Tailored Treatment for HIV+ Persons With Mental Illness:
The Intervention Cascade
Michael B. Blank, PhD* and Marlene M. Eisenberg, PhD†
Abstract: The public health literature demonstrates disturbingly high
HIV risk for persons with a serious mental illness, who are
concurrently comorbid for substance abuse. Many HIV positives have
not been tested and therefore do not know their status, but for
individuals who are triply diagnosed, adherence to HIV treatment
results in meaningful reductions in viral loads and CD4 counts. Barriers
to treatment compliance are reviewed, low-threshold/low-intensity
community-based interventions are discussed, and preliminary evi-
dence is presented for the efficacy of the intervention cascade, defined
as an integrated intervention delivered by specially trained nurses who
individualize a treatment compliance intervention in real time as an
adaptive response to demand characteristics of the individual.
Key Words: HIV risk, SMI comorbid with substance abuse, treatment
adherence, low-threshold/low-intensity community-based interventions
(J Acquir Immune Defic Syndr 2013;63:S44–S48)
EVIDENCE OF HIGH-RISK PROFILE FOR
COMORBID SERIOUS MENTAL ILLNESS, HIV,
AND SUBSTANCE ABUSE
A growing body of research documents that persons
with a serious mental illness (SMI) are at increased risk for
contracting and transmitting HIV.1–3Multiple studies have
confirmed the emerging rates of HIV within the SMI commu-
nity. For example, in a study of metabolic and infectious
disorders in 600 psychiatric inpatients,2more than 10% were
HIV infected, 32% had hepatitis B, 21% had hepatitis C, and
22% had high cholesterol levels. In another study that used
a service utilization model, Blank et al4conducted a cross-
sectional study to calculate the treated prevalence of SMI and
HIV in the Medicaid population and the odds of receiving an
HIV diagnosis given a diagnosis of SMI. When Medicaid
claim data were merged with welfare recipient files, the trea-
ted period prevalence of HIV among Medicaid recipients
without an SMI diagnosis was 0.3% compared with 0.8%
of those with a schizophrenia diagnosis. For those with a diag-
nosis of affective disorder, rates were 1.7% for a total risk
among those with SMI of 1.6%. After controlling for sex, age,
race, and time on welfare, the odds of having an HIV diag-
nosis given a diagnosis of schizophrenia was 1.52 and the
odds given a diagnosis of affective disorder was 3.87. Thus,
the rate of HIV was significantly elevated among those with
SMI. The risk associated with affective disorder was even
higher than that observed for schizophrenia.
The addition of substance abuse (SA) profoundly raises
the risk profile of comorbid SMI and HIV seropositives,
resulting in alarmingly high rates of infection among those
newly admitted to New York City inpatient psychiatric facilities
(5%–8%), among homeless mentally ill men (19%), and more
still among persons dually diagnosed with SMI and SA (23%).5
A large multisite study of HIV prevalence among psychiatric
inpatients and outpatients in Connecticut, Maryland, New
Hampshire, and North Carolina found HIV rates of 3.1% or
roughly 10 times the rate in the general population.6Similarly,
in a large sample of patients with schizophrenia spectrum dis-
orders treated through the Veterans Affairs system, Himelhoch
et al7found an interaction whereby people with schizophrenia
and comorbid SA were at markedly greater risk for HIV
infections. However, in the absence of an SA diagnosis, people
with schizophrenia alone were actually at lower risk for HIV
infections than the general Veterans Affairs population.7
LOW RATES OF HIV TESTING
Although the data solidly demonstrate an emerging
epidemic within individuals diagnosed as SMI and SA, the
rates of HIV testing within this population are unfortunately
low, resulting in significant numbers who are unaware of their
serostatus. In a study that describes the frequency and
associated factors of HIV testing among 150 psychiatric
outpatients (N = 150),8up to 41% of participants had been
HIV tested within the past year. A hierarchical linear regres-
sion model revealed that testing was related to lower educa-
tional attainment, higher HIV risk behavior, greater social
support, homelessness, nonpsychotic disorder, borderline per-
sonality disorder, and greater treatment utilization. After
accounting for psychosocial and behavioral factors, psychiat-
ric factors remained significant correlates of HIV testing.
Although HIV testing occurred among a substantial propor-
tion of participants, a sizeable majority was not tested. In
addition, 45% of individuals engaging in the highest risk
behavior had not been tested within the previous year. Per-
haps, the most comprehensive study to date that evaluated
From the *Department of Psychiatry, Center for Mental Health Policy and
Services Research, University of Pennsylvania, Philadelphia, PA; and
†Department of Psychiatry, Center for Studies of Addiction, Perelman
School of Medicine, University of Pennsylvania, Philadelphia, PA.
