AIDS Behav (2009) 13:60–65
DOI 10.1007/s10461-008-9441-x
REPORT
Gender and Other Psychosocial Factors as Predictors
of Adherence to Highly Active Antiretroviral Therapy (HAART)
in Adults with Comorbid HIV/AIDS, Psychiatric
and Substance-related Disorder
Allison J. Applebaum Æ Mark A. Richardson Æ
Stephen M. Brady Æ Deborah J. Brief Æ
Terence M. Keane
Published online: 9 August 2008
Ó Springer Science+Business Media, LLC 2008
Abstract This study assessed adherence to HAART
among 67 HIV-infected adults, and the degree to which
gender and psychological factors—including depression,
drug and alcohol use, quality of life, and medication side
effects—influenced adherence. Although overall adherence
was greater than rates reported in similar studies, no sig-
nificant difference in adherence was observed between men
and women in the present sample. Medication side effects
were a significant predictor of non-adherence in the sample
at large and among women in particular, while alcohol
dependence was a significant predictor of non-adherence
only in women. Possible explanations are explored.
Keywords Adherence
HIV/AIDS
Gender
HAART
Introduction
A growing body of literature points to a discrepancy in
adherence to antiretroviral medications between HIV-
A. J. Applebaum (&)
M. A. Richardson
T. M. Keane
Department of Psychology, Boston University,
648 Beacon Street, 2nd Floor, Boston, MA 02215, USA
e-mail: aja231@bu.edu
M. A. Richardson
S. M. Brady
D. J. Brief
T. M. Keane
Division of Psychiatry, Boston University School of Medicine,
Boston, MA, USA
D. J. Brief
Department of Psychology, VA Boston Healthcare System,
Boston, MA, USA
T. M. Keane
Research Service, VA Boston Healthcare System, Boston,
MA, USA
123
infected men and women. This includes evidence that HIV-
infected women face different barriers to adherence than do
their male counterparts (Johnston and Mann 2000), and that
certain variables, such as substance use and depression,
influence this relationship between gender and adherence.
Women living with HIV appear to be particularly vul-
nerable to depressive symptomatology (Cook et al. 2002)
and adherence to HAART is adversely affected by
depression (Cook et al. 2007). Adherence is also under-
mined by substance abuse and dependence (for a review,
see Uldall et al. 2004), and alcohol use may be especially
hazardous to adherence in HIV-infected women (Berg et al.
2004). Moreover, depression is highly comorbid with illicit
substance use in HIV-infected women (Cook et al. 2007).
Therefore, among female HIV-infected substance abusers,
adherence to HAART may be especially poor.
Furthermore, adherence to HAART is influenced by
medication side effects, which may include pain, numb-
ness, tingling, fevers, skin rashes, nausea, vomiting, and
pain and bleeding at urination. There is evidence that such
side effects are predictive of poor adherence to HAART,
and that women are bothered by more unpleasant side
effects than are men (e.g., Haug et al. 2005). Therefore,
medication side effects may be a particularly important
predictor of treatment adherence in women.
In addition, adherence appears to be influenced by
quality of life (QOL), an indicator of one’s overall well
being, including psychological, social and physical health
status. Research indicates a positive correlation between
QOL and adherence to HAART (e.g., Carrieri et al. 2003).
Moreover, lower levels of QOL are reported in women than
in men (Shor-Posner et al. 2000), regardless of HIV status,
which may reflect the inverse relationship between QOL
and depression. Therefore, differential rates in adherence
between men and women may be related to QOL.
AIDS Behav (2009) 13:60–65 61

The purpose of the present study was to examine the male, 15 female) met DSM-IV criteria for both an alcohol
influence of depression, substance use/dependence, medi- and drug use disorder.
cation side effects and QOL on adherence to HAART in
HIV-infected men and women with one or more substance- Materials
related disorders and one or more mental health disorders.
The following hypotheses were evaluated: (1) the rate of Psychiatric Symptomatology
adherence to HAART is lower in women than in men; and
(2) depression, drug and alcohol abuse/dependence, QOL A modified version of the Structured Clinical Interview for
and experience of medication side effects account for a DSM-IV (SCID) for Axis I Disorders (SCID-I/P with
greater amount of the variance in adherence in women than psychotic screen) was used, along with the SCID for Per-
in men. sonality Disorders (SCID-II), to assess for psychiatric
eligibility and to create dichotomous variables indicating
the presence or absence during the past month (or within
the past 12 months) of symptoms consistent with a diag-
Methods nosis of a major depressive episode, alcohol abuse or
dependence, and illicit drug abuse or dependence.
