experience negative
psychosocial factors as compared to HIV-uninfected counterparts,32 we also expect that
psychosocial factors will interact with HIV status in such a way that their association with
frailty will be stronger for PLWH.

Methods
Study sample
Data were collected as part of the NIMH-funded Multi-Dimensional Successful Aging
among HIV Infected Adults Study at University of California, San Diego (UCSD), which is
described in an earlier publication.33 Briefly, the study recruited community-dwelling
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PLWH and HIV-uninfected adults 35 to 65 years old. The exclusion criteria were: 1) history
of psychotic disorder or a mood disorder with psychotic features; 2) the presence of a
neurological condition not related to HIV infection and known to affect cognitive
functioning, such as Alzheimer’s disease, stroke or traumatic brain injury; and 3) having a
positive urine toxicology test for drugs of abuse during the baseline visit. During the
screening, participants with unknown HIV status were tested with the HIV/HCV finger stick
point of care test (Abbott Real-time HIV-1 test, Abbott Laboratories, Illinois, USA).
Participants were compensated for participation. The UCSD Institutional Review Board

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approved the study and participants provided written informed consent to participate. The
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sample for the present cross-sectional analyses is based on biomedical and psychosocial data
from the baseline visit and includes 65 PLWH and 62 HIV-uninfected participants who were
administered frailty assessment.1

Primary outcome
Frailty was measured using the FFI criteria.31 Participants’ level of slowness and weakness
was assessed, objectively, by gait speed (15 feet walk time) and grip strength tests. The three
remaining criteria were evaluated by self-reports. Thus, unintentional weight loss was
measured as a “Yes” to a question whether participant unintentionally lost more than 10
pounds in a previous year. Low physical activity was defined as expending less than 383
kilocalories per week for males and less than 270 kilocalories per week for females and
measured by the International Physical Activity Questionnaire (IPAC).34 Exhaustion during
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the past week was evaluated as “Occasionally or a moderate amount of time” or “All of the
time” answers to the two following questions from the CES-D scale:35 “I felt that everything
I did was an effort” and “I could not ‘get going.’” Pre-frailty was defined as the presence of
one or two of the FFI criteria, frailty – as three or more of these criteria. Since only 8.7%
(N=11) participants in our sample were frail whereas 41.7% (N=53) were prefrail, for our
primary analyses, we collapsed frail and prefrail into a “frail” category and others were
categorized as “robust.” In secondary analyses, we also considered a categorical variable
with robust, prefrail, and frail categories.

Psychosocial exposures
The psychosocial factors were assessed by standardized validated scales. Several Likert-type
instruments evaluated positive psychological constructs. Resilience was measured by the
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Connor Davidson Resilience Scale – 10 Item (CD-RISC-10)36,37 and included items such as
“I am not easily discouraged by failure” rated from 1 (not true at all) to 5 (true nearly all the
time). To measure optimism, a six-item Lifetime Orientation Test-Revised (LOT-R)38,39
scale was used. The items on this scale ranged from 1 (strongly disagree) to 5 (strongly
agree) and included statements like “Overall, I expect more good things to happen to me
than bad.” Grit was assessed using the Grit Scale,40 which included 12 items (e.g., “I am
diligent”), ranging from 1 (very much like me) to 5 (not at all like me). Personal mastery
was measured by a 7-item Pearlin-Schooler Personal Mastery Scale (PMS),41 where
responses to questions like “I have little control over the things that happen to me” ranged
from 1 (strongly agree) to 4 (strongly disagree). To assess participants’ degree of
religiousness, we used three-subscale sum from the Brief Multidimensional Measure of
Religiousness/Spirituality42 (e.g., “To what extent do you consider yourself a spiritual
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person?”), with lower scores representing greater religiosity/spirituality. We assessed life

satisfaction by a 5-item Satisfaction with Life Scale43 (e.g., “The conditions of my life are
excellent”), which ranges from 1 (not at all true) to 7 (absolutely true). Additionally, we used
the following two items to evaluate self-rated successful aging:44 “Using your own

1The frailty assessment was introduced after the study began and was administered to all participants enrolled after the introduction of
this measure. We observed no statistically significant demographic differences among the participants who received the frailty
assessment and those who did not, except for in race/ethnicity: the percentage of nonwhite participants was higher among those who
received the frailty assessment than among those who did not (47.2% v. 27.7%, p=0.003).

