Transcript HIV-Aids - International Federation for Emergency Medicine

HIV in the ED
Vicken Y. Totten MD
Director,
UH HIV Initiative
1
Objectives
Define and discuss HIV: the virus & HIV:
the infection
Discuss how HIV infection without AIDS
manifests
Define and discuss AIDS, the disease
Discuss transmission and prevention
Describe the illnesses associated with HIV
infection so you can recognize them and
initiate treatment
Tell a brief history of ED-based HIV testing.
2
AIDS = Acquired Immune
Deficiency Syndrome
 Acquired - because it's a condition one must
acquire or get infected with, not something
transmitted through the genes
 Immune - because it affects the body's immune
system, the part of the body which usually
works to fight off germs such as bacteria and
viruses
 Deficiency - because it makes the immune
system deficient
 Syndrome - because someone with AIDS may
experience a wide range of different diseases
and opportunistic infections
3
What is HIV, the Virus?
Any of several retroviruses that infect
and destroy helper T cells of the
immune system
Most likely, a simian retrovirus
(Zoonosis)
4
The Human Immune Deficiency Virus
5
Two Kinds of Virus: HIV-1 vs.
HIV-2
HIV-1
More virulent
Responsible for
worldwide epidemic
Severity of infection
varies from person
to person
HIV-1 likely
descended from
SIVcpz
HIV-2
Primarily found in
western Africa
Not transmitted as
efficiently
Genome more
closely related to
SIVmm than HIV-1
HIV-2 likely
descended from
SIVsm
6
HIV, the Virus
Retro-Virus: copies itself “backwards” from
RNA into the host DNA. Makes lots of errors
leading to a high mutation rate
Targets macrophages, especially CD4 cells
Most infectious during the first viremic
episodes. Requires “intimate contact” for
transmission
Destroys the body’s ability to fight infections
and certain cancers
Therefore, untreated patients infected with HIV
are at risk for illness and death from:
Opportunistic infections
Neoplastic complications
7
History: When did the zoonosis jump
species?
Three earliest known HIV infections
1959 - serum sample from a man in what is
now the Democratic Republic of Congo
1969 - tissue from a St. Louis teen
1976 - tissue from a Norwegian Sailor
2000 - Dr. Bette Korber estimates SIV-> HIV
occurred about 1930, based on computer modeling.
1979 - The “HIV Epidemic” in the USA brought by
“patient 0”, a homosexual Canadian Airline Steward
who was exceptionally sexually active wherever he
flew.
8
Top HIV/AIDS-Infected Countries
Sub-Saharan
Africa
United
States
1.
South Africa
2.
Nigeria
3.
Zimbabwe
4.
Tanzania
5.
The Congo
11.China
6.
Ethiopia
12.
Brazil
7.
Kenya
13.
Thailand
8.
Mozambique
9.
10.
Russian
Federation
Source: Steinbrook R. The AIDS epidemic in 2004. NEJM.
2004;351:115-117.
9
Population Prevalence
One Baltimore inner city hospital
found that up to 11% of patients had
HIV Antibodies
24% had either HIV or hepatitis B or
C.
Therefore, all contacts with patients’
blood or body secretions must be
considered to be potentially infectious
by ED personnel.
10
HIV Positives in our ED
2006, Radonich et al
Tested 666 samples of discarded
blood from adult ED patients
2.5% sero-positivity.
Of these, 1 / 4 - 1 / 5 are not aware
they are positive
STDs flock together. If you find an
STD, you should test for HIV
11
Proportion of AIDS Cases, by Race/Ethnicity
12
The Life Cycle of HIV-1
Structural Protein and
Enzyme Precursors
Viral
RNA
Viral
DNA
Viral
RNA
1. Binding
and infection
2. Reverse
transcription
and integration
of viral DNA
3. Transcription 4. Modification
and translation and assembly
5. Budding and
final assembly
13
HIV- Course of the infection
Inoculation: via internal contact, either thru a
mucus membrane or into a body tissue
Window period: Before viral replication; after
viremia but before immunologic response can be
detected by RNA probes only
Antibody Tests positive: Saliva, blood, urine (?)