Participants
Table 1 Sociodemographic characteristics of respondents by sex,
The sample included 67 participants in the Boston, MA, valid percentage
arm of the HIV/AIDS Treatment Adherence, Health Out- Variable Male Female P-value
comes and Cost Study (HIV/AIDS Treatment Adherence
Health Outcomes and Cost Study Group 2004), a longitu- N % N %
dinal, multi-site study evaluating the impact of integrated 45 67.2 22 32.8
behavioral and primary health care on treatment adherence, Race/Ethnicity .520
health, and healthcare costs among adults living with African American 11 24.4 6 27.3
comorbid HIV/AIDS, substance-related disorders and Caucasian 23 51.1 10 45.5
mental health problems. The data presented here are taken Latino 9 20.0 5 22.7
from the baseline assessment of participants at the Boston Native American 2 4.4 0 0.0
study site. Participants met the following criteria: had Other 0 0.0 1 4.5
documented HIV-seropositivity; were 18 years or older;
Sexual orientation .134
met Diagnostic and Statistical Manual of Mental Disorders
Homosexual/Gay/Lesbian 6 13.3 1 4.5
(DSM-IV) criteria for substance abuse or dependence
Bisexual 7 15.6 8 36.4
within the past year or were on methadone maintenance
Heterosexual/Straight 32 71.1 13 59.1
therapy; and met criteria during the past year for one or
AIDS diagnosis (yes) 20 44.4 10 45.5 .939
more of a pre-selected group of other DSM-IV Axis I
Employment status .623
Disorders that are highly prevalent among adults living
Full time (36+ h/week) 9 20.0 6 27.3
with HIV disease (major depression, dysthymia, bipolar
Part time 9 20.0 2 9.1
disorder, generalized anxiety disorder, post traumatic stress
Retired/Disability 18 40.0 6 27.3
disorder (PTSD) or adjustment disorder), or presented with
Unemployed 9 20.0 8 36.3
evidence of a lifetime history of non-affective psychotic
Psychiatric diagnosesb
disorder, or met DSM-IV diagnostic criteria for borderline
or antisocial personality disorder. Sociodemographic Major depression 20 44.4 17 77.3 .011a
characteristics of the sample, including select diagnoses PTSD 13 28.9 14 63.6 .426
satisfying psychiatric eligibility, are presented in Table 1. Borderline personality 8 17.8 6 27.3 .377
The sample consisted of 45 men and 22 women, with mean Antisocial personality 27 60.0 11 50.0 .445
ages of 43.0 (SD = 6.3) and 38.9 (SD = 6.7), respectively, M SD M SD P-value
and with modest academic attainment (men: 11.8 ± 2.1
Age 43.0 6.3 38.9 6.7 .017a
years; women: 10.6 ± 2.4 years). Forty-nine percent of
Income 1,029.5 1,066.5 612.9 273.4 .077
participants identified as African American, 22% as Cau-
Years of school completed 11.8 2.1 10.6 2.4 .039a
casian, 21% as Latino and 3% Native American. The mean
monthly income of participants was $892.7 (SD = $906.1), Notes: a Indicates statistically significant differences between men
21% were homeless, 45% reported a medical history con- and women (P \ .05)
b
sistent with AIDS, and the majority of the sample (62%; 27 Participants may meet criteria for multiple disorders

123
62
Depression
The Beck Depression Inventory-II (BDI-II), a 21-item self-
report measure of depressive symptomatology, was used to
determine the presence of current depressive symptoms
(within the past 2 weeks), whereas the SCID measured the
presence of a depressive episode in the last month.
Substance Use
The Addiction Severity Index Lite (ASI-Lite), a semi-
structured interview, was used as one source of demo-
graphic information and as a measure of recent patterns of
alcohol and drug use.
HIV-related Physical Health
The Health Status Questionnaire (HSQ), a brief inventory
designed specifically for the multi-site HIV/AIDS Cost
Study, captured information from both participants’ med-
ical records and their self-report about stage of HIV
disease, and HIV-or-AIDS related conditions and comor-
bidities (e.g., CD4 count, viral load, opportunistic
infections, HIV-related hospitalization).
