Open Journal of Psychiatry, 2011, 1, 132-136 OJPsych
doi:10.4236/ojpsych.2011.13020 Published Online October 2011 (
Published Online October 2011 in SciRes.
HIV encephalopathy presenting as schizophrenia-like
delusions during highly active antiretroviral therapy (HAART)
case report
Mikako Fuji1, Misaki Iseki2, Seisho Takeuchi3, Kyoko Kakeda1, Shinji Shimodera1*,
Hiromi Seo3, Shimpei Inoue1
1Department of Neuropsychiatry, Kochi Medical School, Kochi University, Kochi, Japan;
2Department of Psychiatry, Ichiyou Hospital, Kochi, Japan;
3Department of Medicine, Kochi Medical School, Kochi University, Kochi, Japan.
Email: *
Received 6 August 2011; revised 11 September 2011; accepted 25 September 2011.
After HAART (highly active antiretroviral therapy),
which is a powerful antiviral drug regimen, was in-
troduced into HIV therapy for AIDS patients, AIDS
mortality decreased dramatically. The incidence of
encephalopathy among AIDS patients was reported
to be 10% to 40% in the past, but the introduction of
HAART resulted in a decrease in HIV encephalopa-
thy and an increase in mild CNS-related deficits,
which affect the quality of life of AIDS patients. We
report the case of an AIDS patient who developed
schizophrenia-like delusions associated with encepha-
lopathy. Administration of an antipsychotic drug and
hypnotics was effective in relieving the symptoms of
patients with insomnia, depressed mood, and delu-
sions. Further information on the neuronal mecha-
nism underlying the mental symptoms observed in
our patient will be necessary to understand the proc-
ess of pathogenesis of the encephalopathy and to de-
vise an adequate clinical strategy for treatment.
Keywords: HIV; Encephalopathy; Schizophrenia; HA-
ART; Antipsychotics
There have still been few reports regarding HIV en-
cephalopathy in Japan. 1) According to a WHO report,
since the 1990s the mean worldwide HIV infection rate
of the adult population (15 to 45 years of age) has been
in the 0.8% range. 2) Ever since the powerful antiviral
therapy consisting of combinations of several anti-HIV
drugs, called HAART (highly active antiretroviral ther-
apy), became established, the numbers of persons who
have developed AIDS and died has been decreasing. On
the other hand, as a result of the advent of HAART, the
life span of HIV patients has grown longer, and the
number of patients who develop HIV encephalopathy
has increased 3, 4, 5) HIV encephalopathy often devel-
ops when the CD4 cell count drops below100/μl, and
before HAART therapy was established, it was observed
in 10% - 40% of the patients. Now that HAART has
been established, the CD4 cell count of many HIV pa-
tients is above 200/μl, and HIV encephalopathy has de-
creased. 6) We report the case of a patient who, despite
good control of his HIV infection, progressed to HIV
encephalopathy and exhibited a schizophrenia-like hal-
lucinatory delusional state that was associated with it.
[Patient] A 38-year-old male whose premorbid personal-
ity was introverted and stubborn. His elementary, junior
high, and high school grades were average.
[Chief complaint] A hallucinatory delusional state.
[Complications] Hypertension.
[Family history] Mother: Schizophrenia, hypertension.
Died of a ruptured cerebral artery aneurysm. Father: Hy-
pertension. Died of a cerebral hemorrhage. Nephew:
Epilepsy, mental retardation.
[Drinking history] None.
[Smoking history] None.
[History of use of psychoactive substances, such as
narcotics] None.
[History of the present illness] The second of two
children. Growth and development unremarkable. Both
parents died while the patient was in high school, and his
sister, who was 7 years older, became a parental substi-
tute. After graduating from a vocational-technical school,
he found employment at age 20, but after working for a
company for 2 years, he was unable to stand the pressure
M. Fuji et al. / Open Journal of Psychiatry 1 (2011) 132-136 133
of the work, and resigned. He subsequently performed a
series of part-time jobs. The patient is homosexual.