Asymptomatic: months to years
Symptomatic: Immune system cannot respond
appropriately
Death
14
The Variable Course of HIV-1 Infection
Typical Progresser
months
years
Nonprogressor
months
years
Clinical Latency
CD4 Level
Viral Replication
Primary HIV
Infection
C
Viral Replication
B
AIDS
CD4 Level
CD4 Level
A
Primary HIV
Infection
AIDS
Viral Replication
Primary HIV
Infection Clinical Latency
Rapid Progresser
?
months
years
Reprinted with permission from Haynes. In: DeVita et al, eds. AIDS: Etiology, Treatment and Prevention.
4th ed. Lippincott-Raven Publishers; 1997:89-99.
15
HIV Hides in many organ systems
Colon, Duodenum and
Rectum Chromaffin Cells
Lymphocytes in Blood,
Semen and Vaginal Fluid
Bone Marrow
Skin Langerhans’
Cells
Brain Macrophages
and Glial Cells
Lymph Nodes
Thymus Gland
Lung Alveolar
Macrophages
16
Manifestations of HIV Infection
Primary Infection
Clinical Latency
“A Viral Syndrome” sore Asymptomatic; virus
throat, fever,
“hides” in lymph nodes,
lymphadenopathy, rash
thymus and bone marrow
symptoms 1-6 weeks
after infection
differential includes
EBV, CMV, hepatitis,
toxoplasmosis
Antibody (ELISA,
Western Blot) and Rapid
Test likely negative
Detect/test with RNA
PCR probles
Replicates and destroys
CD4 cells
a decrease in lean body
mass without apparent
total body weight change
Advanced Disease
Symptomatic
Plasma viremia begins to
rise. CD4 cell count falls
further
A decline in nutrient
status or body
composition, weight loss
Opportunistic infections :
vitamin B12 deficiency
fever, lymphadenopathy,
thrush, diarrhea,
increased susceptibility to malignancies, wasting
food and water-borne
syndrome, neurologic
pathogens.
syndrome including
dementia
17
Leading Causes of Death in People
Aged 25-44 Years in the US (19831998)
40
Unintentional injuries
30
Cancer
Deaths per
100,000
Population
20
Heart disease
Suicide
HIV infection
Homicide
Liver disease
Stroke
Diabetes
10
0
1984
1986
1988
1990
1992
1994
1996
1998
Year
Gallant J. Planning for Long-Term Success in HIV Management. Satellite Symposium to the
First IAS Conference on HIV Pathogenesis and Treatment, July 8 – 11, 2001.
18
Metabolic and morphologic complications associated
with HIV.
Sounds a lot like aging, doesn’t it?
Metabolic
Morphologic
Glucose disorders
insulin resistance
Fat accumulation
impaired glucose
tolerance
hyperglycemia
frank diabetes
Lipid elevations
increased triglycerides
increased cholesterol
Hyperlactatemia
lactic acidosis
abdominal obesity
buffalo hump
lipomatosis
breast enlargement
gynecomastia
Fat loss
appendices
face
buttocks
Bone disease
Osteopenia , osteoporosis , avascular
necrosis
19
Morphologic Complications:
Peripheral Fat Loss (Lipoatrophy)
20
Morphologic Complications:
Central Fat Accumulation (Lipohypertrophy)
21
Natural History of Untreated HIV
Infection
22
Transmission and Prevention
“Intimate Contact” is a euphemism for
“direct non-keratinized live tissue to tissue
contact”
Saliva and tears are wet and can have
virus, but also have high levels of
accompanying antibodies
Semen > vaginal fluid have high viral loads
and not so many antibodies
The virus cannot penetrate keratinized skin
or latex; it dies when dried.
23
Who spreads HIV?
Those who don’t know they are infected.
