HIV associated

opportunistic infection
Susanne Burger, MD

Impact of HAART on the

Incidence of Opportunistic
Infections HAART
PCP

MAC

CMV Retinitis
Toxoplasmosis

Typical Relationship of Clinical

Manifestations to CD4 Count in HIV
Infected Patients
Lymphoma
Tuberculosis
Kaposi Sarcoma
Herpes Zoster

5
0

Criteria for Starting, Discontinuing, and

Restarting Opportunistic Infection
ProphylaxisCriteria
forforAdults
with
HIV
Criteria for Criteria for
Criteria for
Criteria for
Criteria for
Initiating
Primary
Prophylaxi
s

Discontinui
ng Primary
Prophylaxis

Restarting
Primary
Prophylaxi
s

Initiating
Secondary
Prophylaxis

Discontinuing
Secondary
Prophylaxis

Restarting
Secondary
Prophylaxi
s

PCP

CD4 < 200

or oral
candidasis

CD4 > 200

for 3 mos

CD4 < 200

Prior PCP

CD4 > 200 for 3 mos

CD4 < 200

Toxoplasmosis

+ serum
IgG
CD4 < 100

CD4 > 200

for 3 mos

CD4 < 100

200

Prior
toxoplasmic
encephalitis

CD4 > 200 sustained

and completed initial
therapy and is
asymptomatic

CD4 < 200

MAC

CD4 < 50

CD4 > 100

for 3 mos

CD < 50
100

Documented
disseminate
d disease

CD4 > 100 sustained

and completed 12 mos
of MAC tx and
asymptomatic

CD4 < 100

Cryptococcosi
s

none

n/a

n/a

Documented
disease

CD4 > 100 200

sustained and
completed initial
therapy and
asymptomatic

CD4 < 100 200

Histoplasmosi
s

none

n/a

n/a

Documented
disease

No criteria
recommended for
stopping

n/a

CMV

none

n/a

n/a

Documented
end-organ

CD4 > 100 150

sustained and no

CD4 < 100 150

OI

Approach to Respiratory
Disease in HIV Infection:
Diagnostic Clues
Parameter Example
Rapidity of onset > 3 days: PCP, Tb
< 3 days: bacteria
Temperature Afebrile: neoplasm
Character of sputum
Purulent: bacteria
Scant: PCP, Tb, virus
Laboratory Tests WBC, LDH
O2 post exercise
X-ray atypical
Pattern: Beware!

Isolation?

Pneumocystis Jiroveci
(Formerly P. carinii)
Taxonomy
Fungus vs. Protozoan

Epidemology
Environmental source unknown

Life Cycle
Unknown

Transmission
Respiratory
Well documented in rodents
Presumptive in man

Diagnosis of Pneumocystis
Pneumonia
A 30 year-old male with HIV infection and fever,
cough, and diffuse infiltrates has a bronchoscopy
performed.
Which of the following is the most sensitive and
specific test to perform to establish whether or not
pneumocystis is the causative pathogen?
[Link] of the bronchalveolar lavage (BAL)
[Link] of the BAL
c. Immunoflourescent stain of the BAL
[Link] of the BAL
[Link] PCR

A patient with HIV infection presents with

PCP (room air pO2=82mHg). He has a
history of a severe exfoliative rash to TMPSMX.

Which of the following therapies would

you recommend:
[Link]-SMX + Prednisone
[Link] + Dapsone
[Link] Pentamidine
[Link] plus pyremethamine
[Link]

A 50 year-old male with HIV and PCP

is receiving pentamidine 4mg/kg IV
over 1 hr qd. On the ninth day of
therapy, while awaiting
transportation home, he has a
syncopal episode.

What is this rhythm?

Toxicity Regarding
Antipneumocystis Therapy
Drug

Issues

TMP-SMX

Toxicities: WBC, Plat, LFT

Creat, Amylase, rash, fever
Cross reactivity: dapsone (+/50%)

Pentamidine

Hypotension, Crea, Amylase,

WBC
Glucose: related to Crea
occurs days-wks post-rx
Torsade de Pointes

Atovaquone

Absorption

Clindamycin + Primaquin

Rash, LFT, diarrhea

Methemoglobinemia
Hemolytic anemia (G-6-PD)

Dapsone

Rash, fever, LFT, Hemolytic

anemia (G-6-PD), peripheral

22 y/o patient with CD4 = 69 and

bilateral interstitial infiltrates on CXR
has been started on treatment with
iv bactrim for presumptive PCP. On
day #3 he still c/o dyspnea and
reports that his symptoms have not
improved since admission to the
hospital. What do you do?

Management of Patients with AIDS

Related PCP Who are Failing TMPSMP

Add corticosteroids (if not already done)

Switch to alternative treatment
Reassess diagnosis
Is PCP correct?
Are there any other pathogens?

Is aggressive/longer term support

appropriate?
Patient wishes
Realistic assessment of prognosis

A 34 y/o man who has been HIV pos for

~ 10 years is brought to the ER after a
witnessed seizure. He had been
receiving HAART until ~ 5 years ago
when he dropped out of care. Family
members report that he has had some
memory loss and unusual behavior for
the past 2 weeks.
On PE is he is confused and disoriented.