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definition, where would you rate yourself in terms of “successful aging?” (from 1 “least
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successful” to 10 “most successful”) and “How old/young do you feel? (Please write a
specific age).”

We also included several measures of interpersonal psychosocial factors. To measure social

support, we used a four-item social interaction sub-scale of Duke Social Support Index
(DSSI),45 which has items like “About how often did you go to meetings of clubs, religious
meetings, or other groups that you belong to in the past week?” ranging from 0 (none) to 7
(seven or more times). Emotional Support Scale (ESS)46 was used to assess support by
others in the three following domains: emotional support (e.g., “How often do your spouse,
children, close friends and/or relatives make you feel loved and cared for?”), instrumental
support (e.g., “How often do your spouse, children, close friends and/or relatives help with
daily tasks like shopping, giving you a ride, or helping you with household tasks?”), and
negative interactions with others (e.g., “How often are your spouse, children, close friends
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and/or relatives critical of what you do?”).

Lastly, we assessed participants’ emotional functioning by several well-known scales. Thus,

depression was measured using the Center for Epidemiologic Studies Depression Scale
(CESD),35 whereas participants’ level of stress was evaluated by the Perceived Stress Scale
(PSS).47 For each of the individual scales described above, we computed a separate
assessment summary score that we used in our analyses.

Covariates
As potential covariates, we considered multiple sociodemographic and biomedical variables
identified by the literature as predictors of frailty and available in our dataset. Potentially
confounding sociodemographic factors included continuous age, gender, race/ethnicity
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(Black, White, Hispanic, other), and years of education. We also considered a number of
comorbidities coded as dichotomous variables – i.e., hepatitis C infection, diabetes mellitus,
hypertension, hyperlipidemia, any cancer, ever smoking, chronic pulmonary disease, lifetime
diagnosis of substance use disorder, and lifetime diagnosis of alcohol use disorder. Lastly,
we considered the following HIV disease characteristics: current CD4 cell count, nadir CD4,
undetectable plasma HIV viral load, AIDS diagnosis, and an estimated duration of HIV
disease. Those variables that were at least marginally associated with frailty (p<=0.1) were
included in our adjusted and multivariate models.

Statistical analyses
All statistical analyses were conducted using Stata 14 software. First, descriptive statistics
were calculated to examine the sample distributions; based on the assumption of normal
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distribution, chi-square tests for dichotomous and t-tests for continuous variables were
performed to determine the differences between the HIV serostatus groups. Second,
bivariate logistic regression models were fit to estimate crude odds ratios and 95%
confidence intervals for associations between psychosocial exposures and frailty. These
models were adjusted as the next step by including biomedical and sociodemographic
covariates as described above. Third, all psychosocial variables significantly associated with
frailty in the adjusted models, were included in principal component analysis (PCA) with

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varimax orthogonal rotation to generate factor variables summarizing psychosocial effects.

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We used the Kaiser-Meyer-Olkin measure of sampling adequacy and Bartlett’s test of

sphericity to check the appropriateness of PCA use. PCA automatically retains components
with eigenvalues greater than 1. For those components retained in the analyses, factor scores
were obtained using Stata predict command. The resulting summary factor variables
represent the linear composites formed by standardizing psychosocial variables included in
PCA, weighing them with factor score coefficients, and summing for each factor.48 Next,
multivariate logistic regression models on frailty were fit to examine the independent effects
of factor variables generated through PCA as well as their interaction terms with HIV status.
The interactive effects were further explored through HIV-stratified analyses. Lastly, we
repeated the multivariate models for a 3-level (robust, prefrail, and frail) categorical outcome
variable, using multinomial logistic regression. Since these models showed patterns of
results similar to those by logistic regression described above and the Wald test for
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combining outcome categories performed after the multinomial regression showed that frail
and prefrail categories can be combined, we report results only for our primary dichotomous
outcome variable, which combines prefrail and frail categories. All our analyses were based
on non-missing data, so the number of observations in various models varied from 117 to
127.