Most who are at risk don’t consider themselves
at risk
“Traditional risk groups” get tested
Those who know they are infected and are
not protecting their partners
Those with low viral loads are LESS infective but still infective
Knowingly infecting someone else is a criminal
offense
24
Relative Amounts of HIV in Body
Fluids
Modes of Transmission:
perinatal, parenteral, sex
High
Moderate
blood/ serum
semen
body cavity fluids
vaginal
fluid
Low/Not
Detectable
breast milk
urine
saliva
feces
sweat
tears
25
Transmission and Prevention
IVDA or Blood / Blood product
transfusions – direct inoculation
Transplantation (including corneas)
Semen into vagina – incomplete conversion
per year in discordant couples
Semen into rectum – higher rate of
conversion
Testing the “tissue donor” in window
period may permit transmission
26
When does perinatal
transmission occur?
Antenatal
Intrapartum
Breastfeeding
∼20%
∼80%
∼14%*
*above baseline
Lancet 340(8819):585
27
HIV Transmission Factors
AIDS / High Viral Load
STD / Exposure; open mucosa
Genital lesions
Frequency of unprotected sex
Lack of Circumcision
28
Who should be tested?
All pregnant women
Anyone presenting with an STD
Anyone with an unusual rash, mysterious
febrile illness or unusual / opportunistic
infection or cancer
Anyone with an unexpectedly low WBC
29
Screening for HIV infection
2006 CDC recommendations changed.
Why? Several year plateau in rate of new
infections. The current new positives
primarily are those who do not see
themselves at risk
Who? All people who come to EDs should
be screened yearly
All people in the US at least once.
30
Occupational Exposure Risk
RNs most often exposed
½ of emergency physicians reported > 1 /
2-year period.
0.3% chance for percutaneous exposure
0.09% for mucocutaneous splash
exposure.
HIV transmission by health care workers to
patients appears to be extremely rare.
31
Post-exposure Prophylaxis (PEP)
(1) type of exposure
(2) HIV status of the source
Separate recommendations for percutaneous vs
mucus membrane or non-intact skin exposures.
Intact skin  no indications for therapy
Deep percutaneous exposures;
visible blood on a device,
injuries sustained during placement of a catheter in a
vein or artery;
lower-risk percutaneous exposures are superficial
or involve solid needles.
32
HIV Status of Source?
High-risk:
symptomatic HIV infection,
AIDS,
acute seroconversion,
high viral load;
Low-risk sources
asymptomatic HIV infection
viral load of less than 1500 copies/mL
Test Source: Negative Rapid Test Results is
adequate to withhold or discontinue therapy.
Consider acute HIV infection -> assay of HIV RNA
levels.
33
Non-occupational Exposure
Rape with significant exposure <72
hours; source known to be HIVinfected
28-day HAART
34
PEP Regimen
Two-drug therapy options include
zidovudine plus lamivudine (available as
Combivir),
lamivudine plus stavudine,
didanosine plus stavudine.
PEP should be initiated within hours.
PEP is 4 weeks, if tolerated.
Discontinue PEP if the source is HIVseronegative.
35
National Clinicians PEP Hotline
providing 24-hour assistance,
CDC/University of California–San
Francisco (UCSF) (1-888-448-4911),
University of California at Los Angeles
(UCLA)'s online decision-making
support webpage
(http://www.needlestick.mednet.ucla.e
du).
36
The diseases associated with HIV
infections
Acute Retroviral Syndrome
Chronic Retroviral Infection ->
Chronic Inflammation & Decreased
Immunity
Opportunistic infections
Cancers
Other diseases of reduced immunity
37
Acute Retroviral Syndrome
Requires a high index of suspicion
May have fever, fatigue, rash,
pharyngitis as most common symptoms
Duration usually <2 weeks, but …
Diff dx: infectious mononucleosis,
secondary syphilis, acute hepatitis A or
B, roseola or other viral exanthems,
toxoplasmosis
KEEP TESTING
38
Non-specific Rashes
39
Acute Retroviral Syndrome
Fever 80 – 90%
Fatigue 70 – 90%
Rash 40 – 80%
Headache 32 – 70%
Lymphadenopathy
40 – 70%
Pharyngitis 50 –
70%
Thrombocytopenia
Arthralgias 5 – 70%
Myalgia 50 – 70%
Night sweats - 50%
GI symptoms 30 – 60%
Aseptic meningitis 24%
Oral/genital ulcers 5 –
20%
Lymphopenia
40
AIDS – the Disease, Defined
HIV + with a CD4 cell count that is or
has been less than 200 cells/mm3
HIV + with a CD4 percent below 14%.