Medication Adherence
Adherence was assessed using the Medication Adherence
Questionnaire, which is composed of questions from the
Adult AIDS Clinical Trials Group (AACTG; Chesney et al.
2000) questionnaire used in national trials of factors
impacting adherence. This questionnaire allowed partici-
pants to describe their medication regimen, general pattern
of adherence over the prior 3 months, side effects of this
regimen, and number of missed pills/doses for each med-
ication participants reported taking during the 3 days
immediately preceding baseline assessment. For the pres-
ent study, adherence was described using an adherence
ratio (1 - average ratio of pills missed to total pills
expected across all medications during the past 3 days),
yielding values from .00 to 1.00.
Medication Side Effects
The impact of medication side effects (experienced during
the 3 months prior to interview) was evaluated using the
following three items from the Medication Adherence
Questionnaire: missed taking your medications because
you wanted to avoid side effects; missed taking your
medications because you felt like the drug was toxic; and
missed taking your medications because you felt sick/ill
from side effects. These items were scored on a 4-point
scale from 0 (never) to 3 (often) and were not drug specific.
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AIDS Behav (2009) 13:60–65
Therefore, endorsement of each item may have referenced
concerns about one or many medications within the par-
ticipants’ overall treatment regimen.
Quality of Life
Quality of life was assessed using the Medical Outcomes
Study Short Form Health Survey-36 (MOS SF-36). This
36-item survey assesses physical and mental health
components through eight health domains: physical
functions, social functions, role limitations due to emo-
tional and physical problems, bodily pain, vitality, mental
health, and general health perception. The Physical Health
and Mental Health composite norm-based scores ranging
from 0 to 100 were used for the present study as indi-
cators of QOL, with higher numbers indicating better
health.
Procedure
Potential participants were prescreened in a brief tele-
phone or face-to-face interview. Those who reported
recent experiences consistent with inclusion criteria were
invited to meet privately with study staff to receive an
overview of the study design and to complete informed
consent procedures. Once written consent was obtained,
participants were scheduled for further evaluation to
assess their eligibility for study entry and to gather
baseline data. One hundred and thirty one potential par-
ticipants completed informed consent procedures and 85
completed baseline assessment procedures and were found
eligible for participation in the longitudinal study. The
present findings relate to the 67 participants who were
taking antiretroviral medications at the time of the base-
line assessment. There were no significant differences
across demographic factors, psychiatric diagnoses, and
quality of life between participants included in the present
analyses and those not on HAART at the time of the
assessment.
Study staff verified participants’ HIV status through
chart review or written confirmation from participants’
HIV/AIDS primary care provider. Absolute CD4 and viral
load values were taken from medical records and when
necessary, new tests were ordered to ensure that they were
current. The comprehensive baseline assessment of physi-
cal health, mental health and psychosocial functioning
included measures of adherence, quality of life, substance
use, psychiatric symptomatology and overall health and
functioning.
All study procedures were reviewed and approved by
the appropriate institutional review boards. Participants
received $10/h, to a maximum of $60, for completing the
baseline assessment battery.
AIDS Behav (2009) 13:60–65
Results
Exploratory analyses revealed that men in the study sample
were significantly older and had completed significantly
more years of education than the women. No other sig-
nificant gender differences were observed on demographic
variables (i.e., race, income). Moreover, there were no
significant correlations between any of the demographic
variables—including age and income—and the predictor
(e.g., QOL, substance abuse) or outcome (i.e., adherence)
variables of interest; therefore, the former were not con-
trolled for in subsequent analyses.
The mean adherence ratio was .890 and .912 for women
and men, respectively. An independent-samples t-test was
conducted to evaluate the hypothesis that the rate of
adherence to HAART was lower in women than in men.
The test (t[65] = -.403, P = .69) indicated no significant
difference in adherence between women and men. Addi-
tionally, at least 95% adherence to medication regimens
was reported by 68.2% of women and 71.1% of men. A
two-way chi-square analysis was conducted to assess for
differences in the proportion of women and men whose
adherence ratio was equivalent to .95 or greater, and those
who did not meet this standard criterion for optimal
adherence. The results were again non-significant, v2 (1, N
= 67) = .384, P = .54.
