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Copyright © 1998 Elsevier Science Ltd. All rights reserved.

University of Miami, Coral Gables, FL, USA

8.10.1 INTRODUCTION 238 Pathogenesis of HIV Infection 238 Health Psychology and HIV Infection 239 Psychoneuroimmunology research and HIV infection 240
8.10.2 PREDICTING ADJUSTMENT TO HIV INFECTION 242 Psychological Challenges in HIV Infection 242 HIV-associated Psychosocial and Behavioral Sequelae 244 Distress and depression 244 Risk behavior and substance use 246 Psychosocial Factors Predictive of Depression and Risk Behaviors in HIV Infection 247 Uncontrollable stressors 247 Stressor appraisals 248 Coping with HIV-related symptoms 248 Social support 248
8.10.3 PREDICTING THE HEALTH COURSE OF HIV INFECTION 250 Biological Factors and Disease Progression 250 Constitutional factors 250 Other viral infections 251 Behavioral and Psychosocial Factors and Disease Progression 252 Behavioral factors 252 Depressive symptoms 253 Stressful life events 254 Stressor appraisals 255 Coping strategies 256 Social support 257 Psychosocial Factors in Long-term Survivors of AIDS 258
8.10.4 INTERVENTIONS, ADJUSTMENT, AND HEALTH COURSE IN HIV INFECTION 259 Health Psychosocial Interventions with HIV-infected People 259 Stress Management Intervention Effects at Different Critical Points in HIV Infection 259 The initial HIV seropositive diagnosis 261 The asymptomatic stage of HIV infection 262 The pre-AIDS symptomatic stage of HIV infection 263 Full-blown AIDS 263 Common Features of Psychosocial Interventions in HIV Infection 264 Relaxation aspects 264 Delivery format 264 Treatment orientation 264 Summary of Completed Studies of Psychosocial Interventions with HIV-infected Persons 265
8.10.5 CONCLUSION 266
8.10.6 REFERENCES 267

238 HIV and AIDS

8.10.1 INTRODUCTION disseminated during this early stage of infection,

suggesting that the course of infection may be Pathogenesis of HIV Infection influenced by the ªseedingº of the virus
throughout the lymph nodes and other immune
The human immunodeficiency virus (HIV) is system components (Tindall & Cooper, 1991).
a retrovirus of the human T-cell leukemia/ Even after this acute stage of the infection it
lymphoma line and is the causative agent of the appears that viral replication is not completely
acquired immunodeficiency syndrome (AIDS). curtailed since it remains detectable in lymph
(Although AIDS is believed to be caused by the nodes during the quiescent stages of the infection
human immunodeficiency virus-type 1 (HIV-1), (Pantaleo, Poli, & Fauci, 1993).
we have for simplicity used the term HIV A period of clinical, but not microbiological,
throughout this chapter.) A unique feature of latency lasting for a number of years follows the
HIV infection is that it can have a long initial sequence of primary infection, viral
asymptomatic phase lasting up to 10±15 years dissemination, development of HIV specific
(Munoz et al., 1988) followed by the appearance immunity, and curtailment of extensive viral
of constitutional signs and symptoms of disease replication. Importantly, during the clinically
progression. In most people full-blown AIDS latent period the disease is still progressing. This
develops next (Kaplan, Wofsy, & Volberding, is observable in an increasing viral load, the
1987), and even with aggressive and timely depletion of CD4 cells in peripheral blood, and
treatment, death often occurs a few years later in the increasing proportion of HIV infected
(Lemp, Payne, Neal, Temelson, & Rutherford, lymphoid cells (Pantaleo et al., 1993). It is
1990). A diagnosis of AIDS is made when a generally accepted that the decline in CD4 cells
person shows laboratory-based signs of severe leaves the infected person susceptible to a
decline in the number of T-helper±inducer number of opportunistic infections and cancers
(CD4) cells (5 200 cell mm73), or clinical signs characteristic of AIDS, though there is evidence
consistent with the emergence of opportunistic that malfunctions in other aspects of immune
infections and neoplasias. Some of these functioning may also be associated with disease
include: candidiasis of the esophagus, trachea, progression. Some of the more commonly
bronchi, or lungs; cryptoccosis; cryptosporidio- observed infections include pneumocystic carinii
sis with diarrhea persisting longer than one pneumonia (PCP) cryptococcal meningitis,
month; cytomegalovirus disease of an organ toxoplasmosis, and candida esophagitis (Ka-
other than the liver, spleen, or lymph nodes; plan et al., 1987). Many other diseases manifest
herpes simplex virus infection causing a muco- in HIV-infected persons are caused by ubiqui-
cutaneous ulcer for longer than one month; tous herpes viruses (e.g., cytomegalovirus
Kaposi's sarcoma; primary lymphoma of the (CMV) associated retinitis is a major cause of
brain; pneumocystis carinii pneumonia; pro- blindness in HIV-infected persons). HIV in-
gressive multifocal leukoencephelopathy; tox- fected persons are also vulnerable to relatively
oplasmosis of the brain; and a variety of other rare cancers including Kaposi's sarcoma and
opportunistic infections and neoplasias. Since Burkitt's lymphoma and, in women, cervical
some infected people can remain free of clinical carcinoma. Interestingly these cancers are
symptoms for a prolonged period of time and believed to be promoted by fairly common
given that appropriate patient management can viruses as well (e.g., human papillomavirus
delay the onset of AIDS, it may be useful to view types are associated with cervical neoplasia and
HIV as a chronic disease. squamous cell cervical carcinoma (Maiman &
Many staging systems for HIV infection have Fruchter, 1996). In contrast, it is rare that these
been developed over the past decade (Walter viruses are successful in eluding the immune
Reed system, World Health Organization, and system for long enough to establish a clinical
Centers for Disease Control), though the most neoplastic process in healthy people, unless
widely accepted system used today is that these people are undergoing pharmacologic
developed by the Centers for Disease Control treatments that suppress the immune system
(CDC) in 1993. People with primary HIV (Antoni, Esterling, Lutgendorf, Fletcher, &
infection often develop an acute mononucleosis- Schneiderman, 1995). HIV-infected persons
like syndrome about a month after initial are then extremely vulnerable to a wide range
infection (Tindall & Cooper, 1991). This period of pathogens normally controlled by the
is associated with a high level of viral load or free immune system and, with time, these individuals
virus released throughout the circulation (i.e., may contract a number of life-threatening
viremia) (Daar, Moudgil, Meyer, & Ho, 1991) diseases over the course of the infection.
which usually occurs 4±12 weeks after the onset Because a person's awareness of their diagnosis
of acute infection (Clerici, Berzofsky, Shearel, & and, more importantly, their symptom status
Tacket, 1991). The virus becomes widely may play an important role in determining their
Introduction 239

perceived psychosocial and physical burdens as know that using a single antiretroviral agent
well as their chosen coping strategies, this may lead to the development of AZT-resistant
chapter shall later refer to different phenomen- strains of HIV which are ultimately harder to
ological stages of HIV infection tied to critical treat; thus contemporary treatment approaches
events as follows: the initial HIV seropositive often focus on combination therapies (e.g., AZT
diagnosis; the (post diagnosis) asymptomatic and ddC). Newly emerging treatments such as
stage; the pre-AIDS symptomatic stage (for- triple combination therapy and protease in-
merly referred to as AIDS related Complex hibitors offer some hope that viral replication
(ARC); and AIDS (often referred to as full- can be slowed more efficiently and with a lower
blown or frank AIDS). likelihood of resistance or undue side effects
Because there is no cure for AIDS, prevention (Lewin, 1996). However, we are now learning
is the major tool for limiting the spread of the that the effectiveness of these newer regimens is
disease. Primary prevention efforts use many critically dependent on the ability of patients to
behavioral change techniques, aimed at increas- adhere to a rigid and demanding medication
ing availability and promoting use of condoms, schedule. Failure to do so can substantially
and substance abuse management and treat- increase the risk of developing drug-resistant
ment (Schneiderman, Antoni, Ironson, LaPier- strains of the virus (Lewin, 1996; Schneiderman,
riere, & Fletcher, 1992). Many of these Antoni, & Ironson, 1997).
techniques are those that are commonly
employed by health psychologists working in
the area of risk management. Secondary Health Psychology and HIV Infection
prevention programs have also been undertaken
to slow HIV spectrum disease progression. Behavioral scientists focusing on HIV infec-
Because only a relatively small proportion of the tion are usually involved in either primary
one million people in the United States infected prevention efforts (e.g., examining factors
with HIV have AIDS (CDC, 1995) and because underlying risk behaviors that lead to infection
of the relatively prolonged period of time in order to inform community-wide interven-
between the onset of infection and the devel- tions and health policies) or secondary preven-
opment of AIDS (Munoz et al., 1989), there is a tion efforts (e.g., examining factors contributing
clear need to develop treatments to manage HIV to the mental and physical health course of
spectrum disease and slow down disease HIV-infected persons in order to develop
progression. Much of this chapter will focus clinical interventions). This chapter will focus
on such secondary prevention activities. on the role of health psychology in such
Many pharmacologic agents have been secondary prevention efforts, though findings
developed to manage symptoms and to slow relevant to primary prevention efforts (e.g.,
HIV progression. These include such agents as predictors of sexual behavior and substance use)
pentamidine (to combat acute PCP and as a will also be addressed.
prophylaxic) and a large number of antiretro- Managing HIV disease involves addressing
virals, the most well-known being azidothymi- psychosocial as well as biomedical issues
dine (AZT), to block the replication of HIV. To (Antoni, Schneiderman et al., 1990; Schneider-
at least some extent advances in patient man et al., 1994). The anticipation and the
management have been successful in ameliorat- impact of HIV antibody test notification, for
ing symptoms and dealing with intercurrent instance, is highly stressful (Ironson et al.,
illnesses (Longini, Clark, & Karon, 1993). In 1990). Here, feelings of life-threat, doom, and
contrast, the benefits of antiviral therapies such anger are usually encountered as is the need to
as AZT, dideoxyinosine (ddI), and dideoxycy- contemplate making major lifestyle changes
tidine (ddC) appear to be only marginally (Christ & Wiener, 1985; Kaisch & Anton-
effective and more controversial. In fact, in a Culver, 1989; Viney, Henry, Walker, & Crooks,
letter to the Lancet, the Concorde Coordinating 1989). Because of the large and accelerating
Committee (Aboulker & Swart, 1993) reported number of people who are infected with HIV,
that although AZT modestly boosted the there is a clear need to develop behavioral
number of CD4 cells in the blood of asympto- interventions to help them cope with the
matic patients, it did not delay progression to psychosocial aspects of their situation. There
AIDS. Previous research had already shown is also some evidence that improving psycho-
that AZT only prolonged the life of HIV infected logical adaptation to HIV may have implica-
people for a few months (Fischl et al., 1987). The tions for physical health among infected
antiviral drugs also have undesirable physiolo- individuals. Two areas that have been the focus
gical (e.g., bone marrow suppression, anemia, of much health psychology research in HIV
neutropenia; Richman, et al., 1987) and psy- infection and AIDS examine how psychosocial
chological (e.g., depression) side effects. We now factors such as distress states and depressive
240 HIV and AIDS

symptoms as well as certain risk behaviors Psychoneuroimmunology research

might contribute to (i) the ways in which people and HIV infection
adjust to the having HIV infection; and (ii) the
actual health course of the infection. To the extent that HIV infection increases
Health psychological studies focusing on distress levels (Antoni, Schneiderman et al.,
HIV and AIDS began in about 1987, coincident 1990; Kaisch & Anton-Culver, 1989; Viney
with the identification of HIV as the putative et al., 1989), which in turn have been shown to
cause of many AIDS-related conditions that influence the immune system (Calabrese, Kling,
were emerging in clinics and hospitals around & Gold, 1987; Ironson et al., 1990; Irwin,
the world. At that time, behavioral scientists Daniels, Bloom et al., 1987; Kiecolt-Glaser
began studying the effects of psychosocial et al., 1987), it is plausible that behavioral
factors such as stressors and stress management interventions that decrease distress may bene-
interventions in people infected with HIV. The ficially impact immune status and possibly
first major reason for this health psychological health status in HIV-infected people. Because
research concerned the issue of psychological the degree to which the immune system becomes
adjustment. HIV infection presents multiple disordered seems to be the strongest predictor of
burdens at the psychological and physical levels, the progression to HIV-related symptoms and
thereby creating a state of chronic stress that death, much biomedical research has been
may overwhelm an individual's coping re- focused upon ways to either slow the growth
sources, thus greatly impairing their ability to of the virus or slow the decline of the immune
emotionally adjust to what will likely be a long system by modulating the function of its cells.
journey. Accordingly, it was reasoned that HIV Psychoneuroimmunologic (PNI) research ex-
infected individuals are among the groups who amines ways in which psychosocial influences
might benefit substantially from interventions such as stressful life events, distress states, and
that teach them to cope with the chronic stress reducing techniques±±all of which may
demands that many people will never have to contribute to successful adjustment to HIV
face. By learning how stress-reducing psycho- infection±±modulate immune system function-
social interventions help such people adapt, ing and, ultimately, disease course. Applying
adjust, and adhere to various lifestyle changes these ideas from the point of view of a chronic
health psychologists gain insight into ways to disease model, to the extent that health
facilitate the coping process in people facing this psychology interventions modify psychosocial
life-threatening condition as well as other factors such as risk behaviors (unprotected sex,
chronic diseases (for reviews see Antoni, 1991; alcohol and drug abuse), emotional distress,
Ironson, Antoni, & Lutgendorf, 1995; Lutgen- maladaptive coping strategies, and social isola-
dorf, Antoni, Schneiderman, Ironson et al. tion, it might also modulate biological factors
1994; Schneiderman et al., 1994). such as certain endocrine and immune system
A second major reason for examining the components. By diminishing the impact of
effects of psychosocial factors in this population psychosocial and behavioral factors on the
follows from a conceptualization of HIV immune system, the individual might retard the
infection as a chronic disease whose clinical onset of disease complications by maintaining
course may be affected by multiple behavioral immunologic status (e.g., by preserving an
and biological factors (Antoni, Schneiderman adequate number of T-helper cells and/or
et al., 1990). As in the case of other chronic maintaining the functioning of surviving im-
diseases, HIV infection is characterized by a mune cells) within a range necessary to defend
disorder in one or more bodily systems wherein against certain infections and cancers.
signs and symptoms of the disorder are There are many studies relating psychosocial
clinically manifest across long periods of time and behavioral factors to the immune system in
as a function of the degree of disorder in the a wide collection of species using an even wider
bodily system(s) affected (e.g., immune system number of different experimental paradigms.
impairment). People with HIV infection become This area is marked by significant agreement
ill or die from the complications of their chronic and disagreement about the ways in which a
disease not the disease itself. Just as diabetics wide range of factors impact the immune system
who are unable to maintain their blood glucose in healthy animal and human populations.
levels within a certain range may develop kidney Clinical researchers have attempted to translate
disease or suffer heart attacks, HIV-infected many of these findings into the clinical arena
people who are unable to retain adequate in order to classify how psychological phenom-
immune system functioning necessary for ena such as self-efficacy and sense of control,
surveillance of pathogens go on to develop coping strategies, social support, and emotional
the life-threatening infections or cancers that states such as depressionÐall reasonable targets
characterize full-blown AIDS. of psychological interventions±±contribute to
Introduction 241