HIV + and has or has had an AIDS
defining illness such as PCP,
toxoplasmosis, MAC, Kaposi’s
Sarcoma, etc. regardless of CD4 cell
count
41
HIV-associated viral conditions
HIV wasting
HIV associated dementia
Progressive multifocal
leukoencephalopathy
CD4+ lymphocyte count of <200
cells/microL
42
AIDS-DEFINING ILLNESSES (1)
HIV infection PLUS:
Cancers:
Invasive cervical cancer, Kaposi's sarcoma (an
Herpes virus infection), Burkett Lymphoma,
Primary Brain Lymphoma
Infections from symbiots
Candida of esophagus, trachea, or lungs
Herpes simplex: chronic ulcers >1 month's
Cryptosporidiosis, chronic intestinal (>1 month's
duration)
43
AIDS defining illnesses (2)
LUNGS:
Recurrent bacterial pneumonia
Pneumocystis jiroveci pneumonia
Cryptococcosis, extrapulmonary
Histoplasmosis: disseminated or
extrapulmonary
Lymphoid interstitial pneumonia or
pulmonary lymphoid hyperplasia complex
44
AIDS defining illnesses (3)
Coccidioidomycosis: disseminated or
extrapulmonary
Cytomegalovirus disease (other than liver, spleen,
or nodes), older >1 month
Cytomegalovirus retinitis (with loss of vision)
Extra-pulmonary histoplasmosis
Salmonella septicemia, recurrent
Toxoplasmosis of brain, onset at age >1 month*
Atypical Infections: M. avium. M kansasii, M. TB
Extrapulmonary coccidioidomycosis
Recurrent Salmonellosis
45
Brief overview of treatment
Anti-Retroviral Drugs
Prophylaxis against chronic
opportunistic infections.
Chronic suppression of illnesses
46
Highly Active Anti-Retroviral Therapy
HAART
Collective name given to the most
effective HIV regimens
Medications must be taken daily
Take all each day or none,
Missing medications can cause
problems
Why?
47
Classes of Drugs
Nucleoside analog reverse transcriptase inhibitors - NRTI
Nucleoside Reverse Transcriptase Inhibitors
Nucleotide Reverse Transcriptase Inhibitors
Non-nucleoside Reverse Transcriptase Inhibitors
(NNRTIs)
Non-nucleoside reverse transcriptase inhibitors - NNRTI
Protease inhibitors - PI
Entry inhibitors - EI
Fusion Inhibitors (one approved by FDA)
Integrase inhibitor - II
Each works by a different mechanism; best used in
combinations:
48
Anti-retroviral Medications
Class: NRTI
Abacavir
Didanosine
Emtricitabine
Lamivudine
Stavudine
Tenofovir
Zidovudine
ABC
DDI
FTC
3TC
D4T
TDF
ZDV
NNRTI
Delavirdine
Efavirenz
Nevirapine
DLV
EFV
NVP
Protease Inhibitors PI
Amprenavir
APV
Atazanavir
ATV
Darunavir
DRV
Fosamprenavir FPV
Indinavir
IDV
Lopinavir
LPV
Nelfinavir
NFV
Ritonavir
RTV
Saquinavir
SQV
hard gel
HGC
tablet
INV
Tipranavir
TPV
49
Newer Classes
CCR5 - Coreceptor Antagonist
Maraviroc MVC
II - Integrase Inhibitor
Raltegravir
RAL
FI - Fusion Inhibitor
Enfuvirtide
T-20
50
Optimal Time to Start Will Change
Over Time as More Data Emerge
Factors Favoring
Later Initiation
Long-term toxicities
- more prevalent
- more serious
Drug development
stalls
Factors Favoring
Earlier Initiation
More drugs
Better drugs
Better management
of toxicities
51
Medication Side Effects
Anorexia
Sore/dry/painful mouth
Swallowing difficulties
Constipation/Diarrhea
Nausea/Vomiting/Altered Taste
Depression/Tiredness/Lethargy
52
Drug Reactions
Drug reactions are extremely common
among HIV-infected patients.
