The Psychoneuroimmunological Data Base for Psychological Interventions in HIV Infection

Gay & Lesbian Issues and Psychology Review, Vol. 4, No. 2, 2008
ISSN 1833-4512 © 2008 Author/Gay & Lesbian Issues & Psychology Interest Group of the Australian Psychological Society
THE PSYCHONEUROIMMUNOLOGICAL DATABASE FOR
PSYCHOLOGICAL INTERVENTIONS IN HIV INFECTION

PETER B. TODD
Abstract

The emergence of multiple drug resistant
strains of HIV creates the need for a renewed
focus upon the status of scientific knowledge
concerning the impact of psychosocial and
emotional factors upon immunity, disease pro-
gression and AIDS mortality in HIV seroposi-
tive persons. To this end, the field of psycho-
neuroimmunology (PNI) has provided a vast
empirical data base of psychosocial determi-
nants of immunity, illness progression and
mortality in HIV infection since the early
1980’s. Such data have demonstrated that
psychosocial factors are highly significant pre-
dictors of behaviour known to enhance risk of
exposure to HIV and therefore need to be
considered as a vital foundation of primary
prevention programs aiming to minimize new
infection rates. This paper reviews the psy-
chosocial factors already identified as signifi-
cant to both primary and secondary preven-
tion while outlining directions for future re-
search, including the need for studies which
permit the use of multivariate techniques such
as hierarchical logistic regression and discrimi-
nant function analyses. Homophobia in par-
ticular seems to be a health menace as a de-
terminant of high risk behaviour, immunosup-
pression and AIDS mortality. Cross cultural
validation of research is emphasized as most
PNI studies have been conducted in the de-
veloped world, especially North America.

Introduction

Kuhnian anomalies suggest the need for a
paradigm shift in the scientific understanding
and treatment of HIV/AIDS. This may involve
a move beyond the traditional medical model,
and towards a multifactorial, ecological or ho-
listic framework which highlights the potential
efficacy of psychological interventions. The
anomalies in the current paradigm include
multiple drug resistance to HIV, resulting in
potentially serious limits to a purely pharma-
cological approach to treatment with antiretro-
viral drugs. Rambaut, Posasa, Crandall and
Holmes (2004) commented in their paper
that the evolutionary significance of HIV and
mutation was underestimated by those who
proposed that highly active antiretroviral ther-
apy (HAART) represented a cure for AIDS.
Commenting upon the marked genetic vari-
ability exhibited within individual hosts, these
authors referred to HIV as ‘one of the fastest
evolving of all organisms’.

Mathematical modelling which had predicted
the eradication of virus from patients within
two or three years has not been fulfilled. Yu
and Weber (2006) observed that one of the
most disturbing events in attempts to counter
HIV infection has been the emergence of mu-
tations that conferred resistance to all 20 FDA
approved antiretroviral drugs then being used
clinically. Further anomalies include the almost
insuperable difficulties with vaccine develop-
ment due to mutation reported by Ho (2005)
and most recently, evidence of increased risk
of seroconversion in one clinical trial reported
by Kresege (2007). Alternative biomedical ap-
proaches to scientific understanding include
the work of Davis (2006) and his colleagues
exploring how HIV hijacks cellular communica-
tion networks to propel itself from one cell to
another and the research of McFadden & Al-
Khalili (1999) in developing a quantum me-
chanical model of ‘adaptive’ or directed muta-
tion. This is particularly relevant in relation to

TODD: PSYCHOLOGICAL INTERVENTIONS IN HIV PREVENTION
mutant strains of tuberculosis, which in con-
junction with HIV seropositive status consti-
tutes a threat to the lives of millions of people,
especially in the developing world. It is in the
context of such anomalies in classical biomedi-
cal research that prioritizing empirical studies
into psychoneuroimmunological aspects of
HIV/AIDS and evaluating psychological inter-
ventions may need to be re-evaluated. HIV is
a threat to both immunological and psychic
identity and self-integration as well as biologi-
cal survival and immortality.