impairments in the immune systems of HIV replication and progression to AIDS (Carbo-
infected individuals (e.g., Antoni, 1990; Solo- nari, Fiorilli, Mezzoroma, Cherchi, & Aiuti,
mon, Kemeny, & Temoshok, 1991). Given 1989; Rosenberg & Fauci, 1991). Because
existing evidence that experimentally induced several herpes viruses are known to have
and naturally occurring stressors, perceived loss immunosuppressive effects, in and of them-
of control, social isolation, and depression are selves, reactivation of these viruses could have
related to decrements in the numbers and implications for compounding HIV-induced
functions of immune cells known to be altered immune system decrements and, possibly,
by HIV infection, it can be reasoned that these disease progression (Griffiths & Grundy, 1987).
psychosocial and behavioral factors might Implicit in much PNI research is the notion
influence immunologic status and, possibly, that psychosocial factors relate to immune
disease course in HIV-infected individuals. system changes by way of stress- or distress-
Similarly, stress management interventions that induced changes in hormonal regulatory sys-
target these factors might provide both psy- tems resulting in neuroendocrine elevations and
chological and physical benefits for infected imbalances (Maier, Watkins, & Fleshner, 1994).
people, especially for those in the early stages of There are several neuroendocrine substances
this chronic disease before the virus has known to be altered as an function of an
established a stranglehold on the immune individual's appraisal (i.e., controllable vs.
system and other physiological regulatory uncontrollable) of and coping response (i.e.,
processes. active vs. passive) to stressful stimuli that have
This line of reasoning can be operationalized also been shown to impair certain components
in the context of HIV infection as follows: of the immune system. Some of these hormones,
because CD4 cells are depleted in the advancing including those produced by the adrenal gland,
stages of HIV infection (Klimas et al., 1991), are also known to be dysregulated in depressed
increases in qualitative aspects of HIV itself individuals (Calabrese et al., 1987) and those
(e.g., mutation and replication rate) (Panteleo reporting significant degrees of loneliness
et al., 1993) and of lymphocytes (e.g., prolifera- (Kiecolt-Glaser et al., 1984). Given that un-
tion [growth and reproductive abilities], and controllable stressors, perceived loss of control
cytotoxicity [recognition and killing abilities]) (similar to low self-efficacy), and social losses
might be important in predicting those HIV such as divorce and bereavement have been
seropositive individuals who do and do not related to alterations in some of these immu-
develop opportunistic infections quickly. The nomodulatory hormones, it has been reasoned
ability of lymphocytes to multiply when that some PNI relationships might be mediated,
challenged by antigens, often evaluated using in part, by neurohormonal changes that are
tests of lymphocyte proliferative responses to linked to an individual's appraisals of and
plant mitogens such as phytohemaglutinin coping responses to environmental burdens (for
(PHA), concanavalin-A (conA), or pokeweed reviews see Antoni, Schneiderman et al., 1990
mitogen (PWM), may compensate to some and Schneiderman et al., 1994). Although many
degree for the smaller number of CD4 lympho- different neurotransmitters, neurohormones,
cytes available as the disease progresses. Innate and other peptides have been studied as
immune functions such as natural killer cell potentially important mediators of stressor-
cytotoxicity (NKCC), a largely CD4-cell in- induced immunomodulation, two well-deli-
dependent function, may also compensate in neated ªstress response pathways,º the
conferring protection against extant viral hypothalamic±pituitary±adrenal (HPA) axis
infections. For instance, herpes viruses such and the sympathetic adrenomedullary (SAM)
as Epstein Barr virus (EBV) or herpes simplex system, have received the most focus.
virus (HSV) are often poorly controlled in the The HPA axis is a complex system that is
context of HIV-induced defects in CD4 cell- regulated by several integrated central nervous
directed cytotoxic function (Biron, Byron & system and peripheral mechanisms, a regulation
Sullivan, 1989; Habu, Akamatsu, Tamaoki & that may be disrupted at several levels in
Okumura, 1984, Bancroft, Shellam, & Chalmer, depressive illness and other affective distress
1981; Bukowski, Warner, Denner & Welsh, states (Amsterdam, Maislin, Gold, & Winokur,
1985). It is plausible that NKCC, which may be 1989). Several of these HPA axis abnormalities
partially preserved in HIV infection, may help gradually normalize with clinical improvement
to survey and control these and other infections in depression (Greden et al., 1983; Amsterdam,
in the HIV-infected host. Conversely, stress- Lucki, & Winokur, 1985). Because immunolo-
induced impairments in NKCC may permit gic function is impaired by cortisol (Plaut, 1987)
herpes virus reactivation to go unchecked in in humans, immunologic correlates (especially
HIV-infected individuals (Glaser & Kiecolt- blastogenesis and NKCC) of depressed states
Glaser, 1987) with subsequent effects of HIV have been studied extensively. Despite the
242 HIV and AIDS

conclusive evidence for immunologic effects and lamine and cortisol elevations) due to sympa-
neuroendocrine changes in depression, the exact thetic nervous system (SNS) activation and
mechanisms involved are lacking (Stein, Miller, dysregulation of the HPA axis. These neuroen-
& Trestman, 1991). However, it has been shown docrine changes may also be accompanied by
that glucocorticoids enhance HIV replication changes in the immune system (redistribution of
(Markham, Salahuddin, Veren, Orndorf, & lymphocytes and decrements in functions con-
Gallo, 1986), are immunosuppressive (Cupps cerning lymphocyte proliferation and NKCC)
& Fauci, 1982), and accompany affective via interactions among neural and neuroendo-
disorder (Gold et al., 1986) and stressful crine signals at the immune cell membrane,
experiences (Borysenko & Borysenko, 1982; intracellular cyclic nucleotide activation, and
Jacobs et al., 1986). On the other hand, one the production of cytokines such as interleukin
study found that 24 hour urinary-free cortisol (IL)-I and II, and g-interferon (g-IFN). Since
levels were not related to CD4 (or CD8) cell these structural (cell counts) and functional
counts in HIV positive individuals (Gorman (proliferation and cytotoxicity) aspects of the
et al., 1991). However, this does not preclude the immune system are known to decline progres-
possibility that distress or depression-associated sively across the course of HIV infection
cortisol elevations impact immune function (Panteleo et al., 1993), it can be further
(e.g., NKCC) in HIV-infected individuals and hypothesized that superimposed stressor-in-
that such functional changes might relate duced changes in the functioning of the immune
directly to HIV disease progression by way of system may increase the rate at which infected
impaired surveillance of latent viruses and other people develop clinical symptoms such as
pathogens. opportunistic infections and neoplasias. This
A separate, but related neuroendocrine model prescribes at least two sets of related
response system, the SAM system, is also targets for intervention: psychosocial experi-
activated during stressful circumstances (e.g., ences and pathophysiological processes (see
bereavement) and releases norepinephrine (NE) Figure 1) (for details see Schneiderman et al.,
and epinephrine (E). Lymphocytes have beta- 1994).
adrenergic receptors (Plaut, 1987), and beha-
vioral stressors (Manuck, 1991; Antoni, Ro-
driguez, Starr et al., 1991; Naliboff et al., 1991) 8.10.2 PREDICTING ADJUSTMENT TO
increase CD8 counts and may induce cyclic HIV INFECTION
AMP-mediated suppression of lymphocyte and Psychological Challenges in HIV
natural killer (NK) function (Plaut, 1987). Infection
Activation of both the HPA axis and the
SAM system, which may interact (Axelrod & A diagnosis of HIV seropositivity is the
Reisine, 1984), during exposure to chronic beginning of a long road of challenging life
uncontrollable stressors, could adversely affect events and extraordinary personal changes that
immunologic status (Cupps & Fauci, 1982; can overwhelm even the most psychologically
Maier et al., 1994; Roszman et al., 1985). These well-adjusted individuals. One unique aspect of
neuroendocrine patterns may also be displayed HIV infection is that it is a chronic physical
when an individual is exposed to uncontrollable disease embedded in an atmosphere of multiple
chronic stressors, has inadequate social sup- chronic psychosocial and physical demands and
port, and uses denial/avoidance coping strate- burdens. From a health psychology perspective,
gies (Antoni et al., 1990; Schneiderman et al., it is plausible to hypothesize that disease-related
1992). If depression and uncontrollable stres- and external ªlife stressorsº operate interac-
sors are associated with impaired immunologic tively and that success at managing one can
function mediated by neuroendocrine changes influence the course of the other. To test these
in HIV-infected individuals, and if intervention- types of hypotheses behavioral researchers have
associated decreases in depressed mood help to for years been examining associations between
normalize neuroendocrine functioning in this the occurrence of stressful life events and
population, then such interventions may con- alterations in people's resiliency or suscept-
currently act to attenuate neuroendocrine- ibility to a wide variety of pathogenic processes
associated immunosuppression. underlying chronic diseases such as coronary
Putting all of this information together it can heart disease, diabetes mellitus, rheumatoid
be hypothesized that stressful events or burdens arthritis, and several types of cancer. In addition
that are interpreted by HIV-infected individuals to studying the impact of stressful events, health
as beyond their control might lead to social psychology researchers, since the mid-1970s,
isolation, loneliness, anxiety, and depressed have also focused on the role of stress
affect which might accompany alterations in ªmoderatingº psychosocial variables (e.g., per-
some neurohormones (e.g., peripheral catecho- sonality characteristics and social support) and
Predicting Adjustment to HIV Infection 243


• Relaxation training • Problem Solving

• Cognitive restructuring • Assertion training
• Coping skills training • Anger management
• Social support

(+) sense of control

(+) self-efficacy
(+) self-esteem
(+) adaptive-coping

(–) anxiety, depression,social isolation

(+) quality of life

(+) parasympathetic activation

(–) sympathetic activation

(–) peripheral catecholamines and/or cortisol


(+) CD4 cell function (+) Herpes virus (+) NK cytotoxicity



Figure 1 Theoretical model for effects of stress management on disease progression in human immunodefiency
virus (HIV) infection (CD4, T-helper-inducer cells; NK, natural killer cells).

psychosocial interventions (e.g., stress manage- individuals who are coping with the complex
ment) that might reduce the negative health and multiple psychosocial demands of a chronic
influences of stressors in medically vulnerable life-threatening illness (Antoni, 1991). Homo-
populations such as those recovering from sexual men comprise a large majority of HIV-
myocardial infarction or taxing treatments for infected individuals in the United States. Today,
some types of cancer. however, an increasingly large percentage of
Because more effective medical treatment for HIV-infected people are heterosexual male drug
HIV infection is becoming available, there is users and women (Centers for Disease Control,
now a fast-growing population of infected 1995). Many of the people who are infected face
244 HIV and AIDS

lifestyle-associated social stigmas in addition to anxiety, and other distress reactions on the
the direct burdens of the HIV infection. They one hand and negative health behaviors on the
endure many of the psychosocial phenomena other. Such lapses, if severe and unremitting,
previously associated with impairments in the may contribute to a negative health course by
immune system. Some of these changes include way of increased mental health problems
overt signs of progressive physical deterioration (Cleary et al., 1988; Jacobsen, Perry, & Hirsch,
(Redfield & Burke, 1988), chronic legal pro- 1990) and acceleration of disease progression
blems (Blendon & Donelan, 1988; Ginzburg & through PNI processes. If so, then psychosocial
Gostin, 1986; Walkey, Taylor, & Green, 1990), interventions may be capable of reducing the
astronomical health-care costs (Bloom & Car- frequency and severity of these lapses with the
liner, 1988), and multiple losses due to AIDS accompanying effect of improving quality of
deaths (Martin, 1988)Ðall of which can be life, reducing immunologic perturbations, and
characterized as severe, chronic, uncontrollable, slowing the progression of the infection.
and unpredictable stressors. At the initial onset Some of the mechanisms that could mediate
of HIV-related signs and symptoms these the effects of stress management intervention on
individuals may be overwhelmed and socially the course of HIV infection have been proposed
isolated, and may employ maladaptive coping (Antoni, Schneiderman et al., 1990). According
strategies such as denial/avoidance possibly to this model, cognitive behavioral stress
resulting in an increased likelihood of depres- management (CBSM) interventions such as
sion and distress, and perhaps sexual risk relaxation training and cognitive restructuring
behaviors and substance useÐall of these are may reduce anxiety, depression, and social
potentially associated with changes in immu- isolation by way of their ability to increase a
nologic status (Antoni, 1991). sense of control, self-efficacy, and self-esteem.
Since HIV infection is a chronic, progressive These psychological changes may also be
disease with an uncertain clinical course lasting accompanied by decreases in peripheral cate-
up to 10±15 years, affected individuals must cholamines and cortisol via decreases in sympa-
develop lifestyle changes, effective coping thetic activation and improved regulation of the
strategies, and, often, new social networks to HPA axis, respectively. These neuroendocrine
meet their daily needs for hope, strength, and changes may, in turn, be associated with a
growth. Adjusting to a long-term progressive partial normalization of immune system func-
lethal illness entails addressing issues such as tions such as lymphocyte proliferation and
changes in self-expectations and preparation for NKCC that facilitate efficient surveillance of
death. These are, indeed, some of the central pathogens. To the degree that such a normal-
tasks in this stage of HIV infection (Hoffman, ization of stress-associated immune system
1991; Lutgendorf, Antoni, Schneiderman, & decrements can be achieved by stress manage-
Fletcher, 1994). A very tangible issue is that ment techniques, then any contribution of
employment status often changes dramatically stressor and stress responses processes to
at this point in the disease (Chuang, Devins, acceleration of disease and expression of clinical
Hunsley, & Gill, 1989; Dilley, Ochitil, Pert, & symptoms might be forestalled or minimized.
Volberding, 1985). One study reported that the It is arguable that such interventions can be
average monthly income of patients with AIDS targeted first to some of the more prevalent
or ARC had fallen by an average of $1000 per psychosocial and behavioral sequelae that HIV-
month since their diagnosis (Ellerman, 1989). infected people may face at various points in the
Intermittent episodes of PCP are highly asso- disease process and some of the potentially
ciated with diminished abilities to maintain changeable cognitive, affective, behavioral, and
employment (Wachtel et al., 1992). Change in social factors that may aggravate or forestall
employment status can pervade many areas of these phenomena. Some of the most well-
lifeÐloss of sources of social support, identity, established sequelae include distress states,
income, and medical insuranceÐthat, in turn, depressive symptoms, and negative health
can deplete one's resources for dealing with the behaviors.
demands of the illness (Lutgendorf, Antoni,
Schneiderman, Ironson et al., 1994).
Even for those who are successful at muster- HIV-associated Psychosocial and
ing the energy and resources for taking this Behavioral Sequelae
journey, there still remain critical stressor Distress and depression
eventsÐemergence of new symptoms, develop-
ment of resistance to a successful drug regime, HIV-infected persons appear to be at some-
loss of health insurance benefits, deaths of what increased risk from DSM-IV-Axis I
friends, rejection from family members, etc.Ð affective and adjustment disorders, and many
which can trigger lapses into depression, suffer significant subclinical distress reactions
Predicting Adjustment to HIV Infection 245