They are on LOTS of nasty drugs
HIV-infected persons have more drug
reactions to ALL / ANY drugs than
uninfected persons.
Dermatologic reactions are particularly
common.
Antimicrobial drugs frequently are
implicated.
53
Adverse Drug Effects
Mitochondrial
Dysfunction
Metabolic
abnormalities
Lipodystrophy
–Fat accumulation
–Lipoatrophy
Hepatic
Hyperlipidemia /
toxicity
? Premature CAD
Hyperglycemia
Pancreatitis Insulin resistance/DM
Bone disorders:
Peripheral osteoporosis and
neuropathy osteopenia
Lactic
acidosis
Hematologic
Complications
Allergic
reactions
Bone marrow Hypersuppression sensitivity
reactions
Skin rashes
54
HIV and Cardiac Disease
HIV infection causes chronic inflammation
The inflammation can cause
Encephalopathy, myocarditis,
Progressive multi-focal leukoencephalopathy
HIV is an independent risk for ASVD
Disorders of Lipid metabolism
Consider HIV an inflammation risk factor
stronger than cigarette smoking.
55
HIV- Complications at CD4>500mm3
Infectious
Acute retroviral syndrome
Candida vaginitis
Other
Generalized Lymph Adenopathy
Guillain-Barre (very rare)
Vague constitutional symptoms
56
HIV- Complications at CD4 200-500mm3
Infectious
Pneumococcal pneumonia
TB
Herpes zoster
Kaposis sarcoma
Oral hairy leukoplakia (OHL)
Oropharyngeal candidiasis (thrush)
Non-Infectious
Cervical Ca
Lymphomas
ITP (Immune thrombocytopenic purpura)
57
White Tongue, ulcer on tonsillar
pillar
58
Oropharyngeal Candidasis
Thrush limited to oropharynx
Esophagitis more serious usually
CD4<100
Odynophagia
Chest pain
Other causes of esophagitis
CMV (usually CD4<50)
Idiopathic ulceration (CD4<50)
59
Palatine Candida
60
Candidal esophagitis
61
Oral Hairy Leukoplakia
Caused by EBV
No treatment required
62
Hairy Leukoplakia
63
Opportunistic Infections
Viruses:
Varicella-Zoster Virus
Herpes Simplex Virus
Cytomegalovirus
Protozoa:
Coccidiosis
(Cryptosporidiosis,
Cyclosporiasis, and
Isosporiasis)
Toxoplasmosis
Leishmaniasis (not in the
U.S., but in Southern Europe
and in many other parts of
the world)
Chagas’ Disease
Malaria
Bacteria:
Mycobacterium Avium
Complex
Mycobacterium
Tuberculosis
Fungi:
Pneumocystis jirovenci
(carinii) Pneumonia
Candidiasis
Aspergillosis
Cryptococcosis
Histoplasmosis
Coccidioidomycosis
Microsporidiosis
64
65
Advanced HIV + Altered Mental
Status, Seizures, HA or Focal Signs
Blood Tests
Toxoplasma IgG
RPR/VDRL
Cryptococcal Ag
CT scan with contrast
or MRI
Focal lesion
No focal lesion
Atypical lesion
+ negative Toxo serology
Treat empirically for
Toxo encephalitis
Lumbar puncture
Stereotactic biopsy
66
Toxoplasmosa gondii
an obligate, intracellular protozoan
cysts ingested in undercooked meats
usually infection is easily contained
organisms can persist as cysts in multiple
organs
CNS disease is the most common
manifestation
if not on prophylaxis, at least 30% of
patients with Toxo Ab will develop toxo
encephalitits
67
Toxoplasmosis: clinical
presentation
headache, confusion/altered mental status,
and fever are the presenting complaints in
~ 50% of patients with intracerebral toxo
50-60% will have focal neurological signs
30% will have seizures
can also present as chorioretinitis
liver, lung & muscle involvement possible
68
Toxoplasmosis: diagnosis
Toxo serology - seropositivity to T. gondi in
HIV infected persons in the US ranges
from 8 - >25%
97 - 99% of patients with AIDS and toxo
have positive serologies (IgG)
Head CT/MRI - often multiple lesions,
typically in brain stem, basal ganglia,