Primary and Secondary Prevention

Psychological interventions would aim to facili-
tate the modification of personality, stress,
emotional and behavioural factors which en-
hance the probability of exposure to HIV as
well as immunosuppression and disease pro-
gression once infection has occurred. In con-
junction with education programs and bio-
medical measures demonstrated by empirical
evidence to reduce the risk of infection, such
measures fall into the domain of primary pre-
vention. The rationalist assumption that simply
providing information about behaviours result-
ing in a high risk of exposure to HIV is a suffi-
cient primary prevention measure has been
known to be flawed since the early 1980’s
(McKusick, 1983, Todd, 1992), while repeat-
ing the errors which have historically charac-
terized attempts to modify behaviour patterns
related to cancer and heart disease (Todd &
Magarey 1978). The often complex and un-
conscious motivations of such high risk behav-
iours must also be taken into account. Similar
considerations apply to behavioural and life-
style factors such as substance misuse which
are likely to impact upon immunity and dis-
ease progression once infection has occurred.

Evidence based psychological interventions
are potentially highly relevant to immunosup-
pression (and enhancement) as well as dis-
ease progression in persons who are already
seropositive to HIV (Solomon, 1987; 1991;
Todd, 1992; Cole & Kemeny, 2001 and Kie-
colt-Glaser & McGuire, 2002). Empirical data
concerning these issues fall into the domain of
secondary prevention and much of the re-
search on psychoneuroimmunological aspects
of HIV/AIDS concerns quantified psychosocial
factors predictive of immunity and disease
outcome. In the remainder of this paper I
shall review empirical studies relevant to both
primary and secondary prevention as well as
the implications for psychological interventions
in considerable detail. Historically many stud-
ies had evaluated the relevance of one or few
psychosocial factors instead of exploring the
possible predictive significance of multiple
variables with respect to immunity, illness out-
come and AIDS mortality.

The Psychophysical Problem

One conceptual obstacle to the acceptance of
psychoneuroimmunological research has been
a conscious or unconscious investment in a
materialist epistemology of science. Reduc-
tionist materialism has viewed consciousness
and mental processes as epiphenomenal and
causally inefficacious by-products of events in
the brain. Such a position either denies causal
significance to psychological factors or regards
mentalistic terms as a linguistic shorthand for
the description of neurophysiological proc-
esses. Historically, this has been one influen-
tial solution to the so-called ‘psychophysical’ or
mind/matter problem.

The contributions of such neuroscientists as
Eccles (1990) and Pribram (2004) have chal-
lenged such mindless materialism, concluding
that philosopher Karl Popper’s three worlds of
brain, culture and mind (Popper & Eccles,
1990) are indispensably necessary for the
achievement of consciousness. The ‘three
worlds’ interact in a feedback loop, so that
consciousness or mind program the brain to
evolve culture which in turn stimulates mental
development. As Pribram (2004) pithily put it
in referring to the mental, ‘the more reflex the
reflex, the less does mind accompany it’. Even
sophisticated brain imaging techniques such
as fMRI do not permit the prediction of the
phenomenological content of consciousness.

Physicists as far back as Erwin Schrödinger
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TODD: PSYCHOLOGICAL INTERVENTIONS IN HIV PREVENTION
(1992) and as recently as David Bohm (2002),
Roger Penrose (2004), Basil Hiley and Paavo
Pylkkänen (2005) have rejected the materialist
reductionist perspective on mind as incompati-
ble with a post classical physics and with
quantum mechanics. They have argued in-
stead for the adoption of a dual aspect rela-
tionship of ‘complementarity’ between mind
and matter in considering the role of the ob-
server. The mental has therefore become a
reputable domain of scientific enquiry, with
one potent source of resistance to psychoso-
matic research and psychoneuroimmunology
being overcome. Making a move beyond phar-
macology and the medical model plausible in
the empirical understanding of HIV.