At age 26, he was diagnosed with HIV infection. In
July of the same year, while an inpatient in the internal
medicine department of university hospital A in another
prefecture for Pneumocystis pneumonia, he attempted
suicide because of anxiety about dying. At age 28, he
was admitted for cytomegalovirus retinitis in September,
but his visual impairment progressed, and he developed
insomnia and suicidal ideation. The patient was exam-
ined in the psychiatry department of the hospital because
he had taken an overdose of a hypnotic agent, and he
was diagnosed with reactive depression. His symptoms
improved in response to treatment with etizolam 1.5 mg
and mianserin 20 mg. Antiviral drug therapy was subse-
quently instituted in the internal medicine department of
the same hospital (zidovudine monotherapy and in com-
bination with didanosine, lamivudine, nelfinavir, etc). At
age 29, treatment with a combination of zidovudine 200
mg, lamivudine 300 mg, nelfinavir 2500 mg was started
in May. He had stopped working because of the visual
impairment, was receiving public assistance, and con-
tinued to live alone. At the time his HIV-RNA load was
under 50 copies per ml, his CD4 cell count was 700/μl -
1000/μl, his HIV infection was well controlled, and his
cognitive functions and personality had been maintained.
At 34 years of age, in mid-October the patient began
to hear the voice of a neighbor saying negative things
about him, and he started to avoid his home and spend
all day outdoors. In early November, when he was
walking around completely nude and banging his head
against walls, he was taken into police custody and ad-
mitted to the internal medicine department of the same
hospital. He was treated with haloperidol 5 mg i.v., but
because the delusions and hallucinations persisted, two
weeks later he was transferred to the psychiatry depart-
ment of the same hospital. Hallucinations and delusions,
a memory disorder, and a consciousness disorder were
noted, and because at a time when his mental symptoms
became more severe an unenhanced T2 high-signal le-
sion was observed in the head of the right caudate nu-
cleus on an MRI examination of the head, reduced blood
flow in the occipital lobe and anterior cingulate gyrus
bilaterally on a SPECT examination, and waves pre-
dominantly in the occipital lobe and sharp waves in the
right occipital area on an EEG, a diagnosis of HIV en-
cephalopathy was made. His scores on the WAIS-R at
the time were: VIQ 78, PIQ 46, full-scale IQ 61. The
mental symptoms were improved by treatment with
haloperidol 12 mg and chlorpromazine 25 mg, and he
was discharged in February of the following year. The
WAIS-R administered before he was discharged showed
an improvement to: VIQ 84, PIQ 63, and full-scale IQ
73. There were no changes in his HIV drugs or their
doses during the course of his illness. Perospirone 16 mg
was substituted because of extrapyramidal symptoms.
The patient later moved close to his sister and lived
alone in an apartment with the assistance of a helper 3
times a week. In July of the same year the patient was
referred to our department by a local physician and ex-
amined. He was transferred to the internal medicine de-
partment of our hospital for treatment of the HIV infec-
tion, and HAART was continued with no changes to the
regimen prescribed. Management in our department
consisted of substituting quetiapine 50 mg because mild
extrapyramidal symptoms had been noted, but the dose
was reduced to 25 mg in November, because the mental
symptoms had stabilized, and quetiapine was discontin-
ued in January of next year. Thereafter only zolpidem 10
mg and etizolam were prescribed for insomnia, and the
mental symptoms were stable. The patient’s HIV-RNA
load was under 50 - 74 copies/ml, and the CD4 cell
count was 700/μl - 1000/μl, and thus his HIV infection
was also well controlled.
At age 37, a feeling of residual urine developed ar-
ound November, and the patient became extremely anx-
ious, thinking that it was a symptom caused by progres-
sion of the HIV infection. Because he developed a de-
pressed mood, decreased motivation, a reduced appetite,
and insomnia in mid-December, he was started on ser-
traline 25 mg. Living alone later became difficult, and
the patient moved in with his sister. At age 38, auditory
hallucinations developed in early January. Because such
hallucinations and delusions as “A police officer came in
a patrol car, and I talked to the police officer” developed
in addition to the depression, the dose of sertraline was
increased to 50 mg, and risperidone 2 mg, levomepro-
mazine 25 mg, and diazepam 10 mg were added. When
the patient subsequently developed dysuria in addition to
poor oral intake, he was admitted to our department as
an emergency 7 days after the onset of the hallucinations
and delusions.