corticomedulary junction
Biopsy - showing tachyzoites in tissue gives definitive diagnosis, but is often not
required
69
Cerebral
Toxoplasmoma
70
Toxoplasmosis: treatment & prophylaxis
Optimal treatment: Pyramethamine +
sulfadiazine or clindamycin
Alternative treatment: TMP/SMX
Optimal prophylaxis: TMP/SMX
Alternative proph: dapsone +
pyramethamine
Prophylaxis required for CD4 ct < 100 if
Toxo IgG positive
71
Cryptococcus neoformans
ubiquitous encapsulated yeast, present in
soil
inhaled, ingested by alvoelar
macrophages, escapes the lung 
cryptococcemia  meningeal seeding
75% of cases occur when the CD4 count is
< 50
subacute course with headache and fever
progresses to altered mental status, coma
and death if untreated
can present with focal neurologic deficit
72
Cryptococcus neoformans
high CSF protein and opening pressure
diagnosis can be inferred by detection of
cryptococcal capsular antigen (CrAg) in
serum (positive in 95-99% of patients with
meningitis) or CSF (sensitivity/specificity
93-100%/93-98%)
treatment: amphotericin B +/- 5-flucytosine
followed by fluconazole completion and
fluconazole life-long maintenance therapy;
can start with fluconazole if mild disease
73
Crypotococci
74
Pneumocystis
Fungus (mRNA sequence, enzyme
structure, cell wall consistent with) vs.
protozoa (morphology and response to
pentamadine)
found almost exclusively in the lungs of
compromised hosts; has never been
successfully cultured
typically seen at CD4 ct < 200
usually presents as pulmonary dysfunction
- extrapulmonary/disseminated disease is
rare
75
Pneumocystis
Pneumocystis carinii
changed its name to
Pneumocystis jiroveci
(pronounced “yee row vet zee” &
named after the Czech
pathologist Otto Jirovec)
76
Should I treat for PCP in this HIV patient
with pneumonia??
PCP
Bacterial
Cough > 7 d
50%
20%
DOE
81%
43%
LDH > 400
62%
29%
pO2 < 75
66%
36%
interstitial
infiltrate
69%
17%
77
Pneumocystis carinii
Diagnosis: induced sputum (using
hypertonic saline) or bronchoscopy/BAL
(sputum induction 75-80+% sensitivity, BAL
95-99% sensitivity)
Treatment: TMP/SMX
Alternative therapy: trimethoprim +
dapsone, atovaquone, clindamycin +
primaquine, pentamadine IV
Prednisone: adjunctive therapy if PO2 <
70mmHg
78
Pneumocystis carinii
prophylaxis
if CD4 ct < 200
may stop after CD4 ct > 200 for 3-6
months
first choice: TMP/SMX M-W-F (QD if
CD4 ct < 100 & Toxo Ab positive)
alternatives: dapsone, atovaquone,
aerosolized pentamadine
79
Diarrhea in HIV patient
History
Antibiotic
exposure
Gay male
or traveler
Seafood
exposure
Concomitant
Proctitis
C. diff. toxin
O&P
r/o
Giardia &
E. histolytica
Vibrio
Cx
gonorrhea
Chlamydia
HSV
syphilis
80
Chronic diarrhea in HIV patient
CD4
count
< 50
< 100
< 200
MAC
10-20%
viruses
(esp. CMV)
10-40%
Microsporidia
15-20%
Isospora
1-2%
Cryptosporidium
20-30%
AFB Blood
culture
biopsy
trichrome
stain of
stool
stool AFB
or DFA
stool AFB
or DFA
81
Mycobacterium Avium Complex
found free in the natural environment
transmission via inhalation, aspiration or
ingestion
signs/symptoms: fever, nightsweats, weight
loss, diarrhea, malabsorption, focal
lymphadenitis, hepatosplenomegaly
pancytopenia, increased alkaline
phosphatase
progressive deterioration and death in 2 - 6
months is the rule if untreated
82
Mycobacterium Avium Complex
Treatment: effective drugs include
ethambutol, clarithromycin, azithromycin,
rifabutin, ciprofloxacin, ofloxacin, and
amikacin