Supported by the Penn Center for AIDS Research, an NIH-funded program
(P30 AI 045008), and National Institute of Nursing Research Grant (#R01
NR008851) Nursing Intervention for HIV Regimen Adherence among
SMIs. Additional support for the supplement was provided by R13
The authors have no conflicts of interest to disclose.
Correspondence to: Michael B. Blank, PhD, Center for Mental Health Policy
and Services Research, University of Pennsylvania, 3535 Market St, Room
3020, Philadelphia, PA 19104 (e-mail: firstname.lastname@example.org).
Copyright © 2013 by Lippincott Williams & Wilkins
S44|www.jaids.com J Acquir Immune Defic Syndr ? Volume 63, Supplement 1, June 1, 2013
predictors of HIV test results among community-based per-
sons with SMI was completed by Desai and Rosenheck.9
Using data from 5890 SMI consumers from the Access to
Community Care and Effective Services and Supports pro-
gram, investigators found that 38.0% of the consumers were
tested for HIV in the 3 months after entry into the Access to
Community Care and Effective Services and Supports pro-
gram and 88.8% returned to receive their test results. Signif-
icant predictors of testing were prior-testing experience, the
presence of more severe psychiatric symptoms and SA,
greater concern about contracting HIV, those who were youn-
ger, less educated, minorities, including African Americans,
homeless for extended periods of time, a history of sexual
assault, history of criminal justice system involvement, and
higher levels of using physical health services. Receipt of
testing results was lowest for consumers with SA problems.
The investigators concluded that the majority of consumers
enrolled in an intensive case management program were not
tested for HIV during the 3-month period after program entry.
However, for those who were tested, the vast majority
received their results. More than any other, this study dem-
onstrates that persons with mental illness should be offered
HIV testing, that they will accept it, and then reliably return
for results. These findings further endorse the suggestion that
testing should be incorporated into the ongoing mental health
programs and interventions.
NONADHERENCE TO HIV TREATMENT
For those who do get tested and know their HIV-positive
status, the impact that results from consistent compliance with
highly active antiretroviral therapy cannot be underestimated
because knowledge about HIV serostatus results in significant
reductions in viral loads and CD4 counts.10,11Adherence to
treatment has also been found to result in more globalized
health benefits, more efficient use of case management serv-
ices, and increased utilization of mental health and SA treat-
ment programs.12Unfortunately, approximately half of those
offered HIV treatment never enter treatment.13–15Perhaps, even
more discouraging are the large numbers who enter treatment
but are not retained16,17and then become at increased risk for
viral resistance.18The timing of treatment is also important as
early initiation of treatment has a potent effect on reduction of
viral load.19In sum, the SMIs are at high risk for HIV infec-
tion, poorly integrated into a reliable HIV testing paradigm,
and nonadherent to HIV treatment when access is available
resulting in higher viral loads and the potential for the devel-
opment of antiretroviral treatment–resistant viral strains. The
confluence of these factors suggests that persons with SMI may
serve as a potent vector of HIV transmission.
THE EFFICACY OF LOW-THRESHOLD/
LOW-INTENSITY BEHAVIORAL INTERVENTIONS
The literature suggests, then, the presence of numerous
barriers to the reduction of HIV risk in those uninfected. For
those already infected, there are barriers that stall or prevent the
successful adherence to an HIV treatment regimen. Addition-
ally, maladaptive belief systems could be outwardly expressed
as either structural or endogenous barriers to treatment accep-
tance and/or adherence. Those at risk could be nonadherent to
treatment because they perceive treatment cost to be prohibitive,
transportation to treatment centers to be inadequate, and/or
office-based treatment that may not be available during the
times when they are most in need. It is also possible that the
considerable stigma associated with treatment may inhibit
service utilization. To overcome these obstacles, interventions
should ideally be designed to appeal to those individuals at
highest risk yet who are least likely to seek and use traditional
treatment programs. In addition, interventions should be easily
accessible to people who would not normally know where to
obtain treatment or who have not yet reached the severity of
addiction that usually brings drug users to the attention of the
treatment system.20–22These features are generally identified as
characteristics of low-threshold interventions.
The design of interventions considered low intensity
may also be particularly constructive for increasing treatment
adherence because they often allow for longer periods of
intermittent contact with the expectation that some form of
contact will serve to maintain treatment benefits over time.
