Introduction to Clinical HIV

1
Introduction to Clinical HIV

• Joe Caperna, MD
• University of California, San Diego
• Presented _at_ Provincial Hospital, PE,South Africa
• 2 Feb 2009

2
ObjectivesAt end of session, participants will
be able to

• 1) Describe HIV, as a retrovirus, and understand
  the basics of its life cycle
• Define AIDS, as a case-based definition

3
Objectives--At end of session, participants will
be able to

• 3) Compare and contrast staging of HIV and
  definition of AIDS
• South African Guidelines
• South African HIV Clinicians Society
• WHO
• CDC
• 4) Be able to explain HIV and AIDS to a patient,
  with emphasis on culturally sensitive useful
  terms

4
AIDS-AdultsCDC

• The 1993 AIDS Surveillance Case Definition of the
  U.S. Centers for Disease Control and Prevention

5
The 1993 AIDS Surveillance Case Definition of the
U.S. Centers for Disease Control and Prevention

• A diagnosis of AIDS is made whenever a person is
  HIV-positive and
• 1) he or she has a CD4 cell count below 200
  cells per microliter OR
• 2) his or her CD4 cells account for fewer
  than 14 percent of all lymphocytes OR
• 3) that person has been diagnosed with one or
  more of the AIDS-defining illnesses listed
  below.

6
AIDS-Defining Illnesses

• Candidiasis of bronchi, trachea, or lungs (see
  Fungal Infections)
• Candidiasis, esophageal (see Fungal Infections)
• Cervical cancer, invasive--HPV
• Coccidioidomycosis, disseminated (see Fungal
  Infections)
• Cryptococcosis, extrapulmonary (see Fungal
  Infections)
• Cryptosporidiosis, chronic intestinal (gt1 month
  duration) (see Enteric Diseases)
• Cytomegalovirus disease (other than liver,
  spleen, or lymph nodes)
• Cytomegalovirus retinitis (with loss of vision)
• Encephalopathy, HIV-related (see Dementia)
• Herpes simplex chronic ulcer(s) (gt1 month
  duration) or bronchitis, pneumonitis, or
  esophagitis
• Histoplasmosis, disseminated (see Fungal
  Infections)
• Isosporiasis, chronic intestinal (gt1 month
  duration) (see Enteric Diseases)
• Kaposi's sarcoma, HHV8
• Lymphoma, Burkitt's, EBV
• Lymphoma, immunoblastic
• Lymphoma, primary, of brain (primary central
  nervous system lymphoma)
• Mycobacterium avium complex or disease caused by
  M. Kansasii, disseminated
• Disease caused by Mycobacterium tuberculosis, any
  site (pulmonary or extrapulmonary) (see
  Tuberculosis)
• Disease caused by Mycobacterium, other species or
  unidentified species, disseminated

7
AIDS-AdultsWHO

• 2006 Update
• All conditions listed in 1993 CDC MMWR
• Plus
• Symptomatic HIV-associated Nephropathy
• Symptomatic HIV-associated Cardiomyopthy
• Atypical disseminated Leishmaniasis
• NOT
• Pulmonary TB, only extrapulmonary TB

8
AIDS-AdultsSouth Africa

• 2004 ARV Guidelines
• WHO Stage 4 Disease

9

• What is HIV?
• What is AIDS?
• How do you describe HIV and AIDS in Xhosa?
• Germ Ngculasi
• CD4 isoldati, or amajoni

10
Practice speaking to patients

• Role play with other member of the class
• Emphasize the importance of being consistent
  about a few basic terms used with all patients,
  then tailer or modify the message to each
  individual patient and his/her needs.

11

• First, we will review WHO guidelines of when to
  start therapy

12
(No Transcript)
13
(No Transcript)
14
(No Transcript)
15
(No Transcript)
16
(No Transcript)
17
CDC guidelines, Nov 2008
18
South African Guidelines1st ed 2004
19
(No Transcript)
20
Outcomes of Care
21
T cell immunophenotyping

• Absolute CD4 WBC (Lymphs)(CD4)
• Diurnal variation in abs CD4 50-150 in normal
  adults, but less in patients with low CD4
• Day-to-day variation
• Other sources of error
• delay in processing sample
• refrigeration
• CD4 is more stable number
• 14 CD4 corresponds roughly to 200 abs CD4

22
Important Principles regarding Opportunistic
Infections in AIDS

• Ockhams razor may not apply
• There may be, and often is, more than one
  opportunistic process occurring simultaneously in
  the same organ or other organs
• Differential diagnosis ranking should take into
  account
• Disease stage (clinical and immunological)?sets
  risk thresholds
• Local relative frequency of specific etiologies
  (prior probabilities)
• Prophylaxis?modifies risk of disease
• Therapy for most opportunistic infections
  includes
• Acute phase management
• Maintenance phase to prevent relapse

