Common Opportunistic
Infections in HIV Patients
Chris Farnitano, MD
Monday, August 31, 2009
Noon Conference
Objectives
• Discuss most common opportunistic
infections (OIs): Dx and Rx
• Discuss immune reconstitution disease
• Review primary OI prophylaxis
Forms
What are the most common OI’s?
• Cohort Studies in pre-triple therapy era:
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Candida
Pneumocystis Carinii
Cytomegalovirus
Mycobacterium Avium Complex
Pneumocystis - second episode
Toxoplasmi gondii
Herpes zoster
Causes of death, PHC HIV clinic
• 2007-9
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RH: Crypto meningitis
TW: street drug overdose
SA: sepsis, pneumonia and massive hemoptysis
DW: metastatic prostate ca
RP: CVA, laryngeal ca
VA: PML (progressive multifocal leukencephalopathy)
AM: bacterial pneumonia, ETOH cirrhosis, wasting
OIs diagnosed, PHC HIV clinic
• 2005-9
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PCP pneumonia
Esophageal Candidiasis
Herpes Simplex
Herpes Zoster
M. Kansasii immune reconstitution pneumonia
Mycobacterium Avium Complex (MAC)
Cryptococcal Fungemia, meningitis
Histoplasmosis
PML
Effect of HAART on
Opportunistic Infection Incidence
• Most OI’s have declined 80-90%
• OI’s seen now mostly in 3 groups
– undiagnosed HIV+
– not in care or not adhering to therapy
– long time “battle-scarred warriors” failing after
a long history of multiple regimens
More people living with AIDS
Pyramid or iceberg model
Strata of Pyramid
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>350 T Cells
350-200
50-200
<50
>350 T Cells
• Increased incidence of diseases that also
affect normal hosts:
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Recurrent Vaginal Candidiasis
Pulmonary Tuberculosis
Pnuemococcal Pneumonia
Cervical Dysplasia
Pulmonary TB
200-350 T Cells:
• Herpes Simplex
• Herpes Zoster
• Thrush
Herpes Zoster (Shingles)
50-200 T Cells:
• Pneumocystis Carinii Pnuemonia
• Toxoplasmosis
• Cryptococcus
Toxoplasmosis
<50 T Cells
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CMV Retinitis
Mycobacterium Avium Complex
Cryptosporidiosis
Progressive Multifocal Leukencephalopathy
PML
Ockham's razor does not apply
for advanced AIDS
• -often multiple diagnoses present
simultaneously
– ie PCP, CMV, KS, Cocci
– 12% of bacterial pneumonias also have PCP
– 10% of PCP pneumonia complicated by
bacterial infection
– search for second etiology if patient not
improving
Immune reconstitution diseases
(HAART attacks)
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MAC adenitis
CMV
TB
PCP
Primary OI prophylaxis
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PCP -T cells <200 or thrush
Toxo -T cells <100 and +Toxo titer
MAC - Tcells <50
TB – INH x 9 months if PPD >5mm or
quantiferon-TB positive
Quantiferon vs. TST in HIV patients
• Quantiferon not approved for use in
immunocomprimised
• 147 HIV patients in New Orleans given both tests:
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36% did not return for TST reading
15 positive by quantiferon
1 positive by TST
Quantiferon is more sensitive but without a gold
standard for latent TB infection cannot say whether it is
more or less specific
• Another study showed similar positive test result
rates but a better correlation with risk factors for
quantiferon vs. TST suggesting quantiferon is a
more specific test
Quantiferon vs. TST in HIV patients
• “Given the high risk for progression to active
disease in HIV-infected persons, any HIVinfected person with reactivity on any of the
current LTBI diagnostic tests should be
considered infected with M. tuberculosis”
• ----CDC guidelines, 3/24/09
PCP Prophylaxis
• Septra SS or DS qd or DS TIW
– Single strength has similar efficacy with fewer adverse
reactions (I.e. late onset rash, hepatotoxicity, fever)
– 25-50% of AIDS pts. D/c Septra DS due to reactions
• Septra Desensitization:
– 1cc qd x 3d, then 2cc qd x 3d, then 5ccqd x 3d, then
