HIV in the ED

1
HIV in the ED

• Vicken Y. Totten MD
• Director,
• UH HIV Initiative

2
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.

3
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

4
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)

5
The Human Immune Deficiency Virus
6
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

7
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 bodys 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

8
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-gt 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.

9
Top HIV/AIDS-Infected Countries

1. South Africa
2. Nigeria
3. Zimbabwe
4. Tanzania
5. The Congo
6. Ethiopia
7. Kenya
8. Mozambique

9. United States 10. Russian Federation 11. Chin
a 12. Brazil 13. Thailand
Sub-Saharan Africa
Source Steinbrook R. The AIDS epidemic in 2004.
NEJM. 2004351115-117.
10
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.

11
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

12
Proportion of AIDS Cases, by Race/Ethnicity
13
The Life Cycle of HIV-1
Structural Protein andEnzyme Precursors
Viral RNA
ViralDNA
ViralRNA
1. Bindingand infection
2. Reversetranscriptionand integrationof viral
DNA
3. Transcriptionand translation
4. Modificationand assembly
5. Budding andfinal assembly
14
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

15
The Variable Course of HIV-1 Infection
Typical Progresser
Rapid Progresser
Primary HIVInfection
Primary HIVInfection
Clinical Latency
AIDS
AIDS
CD4 Level
CD4 Level
Viral Replication
Viral Replication
A
B
months
months
years
years
Nonprogressor
Primary HIVInfection
Clinical Latency
CD4 Level
Viral Replication
?
C
months
years
Reprinted with permission from Haynes. In
DeVita et al, eds. AIDS Etiology, Treatment
and Prevention. 4th ed. Lippincott-Raven
Publishers 199789-99.
16
HIV Hides in many organ systems

• Colon, Duodenum and
• Rectum Chromaffin Cells

Brain Macrophages and Glial Cells
Lymphocytes in Blood,Semen and Vaginal Fluid
Lymph Nodes
Thymus Gland
Bone Marrow
Lung Alveolar Macrophages
Skin Langerhans Cells
17
Manifestations of HIV Infection
Primary Infection Clinical Latency Advanced Disease
A Viral Syndrome sore throat, fever, lymphadenopathy, rash 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 Asymptomatic virus hides in lymph nodes, thymus and bone marrow Replicates and destroys CD4 cells a decrease in lean body mass without apparent total body weight change vitamin B12 deficiency increased susceptibility to food and water-borne pathogens. Symptomatic Plasma viremia begins to rise. CD4 cell count falls further A decline in nutrient status or body composition, weight loss Opportunistic infections fever, lymphadenopathy, thrush, diarrhea, malignancies, wasting syndrome, neurologic syndrome including dementia
18
Leading Causes of Death in People Aged 25-44
Years in the US (1983-1998)
40
Unintentional injuries
30
Cancer
Deaths per 100,000 Population
20
Heart disease
Suicide
HIV infection
10
Homicide
Liver disease
Stroke
Diabetes
0
1984
1988
1990
1986
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.
19
Metabolic and morphologic complications
associated with HIV. Sounds a lot like
aging, doesnt it?

• Metabolic
• Glucose disorders
• insulin resistance
• impaired glucose tolerance
• hyperglycemia
• frank diabetes
• Lipid elevations
• increased triglycerides
• increased cholesterol
• Hyperlactatemia
• lactic acidosis

• Morphologic
• Fat accumulation
• abdominal obesity
• buffalo hump
• lipomatosis
• breast enlargement
• gynecomastia
• Fat loss
• appendices
• face
• buttocks

Bone disease Osteopenia , osteoporosis ,
avascular necrosis
20
Morphologic Complications Peripheral Fat Loss
(Lipoatrophy)
21
Morphologic Complications Central Fat
Accumulation (Lipohypertrophy)
22
Natural History of Untreated HIV Infection
23
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 gt vaginal fluid have high viral loads and
  not so many antibodies
• The virus cannot penetrate keratinized skin or
  latex it dies when dried.

24
Who spreads HIV?

• Those who dont know they are infected.
• Most who are at risk dont 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

25
Relative Amounts of HIV in Body Fluids
Modes of Transmission perinatal, parenteral, sex
Low/Not Detectable
High
Moderate
breast milk urine saliva feces sweat tears
semen
blood/ serum
body cavity fluids
vaginal fluid
26
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

27
When does perinatal transmission occur?

• Antenatal 20
• Intrapartum 80
• Breastfeeding 14
• above baseline
• Lancet 340(8819)585

28
HIV Transmission Factors

• AIDS / High Viral Load
• STD / Exposure open mucosa
• Genital lesions
• Frequency of unprotected sex
• Lack of Circumcision

29
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

30
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.

31
Occupational Exposure Risk

• RNs most often exposed
• ½ of emergency physicians reported gt 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.

32
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.

33
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 -gt assay of HIV RNA
  levels.

34
Non-occupational Exposure

• Rape with significant exposure lt72 hours source
  known to be HIV-infected
• ?28-day HAART

35
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
  HIV-seronegative.