To further evaluate the relationship between gender and
adherence to HAART, a hierarchical regression analysis
was conducted for the entire sample with the predictors
entered as follows: gender was entered in the first step;
depression, alcohol abuse, alcohol dependence, substance
abuse and substance dependence in the second step; and
QOL and medication side effects in the third. The linear
combination of the predictors evidenced a positive pre-
dictive trend but was not significantly related to adherence
(F[11, 48] = 1.78, P = .06), and accounted for about 35% of
the variance in adherence (R2 = .346). Further, the only
variable that was a significant predictor of adherence was
an indicator of aversive side effects of these medication
regimens (i.e., missed taking your medications because you
felt sick/ill from side effects) (t[37] = -2.269, P = .037),
with non-endorsement of this item predicting higher rates
of adherence.
Two-way chi-square analyses were conducted to
examine gender differences on the hypothesized predictors
of medication adherence (recent alcohol and drug abuse/
dependence, depression, and medication side effects). A
statistically significant difference was observed for only
one of these factors. Specifically, a significantly greater
proportion of women (77%) than men (44%) met criteria
for recent major depression, v2 (1, N = 67) = 7.896, P =
.011. In addition, independent samples t-tests yielded non-
significant findings on QOL measures. Responses yielded
63
comparable scores on the SF-36 Physical Health Com-
posite (male: X = 44.9, SD = 9.8; female: X = 43.4, SD =
7.9) and Mental Health Composite (male: X = 37.4, SD =
12.9; female: X = 32.2, SD = 9.7) scales, scores that are
suggestive of slightly compromised general physical and
mental health status (i.e., are indicative of slight medical
limitations, decrements in physical well being and energy
level and some psychological distress, Ware et al. 1995).
To test our second hypothesis that depression, drug and
alcohol abuse/dependence, quality of life and experience of
medication side effects would account for a greater amount
of the variance in adherence in women than in men, hier-
archical regression analyses (with depression, alcohol
abuse, alcohol dependence, substance abuse and substance
dependence entered in the first step and QOL and medi-
cation side effects in the second step) were conducted
separately for men and women. Among men, the linear
combination of the predictors was not statistically signifi-
cant (F[10, 20] = 1.021, P = .461, R2 = .338), and none of
the predictors accounted for a significant amount of the
variance in adherence. Among women, there was a trend
toward significance for the overall model (F[8, 9] = 2.987,
P = .06), with the linear combination of the predictors
accounting for 73% (R2 = .726) of the variance in adher-
ence among women. This analysis also revealed that for
women, an absence of alcohol dependence (t[9] = -2.315,
P \ .05) and non-endorsement of specific concerns about
medication side effects (i.e., missed taking your medica-
tions because you wanted to avoid side effects [t(9) =
-2.324, P = .05] and missed taking your medications
because you felt sick/ill from side effects [t(9) = -2.728,
P = .02]) were significant predictors of adherence.
Discussion
The hypothesis that the rate of adherence to HAART would
be lower in women than men was not supported in the
present study. There was no significant difference in the
reported adherence ratio between men and women, or in
the proportion of men and women meeting the optimal rate
of adherence (i.e., adherence ratio of .95). Indeed, it must
be noted that the reported rate of adherence in the recent
past was quite high for the entire study sample (nearly 70%
of participants reported such near perfect adherence in the
recent past), a rate much higher than reported in prior
studies of adherence involving similar samples (e.g., Berg
et al. 2004; Haug et al. 2005; Turner et al. 2003). Our
results also indicated that for the sample as a whole only
illness as a side effect of HAART was (inversely) predic-
tive of rates of adherence.
Our second hypothesis, that depression, drug and alco-
hol abuse/dependence, quality of life and experience of
123
64
medication side effects, would be differentially predictive
of adherence as a function of gender received partial sup-
port from the present findings. Hierarchical regression
analyses revealed that among women only, alcohol
dependence and specific concerns about medication side
effects were significantly and inversely predictive of
adherence. These findings are consistent with extant liter-
ature suggesting that among women, alcohol use (e.g.,
Berg et al. 2004) and medication side effects (Johnston and
Mann 2000) may be independently associated with non-
adherence. Although quite appropriately there was no dif-
ference in the proportion of men and women meeting
criteria for recent substance-related disorders (required for
study eligibility and verified via preliminary chi-square
analyses), alcohol dependence was a significant predictor
of adherence only in women, in part a reflection of the
relative consistency of such patterns among male
participants.
Somewhat surprisingly, depression did not emerge as a
significant predictor of adherence in the present study.