following the initial news of an HIV seropositive in the future and low levels of syndromal
diagnosis (Cleary et al., 1988; Jacobsen et al., disorder or depressive symptoms (Rabkin,
1990; Rabkin, Wagner, & Rabkin, 1996). Williams, Neugebauer, & Goetz, 1990) sug-
Among diagnosable reactions, adjustment dis- gested that interventions capable of instilling
order with depressed mood may be the most hope and self-efficacy may facilitate psycholo-
common presenting complaint with major gical adjustment. There is evidence that these
depressive disorder being far lower in preva- ªmoderatorº variables are not unique to gay
lence (Perkins, Stern, Golden et al., 1994; men. Psychosocial characteristics of HIV-posi-
Rabkin et al., 1996; Williams, Rabkin, Remien tive hemophiliacs related to elevated depression
et al., 1991). One study found that the suicide and distress included (i) a previous history of
rate among HIV-infected men may be up to 36 premorbid psychiatric disturbance/distress, (ii)
times that of age-matched uninfected men experiencing recent life events involving loss,
(Marzuk et al., 1988; Rundell, Paolucci, & (iii) low social support from spouse, family, and
Beatty, 1988), supporting the view that depres- friends, and (iv) a poor sense of mastery over life
sive symptoms are a common sequel to an HIV (Dew, Ragni, & Nimorwicz, 1990). Although
diagnosis and especially in those with a prior based on a small heterosexual sample and a
history of depression (Rabkin, Rabkin, Harri- cross-sectional design, this work suggests the
son, & Wagner, 1994). Pharmacologic treat- importance of uncontrollable loss-oriented life
ments for depression such as imipramine and stressors, social isolation, and a lack of self-
serotonin reuptake inhibitors have been shown efficacy as deterrents of psychological adjust-
to be safe and effective with HIV-infected ment to HIV infection.
samples (Rabkin et al., 1996). Newer work While the psychosocial sequelae of HIV
suggests that other biological approaches such infection are reasonably well-documented for
as testosterone replacement therapy may also male samples, far less is known about what
offer antidepressant effects (Rabkin et al., women experience during the course of this
1996). The coexistence of feelings of life-threat, disease. Such information is imperative given
doom, anger, and responsibility for making the fact that the incidence of AIDS has
immediate lifestyle changes following a sero- increased at a faster rate for women than for
positive diagnosis (Christ & Wiener, 1985; any other subgroup in the population of the
Kaisch & Anton-Culver, 1989; Viney et al., United States (Carpenter, Mayer, Fisher, Desai,
1989) suggests that psychosocial interventions & Durand, 1989; CDC, 1995a). AIDS incidence
that provide support, teach coping strategies, data through June 1996 indicates nearly 20% of
and offer the opportunity for mastery experi- all new AIDS cases are women (CDC, 1995b).
ences may also be beneficial. Such interventions AIDS cases and infected and at-risk women are
may also help these individuals to ventilate disproportionately represented among minority
feelings such as anger (Miller, 1988) and manage populations, especially Blacks (Antoni, Schnei-
anticipatory grief over the expectation of loss derman et al., 1992; CDC, 1995b). Young,
and death (Cohen, 1990; Pickrel, 1989). To the Black American, low socioeconomic status
extent that HIV infection constitutes a chronic (SES) women have been characterized as a
long-term disease, it is arguable that psychoso- group experiencing the triple stigmas of race,
cial intervention plays a key role in the class, and gender, prior to the addition of the
treatment of HIV-infected persons. We have burden of HIV seropositivity (Quinn, 1993) as
reasoned that all of these putative intervention well as multiple chronic daily stressors (Freu-
effects are likely to be facilitated within a denberg, Lee, & Silver, 1989; Mays & Cochran,
supportive group environment (Antoni, Schnei- 1988). These stressors include drug and alcohol
derman, & Ironson, in press). dependency, poor social networks, medical
Some of the evidence supporting the possible problems, financial problems, overburdened
psychological benefits of a cognitive-behavioral public clinics, lack of transportation, and
treatment orientation for HIV-infected indivi- inaccessibility of child care, all potentially
duals comes from the patterns of results fueling a general feeling of helplessness and
emerging from natural history studies con- powerlessness (Quinn, 1993).
ducted since the mid-1980s. For instance, there These stressors may be compounded even
is growing evidence that the ways in which more by pregnancy (Antoni, Schneiderman
individuals cognitively and behaviorally cope et al., 1992). Relevant stressors here include
with HIV-related stressors can influence their the decision to abort or continue pregnancy to
ability to establish psychological equilibrium at term, fears of becoming too ill to provide for
least within a given stage of the infection. In a offspring, and preparing older children for life
community sample of 208 HIV-positive and as orphans. Seropositive mothers with unpro-
HIV-negative, successful, and well-educated tected partners are also likely to face rejection
gay men, the coexistence of high levels of faith by the father of their children, resulting in
246 HIV and AIDS

emotional and financial isolation at a time when depressive symptoms may be more likely to
these women are most in need of support. occur in HIV-infected men and women who are
Conversely, HIV seropositive women may react substance abusers, especially those who are
to an infected partner with self-isolation, both injection drug users (IDUs) (Rabkin et al.,
of which are likely to leave her and her offspring 1996). Thus, chronic depressive symptoms,
alone. If both mother and child are seropositive, substance abuse, and unprotected sexual beha-
the lack of emotional and financial support viors may be highly interrelated and self-
could make the situation even worse. Thus, the perpetuating.
risk for significant emotional problems in HIV- Psychological factors related to the adoption
infected mothers is obvious. It is critical that and maintenance of reduced sexual risk beha-
future work focus on factors contributing to viors include self-efficacy for safe sex, having
depressive symptoms and mental adjustment in alternative coping strategies for dealing with
these growing populations of HIV-infected high-risk sexual impulses, and possessing skills
persons so that effective interventions can be for negotiating with interpersonal contacts
developed. (Kelly & St. Lawrence, 1988; McCusick, Horts-
man, & Coates, 1985), while similar constructs
such as condom efficacy and perceived vulner- Risk behavior and substance use
ability have been shown to predict sexual risk
In addition to the influence of mood behaviors in injection drug users (Lollis et al.,
disturbances, psychosocial adjustment to HIV 1995). Denial of virulence and denial of
may be intimately related to negative health personal responsibility, and frequent drug and
behaviors. In fact, certain negative health alcohol use preceding sex (which are likely to
behaviors may show a bidirectional relationship facilitate one another) are also associated with
with depression and distress levels. Two such continued high-risk behavior (Martin, 1990b).
negative health behaviors that are salient in the Specifically, Martin (1990b) found consistent
context of HIV infection are sexual risk associations between drug use (marijuana,
behaviors and substance use. It is known for inhaled nitrates, cocaine, hallucinogens, barbi-
instance, that depressed people are often more tuates, and amphetamine) and unprotected
likely to engage in risky (unprotected) sexual insertive and receptive anal intercourse among
behaviors (Gold & Skinner, 1992; Kelly et al., 604 urban, middle-class gay men in the year
1993) and substance abuse (Rabkin et al., 1996). prior to their development of AIDS. Cessation
Beyond the fact that these two sets of behaviors of drug use with sex predicted subsequent lower
are associated with transmission of the virus, it rates of unprotected anal intercourse (Martin,
is also well known that they occur at very high 1990). Thus, one way to intervene to reduce
rates in persons who are having difficulty high-risk sexual behaviors may be to modulate
dealing with being HIV-infected. drug and alcohol use perhaps by improving the
Despite reductions in sexual risk behaviors ways individuals manage HIV-related stressors.
among urban gay men since 1987, a significant Among 624 gay men, two categories of life
number continue to engage in unprotected anal stressorsÐdeaths of loved ones due to AIDS
intercourse (Martin, 1989), the sexual activity and fear of illness and one's own death due to
that carries the highest risk for HIV infection in HIV infectionÐwere associated with high-risk
gay men (Kingsley et al., 1987). Importantly, as sexual behaviors and drug and alcohol use as
many as 15% of those gay men who modified well as psychological distress (Martin, 1989).
their sexual behaviors in the early years of the Perceived self-efficacy and social support have
AIDS crisis have relapsed to unsafe sexual also been shown to be critical for maintaining
activities (Coates, 1991). One important factor adherence to safer sex guidelines (Stall, Coates,
that may influence such risk-taking behavior is & Hoff, 1988). Thus, among HIV-infected
the use of alcohol and drugs during sex (Martin, individuals, in addition to being associated
1990b). The prevalence of alcohol abuse in the with depressive symptoms, low self-efficacy,
gay community is significantly higher (30%) social support losses, and denial coping strate-
than for the general population (5±10%) gies may relate to the onset and maintenance of
(Fifield, 1975; Lohrenz, Connelly, Coyne, & substance use and sexual risk behaviors and
Spare, 1978; Martin, 1990b). Importantly, these may all be interrelated.
alcohol and drug use is strongly asociated with The role of ethnic, racial, cultural, and
sexual behaviors and may determine adherence religious factors in influencing sexual behavior
to safer sex guidelines in gay men (Martin, patterns is also an important consideration
1990b) as well as other populations who are at (Mays & Cochran, 1988); hence sociocultural
risk from HIV infection (Lollis, Antoni, influences on risk behavior reduction need to be
Johnson, Chitwood, & Griffin, 1995; Lollis, understood. For poor ethnic minority women
Johnson, Antoni, & Hinkle, 1996). Finally, who are at risk of HIV infection or are already
Predicting Adjustment to HIV Infection 247

infected, the risk of AIDS is only one risk in a own desire for social insularity and the
long list of multiple risks that are prevalent in avoidance by acquaintances and significant
daily existence. The key to behavior change is others following disclosure of homosexual
where in this list the women place the relatively orientation (Beckett & Rutan, 1990; Gambe
longer-term consequences of AIDS-related risk & Getzel, 1989) may create a chronic lack of
behavior in relation to the short-term conse- resources available to deal with stressors, thus
quences of the risks of daily life (e.g., safety, compounding these adjustment problems. We
food, shelter, human contact). From this now review some of these phenomena in greater
vantage point, behavior change specialists need detail to demonstrate how they interact.
to be aware of more immediate survival needs
which, if met, can provide the opportunity for Uncontrollable stressors
professionals to educate and intervene effec-
tively. Within this deeper understanding of the There are numerous psychosocial challenges
sociocultural milieu is the knowledge that the following a diagnosis of HIV seropositivity.
pervasive powerlessness experienced by disad- Among 240 gay and bisexual men, specific
vantaged women at risk may lead them to stressorsÐreceiving an HIV-positive diagnosis,
disengage from attempts at coping when an AIDS diagnosis, an AIDS-related complex
informed about risk behaviors. (ARC) diagnosis (the prior designation for
having overt HIV-related symptoms but not yet
developing AIDS), and learning of the death or Psychosocial Factors Predictive of AIDS diagnosis of a loverÐwere rated as the
Depression and Risk Behaviors in HIV most emotionally distressing events that these
Infection people deal with (Rosser, Simon, & Michael,
1988). It is well-established that stressful life
There is good evidence suggesting that the events shown to relate to depression and
risk of depressive symptoms in HIV-infected physical health consequences are those which
persons is strongly tied to a prior history of are perceived as being beyond the individual's
depression (Rabkin et al., 1994). Other risk control (Justice, 1985). These events may also
factors include a family history of depression, relate to increases in negative health behaviors.
alcohol abuse, other substance abuse, and social A variety of stressful events have been asso-
isolation (Rabkin et al., 1996). There are also ciated with alcohol consumption (Foy, Sip-
several psychosocial events that may follow the prelle, Rueger et al., 1984; Newcomb & Harlow,
onset of initial HIV diagnosis and related 1986) and low personal control is believed to be a
symptoms (Antoni, Baggett et al., 1991; mediator of this relationship (Beckman, 1980;
Schneiderman et al., 1992) and these may Pearlin & Radabaugh, 1976). Similar findings
predict an increased likelihood of depression are evident in gay men and may be more
and distress, sexual risk behaviors, and sub- prevalent than in other populations given the
stance use. These include: chronic, uncontrol- reinforcement of heavy drinking in gay bars, a
lable, and unpredictable stressors such as primary social gathering place (Nardi, 1982).
treatment nonresponsiveness and side effects, Prevalence may similarly be enhanced in
disease recurrence, stigmatizing behaviors, and homosexual men as well as in ethnic minority
medical costs (Blendon & Donelan, 1988; group members due to the likelihood that
Bloom & Carliner, 1988; Ginzburg & Gostin, alcohol (and drugs) are used to cope with
1986; Redfield & Burke, 1988; Walkey, Taylor, burdens associated with being gay or otherwise
& Green, 1990). Inability to cope with these disenfranchised in the society (e.g., guilt,
mounting stressors may bring about a loss of anxiety, alienation, powerlessness) (Lohrenz
self-esteem and self-efficacy, feelings of help- et al., 1978). According to the identity disrup-
lessness and hopelessness, depression, and an tion model (Lohrenz et al., 1978), negative life
increase in maladaptive, potentially self-de- events that disturb one's self-concept or identity
structive negative health behaviors. The com- have the greatest deleterious effects. Self-con-
bination of uncontrollable life stressors and ceptions determine the way personal informa-
feelings of helplessness may increase cognitive tion is appraised and processed, and the nature
and emotional burdens (Noh, Chandarana, of social interactions. Identity disruptions,
Field, & Posthuma, 1990) that may overwhelm according to this model, may impair functioning
premorbid coping strategies such as active by causing individuals to devote excess time and
problem-solving and positive reframing result- energy to the stressor, and undermine their sense
ing in the use of denial/avoidance coping of control and ability to predict other aspects of
strategies or giving up entirely. Loss of familiar their lives. For those diagnosed with HIV
sources of social support due to deaths of close infection, each HIV-associated stressor experi-
friends (Martin, 1988), the infected person's enced may erode their previous self-concept
248 HIV and AIDS

giving way, possibly, to self-blame for their blame, opportunities for social comparison,
seropositivity (Hoffman, 1991). repertoire of adaptive coping strategies, and the
sense of self-efficacy necessary for using these
strategies. Stressor appraisals
Coping strategies classified as active-beha-
In addition to providing an overt sign of vioral (planning, seeking social support) or
disease progression, physical changes such as active-cognitive (finding meaning in an illness,
skin lesions, muscle wasting, and fungal infec- reframing) have been related to more positive
tions may compromise self-image in HIV- affect and higher self-esteem in various chronic
infected persons (Hoffman, 1991; Ostrow, disease populations (Billings & Moos, 1981;
Monjan et al., 1989). Infected individuals who Bloom, 1982; Fawzy et al., 1990; Felton,
see the onset of these changes as uncontrollable Revenson, & Hinrichsen, 1984). Conversely,
may attempt to cope by way of denial and denial and avoidance strategies are associated
increased substance use (Kaisen & Anton- with greater depression and distress (Billings &
Culver, 1989). These maladaptive strategies Moos, 1981; Namir, Wolcott, Fawzy, &
may affect psychological adjustment, future risk Alumbaugh, 1987). Individual differences in
behaviors, and physical health (Burns et al., available coping strategies for dealing with
1991; Ironson et al., 1992; Penkower et al., stressors may be among the most significant
1991). It is well known that a person's appraisal predictors of depression and future adjustment
of stressful events may determine the indivi- to HIV seropositivity (Namir et al., 1987;
dual's coping responses and emotional state Weimer, Nilsson-Schonnesson, & Clement,
(e.g., depression) (Lazarus & Folkman, 1984). 1989) and may, possibly, play a role in future
Appraisals that are particularly relevant to the clinical disease progression (Ironson et al.,
demands of an HIV diagnosis include those 1992). One group prospectively related coping
concerning harm/loss (e.g., loss of relationships, strategies and immunologic measures in HIV
physical abilities, independence [Beckett & seropositive gay men over the one year period
Rutan, 1990; Ferrara, 1984], threat (e.g., following notification of their antibody test
threat/anticipation of future symptoms [Hoff- results (Antoni et al., 1995a). Asymptomatic
man, 1991]), and challenge (e.g., opportunities seropositive men's coping responses to antibody
for personal growth)Ðthree domains that have status notification were measured concurrently
been studied extensively by Lazarus and Folk- with phenotypic and functional immunologic
man. Thus, one important goal of psychosocial markers, and these immunologic measures were
intervention is to help individuals enhance their taken again one year later. Seropositive men
sense of self-efficacy for dealing with the losses, scoring above the median on postnotification
threats, and challenges characterizing the disengagement coping strategies (denial, beha-
physical and psychosocial sequelae of their vioral disengagement, mental disengagement)
HIV infection. Efforts to build self-efficacy may had significantly lower concurrently measured
be most effective early in the course of the T-helper/suppressor (CD4/CD8) cell ratios, T-
psychosocial intervention and can be enhanced helper±inducer subset (CD4+CD45RA+) %
by constructing a supportive group environ- values, and proliferative responses to PHA than
ment and teaching participants tangible strate- men scoring below the median on these scales.
gies for managing daily hassles as well as major Disengagement coping responses also predicted
environmental stressors and their cognitive, one-year follow-up immune status; greater
behavioral, emotional, and interpersonal re- disengagement predicted poorer lymphocyte
sponses to these events. responsivity to PHA. Together these prelimin-
ary findings suggested that strategies that
distract seropositive individuals from the stress Coping with HIV-related symptoms
of infectivity are related to greater levels of
Individuals previously diagnosed with HIV depressed affect and distress, as well as more
infection, who have not yet developed AIDS- impairment on some immunologic measures,
defining symptoms, report an overwhelming and these relationships appeared to persist over
sense of uncertainty (Dew et al., 1990). This as long as a 12-month period.
uncertainty may actually contribute to the
higher incidence of adjustment disorders re- Social support
ported for those with symptomatic pre-AIDS
conditions vs. those with full-blown AIDS Social resources have been found to buffer
(Dilley et al., 1985). Uncertainty about one's the negative physical and psychological effects
immediate future creates critical demands for of major stressful events ranging from con-
coping, the success of which may depend upon centration camps to hurricanes (Lutgendorf
an individual's appraisals, attributions of et al., 1995; Sarason, Potter, Sarason, & Antoni,
Predicting Adjustment to HIV Infection 249