Evaluation of CNS Mass Lesions

in Patients with AIDS
Toxoplasm
osis
Lymphoma
PML
Tuberculosis
Fungus
Nocardia
Bacterial
Syphilis
Kaposi
Sarcoma
Glioblastom

Radiologic
non specific
extra CNS lesions
Laboratory
Serology Toxo IgG, crypt Ag
Blood culture AFB, fungus
CSF Crypt Ag, CMV PCR, EBV PCR
Urine Histo Ag

Empiric Therapy

How is toxoplasmosis most

often transmitted in the
United States?

Clinical Manifestation of
Toxoplasmosis when Acquired
Post-Partum

Toxoplasmosis - Diagnosis
Definite diagnosis: Biopsy with
demonstration of tachyzoites
Presumptive diagnosis acceptable
when
CD4 < 200
Compatible neurologic disease
No prophylaxis
Serology: positive toxo IgG

Therapy for Cerebral

Toxoplasmosis
Preferred Regimen
Sulfadiazine + pyremethamine

Alternative Regimen
Clindamycin + pyremethamine

Less studied regimens

TMP-SMX
Atovaquone + sulfadiazine
Azithromycin + pyremethamine
Dapsone + pyremethamine

A 35 year-old male with HIV (CD4 = 30, VL 100k copies) not on HAART, is
brought to the emergency room with several weeks of declining
cognitive function, ataxia, and aphasia. CT scan shows multiple
hypodense, non enhancing cerebral white matter lesions. The gray
matter is spared. CSF analysis shows: WBC 25 (100% lymphs), protein
110 mg/dl; glucose 90 mg/dl; VDRL neg, Crypt Ag neg, PCR for JC virus
positive
What therapy is effective for this condition:
a. high dose acyclovir
b. Cidofovir
c. Vidarabine
d. Foscarnet
e. None of the above

Infectious Non-focal Brain

Disease
Clinical
Features
Lesion Type

Temporal
Progression

Level of
Alertness

Fever

PML

Weeks

Preserved

Absent

AIDS dementia
complex

Weeks/months

Preserved

Absent

CMV
encephalitis

Days/weeks

Reduced

Common

HIV associated CMV Disease

Pre-HAART, 30% of patients developed:
Retinitis
Colitis
Others:

Pneumonitis
Ventriculoencephalitis
Myelitis
Radiculomyelopathy
Adrenalitis

Diagnosis of CMV Disease

Serology (IgG, IgM)
Viremia common in asymptomatic persons
with low CD4
Histology required for diagnosis of colitis and
pneumonitis
owls eye intranuclear inclusion bodies
pathognomonic
Rare cells in the absence of clinical disease insignificant

Retinitis clinical diagnoses

Fluffy exudate

CNS CMV PCR

CMV Detection in Specific

Anatomic Sites
Site

Significance

BAL

None

Blood (cells, plasma)

maybe

CSF

Qualitative: probably

Mycobacterium Avium
Intracellulare Complex
Epidemiology: Ubiquitous in dirt, animals etc
Avium: 95% isolates
Transmission
Respiratory and GI, environmental source
undetermined
Person-to-person NOT likely

Clinical manifestations
Fever, wasting, nodes, liver, spleen
Rare as cause of lung disease
Labs: alk pho, Hb (severe), albumin

Mycobacterium Avium Intracellulare:

Diagnosis and Treatment
Compatible clinical syndrome
+
Isolation of M. avium
Source of Isolates
Blood (if patient symptomatic)
Pos culture 80 90 %: Bactec (7-14 days), solid (21 days)
Sputum/Stool/Urine
Low predictive value

Treatment: Clarithro (or Azithro) + Ethambutol (+/Rifabutin) x 1 year

Show and Tell

Cryptococcal Meningitis in
Patients with HIV Infection
Epidemiology: CD4 count < 50 cells/mm3 (75%
cases)
Diagnosis
CSF: Ag positive 95-100%
Serum: CRAG positive 95-99%,
Blood Culture: positive 75%

Poor prognosis
Abnormal mental status
Low CSF WBC

Beware unusual presentations

Skin (molluscum)
Lung (variable x-ray)

Screening with CRAG: Titer > 1:8 should be treated

Therapy of Cryptococcal
Meningitis

Increased Intracranial Pressure

(ICP)
Association of Mortality with Baseline CSF Opening
Pressure
Opening
Pressure

<190 249
mm
n = 102

250 349 mm
n = 59

> 350 mm
n = 60

# (%) of Deaths 21 (21%)

16 (27%)

23 (38%)

Median mos. To
death

10.5

Pts with the highest baseline Ops (>250) also had hig
CRAG and more frequent H/A, meningismus, papilledem
hearing loss and pathologic reflexes

Graybill et al. Clin Infect Dis. 2000;30:47

Management of increased
ICP
For pts with ICP > 250 mm H2O perform daily or
qod LPs. Remove CSF volume up to 30 cc to
reduce OP to 50% of the baseline OP.
Placement of lumbar drain and option, but
infections and drain malfunction are major
concerns.
Ventriculostomy catheter to drain and monitor
ICP. High risk for infection.
Ventriculoperitoneal (internalized) shunt in pts
with or without evidence of hydrocephalus. Risks
include potential infection, dissemination of
cryptococcus, and shunt obstruction.

Serial Crypt Antigen Titers

Serum
Changes do NOT correlate with therapeutic
response

CSF
Changes are helpful but repeated LPs not
necessary if patient is responding well
clinically

Note:
Some clinicians advocate LP with culture and
Ag before stopping maintenance:
controversial