36
National Clinicians PEP Hotline providing 24-hour
assistance,

• CDC/University of CaliforniaSan Francisco (UCSF)
  (1-888-448-4911),
• University of California at Los Angeles (UCLA)'s
  online decision-making support webpage
• (http//www.needlestick.mednet.ucla.edu).

37
The diseases associated with HIV infections

• Acute Retroviral Syndrome
• Chronic Retroviral Infection -gt Chronic
  Inflammation Decreased Immunity
• Opportunistic infections
• Cancers
• Other diseases of reduced immunity

38
Acute Retroviral Syndrome

• Requires a high index of suspicion
• May have fever, fatigue, rash, pharyngitis as
  most common symptoms
• Duration usually lt2 weeks, but
• Diff dx infectious mononucleosis, secondary
  syphilis, acute hepatitis A or B, roseola or
  other viral exanthems, toxoplasmosis
• KEEP TESTING

39
Non-specific Rashes
40
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

41
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, Kaposis
  Sarcoma, etc. regardless of CD4 cell count

42
HIV-associated viral conditions

• HIV wasting
• HIV associated dementia
• Progressive multifocal leukoencephalopathy
• CD4 lymphocyte count of lt200 cells/microL  

43
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 gt1 month's
• Cryptosporidiosis, chronic intestinal (gt1 month's
  duration)  

44
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  

45
AIDS defining illnesses (3)

• Coccidioidomycosis disseminated or
  extrapulmonary  
• Cytomegalovirus disease (other than liver,
  spleen, or nodes), older gt1 month  
• Cytomegalovirus retinitis (with loss of vision)  
• Extra-pulmonary histoplasmosis
• Salmonella septicemia, recurrent  
• Toxoplasmosis of brain, onset at age gt1 month 
• Atypical Infections M. avium. M kansasii, M. TB
• Extrapulmonary coccidioidomycosis
• Recurrent Salmonellosis

46
Brief overview of treatment

• Anti-Retroviral Drugs
• Prophylaxis against chronic opportunistic
  infections.
• Chronic suppression of illnesses

47
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?

48
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

49
Anti-retroviral Medications

• Class NRTI
• Abacavir ABC
• Didanosine DDI
• Emtricitabine FTC
• Lamivudine 3TC
• Stavudine D4T
• Tenofovir TDF
• Zidovudine ZDV
• NNRTI
• Delavirdine DLV
• Efavirenz EFV
• Nevirapine 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

50
Newer Classes

• CCR5 - Coreceptor Antagonist
• Maraviroc MVC
• II - Integrase Inhibitor
• Raltegravir RAL
• FI - Fusion Inhibitor
• Enfuvirtide T-20

51
Optimal Time to Start Will Change Over Time as
More Data Emerge
Factors Favoring Later Initiation
Factors Favoring Earlier Initiation
Long-term toxicities - more prevalent -
more serious Drug development stalls
More drugs Better drugs Better management of
toxicities
52
Medication Side Effects

• Anorexia
• Sore/dry/painful mouth
• Swallowing difficulties
• Constipation/Diarrhea
• Nausea/Vomiting/Altered Taste
• Depression/Tiredness/Lethargy

53
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.

54
Adverse Drug Effects
Mitochon-drial Dys-function Metabolic abnormalities Hema-tologic Compli-cations Allergic reactions
Lactic acidosis Hepatic toxicity Pancreatitis Peripheral neuropathy Lipodystrophy Fat accumulation Lipoatrophy Hyperlipidemia / ? Premature CAD Hyperglycemia Insulin resistance/DM Bone disorders osteoporosis and osteopenia Bone marrow suppression Hyper-sensitivity reactions Skin rashes
55
HIV and Cardiac Disease

• HIV infection causes chronic inflammation
• The inflammation can cause Encephalopathy,
  myocarditis,
• Progressive multi-focal leuko-encephalopathy  
• HIV is an independent risk for ASVD
• Disorders of Lipid metabolism
• Consider HIV an inflammation risk factor stronger
  than cigarette smoking.

56
HIV- Complications at CD4gt500mm3

• Infectious
• Acute retroviral syndrome
• Candida vaginitis
• Other
• Generalized Lymph Adenopathy
• Guillain-Barre (very rare)
• Vague constitutional symptoms

57
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)

58
White Tongue, ulcer on tonsillar pillar
59
Oropharyngeal Candidasis

• Thrush limited to oropharynx
• Esophagitis more serious usually CD4lt100
• Odynophagia
• Chest pain
• Other causes of esophagitis
• CMV (usually CD4lt50)
• Idiopathic ulceration (CD4lt50)

60
Palatine Candida
61
Candidal esophagitis
62
Oral Hairy Leukoplakia

• Caused by EBV
• No treatment required

63
Hairy Leukoplakia
64
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

65
(No Transcript)
66
Advanced HIV Altered Mental Status, Seizures,
HA or Focal Signs
67
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

68
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

69
Toxoplasmosis diagnosis

• Toxo serology - seropositivity to T. gondi in HIV
  infected persons in the US ranges from 8 - gt25
• 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