[Mental symptoms on admission] The patient tended
to be drowsy. He was able to answer questions by shak-
ing his head, but he spoke very little. There was no dis-
orientation. A delusion that “I will be picked up by the
police” and hallucinations whose content was unknown
were noted. Oral intake was poor. The patient resisted
being examined, and he finally closed his eyes and no
longer responded to questions. The findings resembled
the catatonic manifestations of schizophrenia.
[Physical findings] Body temperature: 37.4 C, blood
pressure: 199/147 mmHg, pulse: 116/min, SpO2: 97%
(room air).
[Neurological findings] No nuchal rigidity. Kernig
sign present. No limb paralysis. No sensory abnormaliti-
opyright © 2011 SciRes. OJPsych
M. Fuji et al. / Open Journal of Psychiatry 1 (2011) 132-136
es. Babinski reflex and Chaddock reflex positive.
[Test findings on admission] MRI of the head: A wide
high intensity area was seen in the brain stem, around
the anterior horn of the lateral ventricles, and in the
subcortical white matter on T2WI.
Cerebrospinal fluid examination: Cell count 27/3 μl,
protein 84 mg/dl, Cryptococcus neoformans (-), tubercle
bacillus (PCR method) (-), cytomegalovirus antigen (-),
JC virus antigen (-), HIV-RNA 9.4 × 100 copies.
EEG findings: A low wave occurrence rate and α
wave burst suppression pattern were noted.
[Test findings during the subsequent course] EEG
findings on hospital day 10:8 - 10 Hz, 30 - 50 V occipital
lobe predominant waves were noted.
Blood examination: HIV-RNA load 31000 copies/ml,
CD4 cell count 397/μl.
MMSE: 16/22 points (conducted omitting the 3-step
command, reading, naming, and writing and construc-
tional praxis, which require visual acuity. Unable to an-
swer two questions, i.e., region and floor of the building,
in regard to orientation to place, and one of three ques-
tions in regard to recall.) WAIS-R: VIQ 82 (because of
the visual impairment, the PIQ test with blocks, symbols,
etc., was not performed. The VIQ test alone was per-
formed). HAM-D on hospital day 18:19 points
[Hospital course] A 1500 ml/day i.v. infusion was ad-
ministered to treat dehydration. Based on his course the
patient was concluded to have been overly sedated by
the psychotropic drugs, and the oral psychotropic medi-
cation was discontinued. The anti-HIV drugs were stopped
because of his poor oral intake. An EEG was performed
on hospital day 2, the findings described above were
observed, and a mild consciousness disorder was sus-
pected. Oral intake became possible on hospital day 5.
Communication had improved in comparison with on
admission, but his reactions to conversation were slow,
and an attention deficit disorder was observed. The pa-
tient was capable of simple communication in everyday
life, but he could not converse about difficult content.
Schizophrenia-like symptoms were observed, such as
bizarre speech and conduct in which he seemed to be
having delusions, e.g., “Stealing time…,” or behavior in
which he appeared to be listening to an auditory halluci-
nation and suddenly uttered a word as though he were
conversing with the auditory hallucination, etc. In addi-
tion, there was self-accusatory speech, saying “I’m re-
ceiving public assistance, and I’m taking life easy every
day,” and a tendency to stay in bed and loss of motiva-
tion were observed. An EEG was performed again on
hospital day 10, and signs of an improvement in the
consciousness disorder, such as an increase in the rate of
occurrence of waves, were noted. On the same day,
quetiapine 25 mg was started to treat his mental symp-
toms, and all of the hallucinations and delusions subse-
quently resolved. While nursing care was necessary be-
cause of the patient’s impaired vision, he had become
familiar with the hospital unit and was largely capable of
independent living. On hospital day 14 he was examined
in the neurology department, and HIV encephalopathy
was diagnosed based on a cerebrospinal fluid examina-
tion and the imaging findings. No improvement in the
dysuria was observed even after the psychotropic drugs
were discontinued. Based on the diagnostic images of
the brain the dysuria was judged to be a disturbance
caused by the HIV encephalopathy lesions, and it was
decided to continue the urinary catheterization. Symp-
toms of depression, such a decreased motivation, dimin-
ished interest, etc., were noted, but on hospital day 15
the patient’s score on the HAM-D was 19 points, and his
course was monitored without prescribing any antide-
pressant medication. There was also a slight improve-
ment in the patient’s response to conversation and his
interest in the other person, but he did not recover to his
condition prior to the present episode. On hospital day
42 he was discharged to his sister’s home.