Results
Characteristics of participants
The clinical and demographic characteristics of our participants by HIV status are presented
in Table 1. Mean age was 50.1 (SD=8.9, range: 35-65) for PLWH and 51.0 (SD=7.7, range:
38-65) for HIV-uninfected participants. A majority of the participants in our sample were
men. While there were no group differences in age and sex, when compared to HIV-
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uninfected counterparts, PLWH had fewer years of education and a lower proportion of them
were White. We also found significant group differences in frailty and comorbidities
prevalence. In comparison to the HIV-uninfected individuals in our sample, significantly
higher proportions of PLWH were frail or prefrail (67.7% v. 32.3%), had hypertension
(44.6% v. 16.1%), malignancy (9.2% v. 0%), ever smoked (44.6% v. 12.9%), or were
diagnosed with lifetime alcohol use disorder (50% v. 33.3%). Lastly, the estimated mean
HIV disease duration in our sample was 15.3 years and HIV disease was relatively well-
controlled, with median CD4 count of 637 cells/mL (IQR= 480-855), 68.3% of PLWH
having undetectable plasma viral load, and 43.1% having no history of AIDS.

Bivariate logistic regression models

Out of 14 psychosocial factors tested, 11 were significantly associated with frailty in the
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unadjusted bivariate models (Table 2). When adjusting for covariates (age, HIV status, ever
smoking, hypertension, and hyperlipidemia), 9 out of 11 variables retained statistical
significance. The adjusted analyses showed that positive psychosocial factors significantly
reduced the odds of frailty in our combined sample. For example, an increase in one scale-
point on participants’ optimism score, resulted in a 12% reduction in the odds of frailty
(95% CI=0.80-0.96). The following factors reduced the risk of frailty: higher grit score
(aOR=0.44, 95% CI=0.21-0.95), higher personal mastery score (aOR=0.87, 95%

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CI=0.78-0.96), higher successful aging score (aOR=0.7, 95% CI=0.55-0.88), higher

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emotional support score (aOR=0.4, 95% CI=0.18-0.72), and higher Duke social support
index scores (aOR=0.60, 95% CI=0.44-0.82). In contrast, negative psychosocial factors such
as higher depression score (aOR=1.13, 95% CI=1.06-1.22), higher perceived stress score
(aOR=1.09, 95% CI=1.02-1.16), and a greater number of negative interactions with others
(aOR=2.36, 95% CI=1.37-4.07) significantly increased the odds of frailty in our sample. All
of these adjusted models were significant with p<0.01 and pseudo R2 ranging from 0.15 to
0.22.

Principal component analysis

The nine psychosocial variables significantly associated with frailty in the adjusted models
were further considered for inclusion in PCA. First, the nine variables showed high
intercorrelation (see Appendix 1) and internal consistency (Cronbach alpha=0.78). The
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Kaiser-Meyer-Olkin measure of sampling adequacy for the nine variables was 0.86, well
above the cut-off of 0.5 suggested in the literature,49 and Bartlett’s test of sphericity was
significant (chi2 (36)=433.86, p<0.001). We thus concluded that the use of the PCA was
appropriate.

The PCA with orthogonal (varimax) rotation yielded two factors with eigenvalues>1, which
together explained 59.6% of variance (Table 3). Factor 1, which explained 43.1% of
variance, was labeled “Positive Resources/Outlook” since it had high positive loadings on
grit, optimism, personal mastery, and successful aging; and high negative loadings on
depression, perceived stress, and negative interactions. Two remaining psychosocial
variables, emotional support and Duke social support index, had high loadings on Factor 2,
which was labelled “Support by Others” and explained 16.5% of variance. The PCA also
showed adequate communality among the included psychosocial variables. Only one
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variable (negative interactions with others) showed low communality of 0.2, and the rest of
them had a communality of 0.5 or higher. Since the loading of negative interactions on
Factor 1 was higher than the recommended cut-off of 0.4,50 it was retained in the analysis.
Thus, composite scores for Factor 1 (Positive Resources/Outlook) and Factor 2 (Support by
Others) were created based on the nine psychosocial variables as the last step.