1985; Schneiderman et al., 1992). Buffering (ii) satisfaction with received support (Hays,
effects of social support have been attributed to Turner, & Coates, 1992);
increased opportunities for intimacy, integra- (iii) perceived helpfulness of peers (Hays,
tion through shared concerns, reassurance of Chauncey, & Tobey, 1990);
worth, nurturance, reliable alliance, and (iv) total perceived availability of support as
guidanceÐall potentially facilitating task-or- well as individual dimensions of support
iented thinking and active coping while decreas- (O'Brien, Wortman, Kessler, & Joseph, 1990;
ing helplessness and depression (Sarason, 1979). Turner, Hays, & Coates, 1993; Zich & Te-
On the other hand, socially isolated individuals moshok, 1987);
may be more likely to maintain maladaptive (v) absence of social conflict (Lesserman et
stressor appraisals such as catastrophizing, self- al. 1995; O'Brien et al., 1993);
blame, and helplessness, and may employ denial (vi) greater involvement in AIDS-related
as a chief coping strategy. The many losses in community activities (Lesserman, Perkins, &
interpersonal and institutional support re- Evans, 1992); and
sources (Hoffman, 1991) may be responsible (vii) a greater number of close friends (Hays
for the sense of isolation reported by some HIV- et al., 1990).
infected individuals (Dilley et al., 1985). Each of these aspects of support has been
Issues regarding social support may be associated with lower levels of depression and,
especially salient for HIV-infected women, in some studies, with lower levels of hope-
many of whom are indigent minority group lessness, anxiety, mood disturbance, risk beha-
members who have been marginalized by their viors, and greater overall sense of psychological
social groups leaving them with limited re- well-being in a variety of populations (Christ &
sources available to care for themselves or their Wiener, 1985; Cutrona & Russell, 1987; Don-
children (Guinan, 1987; Nyamathi & Lewis, lou, Wolcott, Gottlieb, & Landsverk, 1985;
1991). This threatens their roles as caregivers Friedman et al., 1991; Namir et al., 1989;
and mothers significantly (Buckingham & Ostrow, Joseph et al., 1989; Zich & Temoshok,
Rehm, 1987; Chung & Magraw, 1992). Trying 1987). One study found that greater support
to cope with being ill and the challenges of satisfaction and greater involvement in AIDS-
motherhood concurrently can be overwhelm- related community activities were associated
ing. Having to disclose to children one's with a greater use of coping strategies such as
serostatus and medical condition are further cognitive reframing and fighting spirit which
challenges that these women face. Women with were in turn associated with less dysphoria and
AIDS feel and experience stigma and shame by greater self-esteem (Lesserman et al., 1992).
being presumed to be dangerous (Chung & Prior studies of HIV-positive men suggest that
Magraw, 1992). Community support efforts social support may determine the choice be-
may appear to them to be primarily directed to tween active behavioral coping and less adap-
gay men and they may respond to this with tive strategies. For instance, greater social
resentment and despair (Mackie, 1993). support availability and satisfaction associated
It is important to remember, however, that with active coping and lower support avail-
gay men may also be at increased risk of social ability is associated with a greater use of denial/
isolation. Given the number of HIV-infected avoidance strategies (Martin, 1989). Also, lack
gay men experiencing multiple bereavements of family support and other important support
(Martin, 1988), coupled with their reported low sources have been proposed as contribitors to
average support network size (comprised alcohol abuse (Nardi, 1982), though little is
mainly of friends) (Namir, Alumbaugh, Fawzy, known about the ways in which ethnicity and
& Wolcott, 1989), any loss in such social socioeconomic status may moderate this rela-
support may be especially devastating. Other, tionship. In a large cohort of gay men in San
less stable, social resources such as employment Francisco, men who reported always using
circles (Chung et al., 1989; Dilley, et al., 1985) condoms had higher levels of social support
may also be lost as the HIV infection progresses, from informal sources of help (friends, sex
with job loss having negative effects on both partners) (Catania et al., 1991). Thus social
financial status, self-esteem, and emotional support may be viewed as a coping resource to
functioning. the extent that it channels, facilitates, or perpe-
In a recently published review, Zuckerman tuates the use of coping strategies with stress-
and Antoni (1995) suggest that certain social buffering properties.
support criteria are related to optimal psycho- Unfortunately, social support may actually
logical adjustment in HIV-positive individuals. decrease as the number of symptoms increases
These include: in HIV-infected individuals (Hays et. al., 1990).
(i) a general sense of feeling supported (Na- This may be due to caregivers and other support
mir et al., 1989); network members pulling back from persons
250 HIV and AIDS

with AIDS (PWA) to prevent burnout and sitive diagnosis may reduce both the availability
emotional exhaustion (Turner et. al., 1993). and utilization of social support (Christ &
Since family members may attempt to distance Wiener, 1975; Donlou et al., 1985) which may
themselves emotionally from this traumatic increase the risk of depression, hopelessness,
situation, the importance of peers and fellow and less adaptive strategies such as substance
PWA's in the social support networks of HIV- use (Friedman et al., 1991; Nardi, 1982; Ostrow,
infected individuals may increase. These people Joseph et al., 1989). Similar phenomena may
can be important sources of informational occur in those diagnosed with HIV symptoms or
support and often provide the greatest oppor- full-blown AIDS for the first time (Namir et al.,
tunity for support (Hays et al., 1990). As such, 1989; Zich & Temoshok, 1987). Thus social
peers often fill in the ªsupport gapsº left behind support may be related to depression, substance
by family and professional caregivers (Zucker- use, and sexual risk behaviors at many stages
man & Antoni, 1995). HIV infection. Its influence may also vary as a
It is important to realize that some forms of function of ethnicity, among other factors such
social interaction may actually be associated as SES and educational level. While available
with increased levels of psychological distress in and adequate social supports might enhance
HIV-infected persons. Among asymptomatic HIV-infected people's ability to manage their
HIV-infected gay men, increases in social infection and related stressors by functioning as
conflict, and dissatisfaction with social support a key coping resource, negative conflictual
in general predicted greater increases in distress social interactions may actually act as a
and depression over a one-year period (Lesser- deterrent to successful adjustment.
man et al., 1995). These social conflicts can
include rejection messages from family mem-
bers, breaking up or declining quality of 8.10.3 PREDICTING THE HEALTH
romantic relationships, and trouble with em- COURSE OF HIV INFECTION
ployers, among others. Another study revealed With the emergence of data in the 1990s from
that the type of support deemed most useful long-term cohort studies, it is now well-
depended largely on the situation confronting established that some patients who are HIV
the individual and the context of the support positive develop symptoms rapidly while others
provision: emotional support was generally remain free of AIDS symptoms over a decade.
seen as being helpful from all providers in From a secondary prevention standpoint this
almost any situation, while informational or means that it is important to isolate factors that
problem-solving support was viewed as helpful account for the wide variability in the transit
only from medical experts and other PWA's time for the clinical manifestations of HIV
(Zich & Temoshok, 1987). The relative effec- infection. Since 1990, new terms have been
tiveness of problem-focused vs. emotional- developed to reflect those who somehow outlive
focused support may also depend on factors or outpace their prognosis following HIV
such as disease stage (asymptomatic vs. AIDS) infection. One grouping consists of nonpro-
and stressor qualities such as controllability. gressors with HIVÐpersons who are HIV-
Folkman and colleagues have suggested that positive yet maintain near normal levels of CD4
problem-focused coping strategies may be most numbers. Another grouping consists of those
useful when directed toward controllable who are asymptomatic low CD4Ðpeople with
aspects of stressors, while emotion-focused very low CD4 counts (5 50 cells mm73) who
strategies may be most effective when targeted remain asymptomatic for extended periods of
toward uncontrollable aspects of stressors time. Finally, there are those termed long-term
(Folkman et al., 1991). Extending the coping survivors of symptomatic AIDS. While the
theory of Folkman and her colleagues to the sources of individual variability in HIV pro-
context of matching social support resources gression remain largely unknown, a growing
(e.g., emotional vs. informational) to situa- body of literature suggests that the key may lie
tional demands (e.g., uncontrollable vs. con- in some combination of biological and psycho-
trollable) has been proposed as a reasonable logical factors (Ironson et al., 1995).
strategy for providing the most useful support
to individuals who are dealing with the different
burdens of HIV infection (Zuckerman & Biological Factors and Disease
Antoni, 1995). Progression
In sum, inadequate social support or a sense Constitutional factors
of social isolation may exaggerate the deleter-
ious effects of stressful events on depression and Some biological factors influencing length of
negative health behaviors in HIV-infected survival (Friedland et al., 1991; Hardy et al.,
persons (Cutrona & Russell, 1987). A seropo- 1991) include age (e.g., younger persons live
Predicting the Health Course of HIV Infection 251

more years once infected [Jacobson et al., 1991; renal transplant, reactivation of one or more
Lemp et al., 1990]), gender (e.g., men live longer of the latent herpes viruses results in severe
following diagnosis with AIDS [Brown, 1989]), morbidity (Ernberg, 1986; McVoy & Adler,
ethnicity, and initial AIDS-related disease 1989; Rinaldo, 1990; Yao, Rickinson, Gaston,
manifestation (having Kaposi's sarcoma vs. & Epstein, 1985). Moreover, herpes viruses are
PCP as the presenting symptomatic criterion for known to suppress a wide number of immuno-
AIDS (Friedland et al., 1991). Risk group logic functions including cytokine production
membership (Detels et al., 1988; Shine et al., and lymphocyte blastogenesis to mitogens
1987) and presence of, or prior history of, other (Rinaldo, 1990). These phenomena suggest that
concomitant sexually transmitted diseases HIV and herpes viruses may interact to
(STDs) also appear important. Disease pro- perpetuate disruptions in the biological control
gression markers, such as CD4 cell counts, may of each respective infection, possibly contribut-
also be predictive of disease progression. For ing to the severity and chronicity of related
instance, prior rate of CD4 decline and body clinical signs and symptoms.
mass index predict the amount of time until the Because several herpes viruses prevalent in
infected people's level of CD4 cells drops below HIV-infected individuals are known to have
200 cells mm73, the point at which symptomatic independent immunosuppressive effects, reacti-
AIDS often occurs (Hoover et al., 1995). vation of these viruses could have implications
for progression to AIDS (Griffiths & Grundy,
1987). Subclinically these surveillance effects Other viral infections
may be observed as rising antibody (IgG) titers
Another set of biological factors influencing to EBV, HHV-6, CMV, and HSV-2. One could
the course of HIV infection may be the degree to speculate that clinically, the inability to survey
which other latent viruses (e.g., several types of these latent viruses may be manifest in EBV-
herpes viruses) become reactivated (Rosenberg associated Burkitt's lymphoma (Doll & List,
& Fauci, 1991). This point, taken in view of the 1982) and oral hairy leukoplakia (Eversole,
psychosocial phenomena reviewed previously, Stone, & Beckman 1988; Greenspan et al.,
is a critically important consideration for PNI 1985); CMV-associated retinitis, encephalitis
research with HIV-infected populations given hepatitis, adrenalitis, and gastrointestinal
that (i) several psychosocial stressors have been pathologies (Blumberg, 1984; Henderly et al.,
related to immune system decrements and to 1987; Schooley, 1990; Tapper et al., 1984); and
signs of reactivation of one or more latent HSV-associated proctitis (Goodell et al., 1983),
herpes viruses, and (ii) increases in sexual risk esophagitis (Levine, Woldenberg, Herlinger, &
behaviors, which may ensue following some of Laufer, 1987), and aseptic meningitis (Dahan,
these psychosocial phenomena, may place Haettich, LeParc, & Paolaggi, 1987).
infected individuals at greater risk of contract- There is also evidence that reactivation of
ing a new herpes virus infection. It has been several of these herpes viruses may act to further
reasoned that if stressors (Glaser & Kiecolt- stimulate HIV replication and progression to
Glaser, 1987) and behavioral interventions AIDS (Carbonari et al., 1989; Hammarskjold &
(Antoni, Esterling, Lutgendorf et al., 1995) Heimer, 1988; Lusso et al., 1989; Rosenberg &
affect the immune system's ability to control Fauci, 1991; Sumaya, Boswell, & Ench, 1986).
latent herpes viruses in a wide variety of CMV, one of the herpes viruses, is an important
populations, then stressors and interventions opportunistic pathogen in HIV infection (Ri-
might also influence herpes virus-mediated naldo, 1990) and has been shown to enhance
progression of clinical disease in HIV-infected susceptibility to secondary opportunistic patho-
individuals. gens in immunosuppressed populations (Pers-
Importantly, herpes viruses persist in the host san et al., 1987). It is among the most
indefinitely once they are infected (Rinaldo, immunosuppressive of the herpes viruses im-
1990). Varicella and HSV establish latent pairing blastogenic responses and g-interferon
infections in neurons, whereas CMV, Human production by T-lymphocytes (Rinaldo, 1990)
Herpes Virus Type-6 (HHV-6), and EBV persist and it has also been shown to alter the growth
in lymphocytes. When an individual is infected and expression of HIV in culture, possibly
with one of the herpes viruses, seroconversion accelerating progression to AIDS among in-
and latency results, with or without the presence fected persons (Biegalke & Geballe, 1991; Paya,
of clinical disease. In healthy individuals, herpes Virelizier, & Michelson, 1991). Webster (1991)
viruses can reactivate spontaneously and often found that among HIV-infected individuals, the
in the absence of clinical symptoms. Under age-adjusted relative risk of developing AIDS
sustained states of cellular immunodeficiency, was 2.5 times higher in those who were
such as in persons infected with HIV or in those coinfected with CMV compared to those who
undergoing immunosuppressive therapy for were CMV seronegative.
252 HIV and AIDS