23
(No Transcript)
24
(No Transcript)
25
(No Transcript)
26
Syndromic Approach to Pulmonary Symptoms
NON-PRODUCTIVE COUGH, FEVER, DYSPNEA
/ - INTERSTITIAL INFILTRATES
HOW IMMUNOSUPPRESSED IS PATIENT?
IS PATIENT AT RISK FOR MAJOR OI? HAS PATIENT
BEEN ON PCP PROPHYLAXIS FOR SEVERAL MONTHS?
IF YES, MODIFIES RISK FOR CURRENT PCP
INITIATE SPECIFIC DIAGNOSTIC TESTS
INDUCED SPUTUM FOR PCP ( 50 SENSITIVE)
LDH CONSIDER DDX
TUBERCULOSIS VIRAL TRACHEOBRONCHITIS OR
PNEUMONIA
MYCOPLASMA, LEGIONELLA
COCCI, CRYPTOCOCCUS,
HISTO INITIATE TREATMENT BEFORE CONFIRMATION
OF DIAGNOSIS USE APPROPRIATE DOSES
(LOOK THEM UP) MONITOR CLOSELY
OXYGENATION WBC, PLATELETS, RENAL
HEPATIC FUNCTION IF DX IS PCP, DON'T CHANGE
PRIMARY DRUG THERAPY UNTIL DAY 5 - 7

27
This is CLINICAL MEDICINE

• Take Syndromic Approach to all patients.
• At presentation, patients present with
  constellation of signs and symptoms, literally
  only a syndrome, and no diagnosis.

28
Mild Pneumocystis Pneumonia
29
PCP
Severe Pneumocystis Pneumonia
30
Residual Cyst 6 weeks after Rx of PCP
31
PULMONARY SYNDROMES
PRODUCTIVE COUGH, FEVER, HYPOXEMIA AND/OR
INFILTRATES
HOW IMMUNOSUPPRESSED IS THE PATIENT? IF
RECENT CD 4 gt 500, MORE LIKELY NON-OPPORTUNISTIC
PROCESS ALWAYS CONSIDER TB REGARDLESS
OF CD4 COUNT OBTAIN SPUTUM GRAM STAIN, AFB,
FUNGUS, LEGIONELLA OBTAIN BLOOD CULTURES
DOES CXR SHOW CONSOLIDATION ----------gt
BACTERIAL PNEUMONIA INTERSTITIAL
PATTERN ---gt CONSIDER OIs DESPITE PURULENT
SPUTUM NODULES CONSIDER FUNGAL
PNEUMONIA, SEPTIC EMBOLI, KS
CAVITATION TB, FUNGAL, NOCARDIA, NECTROTIZING
PNEUMONIAS IS PATIENT NEUTROPENIC? IS THERE A
CENTRAL LINE SOURCE? TREAT PROMPTLY AFTER
CULTURES REMEMBER, IN AIDS THERE IS OFTEN MORE
THAN ONE PROCESS
32

33
(No Transcript)
34
HIV-associated Tuberculosis

• Early HIV infection (CD4gt400)
• Reactivation
• Typical presentation with upper lobe cavitary
  disease most commonly
• Tuberculin reaction 5mm in 80
• Later HIV infection (CD4lt400)
• Either reactivation or progressive primary
• Mediastinal/hilar adenopathy with progression to
  diffuse, somewhat coarse interstitial infiltrates
  or focal infiltrates in mid or lower lung fields
• Extra-pulmonary involvement in 1/2-1/3 of cases

35
Diagnosis of Pulmonary Tuberculosis

• Smear microscopy- Positive in 40-50
• Direct
• Concentrates
• Culture-Positive in 80-90
• Rapid nucleic acid tests
• MTD, Amplicor
• UCSD rule out TB protocol
• 3 induced sputa for AFB smear and culture
• 1 MTD test (on smear if any are smear )

36
(No Transcript)
37
Coccidioidomycosis
38
Disseminated Mycobacterial Diseases

• Tuberculosis
• Mycobacterium avium
• CD4 lt50
• Bacteremia, GI, Lymph Node
• Febrile wasting syndrome
• Mycobacterium Kansasii
• Pulmonary
• Cutaneous
• Osteomyelitis