Multivariate logistic regression models

Both Factor 1 (Positive Resources/Outlook) and Factor 2 (Support by Others) were included
in multivariate logistic regression models presented in Table 4. Model 1 also included the
interaction terms of Factor 1 and Factor 2 with HIV status. This model showed significant
main effects of Factor 2 (aOR=0.3, 95% CI=0.12-0.77) and HIV status (aOR=3.4, 95%
CI=1.23-9.37), as well as interactive effects between HIV status and Factor 1 (aOR=0.23,
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95% CI=0.06-0.87). The model was significant with p=0.001 and pseudo R2=0.30. The post-
regression diagnostics were conducted, including tests for multicollinearity, model fit, and
specification error. No problems were identified.

The interactive effects of HIV-status X Factor 1 are further illustrated by Figure 1, which
shows that Positive Resources/Outlook was more strongly associated with reduced odds of
frailty for the PLWH than for the HIV-uninfected participants. These synergistic effects were

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further explored through HIV-stratified analyses (Models 2-4, Table 4). Models 2 and 3
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showed that Factor 1 was associated with reduced odds of frailty among PLWH (aOR=0.23,
95% CI=0.1-0.56) but not among the HIV-uninfected participants (aOR=1.06, 95%
CI=0.44-2.52). These models also suggested that Factor 2 (Support by Others) was
negatively associated with frailty irrespective of HIV status: it was significant among the
HIV-uninfected participants (aOR=0.31, 95% CI=0.12-0.81) and approached significance
among PLWH (aOR=0.53, 95% CI=0.27-1.01). Lastly, Model 4 repeated the analyses in
Model 3 with inclusion of an HIV-disease characteristic (nadir CD4). Factor 1 (Positive
Resources/Outlook) retained its significance in this last model.

Discussion
Our study represents one of the first efforts to examine psychosocial correlates of frailty
among PLWH. The existing research identified multiple biomedical and sociodemographic
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factors associated with frailty among PLWH but little is known about psychosocial
correlates of frailty among this population.2,6,9–11 Our findings indicate that positive
psychosocial factors reduce the risk of frailty and negative psychosocial factors increase the
risk of frailty among PLWH and HIV-uninfected adults. Additionally, our results revealed
that the associations of psychosocial factors with frailty may differ by HIV status. Thus,
empirically-derived psychosocial factors related to Positive Resources/Outlook reduced the
likelihood of frailty for PLWH but not for HIV-uninfected adults, whereas Support by Others
was inversely associated with frailty irrespective of HIV status. Below, we discuss these
findings in greater detail.

Multiple psychosocial factors were significantly associated with frailty in our bivariate
analyses using a combined sample. Similar to research in the general population, 21–26 we
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found that higher levels of positive psychosocial factors, such as grit, optimism, personal
mastery, or social support, lowered the odds of frailty. In contrast, higher levels of negative
psychosocial factors, such as perceived stress, depression, or negative interactions, increased
the odds of frailty. Contrary to the existing research,24 we found that resilience and life
satisfaction reduced the likelihood of frailty in unadjusted but not adjusted analyses, which
may be due to our somewhat limited sample size. We also found no statistically significant
effects of religiosity on frailty. Based on the existing literature,51 however, we hypothesize
that religiosity may have an indirect effect on frailty via increasing individuals’ wellbeing,
which shall be explored by future research.