In sum, although some mechanisms are still Bregman, 1985). It is noteworthy that several of
being explored, the fact that herpes viruses may these behaviors have been associated with
be related to HIV associated sequelae is immunomodulation in other populations. Ci-
intriguing. For example, because HHV-6 may garette smoking has been associated with
reactivate during EBV infections, and because significant decreases in helper cells and increases
both EBV and HHV-6 may reactivate following in suppressor/cytotoxic cells (Miller, Goldstein,
immunosuppression by HIV, these three viruses & Murphy, 1982). Alcohol use has been related
may potentiate one another in the progression to depressed cell-mediated immunity (Watson,
of clinical disease. Through direct immunosup- Eskelson, & Hartman, 1984), decreased lym-
pression or transactivation of HIV (by CMV or phocyte number and diminished lymphocyte
HSV), latent herpes viruses may be considered blastogenesis (Glassman, Bennet, & Randal,
as potential cofactors in the development of 1985), bone marrow myelosuppression (Tisman
AIDS. It is quite plausible that HIV-associated et al., 1971), and abnormal granulocyte chemo-
effects on the cells of the immune system may taxis (Atkinson et al., 1977). Other work suggests
perpetuate a downward spiral in the functional that alcohol abuse may amplify the suppressive
ability of the immune system to survey and effects of mental depression on immunologic
control latent viruses which, when left un- impairments (Irwin, Caldwell et al., 1990).
checked, may act to increase replication of the Recreational drug usage (e.g., heroine) has been
primary virus. associated with depressed cellular immune
The implication of these findings is that the functioning in one study (Lazzarin, Mella, &
host's ability to control such viruses may be a Trombini, 1984), and with suppressed NK cell
ªdownstreamº immune system marker that has killing in another (Katz, Zaytoun, & Faici,
more meaning as a predictor of HIV clinical 1982). Some of this work has focused specifically
disease and possibly the acceleration of viral on HIV-infected samples. For instance, there is
load than does the CD4 cell count alone. We growing evidence that injection drug use (Seage
know that changes in HIV viral load, viral et al., 1993; Weber, Ledergerber, Opravil,
character (appearance of syncytium-inducing Siegenthaler & Luthy, 1990) and even cigarette
variants), and CD8-directed cytotoxity against smoking (Burns et al., 1991; Nieman, Fleming,
HIV are the key predictors of individual Coker, Harris, & Mitchell, 1993; Royce &
differences in clinical disease progression (Pan- Winkelstein, 1990) may be associated with faster
taleo et al., 1993). These ªpredictorsº all speak to disease progression in HIV-infected people. The
the importance of the host maintaining vigorous specific mechanisms by which these substances
surveillance and control over HIV (through affect immune functioning are still in the process
well-coordinated cytotoxic responses), and sta- of being elucidated. It is noteworthy that some of
bilized HIV replication (reflected in stable viral these substances are associated with alterations
load and predominantly nonsyncytium-produ- in those physiological stress response systems
cing types). Given this understanding of the noted previously. For instance, nicotine in
importance of qualitative aspects of the immune cigarette smoke is associated with catecholamine
system (surveillance functions and signs of discharge (Blaney, 1985) and ethanol consump-
poorly surveyed viruses) in HIV disease pro- tion is also linked with catecholamine elevations
gression, it is surprising that so little research has due to blockage of re-uptake (Davidson, 1985).
been published on the effects of biomedical and Nutritional factors and vitamin deficiencies
psychosocial interventions on qualitative im- may contribute to immunologic decrements in
mune measures including those reflecting sur- HIV infection. Protein-caloric malnutrition is
veillance of specific pathogens such as latent associated with a wide range of immune
herpes viruses. impairments and is believed to explain the
increased susceptibility to disease in under-
nourished populations of many Third World Behavioral and Psychosocial Factors countries (Stites, Stobo, Fudenberg, & Wells,
and Disease Progression 1982). Some work also suggests that alterations
in certain vitamin levels, for instance, vitamin B6 Behavioral factors
deficiencies, may be associated with immune
Behavioral factors such as the use of alcohol, system decrements in HIV-infected persons
tobacco, caffeine, recreational drugs (cocaine, (Baum et al., 1991).
nitrites) during sex, unprotected anal inter- A series of studies has presented evidence for
course, and poor nutrition have also been immunomodulatory effects of sleep deprivation
suggested as possible cofactors of accelerated including decreases in lymphoproliferative re-
HIV disease progression (Chiappelli, Ben- sponses and diminished granulocyte function-
Eliyahu, Hanson & Wylie 1992; Griensven ing (Palmblad et al., 1976; Palmblad, Petrini,
et al., 1990; Haverkos, Pinsky, Drotman, & Wasserman, & Akerstedt, 1979). One study,
Predicting the Health Course of HIV Infection 253

done in the mid-1990s, noted that the decre- accelerated disease course by promoting HIV
ments in immune function (NKCC) evident in replication (for review see Antoni, Esterling,
victims of a hurricane over the months follow- Lutgendorf et al., 1995). Therefore, efforts to
ing the storm were mediated, in part, by sleep modify risky sexual behaviors in already
disruptions (Ironson et al., 1997). Other work infected individuals can be seen as a secondary
has indicated that human IL-1 levels peak at the prevention strategy. Finally, PCP treatment
onset of slow wave sleep (Krueger & Karnovs- prophylaxis, antiretroviral combination ther-
ky, 1987), suggesting that cellular immunity apy, and the new breed of protease inhibitors
may be affected by qualitative, as well as may influence survival after AIDS onset (Saah
quantitative, aspects of sleep and accompanying et al., 1994). From a behavioral standpoint, an
cytokine changes. Important for HIV-infected HIV-infected individual's decision and actions
populations is the fact that sleep disruptions are taken to pursue these treatments, at the earliest
one of the hallmarks of clinical depression. point following the emergence of symptoms or
Numerous other biological factors may alter after dropping below landmark values for CD4
stress hormone levels and immune functioning cell counts (e.g., 5 200 cell mm73), may play a
such as aging, steroid use, sex hormone large role in health maintenance.
fluctuations, radiation treatment, as well as a We have reasoned that if psychological
multitude of medication regimens (Stites et al., factors affect the immune systems of HIV-
1982). Generally these variables are not likely to infected individuals, then even small immune
be responsive to health psychology interven- changes might have clinical relevance since this
tions and thus will not be reviewed here. population's immunologic functioning is al-
However, it is essential that these phenomena ready significantly impaired by the virus
and others be measured and carefully controlled (Antoni, Schneiderman et al., 1990; Schneider-
in any investigations of the influence of man et al., 1994). Healthy uninfected people in
biological, behavioral, and psychosocial factors the normal population possess many checks,
in HIV disease progression. balances, and compensatory mechanisms built
Another variable that may deserve further into their immune systems. Since HIV-infected
attention is heightened sympathetic nervous individuals are just at, or above, the number of
system responsiveness to stressful situations. T-lymphocyte subsets necessary for responding
The stress hormonal elevations known to to encountered pathogens (e.g., 200±500
accompany this hyper-responsiveness (Rose, CD4 cells mm73), then small changes, of un-
1980) may have immunomodulatory effects. known magnitude, could quite possibly have
Interestingly, a growing literature suggests that an impact on the incidence of a wide range
pharmacologic agents that attenuate cardiovas- of infections due to normally harmless bacter-
cular hyper-responsiveness (Bonelli, 1982; ias, viruses, fungi, and other opportunistic
Dimsdale, Hartley, Ruskin, Greenblatt, & pathogens.
Labrie, 1984) may also alter immune function- In addition to behavioral factors, there is
ing (Benschop et al., 1994; Hatfield, Petersen, & some evidence that several psychosocial
DiMicco, 1986; Weisdorf & Jacob, 1987). There variables may also contribute to individual
is also some evidence that HIV-infected persons differences in disease progression among
may display altered cardiovascular, endocrine, asymptomatic HIV-infected individuals as well
and immunologic reactivity to laboratory as contributing to differences in survival time in
stressors (Kumar, Morgan, Szapocznik, & those who have already developed AIDS.
Eisdorfer 1991; Starr et al., 1996), indicating Specifically, longitudinal studies have identified
that these individuals may not respond to and psychological factors such as depressive symp-
recover from stressful challenges in the same toms, stressful life events, maladaptive coping
way that healthy, uninfected people do. strategies, and social isolation that predict
Although there is little known about the either survival time or CD4 changes over a
direct immunomodulatory effects of different period of years.
forms of sexual behaviors, it is plausible that
repeated exposure to novel strains of HIV and
other sexually transmitted pathogens by way of Depressive symptoms
unprotected intercourse (e.g., HSV and human
papilloma viruses [HPVs], may contribute There is considerable evidence that depressive
directly to the development of opportunistic symptoms are correlated with immunosuppres-
infections (e.g., systemic HSV-2 infections) and sion in otherwise healthy individuals (Herbert &
neoplasias (e.g., HPV-associated cervical and Cohen, 1993; Irwin, Caldwell et al., 1990; Irwin,
anal intraepithelial neoplasias [Antoni & Good- Patterson et al., 1990), though available
kin, 1996]). In addition, exposure to these evidence suggests that depression and affective
pathogens may indirectly contribute to an disturbances may be associated with physical
254 HIV and AIDS

disorders in a bidirectional fashion (Cohen & associated with decrements in immune function.
Rodriquez, 1995). Much of the work relating Some of these stressors may be particularly
clinical depression and depressed affect to prevalent among HIV-infected people attempt-
immunologic changes is plagued with incon- ing to cope with their illness and include:
sistencies which may be attributable, in part, to bereavement (Bartrop, Lazarus, Luckhurst,
the use of small samples, variability in control/ Kiloh, & Penny, 1977; Irwin, Daniels, Bloom
comparison groups utilized, and variance in the et al., 1987; Kemeny et al., 1995; Linn, Linn, &
depression diagnostic criteria employed (Stein Jensen, 1981); unemployment (Arnetz et al.,
et al., 1991). However, alterations in NKCC 1984); the stress of being a caregiver for a loved
appear to be the most commonly observed one with a terminal disease (Kiecolt-Glaser,
immunologic correlate of depressed affect and Glaser et al., 1987; Kiecolt-Glaser et al., 1991);
depressive disorder employed (Stein et al., divorce (break-up) (Kiecolt-Glaser, Fisher
1991). Among the more recent and well- et al., 1987); and marital distress (Kiecolt-
controlled studies, Irwin, Caldwell et al. Glaser, Fisher et al., 1987; Kiecolt-Glaser et al.,
(1990) found significant NKCC decrements 1988). Chronic uncontrollable stress has been
associated with depressive disorders. operationalized in one form as people dealing
Longitudinal studies relating depressive with catastrophic environmental changes.
symptoms to rates of immunologic decline These stressors are also associated with immune
and disease progression in HIV-infected per- alterationÐfor instance, both at the Three Mile
sons have produced mixed results (Burack et al., Island nuclear plant disaster (McKinnon,
1993; Lyketsos et al., 1993; Patterson et al., Weisse, Reynolds, Bowles, & Baum, 1989)
1996). Burack and colleagues found that greater and in Miami after Hurricane Andrew (Ironson
depressive symptoms predicted a faster decline et al., 1997; Lutgendorf et al., 1995).
in CD4 counts but were not associated with Recently conducted investigations indicate
time to AIDS or survival time in early-stage that the most consistent immune decrements
HIV-infected gay men followed over a six-year found in studies of stressors are functional
period (Burack et al., 1993). Lyketsos used measures associated with cellular immunity
similar criteria for documenting the presence of (Bartrop et al., 1977; Glaser, Rice, Speicher,
depressive symptoms and found no prospective Stout, & Kiecolt-Glaser, 1986; Glaser, Kiecolt-
relationship with either CD4 count slopes of Glaser, Speicher, & Holliday, 1985; Glaser et
decline or clinical disease progression over a al., 1987, 1990, 1991; Ironson et al., 1995; Irwin
similar period (Lyketsos et al., 1993). However, et al., 1990; Kemeny et al., 1995; Kiecolt-Glaser
there was a tendency for the men in the et al., 1985, 1987, 1988; Kiecolt-Glaser, Dura,
Lyketsos study to be at a more advanced stage Speicher, Trask, & Glaser, 1991; Levy, Herber-
of CD4 cell loss at start of the study than those man, Lippman, d'Angelo, 1987; Linn et al.,
men in the Burack study. Another study 1981). These include, but are not limited to:
following HIV-infected men over a five year (i) decrements in blastogenic responses to
period observed that depressive symptoms phytohemaglutinin (PHA) and pokeweed mito-
predicted shorter survival time after controlling gen (PWM);
for initial symptoms and CD4 cell number (ii) decreased natural killer cell cytotoxicity
(Patterson et al., 1996). Other psychosocial (NKCC);
factors may interact with depressive symptoms (iii) increased antibody titers to Epstein-Barr
or distress levels in predicting changes in Virus (EBV) and Herpes Simplex Viruses
immune status and health. Because depressed (HSV);
affect, substance use, and risky sexual behaviors (iv) poorer DNA repair; and
may all contribute to health outcomes in HIV- (v) disturbance in cytokine regulation in-
infected individuals, it seems reasonable that cluding less g-interferon and interleukin-2
factors which moderate the occurrence of these (IL-2) production and IL-2 receptor gene ex-
sequelae may also have an influence on pression.
immunity and health. Some of these include There are some PNI studies that have related
the occurrence of overwhelming stressful life stress responses to people's ability to respond to
events, stressor appraisals, individual differ- viral pathogens. Cohen and colleagues (Cohen,
ences in coping skills, and differences in social Tyrrell, & Smith, 1991) innoculated volunteers
support. with one of five rhinoviruses (cold viruses) in a
restricted environment and then followed them
over a period of weeks. Subjects with the highest
levels of perceived stress were significantly more Stressful life events
likely to display increases in antibody titers to
There is now ample literature (Herbert & the specific rhinovirus and clinical colds than
Cohen, 1993) showing that stressors are those with the lowest levels of psychological
Predicting the Health Course of HIV Infection 255

stress. Stressors have also been related to positive men. This suggests that life events that
alterations in primary immune responses to are commonly experienced by HIV-infected
other viruses. Glaser et al. (1992) demonstrated individuals may have significant effects on the
that those medical students undergoing a stres- functioning of their immune system, but that
sor (exams) who were least stressed and anxious gross changes in CD4 counts and clinical
were also the most likely to seroconvert (pro- symptoms may take longer to develop. While
duce a primary antibody response to) the the Rabkin et al. (1991) and Kessler et al. (1991)
Hepatitis B virus (HBV) after the first vaccine studies found no association between stressful
innoculation. In addition, participants with the life events and outcome measures, they did not
highest levels of social support had a stronger assess individual differences in subjectsº per-
immune response to the vaccine at the third ceived control over stressful life events nor their
innoculation. Thus, participants with low stress coping responses for dealing with these stres-
and anxiety, and high social support, appear to sors. While other life events have been asso-
have been relatively well protected from infec- ciated with some immune measures in HIV-
tion by HBV. Together these studies suggest infected people (Evans, Pettito, & Leserman,
that stressors may influence mechanisms con- 1992; Goodkin et al., 1992), stressful life events
trolling both primary and secondary immune per se have not been shown to be predictive of a
responses to viruses. This work is important for faster rate of disease progression (Kessler et al.,
understanding the role of stressor±immune 1991). Patterson and colleagues note that the
associations as they possibly relate to health interaction between mounting life events and
outcomes in the context of HIV infection since distress levels may be a more reliable predictor
an HIV-infected person's inability to control of immunologic and health changes in HIV-
viral co-infections may act to aggravate the infected persons (Patterson et al., 1996). Speci-
course of primary HIV infection (Antoni et al., fically, individuals who display the greatest
1995). distress levels during particularly stressful
Despite some of the evidence associating periods may show the poorest health outcomes.
stressful life events with changes in specific It is plausible that those individuals who are at
indices of immune system functioning in healthy greater risk of displaying such distress levels are
populations that has accrued since the mid- those who utilize maladaptive stressor apprai-
1980s, there is less conclusive evidence linking sals and coping strategies and who also have
stressors with immune and health changes in inadequate social resources.
HIV-infected individuals. Briefly, two studies
found that stressful life events were unrelated to
CD4 counts or HIV-related symptoms (Kessler Stressor appraisals
et al., 1991; Rabkin et al., 1991), while another
found that elevated life events were predictive of Some aspects underlying the cognitive pro-
decreases in CD4 counts (Goodkin, Fuchs, cessing of stressors have been associated with
Feaster, Leeka, & Rishel, 1992). It should be measures of physiological activation and im-
noted that Goodkin and colleagues analyzed mune functioning in healthy people. Davidson
their data in line with a stressor±moderator and Baum (1986) found that both intrusive
model which simultaneously takes into account imagery and avoidant cognitions, as measured
the direct effects of life events, plus their by the Impact of Event Scale (IES) (Horowitz,
interaction with theoretically derived modera- Wilner, & Alvarez, 1979), were positively
tor variables such as coping and social support. associated with increased cortisol levels in
Such more sophisticated statistical modeling residents living near Three Mile Island (TMI)
may be necessary to delineate the often following the nuclear reactor accident. Many of
interactive nature of life event effects on the these individuals displayed elevated antibody
immune system and health. titers to certain viruses, suggesting impairments
One stressful event associated with disease in immunologic surveillance years after the
progression in HIV-infected persons is bereave- reactor accident (McKinnon et al., 1989).
ment (Coates, Stall et al., 1989; Kemeny et al., Workman and LaVia (1987) found that in-
1994). Coates, Stall et al. (1989) found that both trusive cognitions (measured by the IES) related
the number of losses and accompanying distress to an impending medical school examination
levels were significantly related to faster HIV were associated with poorer blastogenic re-
progression during a two-year follow-up. Simi- sponses to PHA among young healthy medical
larly, Kemeny et al. (1994) found that a bereaved students. Ironson and colleagues found that the
group of HIV-infected men who had lost a intrusive thoughts and post-traumatic stress
partner had significantly higher serum neopterin symptoms experienced by many victims of
levels and lower proliferative responses to PHA Hurricane Andrew were associated with decre-
than a matched group of nonbereaved HIV- ments in NKCC (Ironson et al., 1997).
256 HIV and AIDS