one SS tab qd
• Dapsone 100mg qd +pyramethamine 50mg qweek
+ leukovorin 25mg qweek
• Aerosolized pentamadine 300mg q month
• Atavaquone 1500mg qd
Aerosolized pentamidine booth
Toxo prophylaxis
• Septra SS or DS qd or DS TIW
• Septra Desensitisation:
– 1cc qd x 3d, then 2cc qd x 3d, then 5ccqd x 3d,
then one SS tab qd
• Dapsone 100mg qd +pyramethamine 50mg
qweek + leukovorin 25mg qweek
• Atovaquone 1500mg qd
MAC prophylaxis
• Zithromax 600mg x 2 tabs qweek reduces
infection rate 59%
• Also seems to reduce risk of PCP
Specific Opportunistic Infections
Case Study: HW
• 51 yo male with poor adherence to meds
• HIV + since at least 1996
• 1st episode thrush March,2005
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C/o dry mouth
Exam: white patches on buccal mucosa
T Cells 54
Treated with fluconazole, sx resolve
Case Study: HW
• Recurrent thrush July, 2005
– Fluconazole again prescribed
• September, 2005
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C/o odynophagia
Dx: probably esophageal candidiasis
Fluconazole again prescribed
Sx resolve in 3 days
Case Study: HW
• Recurrent odynophagia January, 2006
– Switched to itraconazole liquid
– 3 weeks later:
• odynophagia resolved
• Thrush persists, resolved on re-exam March, 2006
• August, 2006-March, 2007
– Recurrent episodes of thrush and esophageal
candidiasis due to non-adherence to intraconazole
– Each episode improves when patient is adherent
Case Study: HW
• April, 2007
– Persistent thrush despite stated adherence
– Switched to Voriconazole
– Sx resolve
November, 2007 T Cells 5 Weight 121# (baseline 198#)
-recurrent odynophagia despite adherence to voriconazole
Admitted for IV Capsofungin
Sx markedly improve in 24 hours
Fungal Cx: Candida Albicans
Sensitivities: resistant to fluconazole, itraconazole and
voriconazole
Case Study: HW
• December 2007-August 2008
– Persistent extensive thrush
– Continued on Voriconazole
– T cells 54 -> 12
August 2008: moves in with sisters after hospital
stay, adherence improves markedly
January 2009: T cells 77, thrush much improved
April, 2009: T cells 239, thrush resolved
Candida
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Thrush
Angular Chelitis
Vaginal Candidiasis
Esophageal Candidiasis
Thrush
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cottage cheese plaques
soft palate, buccal mucosa, tonsils
can be removed with a tongue blade
also erythematous form without exudate
Thrush
Angular chelitis
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pain
fissures
erythema
difficulty opening mouth
Angular Chelitis
Recurrent Vaginal Candidiasis
• less frequent than you would expect, unless
T Cells<100
• can use Fluconazole 200mg qweek for
suppression
Esophageal Candidiasis
• odynophagia
• usually also has thrush (positive predictive value
is 90%, but 18% of esophageal candidiasis
presents without thrush)
• Treat empirically x 5-7 days
• if not better, scope to r/o other causes:
– CMV, HSV, idopathic esophageal ulcers, lymphoma
• Secondary prophylaxis needed
Esophageal Candidiasis
Treatment:
• Fluconazole 100-200mg qd until sx resolve
• Alternatives for resistant Candida:
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Higher dose fluconazole (400-800 mg/d
Itraconazole
Voriconazole
IV Capsofungin
IV Amphotericin
PCP - Who gets it:
• Septra prophylaxis highly efficatious
• Risk if T Cells <200 or thrush
PCP - Symptoms
• insidious onset
– 2-4 weeks of progressive symptoms
• Fever, sweats, weight loss, fatigue,
nonproductive cough
• progressive dyspnea
• retrosternal discomfort
PCP - Signs
• Lung exam usually normal
• CXR: bilateral diffuse interstitial infiltrate
in 80-90%
• LDH>400 in 62%
• PO2<75 in 66%
PCP Pneumonia
Severe PCP
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PCP - Diagnosis
• Induced sputum x 3 in early AM (all on
same day): 50-70% sensitive
• Bronchoscopy (+/-Bx): 80-90% sensitive
• PCR based tests
• To collect sputums or go directly to bronch?