Through exploratory factor analysis (PCA), we also found that the numerous psychosocial
variables that were associated with frailty in bivariate analyses could be reduced to two
composite scores – Factor 1 (Positive Resources/Outlook) and Factor 2 (Support by Others).
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Factor 2 received its name since it had high positive loadings on social support and
emotional support variables. We further conceptualized Factor 1 as positive outlook and
resources since it had high positive loadings on grit, optimism, personal mastery, and
successful aging, and high negative loadings on depression, stress, and negative interactions
with others. It has been noted in the literature that such positive characteristics as grit,
optimism, a sense of mastery or personal control, and few conflictual relationships represent
psychosocial resources unequally distributed among social classes.52 Research suggests that

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lower socio-economic status (SES) is associated with higher likelihood of conflictual

relationships and lower scores on grit, optimism, and personal mastery.52–54 Conversely,
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availability of psychosocial resources is closely related to a more positive outlook,

wellbeing, and better mental health outcomes, such as decreased stress and depression.52
Given the above considerations, Factor 1 was termed as Positive Resources & Outlook.
Future research is needed to further refine this concept and to understand the additional
elements that may influence our identified factor structure. Moreover, this is one of the first
studies that simultaneously considered multiple psychosocial correlates of frailty and
examined factor variables summarizing psychosocial effects, and used this approach
specifically among PLWH. Future studies will examine whether psychosocial factors
associated with frailty have a similar underlying structure in other samples and populations.

The multivariate analyses further revealed that Support by Others was negatively associated
with frailty irrespective of HIV status, while Positive Resources & Outlook reduced the odds
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of frailty for PLWH but not for HIV-uninfected individuals. The significant findings for
Support by Others across HIV status groups are not surprising given the existing research
linking social and/or emotional support to improved health outcomes among PLWH46 and to
the decreased frailty among the general population.22,25 The differential effects of Positive
Resources & Outlook are best understood within the context of research showing that PLWH
and HIV-uninfected adults may experience different sets of psychosocial exposures. In
particular, PLWH as a group are known to face greater levels of adversity than HIV-
uninfected counterparts.32 Perhaps, given this amplified adversity, even small increases in
positive outlook and resources may have stronger associations with decreased frailty for
PLWH as compared to HIV-uninfected individuals.

Lastly, it is important to note that our findings should be understood within the context of
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social class or SES, which in the US maintains intersectionality with gender and race,55 and
can underlie multiple issues in HIV. Research suggests that, among PLWH in the cART era
as well as HIV-uninfected adults, higher frailty may be associated with lower SES (e.g.
fewer years of education, lower income) and related disadvantaged social statuses (e.g., non-
Hispanic Black ethnicity, and female gender).6,17,18 The possible mechanisms for these
sociodemographic differences in frailty can be decreased access to care, housing, and
transportation, as well as the increased levels of food insecurity and stress associated with
low SES. Moreover, as noted above, the psychosocial resources allowing to cope with stress
and adversity may also be unequally distributed among the social classes. Our sample had
relatively high SES, as measured by years of education (M=14.4, SD=2.4) and prevalence of
male gender and White race/ethnicity. We hypothesize that among PLWH with lower SES,
frailty will be not only more prevalent than in our sample but it may be associated with
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different psychosocial effects – whereas positive psychosocial resources may be less

prevalent in lower SES samples, the increase in optimism, grit, and personal mastery scores
may have stronger effects on frailty reduction.

Limitations
Our analyses had several important limitations. First, with mean age of 51 (35 to 65 range),
our sample was relatively young. Examining frailty in this age range is not uncommon for

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research among PLWH.5 In fact, due to the earlier onset of frailty among PLWH, multiple
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studies of frailty among this population had samples with a mean and/or median age well
below 50 years old.5,11,20,56 This younger mean age, however, may be the root of our
relatively low frailty (FFI 3-5) prevalence of 8.7% (N=11) in our combined sample. Given
the low frailty prevalence, and in order to have sufficient numbers for our analyses, we chose
to combine frail and prefrail categories for our primary analyses. Additional limitations were
a cross-sectional nature of our data, somewhat small sample size and missing data for some
variables; although our overall level of missingness was low. Future studies may consider
using larger longitudinal samples to examine the effects of psychosocial variables on frailty
across the life-course.

A further limitation of this study is that our findings may not generalize to other populations
of PLWH. Our sample had high proportions of men (80%) and Whites (53%) residing in the
greater San Diego area of California and may not be applicable to other demographic
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groups, such as women, racial/ethnic minorities, or rural populations. In particular, it is not

clear whether and how our results would be applicable to HIV-infected women, since they
are demographically different from HIV-infected men and are disproportionately African
American. 57 Future studies will be necessary to examine psychosocial correlates of frailty
among specific sub-populations of PLWH.