One study examined how the manner in which appraisal variables, such as optimism, different
HIV-infected individuals processed the stress of cognitive distortions, such as catastrophizing,
seropositivity notification predicted their im- and self-efficacy might relate to the course of
munologic status during the early period of HIV infection.
adjustment to this stressor. They found that
changes in style of cognitive processing of this
stressor were significantly correlated with Coping strategies
changes in affective and immunological func-
tioning over this 10 week period (Lutgendorf, There is some evidence that the use of certain
Antoni, Ironson, Schneiderman et al., 1997). coping strategies for dealing with HIV infection
The IES and the Profile of Mood States (POMS) may be associated with the rate of disease
(McNair, Lorr, & Droppleman, 1981) were progression. Ironson et al. (1994) found that the
administered five weeks before (baseline) and use of denial and behavioral disengagement to
five weeks after notification (week 10). A panel cope with an HIV-positive diagnosis, was
of immune assays were also conducted on blood predictive of lower CD4 counts at 1 year
samples collected at these time points. The IES follow-up (controlling for CD4 counts at entry
instructions required subjects to report on to the study) and greater likelihood of progres-
intrusive thoughts that they had been experien- sion to HIV-related symptoms and AIDS at 2-
cing in the past week regarding one of the most year follow-up. A more fine-grained analysis
salient issues that infected people deal with on a exploring the immunologic changes that oc-
daily basis: the threat of AIDS in their life. The curred in this sample prospectively related
IES also tapped the degree to which they had coping strategies and immunologic measures
attempted to distract themselves or avoid in the HIV seropositive gay men (and a
thinking about this threat over this period. seronegative comparison group of gay men)
Participants were classified as those who had over the 3 week and 1-year period following
IES-Intrusion score increases vs. decreases and notification of their antibody test results
those who had IES-Avoidance score increases (Antoni et al., 1995). Seropositive men scoring
vs. decreases over the 10-week period. Results above the median on postnotification disen-
indicated that men with avoidance increases gagement coping strategies (denial, behavioral
demonstrated greater anxiety, depression, and disengagement, mental disengagement) had
confusion at week 10 than those individuals who significantly lower concurrently measured T-
had avoidance decreases. Subjects with avoid- helper/suppressor (CD4/CD8) cell ratios, T-
ance increases also displayed lower proliferative inducer subset (CD4+CD45RA+) percent
responses to PWM and lower NKCC at the end values, and proliferative responses to PHA
of the 10 weeks compared to those who than subjects scoring below the median on these
decreased in avoidance scores over the study. coping scales. Greater disengagement coping
These findings suggested that postnotification responses also predicted poorer lymphocyte
processing, colored by avoidance, was asso- responsivity to PHA at 1-year follow-up.
ciated with poorer immune system functioning Consistent with these findings, Goodkin et al.
in the weeks after antibody testing among (1993) found that use of passive coping strategies
asymptomatic HIV-positive men. (including denial and disengagement) was
Another stressor appraisal variable that has inversely related to long-term CD4 cell count
received some attention in HIV research in HIV-positive gay men. Solano et al. (1993)
concerns a construct called fatalism. In a series also found that denial/repression was associated
of studies, Kemeny (reviewed in Kemeny, 1994) prospectively with the emergence of symptoms
found fatalistic appraisals to be related to in an HIV-positive sample. Mulder, Antoni,
poorer health outcomes in HIV-infected gay Duivenvoorden et al. (1995) found that active
men. In the first study, fatalistic gay men with a confrontational coping with HIV infection was
diagnosis of AIDS had a significantly shorter predictive of decreased clinical progression over
survival time than men scoring low on fatalism a 1-year period after taking into account
(Reed, Kemeny, Taylor, Visscher et al., 1994). baseline biomedical and behavioral variables.
Interestingly, men who were both fatalistic and Finally, Blomkvist et al. (1994) followed HIV-
bereaved within the past year had the shortest infected hemophiliacs longitudinally and found
survival time (Reed, Kemeny, Taylor, Visscher that self-oriented active-optimistic coping be-
et al., 1994), the steepest declines in CD4 havior was related to prolonged survival after
number and proliferative response to PHA, and controlling for age and CD4 counts at study
a more rapid increase in disease progression entry. Thus, there is some evidence that coping
markers, including neopterin and beta-2 micro- strategies may be reliably associated with certain
globulin (Kemeny et al., 1995). Less is known immunologic and health measures in HIV-
about the ways in which other cognitive infected persons from a variety of risk groups.
Predicting the Health Course of HIV Infection 257

It should be noted that while Reed, Kemeny, Vernon, 1986). However, these associations
Taylor, Wang, & Visscher (1994) found that have not been replicated in other studies.
realistic acceptance was a significant predictor Although a growing body of evidence supports
of decreased survival time in gay men diagnosed the potential benefits of social ties in healthy
with AIDS, Ironson et al. (1994) observed that people and several chronic disease populations
greater use of denial among asymptomatic HIV- (e.g., cancer patients), scientists are just begin-
infected gay men predicted a greater likelihood ning to examine the health correlates of social
of developing symptoms or AIDS two years support in HIV-infected individuals.
later. Thus it appears that being at the extreme A variety of models have been developed to
end of either denial or realistic acceptance might explain the ways in which social support might
be dysfunctional. Kemeny refers to the realistic provide direct influences on psychological and
acceptance factor as fatalism±acceptance, and physical well-being (Cohen & Wills, 1985).
notes, specifically, that ªfatalistic men survived Some of these direct psychological benefits may
a significantly shorter period of time when stem from the possibilities that social support
compared to their less fatalistic counterparts.º helps people define certain stressors as being less
What is not clear is whether this variable overwhelming, provides opportunities for peo-
represents acceptance as a healthy coping style ple to openly express fears, frustrations, and
or a predominantly negative view (pessimism) other emotions, thereby decreasing ruminations
about the future. One study may shed some light and obsessive thinking about stressors. Social
on the notion of a balance between the extremes support also provides key information and
of denial and acceptance. Mulder et al. (in press) informational support provided by knowledge-
found that greater use of distraction (e.g., able others, which may help individuals to
focusing on other things to take the mind off assume a more realistic attitude toward life
things) predicted a slower rate of decline in CD4 goals. In addition, social support may help
cells, less appearance of syncytium-inducing people feel connected, which may increase their
HIV variants, and less progression to immu- sense of self-worth, belongingness, meaning,
nologically defined AIDS (5 200 CD4 cells purpose, and well-being. Finally, social ties may
mm-3) over a 7-year period. Ironson et al. (1995) reduce initial feelings of burden caused by the
notes that together these findings suggest that onset of a stressor (e.g., a medical diagnosis),
strategies which are predictive of longevity may allowing the person to employ active coping
involve using some distraction coupled with strategies to deal with the stressor. Obviously,
staying away from the extremes of either denial all of these benefits of social support may be
or acceptance to the point where fatalism and highly salient for HIV-infected persons (Zuck-
rumination occurs. erman & Antoni, 1995).
Some research suggests that the same me-
chanisms which provide these psychological Social support
benefits from social support also seem to buffer
The health promoting effects of social endocrine and immunologic changes associated
support that have been most widely researched with stress responses (e.g., Baron, Cutrona,
are usually in terms of its ability to buffer the Hicklin, Russell, & Lubaroff 1990; Cobb, 1974;
effects of stressors (Cohen & Wills, 1985). A Esterling, Kiecolt-Glaser, & Glaser, 1996; Levy
person's social support network may also et al., 1987). It has been hypothesized that HIV-
influence their ability to manage, cope with, infected people who maintain strong support
and recover from serious illness (Dimatteo & networks may have less extreme and protracted
Hays, 1981; Taylor, Falke, Shoptaw, & Licht- biological responses to stressors because SAM
man, 1986; Wortman & Conway, 1985). Since and HPA-related stress hormone levels (e.g.,
the 1970s there has been an enormous amount peripheral catecholamines and cortisol) are
of research undertaken studying the ability of better regulated (Antoni et al., 1990). Some
social networks to provide positive physical work provides preliminary evidence that social
health benefits to people (Berkman & Syme, support may relate to the rate of HIV disease
1979; House, Landis & Umberson, 1988; Smith, progression as well. One study found that larger
Fernegel, Holcroft, Gerald, & Marien, 1994; social network size and greater perceived
Wortman & Dunkel-Schetter, 1987). Some informational social support predicted greater
findings have converged across investigations. survival time in HIV-infected men, but only
For instance, it appears that being involved in a among those with AIDS symptoms (Patterson
committed relationship (i.e., marriage) is asso- et al., 1996). Other prospective studies have
ciated with greater survival time among patients found that greater social support availability
who have experienced a myocardial infarction (Theorell et al., 1995) and more frequent use of
(Wiklund et al., 1988; Williams et al., 1992) or a problem-focused support (Solomon, Temoshok,
diagnosis of breast cancer (Neale, Tilley, & O'Leary, & Zich, 1987) were predictive of a
258 HIV and AIDS

slower decline in CD4 counts and longer psychosocial characteristics of long-term survi-
survival, respectively. Another study may illu- vors of AIDS (defined by clinical symptoms)
minate a factor underlying an HIV-infected have been done, and as Ironson and colleagues
person's decision to enlist social support. Cole, note, almost all of these have been cross-
Kemeny, Taylor, Visscher, and Fahey (1996) sectional (Ironson et al., 1995). Ironson and her
followed 80 HIV seropositive (non-AIDS, colleagues did, however, find a good deal of
normal levels of CD4 lymphocytes at entry) consensus on the existence of several different
gay men for 9 years and found that those who psychosocial characteristics of these indivi-
concealed their sexual identity (being at least duals, noting four psychosocial adjustment
ªhalf in the closetº) had a faster decline in CD4 strategies (Ironson et al., 1995): (i) healthy
counts, shorter time to AIDS diagnosis, and self-care behaviors; (ii) a sense of connected-
shorter time to AIDS mortality than those who ness; (iii) a sense of meaning and purpose; and
did not conceal their identity. Therefore, social (iv) maintaining perspective. The first factor
support availability, decisions to utilize available included three components±±medical care, a
support, and identity factors that influence healthy lifestyle, and an awareness and ability to
decisions to make these connections may all take action to meet personal needs. The second
contribute to the course of HIV disease. factor, maintaining connectedness, is closely
In sum, it could be hypothesized that a related to the maintenance of social support.
mounting number of losses and grieving Having at least one confidant is part of this
experiences, which constitute prevalent life factor, as is being able to communicate openly
stressors for HIV-infected individuals, might about concerns and, for homosexuals, disclos-
contribute to a faster rate of disease progres- ing a gay lifestyle. This is interesting in light of
sion. Further work suggests that maintaining the findings of Cole and colleagues (Cole et al.,
fatalistic stressor appraisals could predict short- 1996). The third factor, maintaining a sense of
er survival time among men with AIDS. meaning and purpose, ties into the notion of
Moreover, attempting to avoid dealing with having something to live for and, thus,
intrusive thoughts concerning future AIDS risk represents a cognitive appraisal factor. Ironson
was associated with greater immune system and colleagues note that having an optimistic
decrements in asymptomatic HIV-positive men. attitude, (or conversely being low on negative
The use of coping strategies such as extreme expectancies) are all a part of this. Some long-
denial or acceptance were both associated with term survivors actually report finding new
an accelerated disease course, while a certain meaning as a result of being HIV-positive
degree of distraction (and perhaps low rumina- (Schwartzberg, 1994). Still others find meaning
tion about the disease) was associated with a in their relationship with a higher power, or
slower rate of progression. Finally, people who spirituality/religion as they define it (Woods,
remain socially isolated (and who may be the Antoni, Ironson, & Kling, 1996). The final
least comfortable in approaching their support factor is maintaining perspective. A failure to
network) appear to show the fastest progression maintain perspective is represented by depres-
of disease. sion, negative affect, and hopelessness. Ironson
et al. (1995) note that accepting the reality of an
AIDS diagnosis without seeing it as an Psychosocial Factors in Long-term imminent death sentence is part of this
Survivors of AIDS perspective, as is believing one can live with
AIDS, realizing AIDS is episodic in nature, and
Another research strategy for establishing remembering that AIDS usually includes per-
salubrious psychosocial factors in HIV-infected iods of good health. Using selective distraction
individuals has been to document the char- as a coping strategy and not allowing AIDS to
acteristics of those who substantially ªoutliveº become the sole focus of one's life captures the
their prognosis after a diagnosis of AIDS. This essence of this factor. Ironson et al. (1995)
research has been reviewed by Ironson and conclude that maintaining perspective is quite
colleagues (Ironson et al., 1995). The CDC close to the idea that balance is very important.
currently estimates median survival time after They cogently use the optimism/negative ex-
an AIDS diagnosis (by the 1987 symptomatic pectancies construct and the denial/acceptance
criteria) to be 18±20 months (CDC, personal construct to point out that the extreme at either
communication 1994; Eickhoff, 1994), a num- end is probably the least functional. It remains
ber that increases slowly each year as better to be determined which psychological and
diagnostic and treatment options become biological mechanisms might explain the ways
available. The CDC defines ªlong-term survi- in which these four long-term survivor strategies
vorsº of AIDS as persons who survive twice the relate to health outcomes in HIV-infected
median expected time. Only a few studies of the people.
Interventions, Adjustment, and Health Course in HIV Infection 259