typically 3 (at least 2) agents are used to
prevent the emergence of resistance
Primary prophylaxis when CD4 < 50
Clarythromycin (500 mg BID) or
azithromycin (1250 mg Q week) are the
preferred agents for prophylaxis
83
Other Opportunistic Infections
The 4 H’s :
HCV - 40 % co-infected, highest in IVDU
Human CMV - recent decline in
incidence
HHV-8 - Kaposi’s Sarcoma
HPV
Lymphomas (autoimmune
phenomena)
Rhodococcus
84
Opportunistic Infections (O.I.s’)
Occur only when immuno-suppressed
Increases with decreasing CD4 count
Available medications for prophylaxis
Examples
PCP, Toxoplasmosis, MAC, etc
Increase chance of complications and death
85
Kaposi’s Sarcoma
Clinical manifestations variable in HIV
Usually cutaneous or oral but visceral
involvement also occurs (GI,
respiratory tract)
Causative organism human herpes
virus 8 (HHV-8)
86
K
a
p
o
s
i’
s
87
Presentation of Kaposi's sarcoma
88
Presentation of Kaposi's sarcoma
89
HIV- Complications at CD4 < 200mm3
Infectious
PCP
Histoplasmosis (other endemic fungi)
Miliary TB
PML
Non-Infectious
Wasting
Peripheral neuropathy
Cardiomyopathy
Dementia
90
Pneumocystis carinii pneumonia
Variable presentations
Pneumocystis carinii changed to Pneumocystis jiroveci
20-40% in patients not on HIV rx
Usually subacute presentation of dry
cough, dyspnea
CXR typically reveals interstitial
infiltrates
May have lobar consolidation
Pneumothorax in severe cases
Treatment/ prophylaxis
91
Pneumocystis jiroveckii (carinii)
pneumonia aka PCP
92
Diagnosis of Pneumocystis carinii
93
Histoplasma
Mississippi River Delta
Rarer in SC
Wide spectrum of illness from acute
sepsis like syndrome to acute
pneumonia to cutaneous involvement
94
Oral lesions of disseminated Histoplasma
capsulatum infection
95
Progressive Multifocal
Leukoencephalopathy (PML)
Clinical disease occurs in patients with
advanced disease and onset may be
insidious, over several weeks.
Clinical signs and symptoms include hemiparesis (43%), cognitive defects (22%),
speech deficits (28%),visual deficits (16%),
sensory deficits (14%), and seizures (5%).
96
Progressive Multifocal
Leukoencephalopathy (PML)
Clinical hallmark of disease is patient with
focal neurologic defect, white matter
disease and no mass effect. Lesions do
not enhance on imaging
PML is a demyelinating disease of the
central nervous system caused by infection
of oligodendrocytes by JCV, a papovavirus.
97
Progressive Multifocal Leukoencephalopathy
98
Progressive Multifocal
Leukoencephalopathy
99
HIV- Complications at CD4 < 100mm3
Infectious
Disseminated HSV
Toxoplasmosis
Candida esophagitis
Cryptosporidiosis, microsporidiosis,
isospora
Cryptococcal disease
100
Cryptococcal Meningitis
C. neoformans is an encapsulated yeast,
inhaled into the small airways where it usually
causes sub-clinical disease; dissemination to
the CNS is not related to pulmonary
response.
C. neoformans produces no toxins and
evokes little inflammatory response. The
main virulence factor is the capsule.
101
Cryptococcal Meningitis
Clinical manifestations:
headache (70-90%), fever (60-80%),
malaise (76%), stiff neck (20-30%),
photophobia (6-18%), seizures (5-10%)
nausea.
Average duration of symptoms is 30 days.
Predictors of poor outcomes are altered
mental status, increased opening pressure,
WBC<20 cells/mm3.
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Cryptococcal Meningitis
Diagnosis made by CSF examination with
india ink (74-88%), Crypto Ag serum/CSF
(99%), CSF culture.