Conclusions
Despite these limitations, this study represents an essential first step towards our
understanding of psychosocial factors related to frailty among PLWH. Importantly, our
findings indicate that psychosocial factors related to positive outlook and psychosocial
resources are associated with reduced likelihood of frailty among PLWH. Given the cross-
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sectional nature of our research, we cannot yet make inferences about the directionality of
relationship between the psychosocial factors and frailty among this population.
Nevertheless, the existing longitudinal research among those without HIV25,28,29 shows that
higher levels of negative psychosocial factors and lower levels of positive psychosocial
factors during the baseline increased the odds of frailty incidence during the follow-up. We
therefore hypothesize that impaired psychosocial functioning may precede development of
frailty among PLWH and thus may play an important role in frailty prevention. We also
acknowledge that there may also be a reciprocal relationship between psychosocial factors
and frailty, such that psychosocial factors may affect the likelihood of frailty development
but, once emergent, frailty may result in the development of negative psychosocial factors,
such as stress, depression, and loneliness.

Our findings also have important clinical and research implications. Similar to previous
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research, this study shows that frailty and prefrailty are common and more prevalent among
PLWH than HIV-uninfected adults.6 Our novel results additionally suggest that negative
psychosocial factors, such as stress and depression, are associated with greater likelihood of
frailty, whereas positive psychosocial factors were tied to lower likelihood of frailty in
PLWH. Therefore, from a clinical perspective, screening for frailty, stress, and depression
are advisable among the aging PLWH. There are numerous therapies and interventions
available to clinicians, which have been shown to reduce stress and depression and enhance

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 Rubtsova et al. Page 11

wellbeing among PLWH: e.g., cognitive behavioral therapy,58 transcendental meditation,59

mindfulness-based therapies,60 as well as the antidepressants use.61 From a research
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perspective, psychological factors should be further examined and, perhaps, interventions

that enhance wellbeing and prevent frailty among PLWH should be designed. Future
research is needed to uncover the biological mechanisms underlying the association of
psychosocial factors with frailty.

Acknowledgements
The San Diego HIV Neurobehavioral Research Program group is affiliated with the University of California, San
Diego, the Naval Hospital, San Diego, and the Veterans Affairs San Diego Healthcare System, and includes:
Director: Robert K. Heaton, Ph.D., Co-Director: Igor Grant, M.D.; Associate Directors: J. Hampton Atkinson,
M.D., Ronald J. Ellis, M.D., Ph.D., and Scott Letendre, M.D.; Center Manager: Thomas D. Marcotte, Ph.D.;
Jennifer Marquie-Beck, M.P.H.; Melanie Sherman; Neuromedical Component: Ronald J. Ellis, M.D., Ph.D. (P.I.),
Scott Letendre, M.D., J. Allen McCutchan, M.D., Brookie Best, Pharm.D., Rachel Schrier, Ph.D., Debra Rosario,
M.P.H.; Neurobehavioral Component: Robert K. Heaton, Ph.D. (P.I.), J. Hampton Atkinson, M.D., Steven Paul
Author Manuscript

Woods, Psy.D., Thomas D. Marcotte, Ph.D., Mariana Cherner, Ph.D., David J. Moore, Ph.D., Matthew Dawson;
Neuroimaging Component: Christine Fennema-Notestine, Ph.D. (P.I.), Monte S. Buchsbaum, M.D., John
Hesselink, M.D., Sarah L. Archibald, M.A., Gregory Brown, Ph.D., Richard Buxton, Ph.D., Anders Dale, Ph.D.,
Thomas Liu, Ph.D.; Neurobiology Component: Eliezer Masliah, M.D. (P.I.), Cristian Achim, M.D., Ph.D.;
Neurovirology Component: David M. Smith, M.D. (P.I.), Douglas Richman, M.D.; International Component: J.
Allen McCutchan, M.D., (P.I.), Mariana Cherner, Ph.D.; Developmental Component: Cristian Achim, M.D., Ph.D.;
(P.I.), Stuart Lipton, M.D., Ph.D.; Participant Accrual and Retention Unit: J. Hampton Atkinson, M.D. (P.I.),
Jennifer Marquie-Beck, M.P.H.; Data Management and Information Systems Unit: Anthony C. Gamst, Ph.D. (P.I.),
Clint Cushman; Statistics Unit: Ian Abramson, Ph.D. (P.I.), Florin Vaida, Ph.D. (Co-PI), Reena Deutsch, Ph.D.,
Anya Umlauf, M.S.