8.10.4 INTERVENTIONS, ADJUSTMENT, wait-list control group. The intervention re-

AND HEALTH COURSE IN HIV duced self-reported symptoms of HIV (fever,
INFECTION fatigue, pain, headache, nausea, and insomnia)
and increased vigor and hardiness relative to Health Psychosocial Interventions with controls, but did not change anxiety or
HIV-infected People depression. The authors speculate that if they
had selected a more distressed HIV-infected
Since 1990 a small collection of studies have sample they may have obtained changes in
examined the effects of psychosocial interven- immune status variables and anxiety and
tions in HIV-infected populations. These stu- depression measures. It is also possible that
dies used both psychological and immune stress management interventions may work best
measures as dependent variables, although none if the groups start out with high stress or
of them have completed long enough follow-up encounter a stressor during the course of the
periods to clearly establish a health/disease intervention. The most appropriate way to
progression effect. Most of these interventions evaluate the effects of these types of interven-
employ cognitive behavioral techniques and tions might be to test them in the context of
operate in a group-based format. Comprehen- either high distress states or measurable recent
sive reviews of the psychological effects (Ches- or ongoing stressful events (e.g., bereavement,
ney & Folkman, 1994), and immune and health diagnosis notification) and to include a com-
effects (Ironson et al., 1995) of psychosocial parison group of HIV-negative controls.
interventions in HIV populations are now
available. Stress Management Intervention
The psychological, immune, and health Effects at Different Critical Points in
effects of psychosocial interventions in HIV- HIV Infection
infected individuals are summarized in Table 1.
Studies included in this table are restricted to Some of the most well-documented behavior-
those that monitored intervention-related al interventions applied to HIV-infected in-
changes in both psychological and immunologic dividuals have attempted to use procedures that
status. The first study to examine the effects of reduce distress, promote self-efficacy, and
stress management intervention on psychologi- encourage the use of active coping strategies.
cal and immune status in HIV-infected indivi- Operating from a chronic disease-PNI rationale
duals was conducted by Coates and colleagues we have hypothesized that if behavioral inter-
at the University of California at San Francisco ventions can retard or normalize declines in
(Coates, McKusick, Stites, & Kuno, 1989). immune status by bringing about these psycho-
They randomized 64 HIV-positive gay men to social and behavioral changes, then they may be
either an 8-week stress management training able to forestall the onset of disease complica-
program or a control group. The intervention tions, such as opportunistic infections and
consisted of systematic relaxation (with take- neoplasias (see Figure 1). Our group developed
home tapes), health habit education (diet, rest, a 10-week CBSM intervention for HIV infection
exercise, drug and alcohol use, smoking), and that was based specifically upon the psychoso-
skills for managing stress. While the interven- cial sequelae that have been reviewed previously
tion appeared to change sexual behavior (Antoni, Baggett et al., 1991). For some HIV-
(significantly fewer sexual partners), there were infected people these sequelae include being
no effects on enumerative or functional immune faced with a wide variety of chronic, uncontrol-
measures. The panel of immune assays in- lable, and unpredictable stressors (e.g., such as
cluded: CD4 cells CD4/CD8 ratio, NKCC, changes in health, job status, health insurance,
lymphocyte response to con A, candida antigen and medical costs) and a loss of social support
and CMV. Psychological changes in the inter- resources which is triggered by their own
vention or control groups were not reported withdrawal, the death of close friends, or the
though the authors acknowledge that the responses of friends and family. These are likely
protocol they used may have been ineffective to persist across and grow in magnitude over the
in reducing stress. course of the infection (see Hoffman, 1991).
Another study which had some positive This model reasoned that the combination of
effects on psychosocial variables, but no effect multiple uncontrollable burdens and declining
on CD4 cell number, was done by Auerbach and coping resources may overwhelm HIV-infected
colleagues (Auerbach, Oleson, & Soloman, personsº previously adequate direct coping
1992). Twenty-six symptomatic seropositive strategies such as active coping, positive
gay men were randomized to an 8 week appraisals of burdens, problem-solving, and
behavioral medicine intervention, thermal bio- seeking social support, resulting in the adoption
feedback, guided imagery, and hypnosis, or a of more indirect strategies such as avoidance
Table 1 Psychosocial intervention effects in HIV infection.

Team Intervention Sample Psychosocial effect Immune effect Health

Coates, McKusick et al. 8 week stress 64 HIV-positive gay men ; number sex partners, distress ND no D CD4 ND
(1989) management vs. no no D PHA
tx. ctrl.

Auerbach et al. (1992) 8 week biofeedback 26 HIV-positive gay men : POMS vigor no D CD4 ; HIV sx.
imagery, hypnosis : hardiness no D POMS anx. dep.
vs. WLC

(i) Antoni, Baggett et al. (i)±(iv) 10 week (i), (iii), & (iv) 47 HIV- (i) buffered notification POMS (i) buffered CD4 D, CD56 D, (i), (ii), (iii), &
(1991) CBSM vs. no tx. positive asymptomatic distress D & PHA D (v) ND
(ii) Antoni, Ironson et ctrl. men learning ab. status (i) maintained social support (ii) pre±post notification (iv) 2 year disease
al. (April, 1992) (v) 10 week CBSM vs. (ii) asymptomatic HIV- (ii) ; behavioral and mental : NKCC, : PHA progression
(iii) Esterling et al. WLC positive men disengagement (iii) ; EBV ab. ; HHV-6 ab. correlates
(1992) (v) status known 4 6 mo ; denial (v) ; HSV-2 ab. ; adherence
(iv) Ironson et al. (1994) 40 symptomatic HIV- (v) ; BDI depression (ii), (iii), & (v) no D CD4 : denial
(v) Lutgendorf et al. positive non-AIDS ; POMS distress : distress
(1997) : social support, : acceptance

Mulder et al. (1994, 12 week CBSM, 12 39 HIV-positive ; POMS distress distress D, CD4 D over 2 year ND
1995) week EE vs. WLC asymptomatic gay men, ; BDI depression no D coping,
ab. status known social support emo. exp.

Ironson, Field et al., 4 week daily massage 29 (20 HIV-positive, 9 ; POMS anxiety : CD56, NKCC ND
1995 therapy vs. WLC HIV-negative) gay men : relaxation : cytotoxic cells
no D CD4

tx. = treatment; ab. = antibody; ctrl. = control; WLC = wait-list control; dep. = depression; anx. = anxiety; ND = not done; EE = existential experiential; sx. = symptoms; CD4 = T-helper cells; PHA = lymphocyte
proliferation to PHA; CD56 = natural killer cells; EBV Ab. = Epstein-Barr Virus antibodies; HHV-6 Ab. = human herpes virus type 6 antibodies; HSV-2 Ab. = herpes simplex virus type 2 antibodies; BDI = Beck Depression
Inventory; D = change in.
Interventions, Adjustment, and Health Course in HIV Infection 261

and denial, on the one hand, and substance use to the initial diagnosis of seropositivity; (ii)
and possibly risky sexual behaviors on the adjustment to being infected during the early
other. One self-defeating ªloopº that this model asymptomatic period when individuals are still
highlights follows: the infected person's aware- healthy; (iii) adjustment to the experience of
ness of the ineffectiveness of their coping modes HIV-related symptoms that are not life-threa-
and strategies may increase their sense of low tening but do impact the quality of life; and (iv)
self-efficacy, helplessness, and hopelessness, adjustment to a diagnosis of AIDS (Lutgendorf,
which in turn perpetuates social isolation, Antoni, Schneiderman, & Fletcher 1994).
depressive symptoms, continued substance
use, and other negative health behaviors. The initial HIV seropositive diagnosis
The intervention that was developed ad-
dresses each of these domains by enhancing self- In the first set of studies, 65 gay men who did
efficacy and perceived control, teaching adap- not know their HIV serostatus were randomly
tive coping strategies, and improving social assigned to either a CBSM intervention, an
support availability, satisfaction, and utiliza- aerobic exercise intervention, or a control
tion (Antoni, Schneiderman & Ironson, in group. After 5 weeks of participating in one
press). This program teaches participants a of these conditions, blood was drawn for
variety of active coping strategies (e.g., cogni- antibody testing and the men received news of
tive restructuring, relaxation exercises, assertive their serostatus 72 hours later. The intervention
responses) and may enhance their psychological continued for another 5 weeks (10 weeks total)
functioning by increasing perceptions of self- and the men were followed through the initial
efficacy, personal control, and mastery (Fish- ªadjustmentº period. Across the notification
man & Loscalzo, 1987); changing maladaptive period the HIV-positive controls showed sig-
cognitive distortions (Simons, Garfield, & nificant increases in anxiety and depression,
Murphy, 1984); modifying stressor appraisals whereas the HIV-positive CBSM subjects
and providing the person with an available showed no significant changes in anxiety, or
coping response (Turk, Holzman & Kerns, depression scores (Antoni, Baggett et al., 1991).
1986); decreasing a sense of hopelessness (Rush, The same buffering effect was present for the
Beck, Kovacs, Weisenberger, & Hollon, 1982); HIV-positive men assigned to the aerobic
and increasing the availability and utilization of exercise group (LaPerriere et al., 1990). With
social support networks (Vachon, Lyall, Ro- respect to immune findings, the HIV-positive
gers, Freedman, & Freedman, 1980). controls showed slight decrements in respon-
This CBSM intervention program uses 10 sivity to PHA, NKCC, and NK cell counts pre-
weekly modules to address these aims as to postnotification (with no change in CD4
follows: (i) to increase personal awareness by counts). In contrast, the HIV-positive CBSM
providing information on sources of stress, the subjects had significant increases in CD4 and
nature of human stress responses, and different NK cells and slight increases in PHA respon-
coping strategies used to deal with stressors; (ii) sivity and NKCC, thus showing a ªbufferingº
to teach anxiety reduction skills such as effect (Antoni, Baggett et al., 1991). Exercise
progressive muscle relaxation and relaxing had a similar buffering effect on several immune
imagery; (iii) to modify maladaptive cognitive measures, though these are not reviewed in
appraisals using cognitive restructuring; (iv) to detail here (see LaPerriere et al. [1990] or
enhance cognitive, behavioral, and interperso- LaPerriere et al. [1994]).
nal coping skills through coping skills training, A 2-year follow-up of 23 HIV-positive men
assertion training, and anger management recruited from these studies was conducted by
techniques; and (v) to provide a supportive Ironson and colleagues (Ironson et al., 1994) to
group environment and increase utilization of determine psychological predictors of disease
social support networks. The effectiveness of progression to symptoms and death from
this intervention was systematically evaluated in AIDS. They found that distress at diagnosis,
different cohorts of HIV-infected persons who HIV-specific denial coping (5 weeks postdiag-
were dealing with different landmark challenges nosis minus prediagnosis), and low treatment
known to occur during the infection and adherence (poorer attendance at either CBSM
focused on specific ªcritical pointsº that these or exercise groups, a lower frequency of
HIV-infected people were passing through. The relaxation practice during the 10 weeks for
rationale underlying this approach is that HIV those in the CBSM, and not doing homework
infection comprises not only a ªspectrumº of for those in CBSM group) all predicted faster
diseases, but also a spectrum of psychosocial disease progression. Increases in denial and
challenges that change over time. At least four, better treatment adherence remained significant
somewhat artificial, critical points can be used even after controlling for initial disease severity
to characterize these challenges: (i) responding at study entry (CD4 number). Furthermore,
262 HIV and AIDS

decreases in denial and a greater frequency of Elsewhere the types of issues that these men
relaxation home practice during the 10-week were reporting have been described in greater
intervention period were predictive of higher detail (Lutgendorf, Antoni, Schneiderman,
CD4 cell counts and greater blastogenic Ironson et al., 1994). Some issues included
responses to PHA at 1 year follow-up (Ironson reluctance to terminate relationships, hesitating
et al., 1994). These findings suggest that those to have sex with someone who was uninfected
men who attended intervention sessions reg- for fear of infecting them, deciding to disclose
ularly, and dealt with their denial during the HIV status to family members, and making job
intervention period, were most likely to show and career transitions. The predominant emo-
longer term immune and health benefits. tional experiences reported by these men
There were also several consistent immune included anger, fear, loss, and uncertainty.
changes noted over the total 10 week period of The 10-week CBSM intervention developed
intervention. The CBSM (and exercise) inter- for these asymptomatic men was specifically
ventions were associated with a significant adapted to address these issues (Antoni,
decrease in antibody titers to EBV-VCA and Ironson et al., 1992). The early part of the
to HHV-6 as compared to assessment-only intervention maintained its psychoeducational
controls, whose antibody titers remained con- focus, with sessions on HIV and the stress
stant over the 10-week intervention period and response, cognitive appraisals, refuting, and
elevated relative to healthy male laboratory replacing cognitive distortions. For this cohort,
controls (Esterling et al., 1992). An analysis of the group sessions discussing impending noti-
other psychosocial changes revealed that men in fication and postnotification concerns were
the control group showed significant decre- replaced with a session dealing with unfinished
ments in social support during the postnotifica- issues related to seropositivity notification and
tion period, whereas those in the CBSM group notification of others regarding one's seropo-
maintained their social support levels (Fried- sitivity. Behavior change, assertiveness, and
man et al., 1991). We also found that pre± social support were addressed extensively in
postintervention decrements in social support these group sessions, especially strategies for
were associated with greater declines in NKCC eliciting social support. From a sample of 23
over a similar period (Antoni, Ironson et al., men, 11 were randomized to CBSM and 12 to an
1992) and that the reductions in EBV antibody aerobic exercise program, each lasting 10 weeks.
titers during this period appeared to be Because this was a pilot study there was no
mediated by increases in social support (Antoni control condition. Participants in CBSM sig-
et al., 1996). nificantly reduced their anxiety, depression,
anger, fatigue, and confusion levels, as well as
increasing feelings of vigor (Antoni, Ironson The asymptomatic stage of HIV
et al., 1992). They also reported increased use of
adaptive coping strategies, active coping, plan-
Even asymptomatic HIV disease is accom- ning, and acceptance, and decreases in several
panied by wide-ranging psychosocial challenges maladaptive coping strategies such as mental
including the many uncertainties with regard to disengagement and denial. These individuals
future health course and available resources. also revealed significant increases in blastogenic
The former arises due to the unpredictable responses to PHA and NKCC.
physical course of the HIV infection and the Other groups have also reported significant
latter as a function of uncontrollable stressors reductions in distress (Chesney et al., 1996a,
such as impaired occupational and social 1996b; Kelly et al., 1993; Mulder et al., 1994)
functioning, decreased earning power, high and improvements in self-efficacy (Chesney
costs of medical care, complex medical treat- et al., 1996a, 1996b) with cognitive behavioral
ments, difficulties with self-care, multiple interventions in asymptomatic HIV-infected
bereavements, and declining social supports men. Kelly and colleagues randomized partici-
(Blendon & Donelan, 1988; Ginzburg & Gostin, pants to either cognitive-behavioral group
1986; Redfield & Burke, 1988; Walkey et al., intervention, social support group intervention,
1990). or no-treatment, and found significant reduc-
The effects of CBSM intervention have been tions in depression, hostility, and somatization
examined with gay men who knew of their HIV- in the cognitive-behavioral groups, as well as the
positive status for at least 6 months, but were social support group, compared to controls.
still asymptomatic. Although their physical The cognitive-behavioral group was somewhat
functioning had not yet been affected by the more effective at reducing drug use (Kelly et al.,
virus, knowledge of their positive serostatus, 1993). Mulder and colleagues compared
and its eventual implications, had affected their cognitive-behavioral group intervention and
lifestyle, behaviors, and sense of well-being. existential experiential group intervention in
Interventions, Adjustment, and Health Course in HIV Infection 263