This ability to facilitate repeated or maintained treatment
episodes is especially useful in addressing the cyclical nature
of persons with mental illness, which is often characterized by
relapse.23Low-intensity treatments are particularly well
suited for high-risk individuals because they can provide
a bridge to more intensive treatment. They can also support
maintenance of gains as infrequent “booster sessions” after
the termination of treatment to help maintain treatment gains
DESCRIPTION OF THE INTERVENTION CASCADE
To address both structural and subjective barriers to
adherence to HIV treatment, we propose the intervention cas-
cade, which is designed as an intentional process with the
primary goal of actively coping with barriers to adherence
and to instill confidence in an individual’s ability to self-admin-
ister and monitor medication. The intervention cascade is
derived from the ”Theory of Reasoned Action”(TRA) (Fig. 1)
and the “Theory of Planned Behavior” (TPB) (Fig. 2), which is
particularly germane because of its emphasis on understanding
the mechanisms underlying decisions to seek treatment and to
change behavior. There has been considerable theoretical work
to explain the relationship between the information about health
behaviors and health behaviors themselves. The predecessor
to most health models was the Health Belief Model,24which
held that readiness to engage in health-related behavioral
change was related to 4 components: perceived susceptibility,
FIGURE 1. Theory of Reasoned Action.
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perceived severity, perceived benefits, and perceived barriers.
The TRA25extended this work by placing the individual in
a sociocultural context and has proven particularly valuable in
evaluating HIV prevention interventions. This well-tested the-
ory holds that behaviors are mediated by intentions to perform
them, which in turn are caused by attitudes toward performance
and perceptions of subjective norms. Attitudes are based on an
interaction between knowledge and an internal calculus of out-
come assessments, whereas normative beliefs interact with
motivation. The inclusion of subjective norms is critical because
HIV transmission by definition takes place in interaction with
another person, either through high-risk sexual behavior or sub-
stance use–related behavior. The TPB is an extension of the
TPA including self-efficacy26as a predictor of intentions to
engage in a specific behavior. Self-efficacy is an internal assess-
ment of one’s ability to perform behaviors related to successful
completion of a task, which with regard to HIV prevention are
primarily safe sex practices or abstinence and substance use–
related risk reduction.
TRA/TPB has been shown to be effective in shaping
the success of HIV-preventive behaviors27and has been used
to guide myriad health behavioral change interventions over
the past 3 decades. In addition, intentions to change addictive
behaviors have been found to be an important predictor of
drug treatment outcomes. Individuals with the highest moti-
vation for change seem to be the individuals most likely to
complete drug treatment and consequently display fewer risk
behaviors.28,29The TRA/TPB provides a theoretical frame-
work within which to understand and interpret the cycling
of treatment entry and retention and also decision making
related to risk behavior.
Using the TPB as a guiding paradigm and the
architecture of a low-threshold/low-intensity design, the
intervention cascade is sensitive to the beliefs and behaviors
of persons with mental illness who are at high risk for HIV by
providing an opportunity to be responsive to the level of care
needed via skilled practitioners. In a real sense, it provides
continuity between the processes of identification of high-risk
individuals through HIV testing, increased access to HIV
treatment, and then reinforced treatment adherence. The
skeleton structure of the intervention is predicated upon
the careful interplay between 2 necessary elements. First, the
intervention must be a nurse-led integrated disease manage-
ment (NDM) model with expertise in SMI, SA, and injection
drug use.30,31This translates into the provision of weekly
home-health nursing–focused psychoeducation aimed at
insuring adherence to drug treatment regimen and integrated
care across mental health, SA, and infectious disease. If meet-
ing with other care providers is needed, then the nurses
accompany the patient to appointments or make collateral
contacts with other care providers. Often the nurses serve as
intermediaries to ensure accurate and timely information
exchange. Their specialized training also allows them to mon-
itor side effects of medications, coordinate care for complex
comorbid conditions, and advocate for the patients with their
various specialty providers. In this way, specialty providers
gain patients’ confidence and enable services to be delivered
with adherence supported and maintained.
The second necessary element is the assumption of
continuity of care, which integrates care across inpatient and
community providers and is a process by which patient and
the care providers are cooperatively involved in ongoing
health-care management working toward the goal of high-
quality, cost-effective medical care that is initiated immedi-
ately upon discharge from inpatient care to prevent lapses in
treatment.32The timing of the intervention is important, as is
the long-term patient–provider partnership that develops
when the nurse knows the patient’s history from personal
experience and can integrate new information and decisions
from a whole-patient perspective efficiently without extensive
investigation or record review. The value of the trust that is
engendered by this relationship cannot be underestimated.
The intervention cascade that is superimposed on the
foundation of NDM and continuity of care is an integrated
intervention delivered by specially trained nurses who then
design and modify the intervention based on listening to the
individual’s communication and comprehension needs (Fig. 3).
