53

Sleep and Quality of Life in HIV and AIDS

Louise McGrath and Steven Reid

Summary Insomnia is a common complaint in people living with HIV and AIDS. It contributes to fatigue, functional impair-
ment, and an overall reduction in the quality of life; yet, there remains considerable uncertainty about its cause and significance.
Early reports of sleep-specific EEG changes related to HIV infection, in particular an increase in slow wave sleep, have not
been confirmed in later controlled studies. Sleep disturbance is reported at all stages of HIV infection, but the presence of
cognitive impairment or an AIDS-defining illness is a significant risk factor. Antiretroviral medications have not demonstrated
a class effect, but plasma levels of the non-nucleoside reverse transcriptase inhibitor, efavirenz, do correlate with insomnia.
Amongst the recognized risk factors, the most notable is psychological morbidity which has shown a consistent and strong
association with insomnia in seropositive patients. Insomnia in HIV infection is associated with a reduced quality of life, but
in this population, it remains both under-recognized and under-treated. This may in part be a reflection of uncertainty about
approaches to management, as there is little data on treatment of insomnia in this population. Insomnia in HIV presents a
considerable challenge for the clinician and requires careful evaluation, in particular screening for anxiety and depression, and
a familiarity with non-pharmacological interventions as well as drug treatments for sleep disturbance.

Keywords HIV infections acquired immunodeficiency syndrome sleep disorders insomnia anxiety depression
antiretroviral medication cognitive impairment

when recognized, clinicians often find sleep disturbance a

Learning objectives:
Insomnia is common in people living with HIV and
AIDS, but is under-recognized and under-treated.
Psychological morbidity is a major determinant of
insomnia in HIV infection.
The presence of cognitive impairment, an AIDS-
defining illness, and treatment with efavirenz are
significant risk factors for insomnia in this popula-
tion.
Introduction
Insomnia is a common complaint in individuals with chronic
disease including HIV infection (1, 2). It is reported at all
stages of HIV disease yet often receives little attention.
This may be because it is considered a normal consequence
of the disease and its treatment, or the consequences of
insomnia may be considered insignificant in comparison
with other complications of HIV infection. Furthermore,
difficult problem to manage, with uncertainty about the most
appropriate treatment options. A number of factors have been
implicated in the aetiology of insomnia in HIV infection.
Early studies suggested that somnogenic cytokines, such as
tumor necrosis factor alpha (TNF-) and interleukin-(IL)-1,
were involved (3). As well as immune dysregulation, other
factors such as virus progression, psychological morbidity,
substance misuse, and the adverse effects of antiretroviral
treatment have been considered (2). What is clear however
is that disrupted sleep in people living with HIV contributes
to fatigue, functional impairment, and an overall reduction in
the quality of life (4).
HIV and AIDS
The acquired immunodeficiency syndrome (AIDS) was first
recognized 25 years ago, and infections with HIV are now
seen throughout the world, with an estimated 15,000 new
infections per day (5). The first documented cases of AIDS
were reported in the USA in 1981 when reports appeared