Despite prior evidence that HIV-infected depressed women
are significantly less likely to be adherent to HAART than
their non-depressed counterparts (Cook et al. 2002) and
evidence of differential rates of depression as a function of
gender among participants, this factor was secondary to
alcohol and medication side effects as a predictor of
adherence in the present study. These findings are also in
contrast with prior evidence of poorer generalized quality
of life (e.g., Shor-Posner et al. 2000) and its impact on
chronic, life-affirming behaviors such as adherence to
prescription medication regimens.
It is possible that these findings reflect other character-
istics endemic to the present sample. Participants were
recruited from clinics where they had routine access to
integrated medical and mental health care that emphasized
positive health practices; their comparatively high adher-
ence rates may be at least partially attributable to their
access to such comprehensive routine care. Reported rates
of adherence may also result from characteristics of the
participants themselves, who were willing to endure
extensive assessments in return for the possibility of
gaining access to experimental substance and mental health
treatment designed to enhance adherence, over and above
that routinely available to them. In short, these participants
may have been exceptionally motivated and involved in
their care relative to non-participants or to individuals
enrolled in comparable prior studies. The present findings
may reflect participants’ overall quality of general medical
and psychiatric care, and may also suggest that this sample
included more relatively marginalized men than found in
prior studies. For example, in this sample, significant
gender differences in income levels or rate of
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AIDS Behav (2009) 13:60–65
employment—traditionally demonstrated in similar sam-
ples—were not observed.
Self-reported adherence is viewed by some as more
prone to distortion than are more ‘‘objective measures’’
(e.g., electronic pill bottles/MEMS caps), potentially
increasing the probability of inflated adherence estimates.
However, prior research demonstrated the validity of the
adherence questionnaire employed in the present study as
an indicator of recent behavior (Chesney et al. 2000). As
such, the present findings appear to highlight a more
optimistic appraisal of adherence in a sample of high-risk
adults living with HIV/AIDS than found in earlier studies.
Nonetheless, confidence in the present findings could have
been enhanced by the use of more than one indicator of
adherence (e.g., self-report measures and MEMS caps), as
employed in some prior research on adherence.
It is also likely that the present findings underestimate
the degree to which comorbid psychiatric disorders were
present in study participants, limiting the degree to which
effects of psychiatric morbidity on adherence could be
explored. The version of the SCID utilized in the multi-site
HIV/AIDS Cost study was designed to streamline screen-
ing for eligibility and general risk within diagnostic
domains (e.g., Mood Disorders) in an effort to reduce
overall assessment liability for any given participant, likely
resulting in our failure to identify one or more comorbid
conditions in several participants. Finally, this study’s
relatively small sample and participants’ relatively
restricted range of reported treatment adherence may have
limited its sensitivity to factors affecting the latter.
On the other hand, this study illustrates the relative
contribution of current psychiatric morbidity, substance
use, treatment-related factors and well-being on treatment
adherence among a sample of adults likely to be increas-
ingly represented among people living with HIV in the near
term. Present findings further emphasize the need for
investigators and clinicians alike to attend to patterns of
alcohol use (versus the use of other substances of abuse)
and—in the absence of objective measures of adverse
treatment effects—to carefully attend to subjective reports
of such discomfort in relation to treatment adherence.
Future research involving comparable target samples may
consider participants’ motivation to enhance physical and
mental health functioning and the nature of substance use
in which they are engaged, as well as sources of instru-
mental assistance that may enhance adherence, even in the
face of adverse effects.
Acknowledgements This work was supported by the HIV/AIDS
Treatment Adherence, Health Outcomes and Cost Study, a collabo-
ration of six Federal entities within the U.S. Department of Health and
Human Services (DHHS): The Center for Mental Health Services
(CMHS), which had the lead administrative responsibility, and the
AIDS Behav (2009) 13:60–65
Center for Substance Abuse Treatment (CSAT), both components of
the Substance Abuse and Mental Health Services Administration
(SAMHSA); the HIV/AIDS Bureau of the Health Resources and
Services Administration (HRSA); the National Institute of Mental
Health (NIMH), the National Institute on Drug Abuse (NIDA), and
the National Institute on Alcohol Abuse and Alcoholism (NIAAA),
all parts of the National Institutes of Health (NIH). The content of this
publication does not necessarily reflect the views or policies of these
or any other agencies of the DHHS.
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