Based on individual need, this may translate into the use of
memory aid devices, education regarding side effects and other
treatment aspects, and/or active community outreach. Some
individuals may require more intensive didactic training or
more frequent reinforcement and face-to-face meetings. Using
concepts from the TRA, nurses assess attitudes toward medi-
cations and treatments, norms and beliefs about their use, and
monitor side effects. A primary goal of the cascade is to
actively cope with barriers to adherence and to instill confi-
dence in participants’ abilities to self-monitor. The intervention
cascade becomes operative when HIV treatment adherence
falls below a prescribed set point, in this case 80% adherence
as measured by weekly self-report and pill counts. If either
method of measuring adherence falls below 80%, the partici-
pant is considered to have fallen below threshold. When this
occurs, the intervention cascade shifts to the next higher level
of intervention intensity. If 80% adherence is maintained for 3
observation periods (weeks), the cascade reverts back to the
next lower level. If 80% adherence is not obtained, the cascade
increases in intensity to the next highest level. The least inten-
sive cascade level is the incorporation of the existing social
support network (family, friends, neighbors, and significant
others) to assist in reminders about the medication schedule
and to provide gentle and noncoercive support to adhere to
treatments and attend appointments. We estimate that an addi-
tional 10% will meet the 80% threshold solely through the
activation of social networks.
For the estimated 20% who still are not able to maintain
80% adherence, the next step in the cascade is to continue to
FIGURE 2. Theory of Planned Behavior.
Blank and Eisenberg
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? 2013 Lippincott Williams & Wilkins
promote adherence through the social support network but to
add increased contact with the NDM who will begin real-time
reminders using text messages when medications and other
treatments need to be taken. The rationale here is that those
who continue to be nonadherent will need more individual-
ized persuasive communications to meet the adherence
threshold of 80%. In these cases, NDMs will coordinate calls
by case managers and social network members and make
phone calls themselves to encourage adherence. We estimate
that an additional 5% will require the use of phone contact in
real time to maintain 80% adherence. Finally, of the
remaining 10%, we expect that an additional 5% will require
directly observed therapy. This will be effective with an
additional 5% of the population, leaving 5% who will not
respond to even the most aggressive treatment approach and
will be those who actively resist treatment.
PRELIMINARY EVIDENCE OF THE EFFICACY OF
THE INTERVENTION CASCADE
Using a longitudinal experimental and control group
design, Blank et al4randomly assigned participants to the
Preventing AIDS Through Health for Positives (PATH+)
intervention or control groups. PATH+ participants received
the intervention cascade provided by an advanced practice
nurse who delivered community-based care management at
a minimum of 1 visit per week and coordinated their medical
and mental health care for 1 year. In a randomized, con-
trolled trial, 238 community-dwelling, HIV-positive sub-
jects with SMI who were in treatment at urban public
mental health clinics from 2004 to 2008 were sampled.
The main outcome measures were viral load and CD4 count
at baseline and 12 months and costs. Longitudinal models
for continuous log viral load showed that the intervention
cascade group exhibited a significantly greater reduction in-
log viral load than did the control group at 12 months [d =
20.384 log10 copies per cubic millimeter, 95% confidence
interval: 20.165 to 20.606, P , 0.05]. Differences in CD4
from baseline to 12 months were not statistically significant.
A cost analysis revealed a potential cost savings associated
with the intervention cascade group of approximately
$600,000/yr. This project demonstrated the effectiveness
of the intervention cascade via community-based advanced
practice nurses who delivered a tailored intervention to
improve outcomes of individuals with HIV/SMI. It further
demonstrated that persons with SMI can successfully adhere
to HIV treatment and achieve undetectable viral loads when
provided with appropriate supportive services that are flex-
ible and coordinated with the individual needs in real time.33
The intervention cascade has the strong potential to serve
as an effective intervention for individuals dually diagnosed
who are transitioning from inpatient psychiatric care to
community-based mental health treatment. Many persons with
HIV who are undiagnosed are persons with mental illness and
drug users who are marginalized from the health-care system
and from HIV testing and counseling resources.34To improve
the diagnosis of HIV and linkage to HIV care among persons
with mental illness who also use substances, better strategies of
delivering case management and health-care follow-up are
required. Providing continuity of care via a nurse-led integrated
disease model provides an opportunity to link infected individ-
uals to HIV care services and adjunctive services, including SA
treatment and social services. As a natural consequence of this
program, the continuous relationship developed between nurse
and patient is capitalized through the often long-term relation-
ships that many persons develop with the treatment setting and
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