From: J. C. Verster et al. (eds.): Sleep and Quality of Life in Clinical Medicine 505
c 2008 Humana Press, Totowa, NJ
506
of young men presenting with uncommon diseases including
Kaposis sarcoma and pneumocystis carinii pneumonia (6, 7).
Initially, investigators assumed that AIDS was related to a
homosexual lifestyle, but cases were soon reported in intra-
venous drug users, blood transfusion recipients, and then
increasingly in both adults and children in sub-Saharan Africa.
The human immunodeficiency virus (HIV)-1 was isolated in
1983, and Gallo and colleagues provided the first evidence
that it was the infectious transmissible agent responsible for
AIDS. Subsequently, a less common variant of the virus,
labeled HIV-2, has been isolated, although this is largely
confined to West Africa (8).
An estimated 40 million people were living with HIV/AIDS
in 2006 (5). In 2005, there were 4.1 million new HIV
infections and 3 million AIDS deaths. Currently, 95% of all
infections occur in developing countries with the majority
occurring in sub-Saharan Africa and Southeast Asia, but
numbers are increasing rapidly in both China and India. The
virus is transmitted most commonly by sexual intercourse,
with heterosexual transmission accounting for about 85%
of HIV infection worldwide (9). Other modes of transmis-
sion are through the reuse of contaminated needles by intra-
venous drug users or for therapeutic procedures, and the
receipt of infected blood or blood products, donated organs,
and semen. Perinatal transmission of HIV accounts for virtu-
ally all new infections in children, although infants may also
become infected through ingesting breast milk of a seroposi-
tive mother.
HIV disease progresses through a continuum beginning
with acute seroconversion (primary HIV infection) and ending
with AIDS and death (Figure 53.1) (10). The HIV targets
CD4 T lymphocytes that are an integral component of the
normal immune response. Other cells targeted by HIV include
macrophages and microglial cells in the central nervous
system. HIV infection is characterized by the gradual destruc-
tion of the CD4 cell population. During the chronic phase
of the disease, although minimal symptoms may be experi-
enced, there is an extremely rapid turnover of plasma virus;
the half-life of a single viral particle is so short that half the
entire plasma virus population is replaced within 30 min (5).
The clinical course is highly variable, but depends on the
host immunology, viral properties, and genetic factors (11).
Progression to AIDS is predicted both by CD4 count and by
plasma HIV viral load. The CD4 count remains the primary
marker for the development of opportunistic infections and
other complications, particularly when lower than 200 cells
per microliter. The time from initial infection to the develop-
ment of AIDS varies from 6 months to over 15 years. The
Centers for Disease Control and Prevention (CDC) developed
the HIV disease classification system based on a combination
of clinical signs, the presence of certain conditions, and inves-
tigative findings (12):
Group I Primary HIV infection
Group II Asymptomatic phase
McGrath and Reid
Group III Persistent generalized lymphadenopathy
Group IV Symptomatic infection
Primary HIV infection represents the stage of infection when
antibodies are developing to the virus. Signs of infection
include flu-like symptoms, lymphadenopathy, poor appetite
and weight loss, as well as insomnia. There may be signs
of late-stage disease, such as oral candidiasis, due to a high
rate of viral replication, but this is uncommon. Once these
symptoms subside, the person with HIV begins a chronic
asymptomatic or minimally symptomatic state with CD4
lymphocyte counts generally above 350 cells per microliter.
This phase may persist for 10 years or more before the onset
of overt immunodeficiency (10). Some otherwise well patients
may present with persistent generalized lymphadenopathy, but
there is no evidence that this has an effect on outcome. Even-
tually, the replication of the virus rapidly accelerates leading
to a decline in immune competence. The precipitants for
this change remain unclear. With the onset of symptomatic
HIV infection, patients commonly develop constitutional
symptoms such as fever, diarrhoea, weight loss and night
sweats. Profound immunodeficiency leads to the appear-
ance of opportunistic infections, wasting, neurological disor-
ders and neuropsychiatric disorders, and malignancies (5, 10)
(Table 53.1).
Sleep and the Neuropathology of HIV
From the earliest clinical descriptions of HIV, insomnia has
been recognized as a frequent complaint, and descriptive
studies of seropositive patients using polysomnography indi-
cated abnormalities of sleep pattern (1315). As it was recog-
nized that the HIV penetrates the blood brain barrier by
infecting microglial cells and macrophages, it was suggested
that the reported deterioration in sleep architecture was
a direct consequence of HIV neurotoxicity (3). A partic-
ular area of interest was the role of the proinflammatory
cytokines, particularly TNF- and IL-1, which are released
by infected cells. Studies in animal models and trials of
cancer chemotherapy using TNF- and IL-1 have shown that
exogenous administration of these cytokines may cause exces-
sive sleepiness and fatigue (16). In particular, an increase
in slow wave sleep was observed; similar changes to those
reported in studies of otherwise asymptomatic seropositive
individuals. Norman and colleagues in a series of small
polysomnography studies noted a significant increase in slow
wave sleep, particularly during the late sleep cycles (14, 17,
18). There were also reports of an increased frequency but
reduced duration of periods of rapid eye movement (REM)
sleep (19). The cytokine studies supported the hypothesis
that these changes in sleep architecture were a direct conse-
quence of HIV disease progression. Notably, these studies
lacked controls and made comparisons with normative popu-
lation data. Later, controlled investigations challenged these
observations, finding no differences when compared with