The views expressed in this article are those of the authors and do not reflect the official policy or position of the
Department of the Navy, Department of Defense, nor the United States Government.

Funding

Supported by the Sustained Training in HIV and Aging (STAHR) training grant (R25 MH108389) and R01
MH099987.
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Appendix
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Appendix 1.

Correlation Matrix for Psychosocial Factors Included in PCA.

Grit Optimism Personal mastery Successful aging Depression score Perceived stress Negative interactions Emotional Support Duke social support
Grit 1.00
Rubtsova et al.

Optimism 0.60 1.00

Personal mastery 0.47 0.65 1.00
Successful aging 0.47 0.53 0.55 1.00
Depression score −0.49 −0.41 −0.46 −0.39 1.00
Perceived stress −0.59 −0.70 −0.76 −0.64 0.58 1.00
Negative interactions −0.21 −0.25 −0.24 −0.17 0.22 0.36 1.00
Emotional support 0.15 0.33 0.33 0.29 −0.09 −0.24 −0.16 1.00
Duke social support 0.19 0.28 0.26 0.28 −0.29 −0.31 −0.09 0.36 1.00

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Figure 1.
Adjusted predictions of frailty according to Positive Resources/Outlook (Factor 1) scores in
PLWH versus HIV-uninfected adults: significant interaction HIV X Positive Resources/
Outlook (aOR=0.23; 95% CI=0.06-0.87), such that higher Positive Resources/Outlook
scores were significantly associated with lower likelihood of frailty for PLWH but not for
HIV-uninfected individuals.
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Table 1.

Comparison of Participant Characteristics by HIV Status.

PLWH (N=65) HIV-uninfected (N=62) P-value

N (%) or Mean (SD) N (%) or Mean (SD)
Rubtsova et al.

DEMOGRAPHICS
Age 50.1 (8.9) 51.0 (7.7) 0.55
Gender (% male) 49 (75.4%) 52 (83.9%) 0.24
Race (% white) 27 (41.5%) 40 (64.5%) 0.01
Education, years 13.8 (2.4) 15.2 (2.1) 0.001
FRAILTY
Prefrail (FFI 1-2) 34 (52.3%) 19 (30.7%) 0.01
Frail (FFI 3-5) 10 (15.4%) 1 (1.6%) 0.01
Low physical activity 23 (35.4%) 5 (8.1%) <0.001
Slowness 11 (16.9%) 1 (1.6%) 0.003
Exhaustion 29 (44.6%) 6 (9.7%) <0.001
Weakness 7 (10.8%) 9 (14.5%) 0.40
Unintended weight loss 14 (21.5%) 3 (4.8%) 0.01
COMORBIDITIES
Ever smoking 29 (44.6%) 8 (12.9%) <0.001
Lifetime alcohol use disorder 32 (50.0%) 20 (33.3%) 0.06
Lifetime major depressive disorder 36 (57.1%) 13 (21.7%) <0.001
Hypertension 29 (44.6%) 10 (16.1%) 0.001

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Diabetes 8 (12.3%) 4 (6.5%) 0.26
Hyperlipidemia 29 (44.6%) 11 (17.7%) 0.001
Malignancy 6 (9.2%) 0 (0%) 0.03
HIV DISEASE CHARACTERISTICS
Current CD4, median (IQR) 637 (480; 855) -- --
Nadir CD4, median (IQR) 194.5 (40.5; 321.5) -- --
Est. duration of HIV disease, years 15.3 (8.3) -- --
Undetectable plasma viral load 43 (68.3%) -- --

FFI – Fried Frailty Index

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Table 2.