The Nature and History of Psycho-
neuroimmunology

The late Professor George Solomon was an
eminent scientist and pioneer, actually cred-
ited with coining the term ‘psychoimmunology’
in 1964. Solomon and Engel (1977), who had
called for a revolution in scientific understand-
ing due to research in the field of psychoso-
matic medicine, had seriously challenged the
traditional Jenner-Pasteur model of infectious
disease as well as such immunologically medi-
ated and resisted illnesses as cancer and auto-
immune disorders. Early correlational studies
beginning in the 1930’s on the basis of largely
psychoanalytic insights into the impact of re-
pressed conflicts in ‘object relations’ or attach-
ments and about anger as well as the sym-
bolic meanings of specific organ systems
(such as the breast) had laid the foundations
for psychosomatic hypotheses which, how-
ever, did not permit causal inferences to be
made on the basis of data collected
(Menninger, 1938; Grinker, 1973). The possi-
ble causal significance of psychological and
social factors could be assessed only when the
biological mechanisms mediating the impact of
such variables on disease onset and outcome
could be elucidated and quantified. Psycho-
neuroimmunology was born when both immu-
nological and neuroendocrine pathways were
identified and became susceptible to empirical
measurement. A landmark study was that of
Bartrop (1977), an Australian physician who
demonstrated depression of T lymphocytes
after bereavement, a finding replicated by
Schleifer, Keller, Camerino, Thornton and
Stein (1983). Higher mortality rates in part-
ners within 6 months of bereavement were
observed.

The explanatory theoretical framework pro-
vided by Bowlby (1989) in his work on Attach-
ment and Loss has been a useful source of
hypotheses about the impact of bereavement
and separation upon immunity and illness in-
cluding HIV/AIDS. Bereavement resulting in
guilt and self reproach is not only emotionally
toxic, but like homophobia, deleterious to HIV
seropositive persons as I shall point out in
discussing psychosocial factors as predictors.

Solomon (1987), Ader (1981; 1991), and
Todd, (1992) have provided detailed reviews
of the nature and history of psychoneuroim-
munology, including early studies of HIV/AIDS
within this conceptual framework. Specifically,
empirical research on psychosocial factors as
predictors of behaviour patterns associated
with the risk of infection with HIV, immune
status and the onset of AIDS spectrum disor-
ders in seropositive individuals were reviewed.
I shall now turn to the psychosocial factors
demonstrated to be predictors of immunosup-
pression, illness progression and AIDS mortal-
ity. Psychosocial factors have demonstrated
significance for secondary prevention, that is
to say, to influencing immunity, illness and
AIDS related mortality even with the introduc-
tion and use of antiretroviral drugs, especially
in the developed world. The results of inter-
vention studies based on these data which
appear promising will be discussed briefly in
the next section.

Psychosocial Factors as Predictors

Hypotheses about psychosocial factors likely
to be relevant to the onset and progression of
HIV/AIDS were deduced initially from research
studies of the role of such factors in other im-
munologically mediated and resisted diseases
including cancer, autoimmune disorders and
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TODD: PSYCHOLOGICAL INTERVENTIONS IN HIV PREVENTION
infections such as Epstein-Barr, cytomegalovi-
rus and herpes simplex. This work had been
published in such sources as the volume of
Ader (1981) on psychoneuroimmunology. Viral
causation of certain cancers had been consid-
ered probable even prior to the onset of the
HIV/AIDS pandemic during the early 1980’s.
Solomon (1987) and other members of the
Biopsychosocial AIDS Project at the University
of California, San Francisco including Todd
(1986; 1992) formulated hypotheses about
psychosocial factors as predictors of immunity
and illness in HIV infected persons as well as
the role of such factors as determinants of
behaviour patterns resulting in a high risk of
exposure to HIV. Solomon (1987) reported the
results of pilot studies in the United States.
Summed up briefly, the early hypotheses con-
cerned the possible significance of such psy-
chosocial factors as (a) coping and defence
mechanisms, (b) loss of significant persons
through bereavement or separation, (c) de-
pression manifest as hopeless/helpless reac-
tions to trauma and threat, as distinct from
grief (d) Integration or acceptance of sexual
identity, compared to internalized homophobia
and shame, (e) inward-turning or suppressed
anger, (f) social support and (g) resilience
associated with a sense of meaning in life.