[Post-discharge course] The patient continued to live
with his sister after being discharged from the hospital.
He gradually regained his vitality, and his response to
conversation also returned to its previous level. His mental
symptoms stabilized at quetiapine 25 mg. Because his
HIV-RNA load on post-discharge day 36 was high,
130,000 copies/ml, and his CD4 cell count had declined
even further to 299/μl, the patient was concerned about a
progression of his symptoms, and he wanted to resume
HAART. It was concluded that he was capable of taking
his medication regularly, and on post-discharge day 54
HAART was restarted. On post-discharge day 82 his
HIV-RNA load had decreased to 680 copies/ml, and his
CD4 cell count had risen to 678/μl.
It is generally said that HIV encephalopathy often de-
velops when the CD4 cell count is below 100/l.6) Even
though our patient’s HIV infection was well controlled
by HAART, with an HIV-RNA load under 50 copies /ml
and a CD4 cell count of 700 - 1000/μl, he developed
HIV encephalopathy and exhibited a hallucinatory delu-
sional state, and the symptoms improved in response to
psychotropic drugs without changing the content of the
HAART regimen. The hallucinations and delusions did
not recur after that, even when the psychotropic medica-
tion was stopped, and his HIV infection was well con-
trolled, with an HIV-RNA load of under 50 to 74 copies
/ml and a CD4 cell count of 700 - 1000/μl, however, a
relapse of the HIV encephalopathy was observed 4 years
later, and he once again exhibited signs of hallucinations
Copyright © 2011 SciRes. OJPsych
M. Fuji et al. / Open Journal of Psychiatry 1 (2011) 132-136 135
and delusions. Although our patient had a past history of
Pneumocystis pneumonia and cytomegalovirus retinitis,
he had no clear history of central nervous system infec-
tion other than the retinitis. Since both a process of im-
provement of the consciousness disorder and resolution
of the mental symptoms were observed in regard to the
patient’s hallucinations and delusions, the course of treat-
ment appeared to be different from that of schizophrenia.
In the future it seems that it will be necessary to bear in
mind HIV encephalopathy cases such as our own, in
which the patient exhibited mental symptoms, including
hallucinations and delusions, as a result of a longterm
central nervous system disturbance, and examine the
patients even when their CD4 cell count is adequate. At
age 28, our patient’s CD4 cell count was below 10/μl in
September, and he developed cytomegalovirus retinitis
as a complication. It was estimated that he had probably
contracted the HIV infection more than 20 years previ-
ously. After infection in the periphery, HIV rapidly mi-
grates centrally, and it causes behavior disorders, motor
disorders, and cognitive dysfunction. Our patient’s mother
had schizophrenia, but it is unclear whether that contrib-
uted to his vulnerability to hallucinations and delusions.
The powerful antiviral therapy call HAART was in-
troduced in Japan about 10 years ago, and the number of
patients who die of HIV infection declined, but at that
time there was a very harsh situation in which life and
death were governed by whether HAART had been in-
troduced in the AIDS unit. Our patient had been admit-
ted to the internal medicine department of hospital A for
Pneumocystis pneumonia 3 years before, but at that time
HAART had not been established, and presumably the
patient became depressed and planned to commit suicide
as a result of anxiety of about dying because of seeing
patients around him die day after day and thinking that
one day the same would probably happen to him. The
patient developed cytomegalovirus retinitis as a compli-
cation at precisely that time, and he was one of the first
patients to receive the benefits of HAART after it be-
came available in Japan. Some of the drugs used in
HAART easily pass through the blood-brain barrier, and
others do not. Zidovudine has the highest transfer rate of
the drugs used to treat our patient, i.e., zidovudine,
lamivudine, and nelfinavir, and it has been reported to be
effective against HIV encephalopathy. 7) The fact that
only a 200 mg dose of zidovudine, i.e., one third the
usual dose, could be used in our patient because of im-
paired hematopoiesis may have played a role in the de-
velopment of the HIV encephalopathy.