Psychosocial Correlates of Frailty: Bivariate Logistic Regression Models.

Crude, OR 95% CI 1 95% CI

Adjusted, aOR
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Resilience 0.93 (0.87; 0.98) 0.95 (0.89; 1.01)

Grit 0.27 (0.13; 0.55) 0.44 (0.21; 0.95)
Optimism 0.86 (0.78; 0.94) 0.88 (0.80; 0.96)
Personal mastery 0.84 (0.76; 0.93) 0.87 (0.78; 0.96)
Religiosity 1 (0.99; 1.02) -- --
Life satisfaction 0.93 (0.89; 0.97) 0.95 (0.90; 1.00)
Successful aging 0.65 (0.52; 0.82) 0.70 (0.55; 0.88)
Subjective age 1.01 (0.99; 1.05) -- --
Depression score 1.15 (1.07; 1.24) 1.13 (1.06; 1.22)
Perceived stress 1.12 (1.06; 1.18) 1.09 (1.02; 1.16)
Negative interactions 2.08 (1.29; 3.34) 2.36 (1.37; 4.07)
Instrumental support 0.99 (0.71; 1.37) -- --
Emotional support 0.38 (0.20; 0.73) 0.40 (0.18; 0.72)
Duke social support index 0.65 (0.52; 0.83) 0.60 (0.44; 0.82)

1
Models adjusted for ever smoking, age, HIV status, hypertension, and hyperlipidemia

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Table 3.

Principal Component Analysis with Varimax Rotation.

Factor 1 (Positive Resources/Outlook) Factor 2 (Support by Others) Communality

Rotated factor loadings
Rubtsova et al.

Grit 0.78 −0.04 0.61

Optimism 0.80 0.21 0.69
Personal mastery 0.78 0.26 0.67
Successful aging 0.69 0.28 0.56
Depression score −0.70 −0.09 0.50
Perceived stress −0.90 −0.17 0.83
Negative interactions −0.45 0.02 0.20
Emotional support 0.13 0.83 0.71
Duke social support 0.20 0.75 0.60

Eigenvalue 3.88 1.49

% of total variance 43.09% 16.54%
Total variance 59.63%

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Table 4.

Psychosocial Correlates of Frailty: Multivariate Logistic Regression Models.

Model 1 – Interactions Model 2 – HIV-uninfected Model 3 – PLWH Model 4 – PLWH

aOR 95% CI aOR 95% CI aOR 95% CI aOR 95% CI
Rubtsova et al.

Factor 1 (Positive Resources/Outlook) 0.97 (0.41; 2.32) 1.06 (0.44; 2.52) 0.23 (0.10; 0.56) 0.25 (0.10; 0.64)
Factor 2 (Support by Others) 0.30 (0.12; 0.77) 0.31 (0.12; 0.81) 0.53 (0.27; 1.01) 0.55 (0.24; 1.24)
HIV status (infected) 3.40 (1.23; 9.37) -- -- -- -- -- --
HIV-infected × Factor 1 0.23 (0.06; 0.87) -- -- -- -- -- --
HIV-infected × Factor 2 1.73 (0.58; 5.22) -- -- -- -- --
Participant’s age 0.36 (0.10; 1.31) 0.98 (0.89; 1.07) 0.95 (0.87; 1.04) 0.95 (0.87; 1.05)
Hypertension 2.34 (0.77; 7.08) 4.0 (0.9; 16.17) 1.47 (0.44; 4.95) 1.34 (0.39; 4.66)
Hyperlipidemia 0.74 (0.24; 2.32) -- -- -- -- -- --
Ever smoking 1.21 (0.10; 1.31) -- -- -- -- -- --
Nadir CD4 -- -- -- -- -- -- 1.0 (1.00; 1.01)

Model N 117 53 64 63
Model Chi2 and P 29.9 0.001 8.7 0.07 15.3 0.004 16.6 0.01
Model pseudo R2 0.30 0.15 0.28 0.29

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