PCP - Treatment
• Can begin before Dx confirmed without
affecting diagnostic yield
• Prednisone 40mg BID x 5d. Then taper over
total 21d.
• Septra 15mgTMP/kg/d IV div. Q8h x 21d.
– Switch to po when improved
• give first dose prednisone 15-30 minutes
before Septra
Approach to HIV patient with
Pneumonia
• What is the T Cell Count?
T cell Count >200:
• TB presents in typical fashion
– cavitary in 50-60%
– isolate only if CXR suspicious for TB
• Opportunistic infections unlikely
– can treat empirically for bacterial infection
– S. pneumoniae, H. Flu most common
(encapsulated)
• Also consider: Non-Hodgkin’s Lymphoma
T cell Count <200:
• TB presents as lower lobe disease,
adenopathy, miliary or interstitial pattern
– cavitary in only 29%
– isolate all abnormal CXR until TB ruled out
• Opportunistic infections likely
– obtain definitive diagnosis whenever possible
– Coccidiomycosis, Cryptococcus, Aspergillis
– CMV, KS, M.TB, M. Kansasii
Don’t Treat PCP empirically
• experienced physicians make wrong clinical
diagnosis in 20% of suspected PCP
• patients treated empirically have higher risk of
death than patients who underwent bronch
• High incidence of rash toward end of 21 d. Septra
course
• Adjunctive steroids may exacerbate other OIs
• Many etiologies left uncovered
Cytomegalovirus Retinitis - Who
Gets It?
• Rare above 50 T Cells
• Reactivation disease: most HIV patients
CMV IgG+ (90% of gay HIV+ men)
• 90% of CMV disease is retinitis
Cytomegalovirus Retinitis Symptoms
• painless, progressive visual loss
• unilateral blurry vision
• floaters
Cytomegalovirus Retinitis Signs
• coalescing white perivascular exudates
• surrounded by hemorrhage
• brushfire pattern or tomato and cheese pizza
Cytomegalovirus Retinitis
Cytomegalovirus Retinitis
Cytomegalovirus Retinitis Diagnosis
• if you suspect it, obtain ophthalmologist
confirmation within 24-48 hrs.
Cytomegalovirus Retinitis Treatment
• Valgancyclovir 900mg PO BID x 21 days,
then qd
• Adverse effects:
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neutropenia ANC<500 in 15%
thrombocytopenia
anemia
50%: nausea, vomiting, abdominal pain or
diarrhea
Gangcyclivir intraocular implant
• Consider in addition to systemic therapy:
– Surgically implanted depo device
– Effective for 6 months
– Replace at 6 months if still not immune
reconstituted
– Consider for sight threatening lesions near the
central visual field
Mycobacterium avium Complex Who gets it?
• T Cells <50
• screen with blood culture for AFB x 1 q 3
months to detect subclinical disease
Mycobacterium avium Complex Symptoms
• fever, night sweats
• weight loss
• diarrhea
Mycobacterium avium Complex Signs
• anemia
• neutropenia
Mycobacterium avium Complex Diagnosis
• Blood culture usually positive if
symptomatic but takes weeks to grow
• If need to know sooner then do bone
marrow Bx
• Positive sputum culture usually
colonization, not active disease
• Positive stool culture may be colonization,
not active disease
MAC-filled macrophages in
spleen
Mycobacterium avium Complex Treatment
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Clarithromycin 500mg BID +
Ethambutol 15mg/kg/d +/Rifabutin 300mg qd
Treatment failure rate is high without
immune reconstitution
– drug toxicity
– development of resistance
Forms
Summary:
• Pyramid approach
• Prophylaxis simple: Septra and Zithromax
• Rule out TB in pneumonia with T Cells
<200
• Avoid treating PCP empirically
• An ounce of prevention pills is worth a
pound of Treatment pills
An ounce of prevention pills is
worth a pound of Treatment pills