Before HAART was established, HIV encephalopathy
was observed in 10% - 40% of AIDS patients, but at
present the proportion has declined to 10.5%. On the
other hand, the life span of HIV patients has increased as
a result of the advent of HAART, and the number of pa-
tients like our own who develop HIV encephalopathy
despite receiving HAART has risen, 4) Symptoms of
HIV encephalopathy, such as cognitive dysfunction, mem-
ory disorders, etc., greatly reduce the QOL (quality of
life) of patients with HIV infection. When, as in our own
patient, a long time has passed after being infected, ef-
forts at early detection and prevention of progression of
HIV encephalopathy by means of the HIV Dementia
Scale and even more precise psychological tests, 8) and
quantitative determinations of viral load in cerebrospinal
fluid and other substances that serve as markers, 9) seem
necessary, even in cases that have been well controlled
HIV testing of schizophrenia patients is rare in Japan. As
in our own patient, if there is no advance information in
relation to HIV, there is a strong possibility of HIV en-
cephalopathy not being detected or taking too long to
diagnose. Even though it is rare, it is necessary to recon-
sider including HIV encephalopathy in the differential
diagnosis of schizophrenia patients in routine clinical
[1] Hashimoto, R., Mukai, E., Yokomaku,-Y., Mamiya, N.
and Hamaguchi, M. (2008) Clinical features and courses
of 5 cases with HIV encephalopathy. Clinical Neurology,
48, 173-178.
[2] World Health Organization. (2008) World health statis-
tics, 13-14.
[3] Nakashima, Y., Inoue, M. and Isse, K. (2002) Psychiatric
problems of AIDS and related disorder. Japanese Journal
of Clinical Psychiatry, 31, 925.
[4] Kopnisky, K.L. and Bao, J. (2007) HIV Preclinical thera-
peutics research: Central nervous system approaches.
Journal of Neuroimmune Pharmacology, 2, 1.
[5] Bhaskaran, K., Mussini, C., Antinori, A., Walker, A.S.,
Dorrucci, M., Sabin, C., Phillips, A. and Porter, K. (2008)
CASCADE collaboration. Change in the incidence and
predictors of human immunodeficiency virus-associated
dementia in the era of highly active antiretrovairal ther-
apy. Annals of Neurology, 63, 213-221.
[6] Uehira, T. and Shirasaka, T. (2001) HIV-associated cog-
nitive-motor complex/AIDS dementia complex. Clinic
All-Round, 50, 2738.
[7] Simpson, D.M. (1999) Human immunodeficiency vi-
rus-associated dementia: Review of pathogenesis, pro-
phylaxis, and treatment studies of zidovudine therapy.
Clinical Infectious Disease, 29, 19-34.
[8] Bottiggi, K.A., Chang, J.J., Schmitt, F.A., Avison, M.J.,
Mootoor, Y., Nath, A. and Berger J.R. (2007) The HIV
dementia scale: Predictive power in mild dementia and
HAART. Journal of the Neurological Sciences, 260, 11-
15. doi:10.1016/j.jns.2006.03.023
opyright © 2011 SciRes. OJPsych
M. Fuji et al. / Open Journal of Psychiatry 1 (2011) 132-136
Copyright © 2011 SciRes. OJPsych
[9] Bandaru, V.V., McArthur, J.C., Sacktor, N., Cutler, R.G.,
Knapp, E.L., Mattson, M.P. and Haughey, N.J. (2007)
Associative and predictive biomarkers of dementia in
HIV-1-infected patients. Neurology, 68, 1481-1487.