Level of Crypto Ag is not indicative of
severity of disease or a marker of response
to therapy. Serum Crypto Ag can rule out
clinical disease in HIV positive but not
negative patients.
103
Cryptococcus neoformans
104
Toxoplasmic Encephalitis
Clinical presentation includes focal
neurologic deficit (50-89%), seizures (1520%), fever (56%), generalized cerebral
dysfunction, neuropsychiatric
abnormalities.
Diagnosis is often presumptive based on
characteristic lesions, clinical course, risk
strata and positive serology.
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Toxoplasmic Encephalitis
Presumptive diagnosis is considered
confirmed by tissue sample or response to
TOXO therapy in appropriate time frame.
Patients should show clinical response -neuro deficits, not necessarily fever or
headache -- by day 5 (50%), day 7 (70%),
and day 14 (90%). In contrast, patients
with CNS lymphoma all had worsening of
signs or symptoms by day 10 of therapy.
106
Cerebral toxoplasmosis
107
Cryptosporidium parvum
108
Cryptosporidial organisms
109
Isospora belli
110
HIV- Complications at CD4 < 50mm3
Infectious
Disseminated CMV/Retinitis
Disseminated MAC
Non-Infectious
CNS Lymphoma
111
Disseminated MAC
Usually a sub-acute/chronic illness
characterized by fevers, weight loss,
diarrhea, night sweats, wasting
CD4<50
112
Mycobacterium avium-intracellulare
113
Primary CNS Lymphoma
B-cell malignancies, high-grade (73%).
Occurs in extremely immunocompromised
hosts (CD4 < 50 cells/mm3), unlike
systemic NHL.
Common signs include focal neuro deficits
(38-78%), altered sensorium (57%),
seizures (21%), cranial nerve defects
(13%).
114
Primary CNS Lymphoma
50% of patients will have single
lesions, usually in the gray matter.
Toxo lesions are usually multiple,
smaller and associated with basal
ganglia but the two entities cannot be
distinguished by imaging alone.
115
Primary CNS Lymphoma
Diagnosis is based on clinical presentation,
neuroimaging, CSF studies, and brain
biopsy.
CSF PCR for EBV is sensitive (66-99%)
and specific (60-99%).
Treatment is radiation +/- chemotherapy.
Response is related to stage of disease
and control of HIV.
116
Primary central nervous system lymphoma
117
Cytomegalovirus Retinitis
118
Summary of OIs for Which
Prevention Is Recommended
Primary Prophylaxis
Pneumocystis jiroveci pneumonia (PCP)*
Tuberculosis*
Toxoplasmosis*
Mycobacterium avium complex (MAC)*
Varicella-zoster*
S pneumoniae infections†
Hepatitis A and B†
* Standard of care
Influenza†
† Generally recommended
119
Summary of OIs for Which
Prevention Is Recommended
Secondary Prophylaxis
Pneumocystis jiroveci pneumonia (PCP)*
Toxoplasmosis*
Mycobacterium avium complex (MAC)*
Cryptococcosis*
Histoplasmosis*
Coccidioidomycosis*
Cytomegalovirus*
* Standard of care
Salmonella bacteremia†
† Generally recommended
120
OIs for Which Prevention Is Not
Routinely Indicated
Primary Prophylaxis
Bacteria
(neutropenia)†
Cryptococcosis†
Histoplasmosis†
Cytomegalovirus†
† Evidence for efficacy but
not routinely indicated
Secondary
Prophylaxis
Herpes simplex
virus§
Candida §
§ Recommended only if
subsequent episodes are
frequent or severe
121
Indications for Possible Discontinuation of
Primary and Secondary Prophylaxis
Agent
Recommendation
(only for patients on effective ART)
PCP
Primary: CD4 >200 cells/µL for 3 months
Secondary: CD4 >200 cells/µL for 3 months
Toxo
Primary: CD4 >200 cells/µL for 3 months
Secondary: CD4 >200 cells/µL for 6 months + initial toxo
treatment + asymptomatic
MAC
Primary: CD4 >100 cells/µL for 3 months
Secondary: CD4 >100 cells/µL for 6 months +12212 months
MAC treatment + asymptomatic