70
Cerebral Toxoplasmoma
71
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 lt 100 if Toxo IgG
  positive

72
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 lt 50
• subacute course with headache and fever
• progresses to altered mental status, coma and
  death if untreated
• can present with focal neurologic deficit

73
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

74
Crypotococci
75
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 lt 200
• usually presents as pulmonary dysfunction -
  extrapulmonary/disseminated disease is rare

76
Pneumocystis

• Pneumocystis carinii
• changed its name to
• Pneumocystis jiroveci
• (pronounced yee row vet zee named after the
  Czech pathologist Otto Jirovec)

77
Should I treat for PCP in this HIV patient with
pneumonia??
78
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 lt 70mmHg

79
Pneumocystis carinii prophylaxis

• if CD4 ct lt 200
• may stop after CD4 ct gt 200 for 3-6 months
• first choice TMP/SMX M-W-F (QD if CD4 ct lt 100
  Toxo Ab positive)
• alternatives dapsone, atovaquone, aerosolized
  pentamadine

80
Diarrhea in HIV patient
81
Chronic diarrhea in HIV patient
82
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

83
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 lt 50
• Clarythromycin (500 mg BID) or azithromycin (1250
  mg Q week) are the preferred agents for
  prophylaxis

84
Other Opportunistic Infections

• The 4 Hs
• HCV - 40 co-infected, highest in IVDU
• Human CMV - recent decline in incidence
• HHV-8 - Kaposis Sarcoma
• HPV
• Lymphomas (autoimmune phenomena)
• Rhodococcus

85
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

86
Kaposis 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)

87
Kaposis
88
Presentation of Kaposi's sarcoma
89
Presentation of Kaposi's sarcoma
90
HIV- Complications at CD4 lt 200mm3

• Infectious
• PCP
• Histoplasmosis (other endemic fungi)
• Miliary TB
• PML
• Non-Infectious
• Wasting
• Peripheral neuropathy
• Cardiomyopathy
• Dementia

91
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

92
Pneumocystis jiroveckii (carinii) pneumonia aka
PCP
93
Diagnosis of Pneumocystis carinii
94
Histoplasma

• Mississippi River Delta
• Rarer in SC
• Wide spectrum of illness from acute sepsis like
  syndrome to acute pneumonia to cutaneous
  involvement

95
Oral lesions of disseminated Histoplasma
capsulatum infection
96
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 hemi-paresis
  (43), cognitive defects (22), speech deficits
  (28),visual deficits (16), sensory deficits
  (14), and seizures (5).

97
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.

98
Progressive Multifocal Leukoencephalopathy
99
Progressive Multifocal Leukoencephalopathy
100
HIV- Complications at CD4 lt 100mm3

• Infectious
• Disseminated HSV
• Toxoplasmosis
• Candida esophagitis
• Cryptosporidiosis, microsporidiosis, isospora
• Cryptococcal disease

101
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.

102
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, WBClt20
  cells/mm3.

103
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.

104
Cryptococcus neoformans
105
Toxoplasmic Encephalitis

• Clinical presentation includes focal neurologic
  deficit (50-89), seizures (15-20), fever (56),
  generalized cerebral dysfunction,
  neuropsychiatric abnormalities.
• Diagnosis is often presumptive based on
  characteristic lesions, clinical course, risk
  strata and positive serology.

106
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.

107
Cerebral toxoplasmosis
108
Cryptosporidium parvum
109
Cryptosporidial organisms
110
Isospora belli
111
HIV- Complications at CD4 lt 50mm3

• Infectious
• Disseminated CMV/Retinitis
• Disseminated MAC
• Non-Infectious
• CNS Lymphoma

112
Disseminated MAC

• Usually a sub-acute/chronic illness characterized
  by fevers, weight loss, diarrhea, night sweats,
  wasting
• CD4lt50

113
Mycobacterium avium-intracellulare
114
Primary CNS Lymphoma

• B-cell malignancies, high-grade (73).
• Occurs in extremely immunocompromised hosts (CD4
  lt 50 cells/mm3), unlike systemic NHL.
• Common signs include focal neuro deficits
  (38-78), altered sensorium (57), seizures
  (21), cranial nerve defects (13).

115
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.

116
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.

117
Primary central nervous system lymphoma
118
Cytomegalovirus Retinitis
119
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
• Influenza

Standard of care Generally recommended
120
Summary of OIs for Which Prevention Is Recommended

• Secondary Prophylaxis
• Pneumocystis jiroveci pneumonia (PCP)
• Toxoplasmosis
• Mycobacterium avium complex (MAC)
• Cryptococcosis
• Histoplasmosis
• Coccidioidomycosis
• Cytomegalovirus
• Salmonella bacteremia

Standard of care Generally recommended
121
OIs for Which Prevention Is Not Routinely
Indicated

• Secondary Prophylaxis
• Herpes simplex virus
• Candida

• Primary Prophylaxis
• Bacteria (neutropenia)
• Cryptococcosis
• Histoplasmosis
• Cytomegalovirus

Evidence for efficacy but not routinely
indicated
Recommended only if subsequent episodes are
frequent or severe
122
Indications for Possible Discontinuation of
Primary and Secondary Prophylaxis