The pilot studies and early research reported
by Solomon (1987; 1991) and Todd (1986)
provided some significant data in support of
these hypotheses. Internalized homophobia
was significant in the work of both McKusick
(1983) and Todd (1992) as a determinant of
high risk behaviour with respect to HIV infec-
tion as well as immunosuppression and the
onset of clinical symptoms of AIDS spectrum
illness. However, the need for prospective,
longitudinal studies and controlling for possi-
ble confounding factors such as substance
misuse and with larger sample sizes to opti-
mize statistical power, was noted by workers
as an important direction for future research
as well as more rigorous hypothesis testing
(Solomon, 1991; Todd, 1992; Cole & Kemeny,
2001). Extensive reviews of studies on psy-
chosocial determinants of immune status and
the progression of HIV infection since 1991
have been provided by Cole et al (2001) and
Kiecolt-Glaser and McGuire (2002).

Factors which may have direct implications for
interventions are now summarized. Analyses
focussing upon reactions to highly traumatic
and personally salient events such as diagno-
sis of HIV seropositive status and bereave-
ment have identified relationships with both
immunological and clinical indices of HIV pro-
gression. Kemeny, Weiner, Taylor, Schneider
and others (1994) found that measures of
grief uncomplicated by depression predicted
reductions in immune function over a 2 to 3
year period in a group of seropositive gay
men. This finding was replicated by Kemeny
and Dean (1995) in which guilt and self-
reproach or blame as an aspect of grief follow-
ing bereavement predicted CD4+T cell de-
clines during an 18 month period. However,
other research indicated that actively con-
fronting such traumas as bereavement or the
threat of mortality and finding a sense of
meaning could mitigate immunosuppression
and mortality. For instance, Bower and Ke-
meny (1998) found that those who discovered
meaning experienced a slower decline in
CD4+T cell levels over 2 to 3 years and had
an enhanced survival time during 4 to 9 years.

Defensive denial of seropositive status
(Ironson, Friedman, Klimas, Antoni et al,
1994) and shame based concealment of ho-
mosexual identity were associated with immu-
nosuppression and heightened risk of progres-
sion to AIDS during a 2 year follow up. These
findings confirmed those of the earlier studies
which had demonstrated significant associa-
tions between such factors, high risk sexual
behaviour, immunosuppression and disease
progression while linking acceptance of sexual
identity with a lower probability of exposure to
HIV and a more favourable prognosis. A mat-
ter of serious concern for health professionals
working in the HIV/AIDS field (Todd, 1992).

Cole and Kemeny (1996;1997) investigated
concealment of homosexual identity as a
model of what they termed ‘psychological inhi-
bition’, finding accelerated times to a critically
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TODD: PSYCHOLOGICAL INTERVENTIONS IN HIV PREVENTION
low CD4+T cell level as well as AIDS onset
and mortality among ‘closeted’ members of a
sample of initially healthy gay men followed
up for a period of 9 years. The so-called
‘closeted’ individuals were assessed as particu-
larly sensitive to perceived social rejection,
this factor being an even stronger predictor of
HIV disease progression than concealment per
se. Such data seem to fit well with the notion
of internalized homophobia with its associated
shame and self hatred resulting in both con-
cealment and perhaps through projection, hy-
persensitivity to rejection by others. As I shall
discuss in the conclusions to this paper, the
menace to mental and bodily health is homo-
phobia which could be targeted in both indi-
vidual and group interventions promoting self-
acceptance as a step towards reducing high
risk behaviour and disease progression.

To summarise, well controlled studies have
implicated the following psychosocial factors
as predictors of behaviour placing individuals
at risk of HIV infection, and prone to immuno-
suppression, illness and AIDS mortality. The
factors which can be considered to be poten-
tial foci for psychological interventions include:
(a) depression, (b) bereavement (c) such
grieving responses to bereavement as guilt
and self reproach, identified by Freud (1917)
in his paper on mourning and melancholia, as
repressed feelings towards the deceased, (d)
denial of such traumatic realities as seroposi-
tive status and mortality, (e) concealment
rather than acceptance of sexual identity (f)
internalized homophobia and (g) a sense of
meaning in life in the face of the threat of
mortality.