39
Syndromic Approach to CNS Syndromes (USA)
HEADACHE ( / - FEVER) DDx CNS MASS
LESION, MENINGITIS, SINUSITIS
EXTRA CRANIAL MASS OR INFILTRATIVE PROCESS (e.g.
lymphoma) DRUG INDUCED (e.g.
AZT) VASCULAR,
TENSION FOCAL ABNORMALITIES ON CT OF BRAIN IN
AIDS TOXOPLASMOSIS
50 - 70 PRIMARY CNS
LYMPHOMA 10 - 25
PML
10 - 22 OTHER DISEASES
9
NON DIAGNOSTIC BIOPSIES
10 INFREQUENT ETIOLOGIES OF CNS MASSES
IN AIDS CRYPTOCOCCOMAS, HISTOPLASMOMAS,
COCCIDIOIDAL ABSCESSES ACANTHAMOEBA
(GRANULOMATOUS AMOEBIC ENCEPHALITIS)
TUBERCULOUS ABSCESSES BACTERIAL
BRAIN ABSCESSES FOCAL VIRAL
ENCEPHALITIS HSV, VZV, CMV CANDIDAL
ABSCESSES ASPERGILLOSIS
NOCARDIOSIS METASTATIC TUMORS
ROLE OF TOXOPLASMA SEROLOGY IN DECISION MAKING RE
BRAIN BIOPSY
40
Toward a Syndromic Approach to Meningeal
Syndromes
41
MENINGITIS CRYPTOCOCCAL MENINGITIS
CSF FREQUENTLY WITH NORMAL PARAMETERS (glucose,
protein, wbc) INDIA INK IN 82
CSF ANTIGEN IN gt 90 CSF CULTURE IN
100 BLOOD CULTURES FREQUENTLY
SERUM ANTIGEN FREQUENTLY (at least 12 in
75-99)
ASEPTIC MENINGITIS (HIV RELATED AND NON-HIV
RELATED) LYMPHOCYTIC PLEOCYTOSIS
MILD ELEVATION OF PROTEIN NORMAL
GLUCOSE TUBERCULOUS MENINGITIS
LYMPHOCYTIC PLEOCYTOSIS (25 - 1000)
ELEVATED PROTEIN (45 - 500 mg) GLUCOSE
LOW ( 10-45 mg) MENINGOVASCULAR SYPHILIS
LYMPHOCYTIC PLEOCYTOSIS ( 10 - 100, normal in
45) PROTEIN 45 - 150 (normal in 30)
GLUCOSE NORMAL USUALLY (but
apparently not always) HAVE REACTIVE CSF VDRL
CMV POLYRADICULITIS NEUTROPHILIC PLEOCYTOSIS,
SHELL VIAL, Rx GCV OTHERS BACTERIAL----gt
NEUTROPHILIC PLEOCYTOSIS
LYMPHOMATOUS REACTION TO
PARAMENINGEAL FOCUS
42
Diarrhea without Fecal Leukocytes

• PATHOGEN DIAGNOSIS TREATMENT
• CRYPTOSPORIDIOSIS AURAMINE/AFB SMEAR
  Nitazoxanide, ARVs
• ISOSPORIASIS O P EXAM
  SEPTRA/ P S
• GIARDIASIS O P EXAM
  FLAGYL/QUINACRINE
• MICROSPORIDIA STOOLBIOPSY
  w/E.M. ALBENDAZOLE
• MAI
  AFB Culture CLARI EMB
• 
  BIOPSY
• CMV
  BIOPSY GCV,
  FOSCARNET
• LYMPHOMA BIOPSY
  CHEMOTHERAPY
• AIDS ENTEROPATHY DX OF EXCLUSION
  SUPPORTIVE, ARVs

43
Diarrhea with Fecal Leukocytes

• PATHOGEN DIAGNOSIS
  TREATMENT
• SHIGELLA C S
  CIPRO, SEPTRA
• SALMONELLA C S (blood
  too) CIPRO, AZITHRO
• CAMPYLOBACTER CS
  AZITHRO, CIPRO
• CLOSTRIDIUM DIFFICILE CULTURE,TOXIN
  FLAGYL,VANCO
• CMV
  BIOPSY GCV/FOSCARNET
• AMOEBIASIS (severe) O P, SEROLOGY
  FLAGYLIODOQUINOL

44
Parasitic Etiologies

• Cryptosporidia Isospora

45
Affect of HAART on Opportunistic Infections
46
Immune Recovery Inflammatory Reactions

• Paradoxical inflammatory reactions due to
  concurrent or antecedent opportunistic condition
  after treatment with HAART
• Characteristic syndrome reported for CMV, MAC,
  MTb, Cryptococcus, JC Virus, Hepatitis B C
• Often present with recrudescent fever and focal
  inflammation in setting of declining viral load
  and rising CD4
• DDx includes pathogen reactivation, another
  pathogen, drug reaction

DeSimone et al. Ann Intern Med 2000133447-454
47
Drug Toxicities and Interactions
48
Mitochondrial Toxicity Syndromes

• Hyperlactatemia or lactic acidosis
• Hepatic steatosis
• Non-specific GI symptoms (bloating, nausea)
• Mild transaminase elevation
• Due to nucleoside analog HIV reverse
  transcriptase inhibitor therapy (D4T most
  commonly)
• May have normal anion gap despite elevated
  lactate.

49
Cytochrome P-450, HIV-1 Protease Inhibitors and
NNRTIs
50
Cytochrome P-450, HIV-1 Protease Inhibitors and
NNRTIs
51
CONCLUSIONS

• CD4 count DRIVES all differential diagnoses in
  HIV.
• Think syndromically, in syndromes first, then in
  specific diagnoses or pathogens.
• Ockhams razor may not apply