HIV-infected gay men and found that both support, and in cognitive coping strategies,
groups reduced distress and depressive symp- appear to mediate the effects of the CBSM
toms compared with a wait-list control condi- intervention on the changes in distress noted
tion (Mulder et al., 1994). Finally, Chesney et al, during the intervention. These results suggest
compared the effects of a CBSM group that cognitive coping strategies and social
intervention (Coping Effectiveness Training support factors can be modified by psychosocial
(CET)) (Chesney et al., 1994; Folkman et al., interventions. These changes may in turn be
1991) with an information group and a wait-list important determinants of psychological well-
control group, and found that CET significantly being and quality of life during symptomatic
increased self-efficacy and decreased perceived HIV infection.
stress and burnout compared to the other two
conditions (Chesney et al., 1996a, 1996b). Full-blown AIDS
To date, the bulk of the published empirical The pre-AIDS symptomatic stage of
studies evaluating the efficacy of psychosocial
HIV infection
interventions with HIV-infected people have
The effects of a group-based CBSM inter- focused on gay men at the earlier stages of the
vention have also been evaluated in HIV- infection. While there is a growing literature
positive gay men who are dealing with the documenting those psychosocial factors that are
symptoms of the infection. Forty HIV-infected predictive of both psychological adjustment and
gay men who had mild symptoms (category B of physical health course in AIDS patients (e.g.,
the 1993 CDC definition) were randomly long-term survivor literature reviewed in Ir-
assigned to either the CBSM intervention or a onson et al. [1995]), little or no work exists
modified wait-list control group in which they testing the effects of various interventions with
complete a 10 week waiting period before being patients who have progressed to AIDS. What
reassessed and provided a one day CBSM we do know is that the onset of AIDS may be
seminar. Across the 10 weeks the CBSM group accompanied by a lessening of psychological
showed a significant decrease in depression, distress from the levels experienced by sympto-
anxiety, and antibody titers to HSV-2 (Lutgen- matic (pre-AIDS) HIV-infected men (Dilley
dorf, Antoni, Ironson, Klimas et al., 1997). et al., 1985; Tross & Hirsch, 1988). This may
Moreover, the 10 week decreases in HSV-2 reflect a relief from the unpredictability of not
antibody titers were strongly associated with the knowing if and when the first signs of AIDS
degree to which participants lowered their may occur.
depression scores on the Beck Depression With the steady progression of HIV infection
Inventory (BDI; Beck, Ward, Mendelson, to more and more serious symptoms, and
Mock, & Erbaugh, 1961) over this period. eventually AIDS, individuals go through a
The control group showed no such changes in continual process of emotional crises, recycling
depressive symptoms or antibodies to HSV-2. through the stages that Kubler-Ross (1969)
Subsequently, conducted path analyses revealed originally noted as comprising the dying process
that the effects of CBSM on HSV-2 antibody (Lutgendorf, Antoni, Schneiderman, & Fletch-
reductions appeared to be mediated by the er, 1994). Moreover, HIV-infected patients may
intervention-associated depression changes have emotional reactions that are more intense
(Antoni et al., 1996). Since this structured and labile than those described by Kubler-Ross
intervention was designed to increase cognitive (Hoffman, 1991). The high percentage of HIV-
and behavioral coping skills and support among infected individuals diagnosed with adjustment
group members, we next examined the relative disorders is a testimony to the difficulties
contribution of intervention-related changes in encountered as these people try to come to
coping skills and social support to reductions in terms with their illness and its impact on their
dysphoria, anxiety, and distress-related symp- lives (Hoffman, 1991). While it is clear that these
toms over the study period. Those randomized individuals are in need of psychosocial services,
to CBSM showed significant improvement in one must be cautious in applying what has been
cognitive coping strategies, such as positive learned from asymptomatic and early-stage
reframing and acceptance, as well as in total populations to those with AIDS. There is a lack
perceived social support provisions compared of empirical studies evaluating the effectiveness
to a wait-list control condition (Lutgendorf of psychosocial interventions such as CBSM or
et al., 1996). Cognitive coping changes, speci- other approaches such as Expressive Supportive
fically acceptance of the HIV infection, were therapy conducted in a group or individual-
strongly related to lower dysphoria, anxiety, based format with individuals at this stage of the
and total mood disturbance in this sample. Path infection. It may be that those with AIDS may
analyses suggested that changes in social find structured CBSM techniques useful, but
264 HIV and AIDS

may also require additional emotional support. Delivery format

For these individuals a therapeutic plan that
Regarding delivery format, it is important to
combines a group-based stress reduction inter-
note that most of the psychosocial interventions
vention with individual-based therapy directed
evaluated with HIV-infected persons (including
toward these existential issues may be very
those involving aerobic exercise training [La-
useful. An optimal therapy plan may also
Perriere et al., 1990]) have been conducted in a
involve pharmacologic treatment blended with
group format (Ironson et al., 1995). These
the psychosocial intervention.
CBSM interventions typically employed groups
of approximately 6±8 participants facilitated by Common Features of Psychosocial
two group leaders. The sessions were conducted
Interventions in HIV Infection
in comfortable rooms, ran about 2±2.5 hours in Relaxation aspects duration, and ran on a weekly basis over a 10-
week period. While there was some variability in
It is noteworthy that many of the psychoso-
terms of the duration of programs evaluated
cial intervention studies with HIV-infected
across different research groups (range = 8±12
persons have utilized some form of relaxation-
weeks), the number of participants, group
based technique as part of the intervention
leaders, and session length and frequency were
protocol. This is relevant given the great deal of
quite similar. Because of the fact that these
distress and anxiety that these people experi-
sessions were conducted in a group format, little
ence. Relaxation strategies are also salient given
is known about the effects of these sorts of
the reasonably large literature base relating
techniques with HIV-infected persons when
relaxation to improvement in immune system
delivered as individual-based psychotherapy
functioning (e.g., Ironson et al., 1995; Kiecolt-
sessions or self-help approaches.
Glaser et al., 1985, 1986). With regard to HIV
infection, one of these studies found that
frequency of home relaxation practice was Treatment orientation
related to better immunological functioning
and slower disease progression in HIV-infected Different treatment orientations to psycho-
men (Ironson et al., 1994). social interventions have been compared in
Another study examined alternate ways of HIV-infected persons by one group in the
inducing relaxation in HIV-infected individuals Netherlands (in collaboration with the Uni-
(Ironson et al., 1996)Ðmassage therapyÐ versity of Miami). They examined the influence
because of its expected relaxing effects, and of treatment orientation by comparing the
because it is easy to monitor objectively how psychological (Mulder et al., 1994) and im-
much massage someone is getting. HIV-infected munologic (Mulder, Antoni, Emmelkamp et al.,
gay men showed a significant increase in NK 1995) effects of one group-based intervention
cell number, NKCC, the soluble CD8 receptor, using a cognitive-behavioral orientation vs. one
and the cytotoxic subset of CD8 cells during the using an existential/experiential orientation in
weeks of daily massage intervention compared HIV-infected gay men. These men were re-
to the same men's values during a no-massage cruited from a large cohort study conducted
period. These men also showed significant through the Amsterdam Municipal Health
decreases in 24 hour urinary cortisol output Center. The cognitive-behavioral therapy
during the intervention period, suggesting that (CBT) intervention included training in cogni-
distress decreases and/or relaxation increases tive restructuring, relaxation exercises, behavior
may have mediated these immunologic changes. change, assertiveness skills, coping fit for
Indeed, significant decreases in anxiety and controllable vs. uncontrollable stressors, and
increases in a sense of relaxation were also information on stress responses. As such, it was
observed, which were both correlated with quite similar to the CBSM interventions
increases in NK cell number. This study described previously. The experiential therapy
suggests that the relaxation components of (ET) condition was less structured and focused
CBSM interventions noted previously may on increasing awareness of the here and now, of
contribute directly to both the psychological their inner experiential process, and restoring
and immunologic changes experienced by the congruence between emotional, cognitive, and
participants. Psychosocial interventions used behavioral schemata. The intervention also
with HIV-infected persons use many other attempted to help participants deal with a
techniques in addition to relaxation and also shortened life perspective and anxiety about
vary considerably in terms of format and future illness and death. Despite the differences
theoretical orientation. It is possible to examine in theoretical orientation the authors note that
some of the parameters on which these both interventions were designed to reduce
approaches converge and diverge. stress, improve coping, build social support,
Interventions, Adjustment, and Health Course in HIV Infection 265

and encourage emotional expression. They typically assessed at single time points at the
found that both (CBT and ET) conditions were beginning and end of the intervention period. At
associated with significant decreases in POMS least two studies followed subjects over a 2-year
total mood disturbance, and BDI scores postintervention period (Ironson et al., 1994;
compared to the controls, though there were Mulder et al., 1995).
no changes in coping style, social support, or While the results of this set of studies are not
emotional expression over the intervention entirely consistent, they suggest the potential
period. efficacy of psychosocial interventions for in-
Mulder and colleagues compared the 26 men creasing psychological adjustment, immune
randomized ultimately to either CBT or ET with functioning, and health status in HIV-infected
men from the Amsterdam cohort study who did people at early and middle stages of the disease
not participate in the intervention study for who are dealing with mounting stressors. Less is
differences in slope of immune changes that had known about the effects of these interventions
occurred over the period after the intervention with people at the more advanced stages of the
(Mulder, Antoni, Emmelkamp et al., 1995). disease. One study focused specifically on how a
Those intervention group participants with the time-limited CBSM intervention could moder-
largest decreases in distress, between the begin- ate the acute impact of learning one's HIV
ning of either intervention and 9 months later, serostatus for the first time (Antoni, Baggett
showed the least decline in CD4 cell counts over et al., 1991), while the remainder have examined
a 2-year follow-up period from the beginning of how psychosocial interventions can improve
the intervention. These findings suggest that psychological functioning in people dealing
while theoretical orientation may not determine with the more chronic stress of having had
the psychological improvements gained by HIV for a number of years (Auerbach et al.,
HIV-infected men participating in group-based 1992; Coates, McKusick et al., 1989; Ironson
psychosocial interventions, the size of et al., 1995; Mulder et al., 1994). The most
treatment-related reductions in distress may consistent trends among the psychological
be predictive of longer-term health benefits. effects of these interventions are: a decrease in
This interpretation seems to be in line with the distress and depressed affect; a decrease in the
findings reviewed previously (Antoni, Baggett use of avoidance and denial as coping strategies;
et al. [1991] for short-term effects and Ironson an increase in the use of acceptance and positive
et al. [1994] for longer-term effects). reframing strategies; and an increase or main-
tenance of social support provisions. Summary of Completed Studies of While CBSM intervention has been shown to
Psychosocial Interventions with HIV- reduce antibodies to herpes viruses and to
infected Persons modulate NKCC, no direct effects have been
observed on HIV disease progression markers.
Here we summarized the qualities character- Three group-based stress management inter-
izing the psychosocial intervention studies with ventions reported no significant impact on CD4
HIV-infected individuals that were completed cell counts (Auerbach et al., 1992; Coates,
between 1989 and 1997. These studies recruited McKusick et al., 1989; Mulder, Antoni, Em-
moderate sized samples that were approxi- melkamp et al., 1995), but none of these
mately equally distributed across experimental measured herpes virus antibodies or NKCC,
conditions usually resulting in 10±30 people which were the measures found to be most
actually receiving the intervention in any single responsive to change in some of the other
trial. While individuals participating in these studies (Esterling et al., 1992; Ironson et al.,
studies were all gay or bisexual men, congruent 1996; Lutgendorf, Antoni, Schneiderman, &
with the predominant AIDS incidence patterns Fletcher, 1994). Ironson et al. (1995) note that
occurring in the 1980s, it should be noted that no studies have tested the long-term effects of
women now make up nearly 15% of all AIDS these interventions on 5- or 10-year survival,
cases and current incidence patterns for HIV although one study with a small sample showed
infection suggest that this proportion will that intervention-related variables (denial cop-
increase. Therefore, these studies need to be ing reductions and greater treatment adherence)
replicated with other HIV-infected populations were predictive of 2-year survival (Ironson et al.,
such as indigent women. 1994). Another study (Mulder, Antoni, Em-
Of the interventions tested to date, most were melkamp et al., 1995) showed distress changes
conducted in groups, used trained facilitators or (which can often be modified by psychosocial
therapists, and met at least once weekly over interventions) were related to changes in CD4
periods of 8±12 weeks. Since the studies counts over a similar 2-year period. However, it
evaluating these interventions were designed should be noted that ªassignment to a psycho-
to test their immediate efficacy, cohorts were social interventionº has not been causally
266 HIV and AIDS

related to a slower rate of disease progression or is utilized while, in others, CBSM and experi-
greater survival time in HIV-infected persons. ential techniques have been integrated into the
This lack of a causal effect may be due to the same intervention condition. The efficacy of
limited statistical power offered by the small these different treatment orientations may
samples that have been studied to date. Clinical ultimately be shown to vary systematically as
trials that utilize hundreds of participants may a function of the disease stage and demographic
be necessary to capture the effects of psycho- characteristics of the targeted population.
social interventions on the health course of this Second, these investigations are each recruit-
disease. It is also possible that measures of ing people who meet specific inclusion and
immune function might be more sensitive to the exclusion criteria that are similar across studies.
effects of stress-reducing psychosocial interven- Specifically, the samples are largely gay men at
tions than lymphocyte counts because stress the early to middle stages of the infection (pre-
hormone interactions with receptors that med- AIDS symptoms and a restricted range of CD4
iate cell activity and certain immune functional counts) who are dealing with similar psychoso-
indices may be especially relevant to the cial issues. Shifting demographic patterns of the
pathophysiology of HIV infection in particular. HIV/AIDS epidemic make it imperative to
Finally, it has been suggested that health develop techniques to help other HIV-infected
psychology interventions possessing cognitive populations, such as women of color, manage
and behavioral elements, similar to those just their disease. One study, led by Antoni, Green-
noted, may be quite useful in addressing other wood, and Schneiderman in Miami, is examin-
aspects of HIV infection, such as nutritional ing the effects of a 10-week CBSM intervention
disorders, pain, sleep problems, and medication in HIV-infected African-American women who
adherence, all having a potentially huge impact are developing the first symptoms of the
on the quality of life of infected individuals infection. Another trial is evaluating the effects
(Sikkema & Kelly, 1996). It will be important to of a similar intervention in women who have
incorporate these additional variables into already developed AIDS. Clearly, a next step is
intervention protocols conducted in the future to develop psychosocial interventions to address
as more and more people live longer and longer secondary prevention issues in the growing
with this disease. number of HIV-infected injection drug users.
Third, each study is assessing the psychoso-
8.10.5 CONCLUSION cial effects of these interventions with a
collection of well-validated instruments de-
This chapter has summarized the rationale signed to track changes in distress and depres-
and empirical support for the role of health sion as well as intermediary psychosocial
psychology in the context of HIV infection and variables such as coping, social support, and
AIDS. Based on this work it is plausible to stressor appraisals. In most cases, the most
suggest that psychosocial targets of interven- reliable instruments have been employed in
tions should include reductions in distress and these batteries supplemented with more specific
depression, as well as avoidance, denial, and measures designed to tap the most salient areas
rumination as methods of dealing with the of participantsº lives.
chronic stress of the infection. Equally impor- Fourth, most of these studies currently being
tant intervention targets would involve increas- done reflect an excellent breadth of immuno-
ing active coping and a sense of social logic measures (including qualitative and quan-
attachment as important stress buffers. Several titative indices). For instance, several studies are
studies are underway which further examine the now assessing the effects of psychosocial
effects of psychosocial interventions on psy- interventions on NKCC and blastogenic re-
chological adjustment, immune status, and sponses to PHA. Several studies are also
disease course in HIV-infected individuals. examining changes in IgG antibody titers to a
There are several reasons to be encouraged by panel of relevant herpes viruses (e.g., EBV,
the trends that are apparent across ongoing HHV-6, CMV, HSV) and assessing serum
investigations of psychosocial interventions in neopterin as a subclinical disease progression
HIV-infected populations. marker. In the future it is likely that assessments
First, all of the studies use standardized time- of HIV viral load will join this list of assays as a
limited interventions (10±17 weeks) that have way to monitor treatment-related changes in
been ªmanualizedº with specific treatment disease status. It is also imperative that more
modules and criteria for therapist training disease- and antigen-specific immunologic mea-
and implementation (e.g., Antoni, Schneider- sures be incorporated into assessment protocols
man, & Ironson, in press). In some cases these to better understand specific pathophysiologic
interventions follow a CBSM orientation and in links between psychological changes and health
others a more experiential-existential approach course.
References 267

Fifth, all of the studies are tracking the effects ments in immune function that have been
of their interventions on clinical health changes associated with these psychosocial interventions
using standardized staging procedures and raise the interesting question of whether CBSM
criteria (Centers for Disease Control, 1993). can help reconstitute the compromised immune
Due to the relatively large sample sizes, these system once pharmacologic agents such as
studies should be able to assess long-term effects protease inhibitors have contained the virus.
on survival. All of these studies are also These latter questions constitute the focus of the
monitoring changes in several other behavioral ongoing work using health psychology strate-
measures such as sexual behaviors, substance gies to address contemporary secondary pre-
use, physical activities, sleep, and medications. vention issues in the growing populations of
Information about changes in these additional HIV-infected persons who are attempting to
measures, over the course of the interventions, manage their disease.
may be useful for clarifying the mechanisms
underlying treatment changes in affective,
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