Interventions

Kiecolt-Glaser and McGuire (2002) have pro-
vided a review of psychoneuroimmunological
studies relevant to the understanding and
treatment of cancer and autoimmune disease
as well as HIV/AIDS. With respect to HIV, the
authors paid specific attention to the potential
benefit of psychological interventions as di-
verse as hypnosis, cognitive behaviour ther-
apy, self-disclosure and existential approaches
concerned with the quest for meaning in con-
fronting such highly traumatic events as be-
reavement and mortality. In general terms
they noted that the narrower the scope of a
behavioural intervention and the shorter its
time course, the smaller and less enduring
would be its impact either psychological or
immunological while observing that longer
follow-up periods would be desirable in future
evaluative research. Similarly, Cole et al
(2001) had observed that several randomized
clinical trials had suggested that psychological
interventions addressed, for instance, to be-
reavement, grief and shame based conceal-
ment of sexual identity, may influence immu-
nologic indices of disease progression. While
Kiecolt-Glaser et al observed that intervention
work with HIV seropositive persons had pro-
duced some ‘promising results’, this conclusion
appears to have been based more upon the
mounting evidence that psychosocial factors
are significant predictors of behaviour expos-
ing people to HIV infection and both immunity
and disease progression than the results of
well controlled intervention studies. Such re-
search, however, would establish more of an
empirical evidence base for psychological in-
terventions as well as clarifying those with
greater efficacy in reducing morbidity and
mortality.

Conclusions

In conclusion it may be useful to highlight the
need for sophisticated studies of multiple vari-
ables in psychosocial research, permitting the
use of such multivariate techniques as hierar-
chical logistic regression and discriminant
function analyses, unresolved methodological
issues and future directions for research. The
variance accounted for as well as statistical
significance levels need to be made explicit in
such work relevant to interventions. The need
for further prospective, longitudinal studies
and controlling for such confounding variables
as substance misuse and stage of illness at
the commencement of research, with the lar-
ger sample sizes necessary to optimize statis-
tical power than those in cross-sectional and
pilot work has been noted as important for
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TODD: PSYCHOLOGICAL INTERVENTIONS IN HIV PREVENTION
more rigorous hypothesis testing and the pro-
vision of a solid evidence basis for interven-
tions (Solomon, 1991; Todd, 1992; Cole &
Kemeny, 2001). The simultaneous analysis of
psychosocial factors, biological mediators and
HIV disease progression remain important
questions for research.

Psychological interventions would need to fo-
cus upon the modification of psychosocial fac-
tors demonstrated to be significant predictors
of deleterious behaviours as well as immunity
and disease progression in HIV seropositive
persons. Such implicit or unconscious factors
as denied or repressed homophobia and un-
derlying negative emotions including anger,
shame, guilt and reproach attributed to the
person’s own self may need to be further
evaluated in the context of evaluating the effi-
cacy of interventions. The empirically demon-
strated significance of such implicit or uncon-
scious factors could suggest that psycho-
dynamic insights and techniques may need to
be integrated into intervention programs in
conjunction with other therapeutic modalities
such as CBT. Reactions to bereavement, for
instance, may also need to take into account
the quality of the attachment to the deceased
and whether the loss results in the emergence
of conflicts and feelings about past losses of
significant figures. Well designed evaluation
studies could be considered vital to creating
an empirically solid case for properly funded
psychological intervention programs, inde-
pendently of antiretroviral drug treatment.
Cross cultural validation of research conducted
in the developed world would permit generali-
zation of results.

Author Note

Formerly research psychologist, School of Sur-
gery, UNSW, then Neuropsychiatric Institute,
Prince Henry Hospital, Sydney, then member,
Biopsychosocial AIDS Project, University
of California, San Francisco, USA, then Con-
sultant, Department of Immunology, St. Vin-
cent's Hospital, UNSW and Research Coordina-
tor, Albion Street AIDS Clinic, Sydney. Cur-
rently, psychologist and psychotherapist in
p r i v a t e p r a c t i c e . E m a i l :
pto49976@bigpond.net.au

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